FORENSIC PATHOLOGY REVIEWS Volume 1 - Securimetric

Forensic 

Pathology 

Reviews 

Volume 1 

Edited by 

Michael Tsokos, MD

Forensic Pathology Reviews

FORENSIC PATHOLOGY REVIEWS 

Michael Tsokos, MD, SERIES EDITOR 

FORENSIC PATHOLOGY REVIEWS, VOLUME 1, edited by Michael Tsokos, 2004

FORENSIC 

PATHOLOGY 

REVIEWS 

Volume 1 

Edited by 

Michael Tsokos, MD 

Institute of Legal Medicine, University of Hamburg, 

Hamburg, Germany 

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Forensic pathology reviews, Volume 1 / edited by Michael Tsokos. 

p. cm. 

Includes bibliographical references and index. 

ISBN 1-58829-414-5 (alk. paper) 

1. Forensic pathology. I. Tsokos, Michael. 

RA1063.4.F675 2004 

614.1--dc22 

2003027503

Series Introduction 

Over the last decade, the field of forensic science has expanded enormously. 

The critical subfield of forensic pathology is essentially based on a transverse, 

multiorgan approach that includes autopsy, histology (comprising 

neuropathological examination), immunohistochemistry, bacteriology, DNA 

techniques, and toxicology to resolve obscure fatalities. The expansion of the 

field has not only contributed to the understanding and interpretation of many 

pathological findings, the recognition of injury causality, and the availability of 

new techniques in both autopsy room and laboratories, but also has produced 

specific new markers for many pathological conditions within the wide variety 

of traumatic and nontraumatic deaths with which the forensic pathologist deals. 

The Forensic Pathology Reviews series is designed to reflect this expansion 

and to provide up-to-date knowledge on special topics in the field, focusing closely 

on the dynamic and rapidly growing evolution of medical science and law. 

Individual chapters present a problem-oriented approach to a central issue of 

forensic pathology. A comprehensive review of the international literature that is 

otherwise difficult to assimilate is given in each chapter. Insights into new 

diagnostic techniques and their application, at a high level of evidential proof, to 

the investigation of death will surely provide helpful guidance and stimulus to 

all those involved with death investigation. 

It is hoped that this series will succeed in serving as a practical guide to 

daily forensic pathological and medicolegal routine, as well as in providing 

encouragement and inspiration for future research projects. I wish to express my 

gratitude to Humana Press for the realization of Forensic Pathology Reviews. 

v 

Michael Tsokos, MD

Preface 

The development of specialized areas of expertise within the field of forensic 

science places heavy demands on the forensic pathologist, as well as the medical 

examiner and the coroner, to provide satisfactory answers to the investigating 

authorities in specific cases. Forensic Pathology Reviews, Vol. 1 concentrates on 

common forensic pathological topics likely to be encountered in the daily routine, 

as well as on specific pathological conditions rarely seen in the autopsy room. 

Chapter 1 provides a fundamental and detailed look at what the forensic 

pathologist, as well as the medical examiner and the coroner, can expect when 

dealing with burn victims and offers expert guidance on how best to accurately 

interpret both gross pathology and histological changes. Chapters 2 and 3 focus 

on trauma deaths and provide an interesting insights into the reconstruction of 

events in fatalities resulting from kicking and trampling, as well as an up-to-date 

overview of new immunohistochemical markers applicable to the investigation 

of traumatic brain injury. Chapter 4 provides an exhaustive overview of the 

pathology of the central nervous system in drug abuse and points out clinical as 

well as toxicological implications relevant to the forensic pathologist. Chapter 5 

takes a comprehensive look at the pathological examination of the heart in cases 

of sudden cardiac death and provides details of appropriate dissection techniques 

and the interpretation of histopathological findings. Chapters 6 and 7 present 

medicolegal problems in cases of neonaticide and sudden infant death, pointing 

to possible pitfalls associated with the forensic expertise in such cases. Chapters 

8 and 9 cover the pathological features of Mycoplasma pneumoniae and 

Waterhouse-Friderichsen syndrome, two infectious diseases that have been 

generally overlooked in the textbooks and manuals of forensic pathology. 

Chapters 10 and 11 are of special interest to police officers and other 

members of investigative agencies. These chapters cover the whole spectrum of 

odd scenarios, such as accidental autoerotic deaths and hypothermia fatalities, 

that can present at the death scene and hence may lead the inexperienced 

investigator to the false conclusion about the occurrence of a crime. Chapter 12 

describes the pathological features of maternal death from hemolysis, elevated 

liver enzymes, and a low platelet count (HELLP), showing the relevant aspects 

vii

Preface viii 

every forensic pathologist should know when giving a medicolegal expertise in a 

suspected case of medical malpractice related to this syndrome. Chapter 13 

addresses the pathology of injuries resulting from resuscitation procedures and 

how to distinguish these artifacts from the sequels of a natural disease process or 

trauma that occurred prior to resuscitation. Chapter 14 deals with the interpretation 

of alcohol levels in different specimens from deceased and living persons, 

including the presentation and usage of formulae for the estimation of alcohol 

concentrations, as well as the observance of the legal chain of custody in such 

cases. Chapter 15 devotes attention to a rare, but nonetheless important, 

pathological finding, iliopsoas muscle hemorrhage, and the potential forensic 

differential diagnoses and interpretation of this finding in the light of autopsy. 

I owe great thanks to my contributors who are well-recognized national 

and international researchers and pioneers in their particular scientific fields. 

Each of them deserves my deepest loyalty for making their practical and scientific 

knowledge available. 

Michael Tsokos, MD

Contents 

Series Introduction............................................................................................. v 

Preface ............................................................................................................ vii 

Contributors ......................................................................................................xi 

DEATH FROM ENVIRONMENTAL CONDITIONS 

1 Morphological Findings in Burned Bodies 

Michael Bohnert......................................................................................... 3 

TRAUMA 

2 Kicking and Trampling to Death: Pathological Features, 

Biomechanical Mechanisms, and Aspects of Victims and Perpetrators 

Véronique Henn and Eberhard Lignitz ................................................... 31 

NEUROTRAUMATOLOGY 

3 Timing of Cortical Contusions in Human Brain Injury: 

Morphological Parameters for a Forensic Wound-Age Estimation 

Roland Hausmann ................................................................................... 53 

FORENSIC NEUROPATHOLOGY 

4 Central Nervous System Alterations in Drug Abuse 

Andreas Büttner and Serge Weis ............................................................. 79 

SUDDEN DEATH FROM NATURAL CAUSES 

5 A Forensic Pathological Approach to Sudden Cardiac Death 

Vittorio Fineschi and Cristoforo Pomara .............................................. 139 

CHILD ABUSE, NEGLECT, AND INFANTICIDE 

6 Medicolegal Problems With Neonaticide 

Roger W. Byard....................................................................................... 171 

SIDS 

7 Diagnostic and Medicolegal Problems With Sudden 

Infant Death Syndrome 

Roger W. Byard and Henry F. Krous ..................................................... 189 

ix

Contents x 

INFECTIOUS DISEASES 

8 Fatal Respiratory Tract Infections With Mycoplasma pneumoniae: 

Histopathological Features, Aspects of Postmortem Diagnosis, 

and Medicolegal Implications 

Michael Tsokos....................................................................................... 201 

9 Pathological Features of Waterhouse–Friderichsen Syndrome 

in Infancy and Childhood 

Jan P. Sperhake and Michael Tsokos .................................................... 219 

DEATH SCENE INVESTIGATION 

10 Accidental Autoerotic Death: A Review 

on the Lethal Paraphiliac Syndrome 

Stephan Seidl ......................................................................................... 235 

11 Lethal Hypothermia: Paradoxical Undressing and 

Hide-and-Die-Syndrome Can Produce Very Obscure Death Scenes 

Markus A. Rothschild ............................................................................ 263 

MATERNAL DEATH IN PREGNANCY 

12 Pathological Features of Maternal Death From HELLP Syndrome 

Michael Tsokos....................................................................................... 275 

IATROGENIC INJURY 

13 Injuries Resulting From Resuscitation Procedures 

Mario Darok ........................................................................................... 293 

TOXICOLOGY 

14 Postmortem Alcohol Interpretation: Medicolegal Considerations 

Affecting Living and Deceased Persons 

Donna M. Hunsaker and John C. Hunsaker III .................................. 307 

FORENSIC DIFFERENTIAL DIAGNOSIS 

15 Iliopsoas Muscle Hemorrhage Presenting at Autopsy 

Elisabeth E. Türk ................................................................................... 341 

Index .............................................................................................................. 355

Contributors 

MICHAEL BOHNERT, MD • Institute of Forensic Medicine, University Hospital 

of Freiburg, Freiburg, Germany 

ANDREAS BÜTTNER, MD • Institute of Legal Medicine, University of Munich, 

Munich, Germany 

ROGER W. BYARD, MBBS, MD • Forensic Science Centre, Adelaide, Australia 

MARIO DAROK, MD • Institute of Forensic Medicine, University of Graz, Graz, 

Austria 

VITTORIO FINESCHI, MD, PhD • Institute of Forensic Pathology, University 

of Foggia, Foggia, Italy 

ROLAND HAUSMANN, MD • Institute of Legal Medicine, Friedrich-Alexander- 

University Erlangen-Nürnberg, Erlangen, Germany 

VÉRONIQUE HENN, MD • Institute of Legal Medicine, University of Halle, Halle, 

Germany 

DONNA M. HUNSAKER, MD • Office of the Chief Medical Examiner, Louisville, KY 

JOHN C. HUNSAKER III, MD, JD • Department of Pathology and Laboratory 

Medicine, University of Kentucky College of Medicine, Lexington, KY 

HENRY F. KROUS, MD • Department of Pathology, Children’s Hospital-San 

Diego, University of California, San Diego School of Medicine, San Diego, 

CA 

EBERHARD LIGNITZ, MD • Institute of Legal Medicine, University of Greifswald, 

Greifswald, Germany 

CRISTOFORO POMARA, MD • Institute of Forensic Pathology, University of Foggia, 

Foggia, Italy 

MARKUS A. ROTHSCHILD, MD • Institute of Legal Medicine, University of Cologne, 

Cologne, Germany 

STEPHAN SEIDL, MD • Institute of Legal Medicine, Friedrich-Alexander-University 

Erlangen-Nürnberg, Erlangen, Germany 

JAN P. SPERHAKE, MD • Institute of Legal Medicine, University of Hamburg, 


xi

Contributors xii 

MICHAEL TSOKOS, MD • Institute of Legal Medicine, University of Hamburg, 


ELISABETH E. TÜRK MD • Institute of Legal Medicine, University of Hamburg, 


SERGE WEIS, MD • Neuropathology Laboratory, The Stanley Medical Research 

Institute, Bethesda, MD

Burns 1 

Death From Environmental 

Conditions

2 Bohnert

Burns 3 

1 

Morphological Findings 

in Burned Bodies 

Michael Bohnert, MD 

CONTENTS 

INTRODUCTION 

EXTERNAL FINDINGS 

INTERNAL FINDINGS 

REFERENCES 

SUMMARY 

Morphological findings in burned bodies may cover a broad spectrum. 

They can range from minor, local, superficial burns of the skin to calcined 

skeletal remains without any soft tissue left. The external as well as the internal 

findings in burned bodies depend on the temperature actually applied to 

the body, the time for which it is applied, the kind of transmission of the heat 

to the body, and other prevailing conditions. The consequences are burns of 

the exposed tissue, changes in the content and distribution of tissue fluid, fixation 

of the tissue, and shrinking processes. In case of direct contact with the 

flames, the organic matter is consumed as fuel. Only in very rare cases do the 

effects of the heat cease with the time of death. Consequently, many findings 

seen at autopsy may be of postmortem origin with fluent transitions between intravital, 

perimortal, and postmortem changes. Apart from burns (first- to fourthdegree), 

the external findings may include leathery consolidation and tightening 

of the skin and the presence of partly long splits. The so-called pugilistic attitude 

is the result of the shrinkage of muscles and tendons. The internal organs may be 

considerably reduced in size because of fluid loss and consumption by the fire 

(so-called “puppet organs”). Heat-related fluid shifts may cause vesicular detachment 

of the epidermis (false burn blisters) on the skin and pseudo-hemorrhages in 

From: Forensic Pathology Reviews, Vol. 1 

Edited by: M. Tsokos © Humana Press Inc., Totowa, NJ 

3

4 Bohnert 

the form of heat hematomas inside the body. The latter are most frequently 

seen in the skull but can also occur in the hollow organs of the abdomen. In 

the same way, accumulations of large droplets of fat may occur in the vessels, 

the blood of the right ventricle, or the epidural space. The respiratory tract 

is the most important organ system for the diagnosis of vitality. Where fire 

fumes were inhaled, deposits of soot particles will be found. Edema or bleeding 

of mucous membranes and patchy or vesicular detachment of the mucosa 

may be indicative of an inhalation of hot gases. Consumption by the fire causes 

a progressive loss of soft tissue, exposure of the body cavities, and amputation 

of extremities. Complete cremation of an adult body is reached only under 

extreme circumstances. Even if high temperatures are applied for several hours, 

there will usually still be enough skeletal remains to allow successful determination 

of the species, the body measurements, and the sex as well as to identify 

skeletal anomalies and the presence of possible injuries. 

Key Words: Burns; charring; shrinkage of tissue; consumption by fire; 

heat-related fluid shift; spurious wounds; heat hematoma; skin splitting. 

1. INTRODUCTION 

The rate of annual deaths related to fire is about 13 per million inhabitants 

in the United States and Canada, and 6 per million inhabitants in Germany. 

These are mostly accidents (1–8) followed by suicides (9–16). Homicides 

with subsequent burning of the victim (17–24) or killings by burning (25,26) 

are comparatively rare in Europe just as in the United States and Japan and are 

reported more often from India (27–30) or South Africa (31,32). 

The morphological findings in burned bodies may cover a broad spectrum. 

They can range from minor, local, superficial burns of the skin to calcined 

skeletal remains without any soft tissue left and total incineration. The 

external just as the internal findings depend (a) on the temperature actually 

applied to the body, (b) the time for which it is applied, (c) the kind of transmission 

of heat to the body, and (d) other prevailing conditions. In most cases, 

the effects of heat on the body continue beyond death. Consequently, the 

changes found are largely of postmortem origin. The effects of heat on the 

body are (a) burns of the exposed tissue, (b) changes in the content and distribution 

of tissue fluids, (c) fixation of the tissue, and (d) shrinking processes 

(Table 1). The kind of heat influences the distribution and extent of the consequences 

just mentioned: under the direct effect of a fire, the loss of body mass 

is more pronounced than under radiant heat, because in the first case the organic 

matter of the body acts as fuel, whereas in the second case the loss of 

body mass results from the loss of tissue fluid.

Burns 5 

Table 1 

Effects of Heat on the Body and Related External and Internal Findings 

Effects of Heat External findings Internal findings 

Burns Burns of skin Burns and consumption of internal 

Singeing of hair organs and bones 

Consumption by fire Edema, mucosal bleeding, and 

detachment of the mucosa of airways 

Changes of content Skin blisters Vaporization of body fluids 

and distribution Rupture of abdominal wall with 

of tissue fluid prolapse of intestinal loops 

Leakage of fluid from mouth and nose 

Heat hematoma 

Accumulations of fat in body cavities, 

vessels, or heart 

Heat fixation Leatherlike, brownish Induration of internal organs and 

fixation of skin muscles 

Fragmentation of erythrocytes 

Shrinking of tissue Tightening of skin Shrinking of organs 

Splitting of skin “Puppet organs” 

Protrusion of tongue 

Petechial hemorrhages 

of neck and head 

Pugilistic attitude 

The forensic investigation of deaths related to fire is important in order 

to determine the manner and cause of death, the vitality of the findings, and 

the identity of the victim. The basis of the assessment is a careful evaluation 

of the autopsy findings. Additional investigations, such as outcome of toxicology 

(determination of carbon monoxide-hemoglobin [CO-Hb] concentration 

and cyanide concentration) or histology (particularly of the airways), may 

help to complete the assessment of the case. The present review deals with the 

morphological consequences of the effects of heat with the main emphasis 

being placed on the findings of postmortem origin. The problems associated 

with the diagnosis of vitality and the determination of the cause of death were 

recently described in a review (33). Therefore, they are mentioned on the fringe 

here only. The possibilities to determine the identity of a charred body are not 

dealt with in this review. The methods available for that purpose do not differ 

from those used for other deaths.

6 Bohnert 

2. EXTERNAL FINDINGS 

2.1. General Aspects 

Among the externally discernible changes, the dominant features are the 

various stages of skin burns, the results of tissue shrinkage, and the consumption 

by the fire. Destruction can be so extensive that the less experienced tend to 

consider an autopsy pointless because, in their opinion, it will not produce any 

findings anyway. But this opinion is definitely wrong: even in charred torsos 

with general incineration, exposure of the body cavities, and partial amputation 

of the extremities as a result of the fire, the organs of the thorax and abdomen 

can usually still be assessed quite well. Moreover, sufficient amounts of body 

fluids and tissue samples can be obtained for further investigations. 

2.2. Burns 

Skin burns are categorized into four degrees, with each degree characterizing 

a certain depth of the skin lesion. The categories are: degree 1— 

superficial burns, degree 2a—superficial partial-thickness burns associated 

with necrosis of the upper layers of the epidermis, degree 2b—deep partialthickness 

burns associated with necrosis of the entire thickness of the epidermis, 

degree 3—full-thickness burns with necrosis involving the dermis 

as well, and degree 4—charring in which the heat lesion reaches deeper 

soft-tissue layers. 

Skin burns are the result of temperature and duration of exposure: the 

higher the temperature, the lower the duration of exposure necessary to achieve 

a certain degree of burn. The lowest temperature considered necessary for 

causing damage is an actual skin temperature of 44°C, although under this 

condition no less than 6 hours are required to reach a second- to third-degree 

burn (34–36). Between 44°C and 51°C, a rise in temperature by 1°C halves 

the duration of exposure necessary to cause a certain degree of damage to the 

skin. Above 51°C, the excess heat is no longer conducted away by convection 

via the capillaries of the skin. The heat penetrates into the deeper layers of the 

tissue. For the actual skin temperature the kind of transmitting of the heat to 

the body is of major importance: the penetrating power of moist heat is considerably 

higher than that of dry heat (34–37). 

The usual staging of skin burns according to clinical symptoms is of 

minor importance in the forensic evaluation of findings, because no conclusions 

can be drawn from the degree of the burns to the intravital effects of the 

heat. The question of whether skin burns occurred while the victim was still 

alive is difficult to answer. Erythemas (first-degree burns) are characterized

Burns 7 

by dilated skin vessels. After circulation ceases, these empty so that postmortem 

reddening of the skin is usually no longer recognizable. As a postmortem 

residue of a first-degree burn, a red margin may occasionally be observed 

after the reddening of the skin has faded because of hypostasis (38). This phenomenon, 

which is difficult to detect even histologically, may, however, also 

be the result of postmortem effects of heat on the skin (39–41). The principle 

sign of second-degree burns are fluid-filled skin blisters. However, these can 

be regarded as a vital sign only if cellular reactions, such as the accumulation 

of leukocytes in the blister content, can be demonstrated (39,42,43). Fluidfilled 

blisters of the skin can also form postmortem. Then they are a result of 

a purely mechanical shift of fluid in the skin as owing to the effects of the heat. 

In most fire deaths, the body is exposed postmortem to temperatures of 

several hundred degrees celsius for at least several minutes, often by direct 

contact with the flames. Consequently, burned corpses most often show signs 

of charring on the outside of the body (4,8). In the rather rare cases of prolonged 

exposure to comparatively low temperatures, for example, in a smoldering 

fire, the skin is leathery, firm, and discolored brown (44). DiMaio and 

DiMaio described this aspect as “such as one sees in a well-done turkey” (44). 

A special form of skin changes caused by heat can be seen on the palms 

of the hands and the soles of the feet (45). A whitish discoloration of the 

epidermis associated with swelling, wrinkling, and vesicular detachment up 

to glovelike peeling can be observed (Fig. 1). The findings are reminiscent of 

the so-called washerwoman’s skin, as it is seen after prolonged exposure to a 

moist environment or in drowning deaths. Histological examination shows 

fluid-filled blisters in the stratum germinativum, hyperchromasia, and palisade 

arrangement of the nuclei as well as clumping of the erythrocytes corresponding 

to second-degree burns of the skin (39,46). Consequently, this is a 

morphological variation of a second-degree burn owing to the special anatomy 

of friction skin. 

Skin burns as well as the extent of burn injuries to human remains are 

never distributed evenly. Areas of the body pressed against the supporting 

surface or covered by clothing are often burned less than unclothed skin areas 

(44). Especially tight-fitting clothes can protect the underlying skin from burns 

for a long time. In the same way, it may be possible to prove a homicide by 

manual strangulation in a fire victim with the ligature still in place (47–49). In 

cases of suicidal self-incineration using fire accelerants, burns may be absent 

from the feet and lower legs if the incineration took place while the body was 

in an upright position (50,51). In burns caused by low heat, deep, anatomically 

circumscribed signs of consumption by the fire may occur. These are

8 Bohnert 

Fig. 1. Second-degree burns of the hand: whitish discoloration, swelling, and 

wrinkling of the epidermis of the palmar skin mimicking washerwoman’s skin. 

formed when the fire is maintained according to the wick principle: in those 

parts of the body where the skin has burned away, liquefied subcutaneous 

fatty tissue leaks out and maintains the fire (47,52,53). This process can go on 

for several hours (53). The often bizarre distribution of the burn lesions in 

such cases has given rise to the myth of spontaneous human combustion (54,55). 

Heat changes of the hair occur at temperatures above 150°C. This can be 

used to differentiate between burns and scalds or to indicate the approximate 

temperature reached in smoldering fires. The hair gets frizzy and brittle and 

assumes a fox-red or dark brown to black color. Temperatures of about 200°C 

lead to the formation of gas bubbles in the shaft, at 240°C the hair becomes 

frizzy owing to the melting of the hair keratins, and above 300°C charring 

occurs (56–58). Singeing of the head hair is usually not associated with high 

flames, but with a characteristic smell. In contrast to this, frizzy hair burns 

with high, open, and sustained flames causing severe damage to the neighboring 

skin or mucosa (59). The explanation for this phenomenon is the larger 

distance between the individual hairs, which allows better access of oxygen. 

2.3. Shrinkage of Tissue 

The reason why the tissue shrinks is the loss of fluid caused by the heat. 

Externally, it is characterized by tightening of the skin, splitting of the skin,

Burns 9 

protrusion of the tongue from the open mouth, petechial hemorrhages in the 

region of the neck and head, and the so-called pugilistic attitude. 

After prolonged exposure to high temperatures the skin is generally consolidated, 

of leathery, hard consistency. The surface is reduced because of 

tightening of the skin. Fire victims often show a very similar facial expression, 

which makes identification by inspection more difficult. The mouth is 

usually open with shrunken lips. In most cases the eyes are closed, and the 

shrunken lids can be opened only with difficulty and incompletely. In some 

cases, in which no or only a minor degree of postmortem burning occurred, 

there may be areas without burns and/or soot deposits in the angles of the eyes 

(Fig. 2) (47,60). These so-called “crow’s feet” are usually regarded as a sign 

of vitality and clue to a flash fire. However, this opinion is not undisputed. For 

instance, Bschor pointed out that “crow’s feet” may also occur in fire deaths 

without a flashover (60); therefore, squinting of the eyes as a reflex to the 

smoke was also considered a possibility. But one could also imagine a different 

mechanism of formation, namely shrinkage of the skin because of heat, 

resulting in a smoothing of the wrinkles of the face. Then the unsooted base of 

the wrinkles would become visible, which would manifest itself as “crow’s 

feet” around the eyes. Because of the shrinkage of the skin, pre-existing lesions 

become smaller and change in shape (47). For example, originally slitlike skin 

lacerations (e.g., stabs) may assume a circular shape. Moreover, lesions may 

migrate toward the center of the thermal damage (61). Because of the shrinkage 

of the perianal tissue, the anus gapes, which may be misinterpreted as the 

result of anal penetration (41). 

Splitting of the skin is a frequently observed phenomenon, particularly 

in charred bodies (Fig. 3). It is very rare in burns of minor severity. In these 

cases, prolonged exposure to the heat has to be assumed. The splits have sharp 

edges that can be brought into apposition, are often linear, but occasionally 

are also angled. In most cases, they reach the subcutaneous fatty tissue and, 

sometimes the outer muscle layers. This may be explained by the shrinkage 

of the skin caused by the heat (40,41,62). In this context, little attention is paid 

to the fact that the tissue exposed in the depth of the splits is usually unburned 

and often not even sooted. Possibly the splits form only during the cooling of the 

body or at least become wider in this process. They could also form as a consequence 

of manipulating the body while recovering and putting it into the coffin, 

when the skin, which is brittle owing to the heat, may tear easily. The appearance 

of heat splits in the skin may lead the inexperienced to interpret them as vital 

injuries. For the diagnosis of a genuine, penetrating wound, corresponding hemorrhages 

and wound tracks in the deeper tissue layers must be present.

10 Bohnert 

Fig. 2. “Crows feet” and protrusion of the tongue as a result of the heatmediated 

shrinkage of skin and soft tissue. 

Protrusion of the tongue from the open mouth is a result of the heatrelated 

shrinkage of the soft tissue of the neck (Fig. 2). In the presence of 

severe burns on the neck and/or thorax, petechial hemorrhages may occasionally 

be found in the lids and conjunctivae (60,63–65). The mechanisms involved 

in their formation are congestion in the upper parts resulting from the shrinkage 

of the soft tissue of the neck by heat or heat rigidity of the thorax while the 

circulation is still intact (60,64,65). So petechial hemorrhages in the region of 

the neck and head would have to be regarded as a vital sign. 

The typical posture of charred bodies is called pugilistic or boxer’s attitude, 

with the arms being abducted in the shoulder joint and flexed in the

Burns 11 

Fig. 3. Heat splits of the skin of the right leg and pseudo-washerwoman’s 

skin of the sole of the foot. 

elbow joint and the legs being abducted in the hip joint and flexed in the hip 

and knee joint (Fig. 4). The reason for this phenomenon is the shrinkage of 

muscles and tendons caused by the heat (60,63,66). The flexion in the joints 

of the extremities is because of the predominance of the flexor muscles. This 

flexion is particularly recognizable on the hands, which are clenched into fists 

in most cases. This may even result in the dislocation of the wrist. In the same 

way, contracted feet may be observed, especially after advanced consumption 

of the legs. In female corpses found faceup, the pugilistic attitude may be 

mistaken for the result of rape (60). However, the position of a charred body 

cannot always be explained by the effects of the heat alone. For example, 

mechanical obstacles, such as rubble from the fire lying on the legs of the 

deceased, may prevent flexion of the hip and knee joint. Also, in a side-lying

12 Bohnert 

Fig. 4. Pugilistic attitude of a burn victim. 

position (sleeping position), the pugilistic attitude is only vaguely discernible, 

if at all (60). When the body lies in prone position, the pugilistic attitude is not 

as pronounced as when it lies on its back. 

2.4. Consumption by the Fire 

The destruction of a body results from the direct exposure to flames. 

It causes loss of soft tissue, exposure of the body cavities, amputation of 

the extremities, and finally, consumption of the internal organs. Although 

the skeleton is also damaged by the fire, it is not consumed completely. 

Even if it is exposed to a fire with high temperatures over a long period of 

time, there will usually still be remains to allow macroscopic assessment 

and successful determination of the species, the body measurements, and

Burns 13 

Table 2 

Classification of the Destruction by Burns According to Eckert et al. (69) 

Level 1 Complete consumption by the fire—only ashes left 

Level 2 Incomplete consumption by the fire—bone fragments without soft tissue left 

Level 3 Partial consumption by the fire—soft tissue still present 

Level 4 Charring without loss of internal organs 

Table 3 

Classification of the Destruction by Burns According to Maxeiner (4) 

Level 1 Burns up to third degree, 50% of the body surface 

Level III Burns up to fourth degree, 75% of the body surface 

Level V Partial destruction of the body by charring,

14 Bohnert 

Table 4 

Crow–Glassman Scale (CGS) of Burn-Related Destruction of Corpses (76) 

Level 1 Second-degree burns, sometimes singeing of the hair; visual identification 

possible 

Level 2 Burns of varying severity, sometimes with thermal destruction/amputation 

of ears, genitals, hands, or feet; visual identification may still be possible 

Level 3 Consumption by the fire with partial amputation of arms and/or legs; cerebral 

cranium intact 

Level 4 Bony lesions of the cerebral cranium; residual extremities still present 

Level 5 Fragmented skeletal remains without soft tissue 

Table 5 

Classification of the Destruction by Burns According to Gerling et al. (7) 

Level A Minor loss of soft tissue, sometimes with rupture of the abdominal wall 

Level B Moderate loss of soft tissue, especially of the legs, with opening of the 

thoracic and/or abdominal cavity but sparing the head 

Level C Loss of soft tissue of the extremities and exposure of the skull; sometimes 

in combination with exposure of the thoracic and/or abdominal cavity 

higher temperatures produced by these fires. Massive destruction not only 

requires higher temperatures but especially a longer duration of exposure (8,77). 

The question as to what extent the level of charring in a burned body 

allows one to draw conclusions regarding the duration of the fire is rarely 

asked (21,38). In the literature there are few reports on this topic, most of 

which refer to observations made during cremations (23,77–80). Apart from 

these, there is a small number of case reports on fire deaths in which the duration 

of the fire is known (21,38,79,81). Systematic studies showed that the 

course of events follows a fixed chronological order: 30 minutes after the fire 

has been in full progress all body cavities are exposed and the distal portions 

of the extremities are amputated. The exposed bones show signs of calcination. 

After a minimum of 50 minutes and a maximum of 80 minutes, the internal 

organs are largely incinerated and the burned torso breaks apart (77). 

However, when applying these findings to real fire deaths one should take 

into consideration that the bodies in those cases are usually not exposed to a 

constant temperature level for a long period of time, but that a fire develops in 

several stages, and it will often not be possible to reconstruct the temperatures 

reached in the individual stages (79,82,83).

Burns 15 

3. INTERNAL FINDINGS 


The internal findings in fire deaths are the result of a fixation of the 

tissue by the heat, processes of shrinking, thermal changes of the content and 

distribution of tissue fluids, and a rising gas pressure in hollow spaces. After 

the body cavities have been exposed by the effects of the fire, direct burns 

occur also on the internal surfaces, and the organs are consumed by the fire. 

Before death, direct exposure of internal organs to the fire is possible in the 

respiratory tract. The inhalation of hot gases causes damage to the mucosa. 

The characteristic findings produced by this constellation are used especially 

in the diagnosis of vitality (33). 

The prolonged effect of high temperatures on the body results in the vaporization 

of body fluids. In closed cavities, such as the body cavities but also 

in hollow organs, high pressure may build up causing the wall to rupture. A 

frequently observed finding is the prolapse of intestinal loops following exposure 

of the abdominal wall due to the fire. Moreover, fluid can be pressed 

from the openings of the body, resembling changes resulting from putrefaction 

(38). 

The loss of fluid and, after exposure of the body cavities, the direct effect 

of the heat cause shrinking of the internal organs, which become firm, 

hardened, and cooked by the heat, the so-called “puppet organs” (Fig. 5) (84). 

Systematic observations of cremations showed that these changes occur 

between the 30th and 50th minute (77). If the fire continues, the surface of the 

organs becomes increasingly bosselated and is reduced to a spongelike residual 

structure in the end. The tissue is meanwhile completely desiccated and disintegrates 

into ash at the slightest touch. This condition was described as 

“Zermürbungspunkt” (crumbling point) by Gräff in his investigations of victims 

of the firestorm resulting from the air raid of Hamburg, Germany, during 

World War II (84). 

3.2. Respiratory Tract 

The respiratory tract is the most important organ system for the diagnosis 

of vitality. Where fire fumes were inhaled, deposits of soot particles will 

be found. On the other hand, the presence of soot aspiration does not necessarily 

prove that the victim was still alive when exposed to the fire, although this 

distinction is rarely made (4,33,40). Edema, mucosal bleeding, and patchy or 

vesicular detachment of the mucosa in the nose, mouth, pharynx, larynx, trachea, 

and bronchi may be indicative of an inhalation of hot gases. In the same

16 Bohnert 

Fig. 5. Comparison of a normal kidney (above) and a shrunken kidney (below) 

after heat exposure of the body (“puppet organ”). 

way, the upper portion of the esophagus may also be damaged. Often, increased 

secretion of mucus is observed in the air passages. This may be interpreted 

as an attempt to cool the surfaces of the air passages and thus as a sign 

of vitality, if other causes for the secretion of mucus (bronchial asthma, catarrhal 

bronchitis) have been ruled out (33,39). Damage caused to the respiratory 

tract by dry heat is limited more to the upper portions (85). The inhaled hot air 

is sufficiently cooled down by the mucosa of the airways, so that after exposition 

to a “normal fire” hardly any changes are found in the medium and small 

bronchi (33,39,85). But if hot steam is inhaled, the temperature hardly declines 

in the course of the air passages so that direct thermal damage may occur even 

in the peripheral parts of the respiratory tract (85). For differentiation between 

hot steam and dry air, the so-called “pleura sign” can be used at autopsy. If hot

Burns 17 

steam was inhaled, the parietal pleura is reddened, whereas the costodiaphragmatic 

angles are pale (86). In deaths caused by the effects of dry heat, this sign 

is absent even if the circumstances suggest a fire with high temperatures. 

3.3. Vessels 

Fig. 6. Large droplet of fat in the right ventricle of the heart. 

When performing an autopsy on fire victims, intensive red discoloration 

of the intima of the vessels, similar to that seen in changes resulting from 

putrefaction, is very often observed even in cases in which there are no other 

signs of putrefaction. This finding is the result of hemolysis (87) occurring at 

temperatures above 52°C (88). Already, at 48°C erythrocytes begin to dissolve, 

with the hemoglobin-containing fragments behaving like intact erythrocytes 

in serological tests (89). If the circulation is still intact, the erythrocyte 

fragments (“fragmentocytes”) can also be demonstrated microscopically in 

other organs, which has to be interpreted as a sign of vitality (86). 

The effect of heat on the body leads to shifts of the fluid content in the 

tissue, which may result in blood extravasates in cavities or organs. Another 

consequence may be accumulations of large droplets of fat in the epidural 

space, in greater vessels, or in the blood of the right ventricle (Fig. 6) (90,91). 

The intravasal spread of fat is no sign of vitality, but a result of postmortem 

thermal damage with mobilization and displacement of depot fat away from

18 Bohnert 

the center of the heat (92,93). The accumulation of fat in the veins of the 

greater circulation or the blood vessels of the lungs must not be confused with 

vital fat embolism, occuring after mechanical trauma. 

3.4. Gastrointestinal Tract 

The abdominal organs are protected by the abdominal wall from direct 

damage by the flames for a relatively long period of time. As a result of the 

heating of the body, the tissue fluids boil away and the pressure inside the hollow 

organs and the abdominal cavity builds up, which often leads to the rupture 

of the abdominal wall and the prolapse of intestinal loops. Consumption of the 

abdominal wall by the fire further promotes the rupture. In rare cases, heatrelated 

ruptures of the gastrointestinal organs are found, before they were directly 

exposed to the fire. Schneider reported on the rupture of the stomach in 

a 2-year-old child and a rupture of the colon in a 3-year-old child (94). In both 

cases, the abdominal wall was charred without exposing the abdominal cavity. 

In a case from our own autopsy material, in which the victim had remained 

in a sauna for several hours after death, there were ruptures of the large intestine 

with several liters of fluid in the abdominal cavity. 

Berg and Schumann described a heat hematoma of the stomach (63). In 

that case, in which the gastric wall was actually charred, a layer of blood had 

been found on the chyme. The swallowing of blood could be ruled out. The 

authors assumed that the heat hematoma could have been promoted by strong 

congestion of the blood vessels in the gastric wall owing to hyperemia during 

digestion. 

3.5. Bones 

Bones are highly resistant to heat in their gross structure and usually 

allow macroscopic assessment even after the body was exposed to high 

temperatures for several hours (69,70,74). At temperatures above 700°C, complete 

combustion of the organic substances with incineration and recrystallization 

of the inorganic matter occurs, which is called “calcination” (95,96). 

The bones are grayish-whitish, desiccated, and disintegrate easily. The surface 

shows characteristic tears, partly reflecting the course of the trabeculae 

but often also being irregular in structure (41,68,69,77). As all other organs, 

bones can also shrink in the heat. In long bones, the reduction in length can be 

up to 10% (68). 

Both von Hofmann (97) and Merkel (47) described the problems of differentiating 

between vital and postmortem fractures. On the one hand, fractures 

may be caused by the direct effect of the fire. On the other hand, they

Burns 19 

may have occurred after death, for example, when walls or timber collapsed. 

Especially in charred or calcined bones, a minor mechanical strain may be 

enough to cause fractures. Therefore, in fractures localized within charred bone 

areas, the possibility of artifacts should be considered. On the other hand, 

several authors have stressed expressly that injuries sustained during life can 

be demonstrated even on charred or calcined bones (47,68,69,74). Eckert et 

al. (69) found a fracture of the iliac bone caused by blunt force on the pelvis of 

a female body largely consumed by fire. Merkel (47) and also Herrmann (68) 

pointed out that traces of sharp force especially can be demonstrated quite 

well on the skeleton of burned bodies. Fractures away from areas of burned 

bone are in all probability not a result of thermal effects (23,24). 

In the assessment of burned bones, special attention must be paid to the 

bony skull cap. In about one-third of all fire deaths, the skull cap is partially 

destroyed and the interior of the skull is exposed (8), which makes assessment 

even more difficult. Isolated fractures of the external table are seen, especially 

in those cases where a defined area of the skull cap was in direct contact with 

the flames (23,41). Prolonged exposure to heat causes fractures of the entire 

thickness of the skull cap with occasional bursting of the sutures of the skull 

(23). The tears in the skull cap caused by heat may radiate from a center, but 

can sometimes also be elliptic or circular in shape or resemble a spider’s web 

fracture (41,68). In rare cases, round or oval bone fragments may burst outward 

(Fig. 7). Distinction of this finding from a gunshot injury may be difficult 

(98). Careful examination and consideration of the other findings and the 

circumstances of the case allow differentiation of mechanical trauma sustained 

during life from postmortem trauma or heat artifacts, even when consumption 

by the fire is far advanced (24,47,74,97). 

3.6. Cranial Cavity and Brain 

A frequent finding is the epidural hematoma caused by heat. This is a 

postmortem effect resulting from the shift of fluid from the diploe (99) and the 

venous sinuses (100) when the skull cap is in direct contact with the flames. 

Accordingly, charring of the bony skull is usually found above the site of the 

heat hematoma. Less often the heat hematoma is localized on the side opposite 

to the site where the fire had its maximum effect. It is dry, crumbly, and of 

brick-red color. Occasionally it may be surrounded by fat, and in rare cases 

accumulations of fat without extravasations of blood can also be found in the 

epidural space. Apart from that, the hematoma is sometimes found to be interspersed 

with brain tissue when the dura mater is torn owing to shrinkage by 

heat (99–103). The shift of brain tissue into the epidural space is caused by the

20 Bohnert 

Fig. 7. Burn defect of the skull cap resembling a gunshot wound. 

elevated steam pressure in the cranial cavity resulting in an enlargement of the 

brain (99,103). 

Dotzauer pointed out that postmortem extravasates of blood can occur in 

all cavities of the skull including the ventricles of the brain (99). But hemorrhages 

can also be found in the brain tissue itself. In these cases, distinction 

between postmortem and vital hemorrhages can be particularly difficult 

(102,104,105). Generally, intracerebral bleeding could be a result of the shrinkage 

of tissue with laceration of small blood vessels (102,105). One case with 

postmortem hemorrhages in the pons and the basal ganglia as a result of an 

injury caused during recovery was described by Dirnhofer and Ranner (104). 

When the skull cap is intact, the brain of fire victims is often shrunken 

and of a hardened consistency with filled sulci on the surface (Fig. 8). Dotzauer 

and Jacob described the finding as “a reduction of the brain volume associated

Burns 21 

Fig. 8. Smoothing of the brain surface in combination with reduction of the 

brain volume in a burn victim. 

with swelling of the internal matter” (106). Histologically, condensation of 

the vessels and widening of the Virchow–Robinson spaces have been described 

(39,106). Again, this finding may be explained as the result of a loss of fluid 

and does not prove a vital thermal damage to the tissue. Evidence of a vital 

heat trauma may possibly be obtained by examining the ultrastructure of the 

brain (blood–brain barrier) and/or the expression pattern of various neurochemical 

mediators (107–109). According to animal experiments, hyperthermic 

brain damage manifests itself by changes in the shape of nerve and glia 

cells, edema, disturbances of the blood–brain barrier, and an increased expression 

of glial fibrillary acidic protein, vimentin, heat shock protein, nitric oxide 

synthase, and heme oxygenase (107). Quan et al. showed that intranuclear 

ubiquitin immunoreactivity of the pigmented substantia nigra neurons in the

22 Bohnert 

midbrain was induced by severe stress in fires (108). Iskhizova and Tumanov 

examined the ultrasound and histological changes in the central nervous system 

in cases of thermal trauma. These authors found that derangements of 

interneuronic bonds and of interrelations between the neurons and capillaries 

are typical vital changes in the brain (109). 

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Med Ekspert 46, 7–9

Kicking and Trampling to Death 29 

Trauma

30 Henn and Lignitz


2 

Kicking and Trampling to Death 

Pathological Features, Biomechanical 

Mechanisms, and Aspects of Victims 

and Perpetrators 

Véronique Henn, MD and Eberhard Lignitz, MD 

CONTENTS 

INTRODUCTION 

PATHOLOGICAL FEATURES 

BIOMECHANICAL MECHANISMS 

ASPECTS OF VICTIMS AND PERPETRATORS 

EPIDEMIOLOGY 

REFERENCES 

SUMMARY 

Kicking and trampling to death is an entity of violence that increased 

considerably in the northeastern parts of Germany over the final years of the 

last century. Most of the injuries are located at the head followed by injuries 

of inner organs and thoracic bones. More than 50% of victims of kicking and 

trampling deaths have fractures of the calvaria, skull base, or facial bones. In 

such cases, subdural and subarachnoidal bleeding, brain contusion, and intracerebral 

hemorrhage is a frequent cause of death. The frequency of injuries 

deriving from defensive action is associated with the blood alcohol content 

(BAC) of the victim. These kinds of injuries are rare when the BAC of the 

victim is higher than 200 mg/dL, and injuries deriving from defensive action 

can be found in approximately 52% of the cases where the BAC is lower than 

200 mg/dL. The injury pattern deriving from kicking and trampling is highly 



31

32 Henn and Lignitz 

dependent on the location of the impact. Between the skin of the head and the 

skull there is only little adipose tissue so that the injury pattern often points 

out to the used underlying mechanism of violence. On occasion, a sole imprint 

pattern deriving from the shoe used as a “weapon” can be identified, whereas 

kicking and trampling to the abdomen can occur without leaving any characteristic 

morphological signs. Special computerized classification systems may 

enable the identification of a particular shoe by analyzing sole imprints on the 

victim’s skin. Kicking as well as punching can be performed with the same 

energy (350–1200) without dependence on gender. Even kicking with bare 

feet can lead to fatal injuries. When the head of a victim is kicked, the head 

can experience a maximum acceleration comparable to that in a frontal car 

crash at 50 km/h. Many of the victims and perpetrators belong to lower social 

classes of society. Many of the victims have been repeatedly maltreated in the 

past and have been used to an environment where violence occurred frequently. 

In most cases, the offender acts alone. Perpetrators acting in a group are generally 

younger than offenders acting alone. In many cases with elder offenders, 

the existence of an intimate relationship between victim and perpetrator 

can be established. Group dynamics especially can have negative influence on 

social behavior patterns in these fatalities. In former East Germany, the frequency 

of killing by kicking and trampling has increased with the frequency 

of unemployment in specific regions. 

Key Words: Kicking; trampling; blunt-force injuries; injury pattern; victims; 

perpetrators. 


In a considerable number of homicide cases, it is difficult to interpret 

underlying biomechanical mechanisms of blunt force because of the variety 

of injury patterns. On the one hand, injuries can be so unambiguous that the 

underlying killing mechanisms of blunt force and the cause of death are obvious. 

On the other hand, there may be different simultaneous signs of violence 

that make it hard to determine the exact chronology and significance of injuries 

and to identify the lethal injury. Detailed analyses of the underlying blunt 

force mechanisms and the resulting cause of death as well as professional 

experience are the most important basics for a profound interpretation and 

reconstruction of such cases. It is necessary to examine the victim and the 

crime scene as well as the perpetrator, if possible (1). 

If the history of the case and the circumstances are unknown at the time 

of autopsy, they have to be elucidated by a thorough analysis of the victim’s 

injury pattern and the crime scene so that a profile of the perpetrator can be


created. One should keep in mind that in some instances the kind of violence 

and injury pattern can be the same in homicides and suicides, respectively. 

Since the 1900s, we could observe an increase of an unkind and extremely 

brutal type of external violence leading to death—kicking and trampling. In 

Germany, this kind of violence as cause of death was described in some case 

reports as early as in the 1930s. Now the large number of cases makes it possible 

to present an overview of frequent locations of injuries, injury patterns, 

causes of death, biomechanical mechanisms, epidemiological aspects as well 

as scene circumstances, and aspects of victims and perpetrators. 

2. PATHOLOGICAL FEATURES 


In 1933, Schrader described a case of “kicking to death” (2), which is 

presented here because of its relevance to the present. The case involved a 

25-year-old man who was attacked by political enemies on his way home. 

Twenty-four hours after being taken to the hospital, the man died from the 

severe injuries he had sustained. The autopsy revealed the following injuries: 

. . . numerous lacerations at the back of the head, the bone was 

uninjured. . . . The findings of considerable importance were detected 

at the skull. On the right side comminuted fractures of the 

parietal and temporal bone as well as the lateral parts of the frontal 

bone were found. Some fracture lines showed a particular ovalshaped 

arched pattern of 6 to 10 cm in diameter. Other fracture 

lines reached from this oval-shaped area to the frontal bone. At the 

base of the skull, fractures of the orbital roof, ethmoidal and right 

side of the sphenoidal bone were detected. Outcome of autopsy: The 

injury of the head was caused by kicking with the foot. The ovalshaped 

fracture lines possibly show the contour of a heel . . . . . 

A witness as well as one of the perpetrators declared: “. . . was beaten with a 

stick and broke down when he tried to run away and received several hits 

against the back of his head. One of the perpetrators kicked the side of his 

head when he was lying on the floor.” The quoted findings were described in 

1933 and fit exactly the skull fracture shown in Fig. 1, which was seen by the 

authors in a case of kicking to death that took place in November 2000. 

Over the last few decades, the frequency of kicking and trampling to 

death has significantly increased in Germany (3,4). The high number of such 

cases in the northeastern parts of Germany that we as well as others from 

different Institutes of Legal Medicine in Germany have studied (Table 1) makes 

it possible to give an overview of the characteristic findings in such cases.


Fig. 1. Arched fracture lines on the skull as a result of kicking. 

Because most of the victims were in a state of inebriation that alone could 

have been fatal, only such cases were included where injuries resulting from 

kicking and trampling were undoubtedly the cause of death (3–7). 

In all studies, most of the victims were maltreated by kicking and other kinds 

of violence. In 4.5% (Rostock, former East Germany) and in 17.1% (Hamburg, 

former West Germany), respectively, sole signs of kicking were present. In some 

of these cases, the victim fell down after an initial punch and was then kicked by 

the perpetrator while lying on the ground. The majority of the victims were also 

punched multiple times or received blows with different kinds of objects. Strangulation 

and asphyxia caused by the perpetrator sitting or kneeling on the victim’s 

thorax, stab wounds, and/or cuts were rare in these cases (3,4,8–10). 

2.2. Location of Injuries 

Out of 127 victims of kicking and trampling deaths who were autopsied 

in Hamburg and Greifswald (former East Germany), 81 (64%)—as well as 11 

(50%) out of 22 victims examined in Rostock—showed fractures of the calvaria, 

skull base, or facial bones. In Hamburg, 63% (22 out of 35), in Greifswald 

47% (43 out of 92), and in Rostock 55% (12 out of 22) of the maltreated 

individuals had injuries of inner organs (including diaphragm and vena cava). 

Fractures of the thoracic bones were found in 54% of all cases analyzed (Hamburg 

54%, Greifswald 53%, and Rostock 59%).


Table 1 

Examined Cases of Kicking and Trampling to Death in Northeastern 

Parts of Germany That Served as the Database for the Current Review 

Institute of Legal Medicine Investigation period Number of cases studied 

Hamburg (4,5) 1982–1995 35 

Greifswald (4,5,8) 1982–2000 92 

Berlin (7,26) 1980–1997 152 

Rostock (3) 1958–2000 143 

Note. Reference numbers are given in parentheses. 

Trauma to the neck, including fractures of the hyoid bone, laryngeal skeleton, 

and vertebra, was found in one-third of the cases. Lesions of the genital 

region could be established in two cases. The distribution of injuries is shown 

in Fig. 2. 

Missliwetz and Denk analyzed the autopsy protocols of the Institute of 

Forensic Medicine in Vienna, Austria over a 10-year period during which 5500 

autopsies were carried out. Seventy-six individuals died after being maltreated 

by punching and/or kicking (10); 60.5% of the victims showed head injuries 

including subdural bleeding and arteriorrhexis; injuries of thoracic and 

abdominal organs were registered in 46% of the cases. 

2.3. Injury Patterns 

2.3.1. Injuries to the Head 

Injury patterns depend on the location and force applied by kicking or 

punching (1,11,12). The fact that the head is relatively small when compared 

to the body makes it impossible to believe the statement of perpetrators at 

court that they just kicked a person’s body without looking where they hit it. 

One can consider the head as a preferred “target of choice.” Apart from abrasions 

and lacerations of the skin, most of the head injuries were fractures of 

the facial bones as well as of the upper and lower jaw bones. Complications 

following head trauma were epidural and subdural hemorrhage, subarachnoid 

bleeding, brain contusion, and/or cerebral hemorrhage (Table 2). 

Very often, injury patterns of the head can be the conclusive proof of the 

applied type of violence. Because there is only little fatty tissue and muscles 

between the skin of the head and the skull, blunt-force trauma often leads to 

characteristic abrasions of the skin and lacerations (1). After a kick or stomp 

with a shoe, the skin and subcutis may show contusions that mirror the pattern


Fig. 2. Distribution of injuries (data based on studies in Hamburg, Greifswald 

and Rostock, Germany, n = 149). 

of the sole of the shoe as well as the contour of the heel (Figs. 3–5). The 

mechanism that leads to this injury pattern is the same as is known to result 

from impacts with a baseball bat or a belt (13,14). 

2.3.2. Injuries to the Neck 

Neck injuries can be seen in up to 40.9% of cases (Table 3) and can give 

important information about the applied violence. Nevertheless, one should 

not confuse these lesions with those found in homicidal asphyxia and suicidal 

or accidental hanging. 

Fractures of the throat skeleton (detected in 19 victims [29%] of the cases 

investigated in Greifswald) were more frequent in victims of kicking and trampling 

to death than in victims of ligature strangulation in homicidal asphyxia, 

where this kind of injury was detected in 12.5% of the cases (15) but less than 

in victims of suicidal or accidental hanging. In the latter, skeleton fractures 

were seen by Betz and Eisenmenger in 73 out of 109 autopsy cases (67%) (16). 

In some cases, injury patterns of the thorax or neck can indicate the type 

of weapon or in single cases even the kind of shoe used to maltreat the victim. 

The causative mechanism of the injury pattern can be easily explained by the

Table 2 

Injuries of the Skull and Intracranial Findings 

in Victims Killed by Kicking, Trampling, and Punching 

Rostock 

Hamburg Greifswald Berlin Rostock (kick + punch) 

1982–1995 1996–2000 1980–1997 1982–1995 1958–2000 

Number of cases examined 35 92 152 22 136 

Injuries of the skull 

Orbita 2 (5.7%) 14 (15.2%) � 3 (13.6%) 14 (10.3%) 

Nasal bone 4 (11.4%) 23 (25.0%) 39 (25.7%) 5 (22.7%) 29 (21.3%) 

Cheek bone 3 (8.6%) 11 (12.0%) � 3 (13.6%) 19 (14.0%) 

Maxilla 8 (22.9%) 9 (9.8%) 14 (9.2%) 2 (9.1%) 11 (8.1%) 

Mandible 7 (20.0%) 8 (8.7%) 14 (9.2%) 2 (9.1%) 13 (9.6%) 

Calvaria 5 (14.3%) 8 (8.7%) � 3 (13.6%) 43 (31.6%) 

Base of the skull 6 (17.1%) 10 (10.9%) � 6 (27.3%) 51 (37.5%) 

Intracranial findings 

Epidural hemorrhage 13 37.1%) 21 (22.8%) � * 13 (9.6%) 

Subdural hemorrhage 14 (40.0%) 27 (29.3%) 40 (28.3%) * 63 (46.7%) 

Subarachnoidal bleeding 4 (4.3%) 27 (17.8%) * 69 (51.1%) 

Contusion, cerebral hemorrhage 8 (22.9%) 17 (18.5%) 33 (21.7%) 10 (45.5%) 73 (54.1%) 

Note. � = these data cannot be compared with those of the other studies; Taymoorian (7) described multiple fractures of facial bones in 

10 cases (6.6%). * = 50% of the cases analyzed by Brandt (3) showed epidural and/or subdural hemorrhage. 

Kicking and Trampling to Death 37


Fig. 3. Lacerations of the skin. Injury pattern mirroring a part of the sole 

of a shoe. 

Fig. 4. Laceration of the left eyebrow caused by a kick with a shoe and 

hematoma on the left part of the forehead outlining the heel of a shoe.


Fig. 5. Pattern of a shoe on the forehead of a victim. 

following case (Figs. 6 and 7): the imprint of the sole of a shoe is visible as a 

negative mark on the skin. The prominent parts of the sole are seen as pale 

areas that are surrounded by sharp-edged abrasions and bleedings of the skin. 

Blood has been forced out of blood vessels and extravasated to neighboring 

tissue. According to Bodziak, the injury pattern depends on the power of the 

kick, a fact that should be kept in mind when interpreting the imprint pattern. 

In case of very powerful kicking, confluence of bleedings can occur so that 

sole prints are not recognizable (17). 

2.3.3. Injuries to the Thorax and Inner Organs 

Dependent on an individual’s age, the thoracic organs are normally well 

protected by the ribs. With the increase of age, ribs are more vulnerable because 

of the decrease of elasticity and possible manifestation of osteoporosis. In 

Greifswald, only 25% of the victims younger than 21 years who were killed 

by kicking and/or trampling had fractures of ribs or sternum compared to 46.9% 

in individuals who were between 21 and 40 years of age and 58.9% in the age 

group between 41 and 60 years.

Table 3 

Injuries to the Neck in Victims Killed by Kicking, Trampling, and Punching 

Rostock 


1982–1995 1996–2000 1980–1997 1982–1995 1958–2000 


Hyoid bone 9 (25.7%) 13 (14.1%) � 2 (9.1%) 16 (11.8%) 

Laryngeal cartilage/bone 7 (20.0%) 14 (15.2%) 21 (13.8%) 5 (22.7%) 24 (17.7%) 

Fracture of the cervical spine 0 2 (2.2%) 6 (3.9%) 3 (13.6%) 4 (3.0%) 

Only soft tissue injuries 2 (5.7%) 8 (8.7%) � 2 (9.1%) 46 (33.8%) 

At least one of the injuries 13 (37.1%) 27 (29.3%) � 9 (40.9%) � 

mentioned above 

Note. � = these data cannot be compared with those of the other studies. 

40 Henn and Lignitz


Fig. 6. Injury pattern (sole imprint) on the neck and upper thorax. 

Fig. 7. The “weapon”: a sneaker (same case as Fig. 6).


Kicking and trampling led to multiple rib fractures in one-third of the 

cases examined in Greifswald. Fractures of ribs in combination with fractures 

of the sternum were seen in 8.7%. Taking a look at the injuries of inner 

organs, it is not astonishing that more than 25% of the victims showed ruptures 

of the liver. Because of its location, this organ is very easily injured. 

Kicking against the abdomen and especially trampling on a victim who is 

lying on the ground leads to severe injuries of inner organs (Table 4). In the 

case of blunt force against the abdomen, characteristic signs can be weak or 

totally missing (Fig. 8). The external lack of signs of a preceding trauma 

does not have to lead to the conclusion that there are no severe injuries of 

inner organs (Fig. 9). 

Findings from the external examination of the body and autopsy findings 

have to be documented in detail starting with the description of the victim’s 

clothing. Multiple layers of clothing as well as thick adipose tissue and muscles 

can function as a crumple zone so that kicking and/or trampling can be without 

any external morphological correlate (12), and therefore the clothing may 

be the only objects to give the death investigator important informations. To 

document a sole imprint to a scale of 1:1, it can easily be drawn on a transparent 

film. Another simple method is the photo documentation with a scale next 

to the lesion. For a more specialized three-dimensional documentation of the 

injury pattern, serial photographs must be taken of all dimensions with a constant 

distance between camera and object. The same measurements must be 

taken of the weapon (e.g., shoe) used. The photographs of injury pattern and 

weapon can be analyzed by a computer program and matching figures can be 

established (18). 

In several countries, computerized footwear classification systems are 

available. In Switzerland, this system is especially designed for partial footwear 

impressions (19–22). Though these systems were originally developed 

for crime scene footwear classification, they may help to identify shoes worn 

by the perpetrator while kicking a victim by describing the sole pattern using 

special classification codes. 

In some cases, overlapping injury patterns caused by kicking can occur. 

On the one hand, an imprint of the weapon is visible, and on the other hand, 

the structure of the clothing can be mirrored. Not only injuries of the skin and 

soft tissue, but also (imprint) fractures of the skull can point to the type of 

weapon used by the perpetrator. 

2.3.4. Injuries Caused by Defensive Action 

Less than 50% of the victims examined in Greifswald showed injuries 

caused by defensive action like hematomas at the ulnar region of the forearms

Table 4 

Frequency of Injuries to Inner Organs in Victims Killed by Kicking, Trampling, and Punching 

Rostock 


1982–1995 1996–2000 1980–1997 1982–1995 1958–2000 


Injuries of the lungs 5 (14.3%) 15 (16.3%) 21 (13.8%) 6 (27.3%) 20 (14.7%) 

Rupture of heart 5 (14.3%) 3 (3.3%) 11 (7.2%) 1 (4.5%) 9 (6.6%) 

Rupture of diaphragm 0 1 (1.1%) � 2 (9.1%) 8 (5.9%) 

Injury of vena cava 0 0 � 1 (4.5%) � 

Rupture of liver 9 (25.7%) 17 (18.5%) 30 (19.7%) 3 (13.6%) 16 (11.8%) 

Rupture of spleen 6 (17.1%) 7 (7.6%) 7 (4.6%) 1 (4.5%) 5 (3.7%) 

Contusion/rupture of kidney 7 (20.0%) 6 (6.5%) � 6 (27.3%) 16 (11.8%) 

Rupture of intestine/bowl 3 (8.6%) 3 (3.3%) � 3 (13.6%) 11 (8.1%) 

Injuries of mesentery 6 (17.1%) 15 (16.3%) � 6 (27.3%) 21 (15.4%) 

Note. � = these data cannot be compared with those of the other studies. 

Kicking and Trampling to Death 43


Fig. 8. Without the knowledge of the details from the witness report, it would 

have been hard to realize that the small abrasions of the skin were a result of 

jumping on the victim. 

Fig. 9. Rupture of the liver caused by jumping on the victim’s abdomen (same 

case as Fig. 8).


Fig. 10. Frequency of injuries deriving from defensive action in dependence 

on blood alcohol content (BAC). 

and hematomas of the upper arms. It is noticeable that only 18% of the victims 

with a blood alcohol content (BAC) >200 mg/dL showed such injuries, whereas 

in 52% of the victims with a BAC


3. BIOMECHANICAL MECHANISMS 

In cases of tangential violence, the findings depend on the tissue layers 

above and underneath the skin. The weapon (e.g., shoe) as well as the clothing 

can cause scale-like excoriations. The shreds of the epidermis can show the 

direction of violence (24). Bleeding of subcutaneous wounds can occur when 

the dermis is sheared off the subcutaneous fatty tissue. Depending on the direction 

of violence, shearing of the skin off the subcutaneous tissue may be seen 

in different ways, and different wrinkles of the skin may develop if the same 

area was kicked or punched repeatedly. 

In 1987, Böhm and Schmidt (25) analyzed the biomechanical mechanism 

of wrinkling by pressing an acrylic sole against skin that was marked 

with a set pattern. Because of the transparency of the sole, it was demonstrable 

that the set pattern was contorted in different ways. Kicking the gluteal 

region from the side caused a clearly recognizable shift of the set pattern, 

whereas it was not visible when kicking from above. 

In cases of kicking in combination with sharp-force violence, it is relatively 

easy to relate the injury pattern to the type of violence, whereas this can 

be hard and sometimes impossible when kicking is combined with punching 

and no sole imprint pattern is visible. 

In experimental studies, Böhm and Schmidt showed that one can achieve 

similar power by kicking and punching, respectively (25). They recorded the 

energy of women and men kicking and punching a “punch-ball” that was connected 

to a special registration unit. The energy of the most powerful punching 

by women was between 350 and 550 N, and when men punched, energy 

between 500 and 850 N was registered. The women reached 500–750 N when 

kicking. Men kicking the “punch-ball” reached energy between 750 and 1200 N. 

The results of this experiment were summarized by Böhm and Schmidt in one 

sentence: “The lowest registered power by kicking and the highest power by 

punching are overlapping without dependence on gender.” It is suggested that 

these measured values are surpassed when the offenders are in a state of excitement 

so that involuntary energy is set free (25). 

Glißmann (8) used a special registration unit to analyze the acceleration 

of a dummy’s head that was kicked (the dummy was lying on the ground). The 

maximum acceleration of the head was 103 Gy, which is comparable to the 

acceleration of the head in a frontal car crash at 50 km/h. These findings and 

the study of Taymoorian (7) in which a case of kicking to death bare-footed is 

described confirm the assumption that kicking, without dependence on the 

shoe worn by the perpetrator or even when bare-footed, as well as punching, 

can easily lead to fatal injuries.


4. ASPECTS OF VICTIMS AND PERPETRATORS 

4.1. Victims 

Most of the victims (68–80%) were male with an average age of 43 years. 

The female victims were 2–5 years older (3,6,7). In the cases examined in 

Greifswald and Rostock, all victims were Germans, whereas 11% of the victims 

investigated in Berlin came from other countries. 

Half of the victims examined in Greifswald and Hamburg knew their 

perpetrator prior to the offense. They were integrated in a circle of acquaintances 

where most of the individuals had severe alcohol problems. Some of 

them had been in a relationship with each other. These circumstances explain 

why most of the individuals were maltreated in the apartments of either the 

victims or the offenders (6,9,26). In most cases, the involved persons, victims 

as well as perpetrators, were under the influence of alcohol when starting a 

trivial discussion that led to a severe struggle that ended fatally. 

In blood samples of the victims, an alcohol content of more than 200 mg/dL 

was regularly found (3,6,26) and registered in 34.8% of the victims examined 

in Greifswald; in 9% of the cases, the victims had a BAC below 200 mg/dL 

but a urine alcohol content (UAC) of more than 200 mg/dL. 

Many of the victims belonged to the so-called lower social class. They 

were unemployed and depended on social welfare. They often originated from 

broken homes where parents were unemployed alcoholics. Many of them had 

been repeatedly maltreated in the past and could be considered to be used to 

an environment where violence occurred frequently. 

The advanced age of the victims, when compared to offenders, and the 

weakening of the body by alcohol abuse for many years as well as the acute 

inebriation give reasons for their vulnerability. 

4.2. Perpetrators 

In most cases, the offender acted alone. According to our own studies, 

the average age of solitary perpetrators is about 30 years and perpetrators who 

acted in a group are about 22 years old. In many cases with elder offenders, 

there existed an intimate relationship between victim and perpetrator and both 

lived under plain or even primitive conditions (5,26). 

The difference in age between solitary and in-group acting offenders 

points out that group dynamics can have negative influence on social behavior 

patterns. On the one hand, the group can encourage a member, e.g., to kick or 

trample, and on the other hand a group member may act brutal because he or 

she does not want to be excluded from the group (5).


In Greifswald and Hamburg, women acted only in groups and never solitarily 

(4,6), whereas 3.1% of single offenders in Rostock and 9.7% (15 out of 

155) of those in Berlin were women (3,26). Strauch et al. reported that 14 of 

15 female single offenders had cultivated a friendship or deeper relationship 

with their victims in the past (26). 

Many of the offenders had only a poor education and no vocational training, 

were unemployed, and commonly abused alcohol. In many cases, the perpetrators 

pointed out during police interrogation that they had been severely 

drunk at the time of the offense and were unable to control their action. They 

testified in court their consumption of alcohol during the respective day. According 

to those statements, they must have had BACs of more than 200 mg/dL at the 

time of the fight. The inebriation may be the main reason why the perpetrators 

did not use any weapons. Kicking and punching the victim points toward a 

spontaneous reaction following a prior verbal argument and “weapons” like 

fists and feet are always available. 

In comparison with the cases before 1996 where the main reason for the 

fight was trivial, it was remarkable that from 1996 to 2000 offenders who 

acted in groups in Greifswald and environment admitted at court that they 

maltreated the victim “just for fun” or because “[they] were bored and didn’t 

know what else to do” or that “[they] thought homeless live off other people, 

so they deserve this treatment.” The behavioral pattern of the perpetrators is 

illustrated by the following case report: in summer 2000, a homeless alcoholic 

came to a village (in former East Germany) close to the Baltic Sea and took a 

rest behind a church when he was seen by a 24-year-old man who was known 

to be a Nazi and some juveniles. They hit and kicked the homeless man without 

prior warning and for no apparent reason and then went to a youth club. 

There, one of the juveniles bragged about this action and demonstrated blood 

of the victim on his shoes. A few hours later, after having some beer, they 

came back and saw that the maltreated man was still alive, smoking a cigarette. 

Immediately, they started kicking him again, so that the victim didn’t 

even have the time to shout for help. Later, one of the perpetrators jumped on 

his thorax. After some time, they left and went home without thinking about 

the possibility of fatal injuries. The victim died the same night of the severe 

injuries he had sustained. He was found the next morning. After a short period 

of investigation the perpetrators were caught. The one known to be a Nazi 

confessed that he kicked and trampled the man because “homeless people do 

not fit into our society.” He was already known to the authorities from multiple 

prior criminal offenses and previous convictions. He lived on social welfare 

in a municipal housing unit. His criminal career dated back 7 years and


consisted of nine cases including theft, receiving stolen goods, extortion under 

threat of force, and grievous bodily harm (kicking and punching someone 

else’s face). 

5. EPIDEMIOLOGY 

Concerning killing mechanisms, one can see regional special features. In 

the United States, killing by shooting and in Germany and Austria killing by 

blunt force occur most frequently (27–29). In the former East Germany, killing 

by kicking occurs more frequently in regions with a high percentage of 

unemployment (3). The reason may be the offenders’ inability to socially integrate, 

their alcohol abuse, and their dissatisfaction with their private conditions. 

However, recent systematic studies are missing in the literature. 

REFERENCES 

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2. Schrader S (1933) Wunde und Werkzeug. Tödliche Schädelverletzung durch 

Fußtritte. Arch Kriminol 92, 229–231. 

3. Brandt AK (2003) Morphologie und Phänomenologie des Totschlagens und 

Tottretens. Eine Auswertung der Kasuistiken im Einzugsgebiet des Rechtsmedizinischen 

Instituts der Universität Rostock 1958–1989 versus 1990–2000 sowie vergleichende 

Darstellung von Kasuistiken des Tottretens im Einzugsbereich des Rostocker und 

Hamburger/Greifswalder Institutes für Rechtsmedizin 1982–1995. Med. Thesis, 

University of Rostock, Germany. 

4. Henn V, Lignitz E, Philipp KP, Püschel K (2000) Zur Morphologie und Phänomenologie 

des Tottretens (Teil I). Arch Kriminol 205, 15–24. 

5. Henn V, Lignitz E, Philipp KP, Püschel K (2000) Zur Morphologie und Phänomenologie 

des Tottretens (Teil II). Arch Krimonol 205, 65–74. 

6. Henn V, Lignitz E (2003) Tötungsdelikte durch Tritte—Biomechanik, Morphologie, 

Motivation und Wahl der Opfer. In Häßler F, Rebernig E, Schnoor K, Schläfke D, 

Fegert JM, eds., Forensische Kinder-, Jugend- und Erwachsenenpsychiatrie. 

Schattauer, Stuttgart, New York, pp. 112–124. 

7. Taymoorian U (2000) Rechtsmedizinische Analyse von Todesfällen durch Treten. 

Med. Thesis, University Hospital Berlin Charité, Germany. 

8. Glißmann C (2002) Wirkung von Fußtritten gegen Kopf und Thorax. Med. Thesis, 

University of Greifswald, Germany. 

9. Graß H, Madea B, Schmidt P, Glenewinkel F (1996) Zur Phänomenologie des Tretens 

und Tottretens. Arch Kriminol 98, 73–78. 

10. Missliwetz J, Denk W (1992) Tod infolge Mißhandlung (durch Faustschläge und 

Tritte). Rechtsmedizin 3, 19–23. 

11. Böhm E (1987) Zur Morphologie und Biomechanik von Trittverletzungen. Beitr 

Gerichtl Med 45, 319–329.


12. Taere D (1960/61) Blows with the shod foot. Med Sci Law 1, 429–436. 

13. Reh H, Weiler G (1995) Zur Traumatologie des Tottretens. Beitr Gerichtl Med 33, 

148–153. 

14. Smock WS (2000) Recognition of pattern injuries in domestic violence. In Siegel JA, 

Saukko PJ, Knupfer GC, eds., Encyclopedia of forensic sciences. Academic Press, San 

Diego, San Francisco, New York, Boston, London, Sydney, Tokyo, pp. 384–391. 

15. DiMaio VJ (2000) Homicidal asphyxia. Am J Forensic Med Pathol 21, 1–4. 

16. Betz P, Eisenmenger W (1996) Frequency of throat skeleton fractures in hanging. 

Am J Forensic Med Pathol 17, 191–193. 

17. Bodziak WJ (1990) Footwear impression evidence. Elsevier, New York, Amsterdam, 

London. 

18. Brüschweiler W, Braun M, Fuchser HJ, Dirnhofer R (1997) Photogrammetrische 

Auswertung von Haut- und Weichteilwunden sowie Knochenverletzungen zur 

Bestimmung des Tatwerkzeuges - grundlegende Aspekte. Rechtsmedizin 7, 76–83. 

19. Alexandre G (1996) Computerized classification of the shoeprints of burglar’s soles. 


20. Ashley W (1996) What shoe was that? The use of computerized image database to 

assist in identification. Forensic Sci Int 82, 7–20. 

21. Geradts Z, Keijzer J (1996) The image-database REBEZO for shoeprints with developments 

on automatic classification of shoe outsole designs. Forensic Sci Int 82, 21–31. 

22. Mikkonen S, Suominen V, Heinonen P (1996) Use of footwear impressions in crime 

scene investigations assisted by computerized footwear collection system. Forensic 

Sci Int 82, 67–79. 

23. Hiss J, Kahana T, Kugel Ch (1996) Beaten to death: Why do they die? J Trauma 40, 

27–30. 

24. Pollak S, Saukko PJ (2000) Blunt injury. In Siegel JA, Saukko PJ, Knupfer GC, eds., 

Encyclopedia of forensic sciences. Academic Press, San Diego, San Francisco, New 

York, Boston, London, Sydney, Tokyo, pp. 316–325. 

25. Böhm E, Schmidt BU (1987) Kriminelle und kinetische Energie bei Tötungshandlungen 

durch stumpfe Gewalt. Beitr Gerichtl Med 45, 331–338. 

26. Strauch H, Wirth I, Taymoorian U, Geserick G (2001) Kicking to death—forensic 

and criminological aspects. Forensic Sci Int 123, 165–171. 

27. Fischer J, Kleemann WJ, Tröger HD (1994) Types of trauma in cases of homicides. 


28. Missliwetz J (1990) Tatumstand und Verletzungsbild bei vorsätzlicher Körperverletzung 

(unter besonderer Berücksichtigung des Waffengebrauchs). Beitr Gerichtl Med 8, 

299–307. 

29. Murphy GK (1991) “Beaten to death.” An autopsy series of homicidal blunt force 

injuries. Am J Forensic Med Pathol 12, 98–101.

Traumatic Brain Injury 51 

Neurotraumatology

52 Hausmann


3 

Timing of Cortical Contusions 

in Human Brain Injury 

Morphological Parameters for a 

Forensic Wound-Age Estimation 

Roland Hausmann, MD 

CONTENTS 

INTRODUCTION 

MORPHOLOGICAL CHANGES AFTER TRAUMATIC BRAIN INJURY 

MEDICOLEGAL SIGNIFICANCE 

REFERENCES 

SUMMARY 

Information on the course of destructive and reactive morphological 

changes following traumatic brain injury (TBI) is the basis used in forensic 

wound-age estimation. Several studies have already examined the temporal 

course of the wound-healing process in the central nervous system (CNS) by 

use of conventional histological and by enzyme histochemical or immunohistological 

techniques. The earliest appearance of a parameter is of particular 

interest as it determines the minimum age of a lesion showing a positive reaction 

for it. If morphological changes occur regularly during a particular 

postinfliction interval, the absence of this parameter in an unknown lesion 

indicates a wound age of less or more than the corresponding time interval 

established in published series. Cortical contusions are characterized by early 

morphological changes such as hemorrhages or microscopically visible signs 

of neuronal degeneration, followed by the phase of local cellular reactions. 



53

54 Hausmann 

Immunohistochemical studies on the time-dependent course of the inflammatory 

response revealed evidence of neutrophil accumulations (CD15) at the 

lesion site as early as 10 minutes after the injury, whereas different leukocyte 

subtypes (LCA, UCHL-1, CD3) could be detected first about 1–4 days after 

the injury. Clearing processes are induced by phagocytic mononuclear cells 

(macrophages, microglia cells) as early as a few hours but peak during the 

first week after the trauma. The phase of reactive gliosis is characterized by 

hypertrophy and proliferation of astroglial cells accompanied by neovascularization 

and deposition of a dense fibrous glial scar at the lesion site. In 

addition to the findings of several histological studies using conventional 

stainings, the demonstration of time-related changes in the astroglial immunoreactivity 

can provide further information on the age of a cortical contusion. 

It could be demonstrated that a significantly increased number of glial 

fibrillary acidic protein-positive astrocytes adjacent to the damaged area indicates 

a wound age of at least 1 day. Injury-induced glial staining reactions 

could be observed, at the earliest, after a postinfliction interval of 22 hours for 

vimentin, 3 hours for �1-antichymotrypsin, and 7 days for tenascin. Regarding 

the vascular response to brain injury, a significantly increased immunoreactivity 

could be detected in human cortical contusions after a postinfliction 

interval of at least 3 hours for factor VIII, after 1.6 days for tenascin, and after 

6.8 days for thrombomodulin. 

Key Words: Human brain injury; cortical contusions; morphological findings; 

wound-age estimation; forensic histopathology. 


Forensic wound-age estimation is based on the temporal classification of 

traumatically induced morphological changes, which occur during a certain 

time after the injury. Each phase of the healing process is characterized by 

chronological events that tend to overlap but that are sufficiently distinct and 

can be demonstrated by conventional histological and by enzyme histochemical 

or immunohistological techniques. The earliest appearance of a particular parameter, 

as established in systematic investigations, determines the minimum age 

of the lesion showing a positive reaction for it. If a parameter occurs regularly 

and consistently within a certain period of time, failure to demonstrate it points 

to a wound age of less or more than the corresponding time interval already 

established in published series. The latest known appearance of a particular 

parameter can be useful for the estimation of advanced wound age, but this 

criterion is considerably influenced by the initial extent of the wound area and 

is, therefore, of limited diagnostic value.


Regarding morphological findings, the following states of the woundhealing 

process can be differentiated in the central nervous system (CNS): 

tissue destruction, inflammatory cellular response, macrophage-/microglial 

reactions, and reactive gliosis/glial scar. 

The phase of tissue destruction is determined by the mechanical disruption 

of tissue continuity. This tearing can lead to the local disruption of structures 

or to vessel lesions resulting in ischemia and/or hemorrhage as well as in 

neuronal damage. These alterations are followed by an acute inflammatory 

response owing blood cell reactions (platelets, neutrophils, lymphocytes) as 

well as by clearing processes, which are performed in general by cerebral 

macrophages and microglial cells. After clearing necrotic nerve cells and damaged 

axon material, the phase of reactive gliosis follows next. This is a common 

phenomenon in the CNS characterized by astrocytic proliferation and 

extensive hypertrophy of the cell body and cytoplasm, accompanied by angiogenesis 

and deposition of intermediate filaments, finally forming a glial scar. 

After briefly reviewing the regular temporal sequence of the woundhealing 

process in the CNS, the findings of systematic studies dealing with 

time-dependent changes of morphological parameters after traumatic brain 

injury (TBI), which can be suitable for a forensic wound age estimation, are 

presented (1). 

2. MORPHOLOGICAL CHANGES AFTER TRAUMATIC BRAIN INJURY 

2.1. Cortical Hemorrhages 

Cortical hemorrhages are the earliest morphological changes in TBI (2). 

Erythrocytes appear almost immediately in perivascular areas (3–6) and extend 

into adjacent brain tissue during the next several hours to a maximal accumulation 

about 24 hours after the injury (3). However, intact red blood cells can 

be observed up to 5 months postinjury as a result of repeated diapedetic hemorrhages 

(4,5). Blood plasma is leaking into regions of the brain some distance 

away, where it gives the appearance of edema. The surrounding nerve 

cells are damaged by the traumatic event and/or by secondary disturbances 

(e.g., edema). 

2.2. Neuronal Degeneration 

An early histological sign of neuronal degeneration is “cloudy” swelling 

of neuronal cells followed by shrinkage, eosinophilia, and nuclear pyknosis 

(“red neurons”). Because neuronal damage may occur in waves, such morphological 

changes can be observed at the periphery of lesions for as long as

56 Hausmann 

5 or 6 months after the initial event. Red neurons may remain in tissue for 

many years and become mineralized in situ (“ferruginated neurons”). Phagocytosis 

(neuronophagy) can be observed in some cases between 12 and 24 hours 

and up to 5 days after the injury (3,4). 

Laboratory studies have determined that TBI produces loss of cytoskeletal 

proteins including neurofilaments such as NF68 (7), NF200 (7,8), spectrin 

(9), or microtubule associated protein 2 (MAP2) (10–13). Furthermore, there 

is evidence of alterations in NF68, NF300, and MAP2 immunolabeling 3 hours 

following unilateral cortical injury in rats (7). A review of the literature revealed 

no data of time-related cytoskeletal changes in human neuronal tissue after 

brain injury that could be considered for a forensic wound-age estimation. 

Axonal injury is a consistent feature of traumatic brain lesions in both 

animal and man (3,14). The first histologically appreciable alteration is the 

development of swollen axons, “spheroids,” which appear as round to ovoid 

eosinophilic masses that are argyrophilic. Ultrastructurally, the spheroids represent 

compactions of organelles, such as neurofilaments, mitochondria, 

endoplasmatic reticulum, and lysosomes (15). Swollen and ballooned axons 

can be found in and around the contusion but also at great distances from it 

(diffuse axonal injury). Such histological changes have been observed between 

24 and 48 hours after the injury. They may persist, wherever found, for many 

years in the neuronal tissue (3). Oehmichen et al. (16,17) investigated a forensic-neuropathological 

case material in order to determine the significance of 

diffuse axonal injury (DAI), which was demonstrated by immunohistochemical 

detection of the expression of �-amyloid precursor protein (�-APP). This method 

has proved to be both sensitive and highly specific (18,19) since �-amyloid is 

a neuronal glycoprotein conveyed by rapid anterograde transport (20), that 

accumulates at the lesion site as a result of traumatically induced alterations in 

the axoplasmic transport. DAI could be detected in the majority of cases with 

TBI surviving for 3 hours or more, whereas experimental studies in animals 

revealed evidence of �-APP as early as 105 minutes (21) or 120 minutes (16,22) 

after the injury. 

Recently, the �-APP binding protein FE65 was identified (23), and it 

could be demonstrated by use of a real-time polymerase chain reaction (PCR) 

in a rat model that FE65 expression increases dramatically as early as 30 minutes 

after injury and decreases after peaking 1 hour after the injury (24). 

2.3. Inflammatory Cellular Response 

Comparatively few reports exist on the course of the inflammatory cellular 

response to cortical contusions in human brain tissue and in animals. In


contrast to peripheral tissue, the cellular reaction in the CNS was found to be 

characterized by a minimal neutrophil exudation and a delayed increase in 

mononuclear cell numbers (25–27). Protective mechanisms of the CNS parenchyma, 

such as the presence of the blood–brain barrier and the specialized 

nature of the cerebral endothelium or the downregulated microglial activity 

might be responsible for this comparably late inflammatory response in the 

brain (25). Concerning the velocity of leukodiapedesis, varying results have 

been reported in the literature. According to the findings of experimental studies 

in rats, early neutrophil accumulation within the first 24 hours after TBI, as 

measured by myeloperoxidase activity, was thought to indicate the beginning 

of the inflammatory reaction (28-31). Histological investigations of 

experimental brain injuries, however, revealed no relevant granulocytic 

recruitment (25,26,32), whereas in other morphological studies some polymorphonuclear 

(PMN) neutrophils were detectable in damaged cortex 4 hours 

after the trauma (33). PMN neutrophil infiltrations adjacent to the necrotic 

neuronal parenchyma of rats were present earliest at Day 2 and decreased 

further with time (33). In human brain tissue PMN neutrophils have been 

found within a few hours after the injury (3,4,34,35). In contrast, a rather 

early leukocytic reaction adjacent to the damaged cortex could be found by 

immunohistochemical staining (36): CD15-labeled granulocytes (Fig. 1A) 

were found earliest in a cortical lesion with a postinfliction interval of 10 minutes. 

Maximal cell numbers occurred within the first 2 days after human 

brain injury and according to other studies infiltrations were visible up to a 

postinfliction interval of 4 weeks (3,32). 

With regard to the mononuclear cellular response in human brain injury, 

a diffuse lymphoid reaction could be detected 3 or 4 days at the earliest (3,4) 

and up to a postinfliction interval of 44 years (4). In experimental brain contusions, 

an inflammatory mononuclear cell response was evident on Day 2 with 

a maximum on Days 5 and 6, and signs still remained 16 days after the trauma. 

The majority of these inflammatory cells has immunohistochemically proved 

to be activated T cells that may have receptormediated cytotoxic or modulating 

effects on cells in the CNS (26,37). In accordance to these experimental 

findings, mononuclear cell reactions could also be demonstrated in human 

cortical contusions (36): significantly increased numbers of T cells labeled by 

CD 3 (Fig. 1B) were detectable adjacent to cortical lesions after a posttraumatic 

interval of at least 2 days. UCHL-1 positive lymphocytes (Fig. 1C) 

occurred 3.7 days after the trauma at the earliest and the leukocyte common 

antigen showed a positive reaction in traumatically injured brain lesions with 

a wound age of at least 1.1 day.

58 Hausmann 

Fig. 1. Inflammatory cellular response to human brain injury. (A) CD15 positively 

stained polymorphonuclear neutrophils adjacent to damaged neuronal 

parenchyma in a cortical contusion with a postinfliction interval of 1.3 days. 

(B) Mononuclear leukocytes showing a positive reaction with the CD3 antibody 

in a cortical lesion 10 days after the injury. (C) UCHL-1 positive lymphocytes 

in a cortical contusion with a wound age of 12 days.


2.4. Macrophage–Microglial Reactions 

In recent years, it has been recognized that the major component of the 

response to nerve injury derives from microglia cells and macrophages (32). 

Cerebral macrophages were first described by Nissl (38) and extensively evaluated 

by Rio-Hortega (39). Today it is widely accepted that this cell type is 

ontogenetically related to the monocytic lineage (40,41) and invades the CNS 

during fetal development. Microglia, the resident macrophages of the CNS, 

take on an activated phenotype: the typical ramified microglial cells adopt an 

amoeboid form, thus they cannot be discriminated from infiltrating monocytes 

(42,43). Furthermore, there is evidence that activated microglia 

upregulates its expression via cell surface antigen molecules, such as the leukocyte 

common antigen vimentin (44), CD4 (32,45,46), and the major histocompatibility 

(MHC) antigens class I and class II (47,48). Because the 

distribution as well as the number and functional state of cerebral macrophages 

depends on the survival period, information on the course of morphological 

and immunological features after tissue destruction can contribute to a 

forensic wound-age estimation. 

Conventional histological studies revealed varying results concerning 

the temporal appearance of brain macrophages in cortical lesions: some 

authors observed cerebral macrophages as early as a few hours after the injury 

(3,49,50). On the other hand, a significant macrophage reaction has been 

reported 12–14 hours (4,34) or 1–2 days (51–53) after the injury at the earliest. 

A further classification of cerebral macrophages according to the different 

kind of incorporated material can also be useful for estimating the age of a 

traumatic brain lesion. Macrophages containing hemosiderin (siderophages) 

have been found in cortical lesions in cases with survival periods of at least 

2–5 days (3,54–60) whereas the non-iron-containing pigment hematoidin was 

detectable 1–2 weeks after the injury at the earliest (3,55,60). Macrophages 

showing fatty granules could be observed 3 days after the trauma (55). The 

macrophage activity in traumatically injured human brain was extensively 

investigated by Oehmichen et al. (34). The authors described intracellular lipid 

deposits as early as 24 hours and regularly 5–6 days after the trauma. The 

minimal survival period was 10 days for the appearance of anisotropic lipids 

(cholesterol), 16 days for erythrophages, 71 hours for siderophages, 13 days 

for hematoidin, and 101 hours for ceroid. 

Regarding the time-dependent immunoreactivity of cerebral macrophages 

some experimental studies in animals demonstrated elevated numbers of acetylated 

low-density lipoprotein expressing microglia cells at the earliest 5–8 hours 

after TBI in rats (61). Two days after trauma, a positive immunoreactivity could

60 Hausmann 

be observed for MHC I (62,63) as well as for MHC II and ED1 and ED2 (26). 

In damaged rat brain with a wound age of at least 3 days, microglia cells were 

positive for OX42 (64). However, the data of such experimental studies cannot 

easily be used for a wound-age estimation under forensic aspects. But 

there are only few reports concerning the immunoreactivity of cerebral macrophages 

in human brain: Meyermann et al. (42) investigated neuronal tissue 

from 17 patients with a wound age ranging between 6 hours and 6 months. 

According to the results of this study, microglia cells express HAM-56, MRP-8, 

and MRP-14 after a delay of more than 72 hours after trauma. The authors 

noted that the expression of these antigens did not correlate with proliferation, 

as they could not find a nuclear MIB-1 labeling. In contrast to these findings, 

a study of this author including 104 individuals with blunt head injuries revealed 

evidence of MIB-1-positive macrophages in a certain phase of the woundhealing 

process (65). The earliest nuclear MIB-1 staining reaction could be 

observed in a cortical contusion with a wound age of about 3 days and in the 

posttraumatic interval between 7 and 11 days all cases showed MIB-1-positive 

cells adjacent to the damaged area (Fig. 2A). Furthermore, numerous large 

round-shaped glial cells that showed a positive immunoreactivity for vimentin 

could be detected regularly in cortical lesions 1–4 weeks after the injury (Fig. 2B). 

2.5. Reactive Gliosis and Glial Scar 

Reactive gliosis is a common phenomenon in the CNS following tissue 

destruction, characterized by hypertrophy and proliferation of astroglial cells 

accompanied by neovascularization and deposition of a dense fibrous glial/ 

meningeal scar at the lesion site (66). Time-dependent histological changes of 

glial cells after traumatic injury to human brain have been investigated by 

Eisenmenger (55). A diminished stainability of oliogodendro and astroglia 

cells as a result of tissue edema could be observed within 10 minutes after the 

injury and 12–14 hours after the injury a swelling of the cell nuclei was obvious. 

Furthermore, the author reported a proliferative activity of glial cells in 

cortical lesions with a wound age of at least 3–4 days. After a postinfliction 

interval of 9 days, large round-shaped glial cells appeared at the lesion site. 

Colmant (67) observed protoplasmic astrocytes for the first time 24 hours after 

brain damage. Fibrillary astrocytes as well as progressive alterations (e.g., 

increase in capillaries, fibroblasts, and collagenous fibers) could be detected 

in damaged brain tissue with a wound age of at least 4–6 days (5,58) or 1 week (3). 

Further information on the course of reactive gliosis following brain injury 

was obtained by immunohistological staining of astrocytes, which have 

been demonstrated to play an important role in the healing phase after tissue


Fig. 2. Macrophage–microglial reactions 10 days after traumatic brain injury. 

(A) Macrophages showing a positive nuclear staining for MIB-1 adjacent to the 

damaged cortical tissue. (B) Numerous large round-shaped glial cells positive 

for vimentin at the lesion site. 

destruction by actively monitoring and controlling the molecular and ionic 

contents of the extracellular space of the CNS (69). Astrogliosis is characterized 

by a rapid synthesis of intermediate filaments, finally forming a glial scar 

(70). As the glial fibrillary acidic protein (GFAP) was found to be the major 

component of glial filaments (70,71), reactive astrocytes have been most commonly 

demonstrated by immunohistochemistry using specific antibodies to 

this protein. Increasing numbers of GFAP-positive astroglial cells following 

TBI have been described in several experimental studies in animals. Li et al.

62 Hausmann 

(72) found elevated numbers of GFAP-positive astrocytes at the earliest 4 hours 

after injury at the impact site in a fluid-percussion model in cats. Other authors 

observed an astroglial immunocytochemical response in cortical lesions after 

a postinfliction interval of at least 1 (73,74), 2 (75-77), 3 (78,79), or5days 

(80). These data correlate with an elevation in GFAP gene expression (mRNA) 

which could be detected in response to mild cortical contusions in animals 

(80). The increase in GFAP staining can result either from dissociation of 

glial filament bundles owing to edema or as a result of increase in GFAP 

synthesis (71) or by fibrous astrocytes which are thought to derive from protoplasmatic 

astrocytes of the gray matter (II–VI layers) without cell division 

(80). On the other hand, it could be demonstrated that GFAP-containing 

astrocytes located in the molecular layer (I) of the cortex and the white 

matter have the capacity to proliferate after trauma (77). In addition to 

these experimental models, our own studies examined the course of GFAP 

expression during the wound-healing process in human brain tissue under 

forensic aspects (81). The material investigated was brain tissue with macroscopically 

visible cortical contusions from 104 individuals who had sustained 

closed head injury. The survival periods ranged between a few 

minutes and 30 weeks. With regard to the presence of GFAP-positive astrocytes 

in normal brain tissue, a morphometrical analysis has been performed 

to obtain reliable information on chronological changes in absolute cell 

numbers following the brain injury. Compared to the average cell numbers 

in uninjured brain regions, the GFAP immunoreactivity was significantly 

increased 1 day after the injury at the earliest and remained elevated up to 

4 weeks in all cases (Fig. 3A). 

As various other molecules have been shown to be modulated in glial 

cells after injury in experimental studies, time-related changes in astroglial 

immunoreactivity for vimentin, tenascin, and �1-antichymotrypsin (�1-ACT) 

were investigated in the above-mentioned human material (82). 

Vimentin is a major cytoskeletal component in the immature glia. It is 

considered to be expressed by radial glia and immature astrocytes in the early 

phase of the development of the CNS and is replaced by GFAP during maturation 

(76). Adult astrocytes appear to recover the capacity to express vimentin. 

Furthermore, the coexpression of GFAP and vimentin by reactive astrocytes 

has been described in experimental models during the first two postlesional 

weeks (83). Other authors found vimentin-positive astrocytes 5 (80) or 7 days 

(84) after injury at the earliest. In accordance with these data, our study demonstrated 

elevated astroglial vimentin expression in cortical lesions with a 

wound age of at least 6 days and up to 4 weeks after trauma (Fig. 3B).


Fig. 3. Reactive gliosis. (A) Increased numbers of GFAP-labeled astrocytes adjacent 

to a cortical contusion with a postinfliction interval of 11 days. (B) Elevated 

astroglial vimentin expression surrounding the damaged area of a cortical lesion 

with a wound age of 13 days. (C) Intensive tenascin reactivity of proliferating 

blood vessels at the edge of a cortical contusion spreading into the damaged 

tissue 2 weeks after blunt brain injury.

64 Hausmann 

Tenascin is an extracellular matrix protein that is synthesized and released 

by immature astrocytes during embryonic and early postnatal development of 

the CNS (33,85–89). Whereas in the adult nervous system, tenascin can be 

detected only at very low levels, it has been shown that stab wounds to adult 

mouse cerebellar and cerebral cortices resulted in an enhanced expression of 

tenascin in a discrete region around the lesion site that is associated with subsets 

of GFAP-positive astrocytes (90,91). In the human brain, localized 

upregulation of tenascin was demonstrated by Brodkey et al. (90). The authors 

described a dense tenascin immunostaining in extracellular areas as well as 

some cellular staining (presumably astrocytes), which was located around a 

gunshot wound with a survival time of 96 hours. In accordance with these 

findings, tenascin could not be detected in uninjured human brain tissue in our 

study (82). Increased tenascin expression was, however, evident following 

brain injury, and about 75% of cases with cortical lesions aged between 7 and 

14 days showed a distinct staining of glial cells exclusively located around the 

damaged area. As described in the literature, the tenascin-positive glial cells 

were associated with GFAP-positive astrocytes at the lesion site. The findings 

suggested that tenascin upregulation in the injured adult brain may be directly 

involved in failed regeneration or indirectly involved through interaction with 

other glycoconjugates that either inhibit or facilitate neurite growth, as discussed 

by Laywell et al. (91). 

The serine protease inhibitor �1-ACT is an acute phase protein that is 

present in the amyloid plaques that form the pathologic hallmark of Alzheimer’s 

disease (AD) (92–94). Studies using in situ hybridization indicated that �1- 

ACT found in AD plaques is produced primarily by astrocytes (20,95). Reactive 

astrocytes expressing �1-ACT have also been found in other neurologic 

diseases, including Huntington’s chorea, Parkinson’s disease, and ischemic 

infarction of the brain (96). Recently, it was demonstrated that the expression 

of �1-ACT by reactive astrocytes can also be induced acutely in mice by focal 

injury (92). This finding was confirmed by the immunohistological investigations 

of our human material, where �1-ACT-positive glial cells were observed 

3 hours after the trauma at the earliest (82). In the postinfliction interval, ranging 

between 1 and 13 days, the majority of cases (about 69%) were positive 

for �1-ACT. These results support the assumption that increased �1-ACT 

expression may represent a consistent component of the astroglial response to 

neural injury (92). 

Some further antibodies have been employed in order to investigate early 

posttraumatic reactions of astrocytes after experimental brain trauma in animals: 

Li et al. reported a decrease of the neuron-specific enolase 1–2 hours


after the injury using a fluid-percussion model in cats, whereas significant 

changes in the S-100 protein-staining reaction could not be observed (72). 

Other studies revealed that S-100-positive reactive astrocytes proliferated in 

mouse cerebral cortex at 3–4 days after stabbing (97-99). Recently it has been 

reported that a rapid alteration in the cellular distribution of apoliprotein E 

(apoE) is induced in astrocytes and neurons 2 hours after human brain injury. 

These findings were thought to reflect a role for apoE in neuronal restoration 

and reorganization (100). 

The new formation of blood vessels is a common but not specific phenomenon 

following TBI. Proliferating capillaries at the lesion site, partly 

spreading into damaged areas, can be observed histologically during the first 

week after the trauma (4,35,55,68). Further data on the time course of the 

vascular response to human brain trauma could be obtained by investigating 

the immunoreactivity of blood vessels for laminin, type IV collagen, tenascin, 

thrombomodulin, and factor VIII in cortical contusions from 104 individuals 

who had sustained blunt head injury (101). Compared to the immunoreactivity 

in unaltered control tissue, a significantly increased vascular expression 

could be detected in cortical contusions after a postinfliction interval of at 

least 3 hours for factor VIII, after 1.6 days for tenascin (Fig. 3C), and after 

6.8 days for thrombomodulin, respectively, whereas the immunostaining for 

laminin and type IV collagene was regularly positive even in the vascular 

endothelium of uninjured brain tissue. 

Proliferative processes in the CNS have shown to be regulated by different 

types of growth factors such as fibroblast growth factor (102), plateletderived 

growth factor (103), nerve growth factor (104) or transforming growth 

factor � (105). The expression of these factors was temporarily induced after 

experimental TBI in animals (106–109). However, a review of the literature 

revealed no data deriving from human brain tissue that could be suitable for a 

forensic wound-age estimation. 

3. MEDICOLEGAL SIGNIFICANCE 

The value of a morphological parameter for forensic wound age estimation 

essentially depends on its unambiguous and consistent evidence during a 

certain phase of the healing process as well as on the absence of artificial 

changes (e.g., background staining in immunohistochemical slides). Positive 

findings are of particular diagnostic value and the earliest appearance of this 

parameter determines the minimal age of a traumatic lesion. Negative staining 

results can provide information if the regular appearance of the parameter has 

been well established by the systematic evaluation of a sufficient number of

66 Hausmann 

Table 1 

Earliest Appearance/Observation Period of Parameters 

for the Age Estimation of Cortical Lesions Detectable in Routine Histology 

Earliest appearance/ 

Cellular response Observation period References 

Erythrocytes 0–5 months 4–6 

Neutrophils (PMN) >2 hours 5 

130 minutes–28 days 4 

>4 hours 33 

>12 hours 27 

>3/4 days 55 

Lymphocytes 3/4 days 3 

71 hours–44 years 4 

Macrophages few hours 3 

>4 hours 50 

>6 hours 49 

>12 hours 39 


>24 hours 52,53 

>48 hours 51 

Hemosiderophages >48 hours 58,60 


>3 days 56 

3/4 days 3 

>4 days 59 

>4–5 days 55 

>5 days 57 

Hematoidin >6 days 60 

>11 days 55 

10–12 days 3 

12 days–12 months 4 

Lipophages 24 hours 34 

>3 days 55



Neuronal changes Observation period References 

Degeneration, shrinkage Immediately after the injury 4,5 

Immediately after the injury 3 

up to 5–6 months 

Vacuols Immediately after the injury 55 

Incrustation 1–3 hours 55 

Axonal swelling 10–20 hours 67 

24–48 hours 3 


Neuronophagy 12–24 hours–5 days 3 

14 hours–5 days 4 


Glial changes Observation period References 

Edematous swelling Immediately after the injury 55 

Diminished stainability >10 minutes 55 

Nuclear swelling 12–24 hours 55 

Glial proliferation 3–4 days 55 

Protoplasmic astrocytes >24 hours 67 

101 hours 4 

Siderin-containing astrocytes >5–6 days 55 

8 days 4 

Fibrillary astrocytes 6 days 4 

7–10 days 3 

>26 days 55 


Mesenchymal changes Observation period References 

Edema 0–9 days 4 

Vascular proliferation >12–24 hours 55 


4–6 days 35,58,68 

5–7 days 3 

Fibroblasts/fibrocytes 4–6 days 35,55,58,68 

6 days–8 months 4 

1 week 3 

Collagen fibers 4–6 days 35,55,58,68 

Note. Modified from ref. 1. 

9 days–58 years 4

68 Hausmann 

Table 2 

Earliest and Frequent Appearance of Immunohiostochemically 

Detectable Parameters Useful for the Timing of Cortical Contusions 

Antigen Earliest appearance Routine appearance 

Cellular reaction 

CD15 10 minutes 14 hours–1.6 days 

LCA 1.1 days 9–21 days 

CD3 2 days 13.3–19 days 

UCHL-1 3.7 days 10–19 days 

Reactive gliosis 

�1-ACT 3.1 hours — 

Vimentin 22 hours 5.5 days–4 weeks 

GFAP 1 day 1–4 weeks 

MIB-1 3.1 days 7–11 days 

Tenascin 7 days — 

Vascular reactions 

F VIII 3 hours 6 days–4 weeks 

Tenascin 1.6 days 1–4 weeks 

Thrombomodulin 6.8 days 1–2 weeks 

MIB-1 1 week 1–2 weeks 

cases with well-known wound ages. Some of the morphological parameters 

such as GFAP have been demonstrated also in uninjured brain tissue. Thus, a 

quantitative (morphometrical) analysis is required in order to get reliable information 

on trauma-induced changes in immunoreactivity. Furthermore, it should 

be noted that the majority of the presented parameters is not specific for brain 

trauma but may also occur under pathological conditions such as ischemia, 

toxic lesions, encephalomyelitis, or brain tumors. Finally, the data obtained in 

experimental studies using different animal models of TBI cannot easily be 

transferred to the human brain response. Taking these aspects into consideration, 

the data in Tables 1 and 2 can be used for estimating the age of cortical 

contusions in forensic autopsy cases. 

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CNS Alterations in Drug Abuse 77 

Forensic Neuropathology

78 Büttner and Weis


4 

Central Nervous System 

Alterations in Drug Abuse 

Andreas Büttner, MD and Serge Weis, MD 

CONTENTS 

INTRODUCTION 

OPIATES 

COCAINE 

CANNABIS 

AMPHETAMINE AND METHAMPHETAMINE 

AMPHETAMINE AND METHAMPHETAMINE DERIVATIVES 

REFERENCES 

SUMMARY 

Drug abuse represents a significant forensic issue worldwide. The major 

substances abused include cannabis, opiates, cocaine, amphetamine, methamphetamine, 

and “ecstasy.” Besides cardiovascular complications, psychiatric 

and neurologic symptoms are the most common manifestations of drug toxicity. 

A broad spectrum of changes affecting the central nervous system is seen 

in drug abusers. The major findings result from the consequences of cerebral 

ischemia and cerebrovascular diseases. Especially persons with underlying 

arteriovenous malformation or aneurysm are at higher risk for such events. So 

far, except for a few instances of vasculitis, the etiology of these cerebrovascular 

events is not completely understood. Besides pharmacologically induced 

vasospasm, impaired hemostasis, platelet dysfunction, and decreased cerebral 

blood flow have been proposed. Based on animal experiments, the abuse of 

amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine 

(MDMA) has been related to neurotoxicity in human long-term abusers and to 



79

80 Büttner and Weis 

the risk of developing Parkinson’s disease. However, whether such neurotoxicity 

occurs remains to be established. A major focus of research in the neurobiology 

of addiction has been put on the drug-induced adaptations within the brain 

reward system. Alterations of the intracellular messenger pathways, transcription 

factors, and immediate early genes in these reward circuits seem to be fundamentally 

important for the development of addiction and chronic drug abuse. 

Key Words: Amphetamine; drug abuse; cannabis; central nervous system 

(CNS); cocaine; ecstasy; forensic pathology; heroin; methamphetamine; opiates. 


Although no brain lesion specific for drug abuse exists, a broad spectrum 

of changes affecting the central nervous system (CNS) is seen in drug 

abusers (1–3). Despite the neuroradiological observations of subtle changes 

in cerebral blood flow (CBF), glucose metabolism, receptor densities, or 

metabolite profiles (4–11), no morphological correlates of these changes are 

usually apparent on gross or microscopic examination. Furthermore, the CNS 

alterations may not only be caused by the abused drug itself but may also be a 

result of adulterants. Considering the various changes found in the CNS of 

drug abusers, another problem consists of distinguishing between substancespecific 

effects related to the properties of the drug itself and secondary effects 

related to lifestyle of the affected individual, for example, malnutrition, infections, 

and peripheral diseases. In addition, the possibility that a preexisting 

condition may have contributed to the CNS alterations cannot be excluded. 

Because polysubstance abuse is seen in the majority of cases (12–15), it is 

difficult to relate the observed CNS findings to a single substance. Little is 

known about the long-term adverse CNS effects of “designer” or “club” drugs, 

such as “ecstasy,” �-hydroxybutyrate (GHB), ketamine, and herbal substances 

that constitute the major trend in illicit drug use since the early 1990s in younger 

people (16–23). Therefore, in many cases the exact etiology of the various 

CNS alterations is unclear. 

The rewarding (reinforcing) properties of a number of commonly abused 

drugs are mediated by activation of the mesolimbic dopaminergic system, the 

orbitofrontal cortex, and the system of the extended amygdala (24–35). A major 

focus of research in the neurobiology of addiction has been put on the drug-induced 

adaptations within these neural systems. Alterations of the intracellular messenger 

pathways, transcription factors, and immediate early genes in these reward circuits 

seem to be fundamentally important for the development of addiction and the consequences 

of chronic drug abuse (26,30,31,36–38). Nitric oxide (NO), which acts 

as a neuromodulator, might also be involved in drug dependence (39).


Drug abuse and dependence are neurobehavioral disorders of complex 

origin. Although environmental factors contribute to drug abuse and addiction, 

genetic factors also play a significant role. Despite the discovery of certain 

genes that are thought to be involved in drug abuse, the precise genetic 

risk factors for drug addiction and the changes in gene expression that are 

associated with drug abuse remain mostly unknown (40–46). Furthermore, 

most of our knowledge has been derived from animal models, whereby detailed 

human studies are lacking. It should be remembered, therefore, that findings 

in one species (e.g., rat) may not correspond well with what is found in 

another (e.g., mouse, monkey, human) possibly because of differences in 

pharmacokinetics. 

In the following, an overview is given describing the different types of human 

CNS lesions found in commonly abused drugs including a brief survey of the 

neuroradiological alterations and the numerous data derived from animal studies. 

2. OPIATES 

Fatalities in opioid abusers are a major public health issue worldwide. 

Significant risk factors include loss of tolerance after a period of abstinence 

and concomitant use of alcohol and other CNS depressants. Moreover, systemic 

disease, for example, pulmonary and hepatic disease as well as HIV 

infection, may increase susceptibility to a fatal overdose (12–15,47–55). 

2.1. Neuroimaging 

On computed tomography (CT) scans, cerebral atrophy has been shown in 

chronic heroin abusers (56–59); however, other studies were not able to show any 

gross abnormalities (60). Using magnetic resonance imaging (MRI), areas of 

demyelination in the deep white matter have been described (61), but other studies 

could not detect specific differences between drug abusers and controls (61–63). 

Single photon emission computed tomographic (SPECT) and positron emission 

tomographic (PET) studies demonstrated perfusion deficits in chronic opiate abusers 

without corresponding morphological CNS abnormalities (60,64–66). In longterm 

heroin abusers, a reduction of N-acetylaspartate in the frontal cortex was 

demonstrated on magnetic resonance spectroscopy (MRS); this finding was interpreted 

to be indicative of neuronal cell damage (67). 

2.2. Autopsy Findings 

Rapid death after heroin injection will not always lead to any morphological 

evidence of cellular injury. In cases of delayed death, hypoxic nerve


Fig. 1. Vascular congestion (thalamus, hematoxylin and eosin, original magnification 

× 200). 

cell damage will be apparent. In up to 90% of all deaths resulting from opiate intoxication, 

cerebral edema, and vascular congestion (Fig. 1) with increased brain weight 

are seen at autopsy (68–72). On histological examination, ischemic nerve cell 

damage (Figs. 2A,B), characterized by cytoplasmic eosinophilia, loss of Nissl substance, 

and nuclear shrinkage, is seen in almost all cases after a survival period of 5 

hours or longer (70,71). In an immunohistochemical study of the hippocampus, 

morphine has been selectively demonstrated in neurons, axons, and dendrites (73). 

In the globus pallidus, neuronal loss has been described (74). Bilateral, 

symmetrical ischemic lesions/necrosis of the globus pallidus can be found in 

5–10% of heroin addicts, which corresponds to hypodensities seen on CT scans 

(72,75–79). These alterations are believed to be caused by recurrent episodes 

of hypoxia during opiate intoxication rather than to be related to direct neurotoxic 

effects of the drugs (72,75,78,80). Similar lesions are found after carbon 

monoxide (CO) intoxication (80). 

2.3. Cerebrovascular Complications 

Stroke in heroin addicts occurring in the absence of endocarditis or 

mycotic aneurysms has rarely been observed (53,81–91). The pathogenetic 

mechanisms proposed by different authors include: (a) global cerebral hypoxia 

due to hypoventilation and/or hypotension during heroin intoxication


Fig. 2. Hypoxic-ischemic nerve cell damage with cytoplasmic eosinophilia, 

loss of Nissl substance, and nuclear shrinkage. (A) Frontal cortex (hematoxylin 

and eosin, original magnification × 100). (B) Hippocampal formation 

(hematoxylin and eosin, original magnification × 200). 

(81,84,87,88,91), or a focal decrease of the perfusion pressure (89) leading to 

borderzone infarcts, (b) vascular hypersensitivity reaction to heroin in persons 

who where re-exposed to the drug after a period of abstinence (85,88,92,93),


Fig. 3. Nerve cell loss in long-term heroin addiction (olivary nucleus, Luxol- 

Fast-Blue stain, original magnification × 200). 

(c) cerebral arteritis, necrotizing angiitis (88,93,94,95), or vasculitis 

(83,84,89,92) as shown by cerebral angiography, (d) embolism from adulterants 

(81,82,88,90,91), or (e) positional vascular compression (3). Recently, 

µ-opioid receptors were discovered on human erythrocytes that were significantly 

elevated in chronic opiate abusers and showed high deformability (96). 

Necrosis in the arterial boundary zones between the major arteries are owing 

to a marked sudden hypotension (3,81,89). 

2.4. Hypoxic-Ischemic Leukoencephalopathy 

Hypoxic-ischemic leukoencephalopathy results from hypoxia secondary 

to respiratory depression and affects the cerebral white matter (79,80,97). In 

addition, loss of neurons in the hippocampal formation, Purkinje cell layer, 

and/or olivary nucleus (Fig. 3) is frequently seen and is attributable to primary 

respiratory failure (70). In nearly 80% of these cases, enhanced expression of 

glial fibrillary acidic protein by astrocytes and/or a proliferation of microglia 

have been found in the hippocampus (70). Because such reactive processes 

are the result of primary neuronal damage, it can be assumed that chronic 

intravenous drug abuse obviously results in ischemic nerve cell loss. 

Perivascular pigment laden macrophages are sometimes observed and 

are attributed to repeated intravenous injections of impure heroin (98).


Fig. 4. Cerebral mucormycosis, large branching hyphae invading the brain 

tissue (periodic acid-Schiff reaction, original magnification × 85). 

2.5. Infections 

Infections in heroin abusers mainly result from unsterile injection 

techniques and from the immunosuppression caused by chronic opiate 

abuse (3). Brain abscess, meningitis, or ventriculitis resulting from bacteria 

(72,99) as well as fungal infections (100–105) (Fig. 4) have occasionally 

been reported. Endocarditis might lead to septic foci in the brain 

(Fig. 5A,B) (3,72,99,100,106–109) or to intracranial mycotic aneurysms 

with subsequent rupture and development of subarachnoidal hemorrhage 

(72,99,100,110). The occurrence of lymphocytic meningitis is indicative 

of an early stage of HIV-1 infection (98,112,113). 

2.6. Transverse Myelitis/Myelopathy 

Transverse myelitis/myelopathy is an exceptionally rare pathological 

condition that has been reported in recurrent heroin abusers after a period of 

abstinence (3,72,113–119) as well as during the course of heroin addiction 

(114). The affected persons present with a sudden paraparesis or paraplegia of 

the thoracolumbar region leading to death in some cases (72,113–119). The 

etiology is still unclear and neither the clinical picture nor the pathological 

changes conform to any particular pattern.


Fig. 5. Metastatic meningoencephalitis in a heroin abuser with endocarditis. 

(A) Macroscopical view. (B) Intracerebral perivascular exsudate of leukocytes 


2.7. Spongiform Leukoencephalopathy 

A distinct entity, spongiform leukoencephalopathy (nonspecific toxic 

demyelination), has been described to occur worldwide almost exclusively 

after inhalation of preheated heroin (“chasing the dragon,” “Chinese blow-


ing”) (3,120–140). The clinical features progress from motor restlessness and 

cerebellar signs to pyramidal and pseudobulbar signs and, in some patients, to 

a terminal stage with spasms, paraparesis, and death (129,130,139). A lipophilic 

toxin related to contaminants in conjunction with cerebral hypoxia is 

considered to be the cause, but a definite toxin has not yet been identified 

(123,130,133,139). Others postulated that spongiform leukoencephalopathy 

may be the outcome of a complex mechanism directly triggered by heroin that 

causes mitochondrial as well as hypoxic injury in specific and limited areas of 

the cerebral white matter (137). However, the mitochondrial respiratory chain 

complexes IV, III, and V are unchanged (131). On neuropathological examination 

there is a diffuse spongiosis of the white matter with loss of oligodendrocytes, 

axonal reduction, and astrogliosis. The gray matter is usually 

unremarkable and the brainstem, spinal cord, and peripheral nerves are spared 

(3,129,131–133,135). The presence of spongiosis with astrogliosis and the 

absence of typical hypoxic lesions distinguish these cases from those with 

delayed leukoencephalopathy following severe hypoxia (131). Toxic leukoencephalopathy 

has also been observed after exposure to alcohol, toluene, cocaine, 

and hallucinogens (141). 

2.8. Alterations of Neurotransmitters, 

Receptors, and Second Messengers 

All opiate effects are mediated via several specific types of opioid receptors. 

Of these, the µ-receptors mediate analgesia, euphoria, respiratory depression, 

hypothermia, bradycardia, and miosis (31,142–146). Long-term opiate 

abuse seems not to be associated with a reduced density of CNS µ- and �-opioid 

receptors because the density and affinity of these receptors were similar to 

those in controls in the frontal cortex, thalamus, and caudate nucleus (147–152). 

However, in an immunohistochemical study, an increased density of µ-opioid 

receptor-immunoreactive neurons has been demonstrated in Brodmann Area 

11 of the human cerebral cortex (153). The authors hypothesized, that this 

receptor upregulation might be associated with a state of functional hypersensitivity 

in acute heroin intoxication. In investigating the acute and chronic 

effects of opiates on the CNS and the molecular mechanisms underlying opiate 

addiction, the second messenger-signaling system seems to play a crucial 

role (141,154–158). The coupling of opioid receptors to their effectors is 

mediated by guanosine triphosphate-binding (G) proteins that transmit extracellular, 

receptor-detected signals across the cell membrane to intracellular 

effectors (31,153). Opiates acutely inhibit adenylyl cyclase activity (which 

converts ATP to cAMP [cyclic adenosine monophosphate]) via G proteins


resulting in decreased cellular cAMP levels. Chronic opiate exposure induces 

an upregulation in this adenylyl cyclase-cAMP system, which is interpreted to 

be a compensatory response to the sustained inhibition of the opioid receptor 

system in order to maintain homeostasis (31,154,156–158). This long-term 

effect of opiates on the cAMP pathway is mediated via the transcription factor 

CREB (cAMP response element-binding protein), with the locus coeruleus, 

the mesolimbic dopaminergic system, and the extended amygdala being the 

major target areas (150,159). This activation of the reward system in human 

opiate addiction could be demonstrated by functional neuroimaging (160). 

Autopsy studies revealed that long-term heroin abuse causes an increase in 

certain G proteins in different regions of the brain of heroin addicts (154,157). 

This has been demonstrated for the Gß subunit in the temporal cortex (154) 

and for the subunits G�·i 1/2 , G�o, G�s, and Gß in the frontal cortex (157). 

From these studies it is concluded that opiate addiction is associated with abnormalities 

in second messenger and signal transduction systems involving G 

proteins (149,154,157). Other studies have shown a decreased level of Ca 2+ - 

dependent protein kinase C (PKC)-� in the frontal cortex of opiate addicts 

(148) and an increased level of a membrane-associated G protein-coupled receptor 

kinase (161). It is assumed that the downregulation of the PKC-� would 

enhance the upregulation of G�·i 1/2 proteins for compensating the opiateinduced 

desensitization of the µ-opioid receptor system (148). 

Further findings in the brains of heroin addicts include a significant 

downregulation of the adenylyl-cyclase subtype I in the temporal cortex, which 

may play an important role in the molecular mechanism of chronic opiate 

addiction (156,158), a significant decrease in the density of � 2 -adrenoreceptors 

in the frontal cortex, hypothalamus, and caudate nucleus without changes in 

affinity values (147), and a marked decrease in the immunoreactivity of 

PKC-�ß in the frontal cortex (162). The observation of markedly decreased 

levels of immunoreactive neurofilament proteins in the frontal cortex of chronic 

opiate addicts may represent a specific long-term effect indicating neuronal 

damage after chronic abuse (163). 

In a postmortem study of chronic heroin abusers, the density of dopaminergic 

nerve terminals was not reduced in the striatum (164). In the nucleus 

accumbens, the levels of tyrosine hydroxylase protein and those of the dopamine 

(DA) metabolite homovanillic acid were significantly reduced associated with 

a trend for decreased DA concentration. These changes could reflect either a 

compensatory downregulation of DA biosynthesis in response to prolonged 

dopaminergic stimulation caused by heroin, or reduced axoplasmic transport 

of tyrosine hydroxylase (164). Striatal levels of serotonin (5-hydroxytryptamine


[5-HT]) were either normal or elevated whereas the concentration of the 5-HT 

metabolite 5-hydroxyindoleacetic acid was decreased (164). According to the 

authors, chronic heroin exposure might produce a modest reduction in dopaminergic 

and serotonergic activity that could affect motivational state and impulse 

control, respectively. 

The density of I 2 -imidazoline receptors and the immunoreactivity of the 

related receptor protein were decreased in astrocytes of the frontal cortex, 

indicating that chronic opiate abuse induces downregulation of I 2 -imidazoline 

receptors in astrocytes, and presumably downregulates the functions associated 

with these receptors, for example, reduced growth of astrocytes (165). 

2.9. Heroin Maintenance Treatment 

Codeine, dihydrocodeine, methadone, and buprenorphine are increasingly 

important in the context of deaths associated with maintenance treatment for 

heroin addiction (166–181). Monointoxication with one of these substances is 

the exception and, in the majority of cases, additional CNS depressant drugs, 

mainly alcohol and benzodiazepines, can be detected. The neuropathological 

findings are similar to those encountered in heroin deaths and consist of edema 

and hypoxic nerve cell changes. 

3. COCAINE 

Cocaine abuse represents the third most common addiction disorder 

next to alcohol and cannabis and is of increasing social and medical concern 

(3,182–185). 

Cocaine crosses the blood–brain barrier (BBB) rapidly due to its high 

lipophilic properties (186,187). In the absence of alcohol, cocaine is mainly 

metabolized to form the inactive metabolites ecgonine methyl ester (EME) 

and benzoylecgonine (BE), which do not significantly cross the BBB 

(3,146,186). Although the uptake of BE into the brain is very low, the enzyme 

butyrylcholine esterase, which catalyzes the metabolism of cocaine to BE, is 

abundantly present in the cerebral white matter (188). In the presence of alcohol, 

cocaine is metabolized to cocaethylene (CE), which crosses the BBB rapidly. 

With a longer half-life time, CE accumulates to a four times higher 

concentration and possesses a similar pharmacologic profile to cocaine 

(146,189–191). 

Throughout the brain, cocaine and its major metabolites are widely distributed 

and receptors with varying affinities for cocaine are found (192–195). 

The region with the highest density of cocaine receptors, which is also the


region containing the receptors with the greatest affinity for cocaine, is the 

striatum (192,194). Lower levels of activity are found in the frontal and occipital 

cortex (195). 

Most of the CNS effects of cocaine are mediated through alterations of the 

neurotransmitters DA, norepinephrine (NE), 5-HT, acetylcholine, and �-aminobutyric 

acid (GABA). Cocaine blocks the presynaptic reuptake of neurotransmitters 

resulting in their accumulation in the synaptic cleft, thus producing a 

sustained action on the receptor system followed by neurotransmitter depletion 

(3,146,184,196). Furthermore, cocaine enhances DA neurotransmission by interacting 

with the dopamine transporter (DAT), inhibiting the clearance of DA 

and stimulating the enzyme tyrosine hydroxylase (3,146,185). The interactions 

of cocaine in the mesolimbic dopaminergic system constitute the basis for its 

reinforcing properties (30–35,197). The abuse potential of cocaine is mainly 

based on the rapid development of tolerance to the euphoric effects, which 

requires the user to increase either dose or frequency of abuse or both to sustain 

the effects (146,185,198). 


In chronic cocaine abusers, CT scans revealed significant diffuse cerebral 

atrophy, which was positively correlated with the duration of cocaine 

abuse (199). Age-related hyperintense areas in the white matter have been 

described on MRI in cocaine-dependent persons, which were attributed to 

ischemic lesions (61,188). Evidence of caudate nucleus and putamen enlargement 

has been shown on MRI (200). However, other studies could not find 

significant differences in the total brain volume or the presence of white matter 

lesions in cocaine abusers (201,202). A global reduction in cerebral glucose 

metabolism and CBF alterations have been demonstrated in PET and 

SPECT, studies (203–210). Focal perfusion deficits in different brain regions, 

could be observed using PET and SPECT, which were partially reversible 

after abstinence (203–205,208,210,211). 


Although different complications have been described in cocaine abuse, 

most persons experience cerebrovascular events. Cocaine is the most common 

drug of abuse associated with cerebrovascular events (88,212,213). Intracerebral 

and subarachnoidal hemorrhages as well as stroke have been reported, 

manifesting minutes to hours after cocaine abuse (83,90,186,214–237). After 

alkaloidal cocaine consumption, ischemic and hemorrhagic strokes are equally 

likely, whereas after cocaine hydrochloride, hemorrhagic stroke occurred twice


Fig. 6. Cocaine-induced ischemic infarction in the region of the middle 

cerebral artery. 

as often as ischemic stroke (213). In contrast to the non-drug-using population, 

cocaine-associated stroke occurs primarily in young adults with a peak 

in the early 30s (3,182,183,213,215,221). Other studies could not detect a relationship 

between cocaine abuse, either infrequent or frequent, and nonfatal 

stroke in persons aged 18–45 years (232). 

In an autopsy study of 72 cocaine-associated deaths, cerebrovascular 

events were not mentioned (238). Others reported intracerebral hemorrhage 

as the cause of death in about 2–20% of the cases (227,235). 

Cocaine-associated ischemic infarctions (Fig. 6) can be found in every 

brain region, and nearly half of the patients presented with neurological deficits 

within the first 3 hours after cocaine intake (3,213,217,219,236). The underlying 

cause is attributed to cerebral vasospasm as a result of the vasoconstrictive 

and local anesthetic effects of cocaine (88,204,208,213,216,222,240–242). Using 

MR angiography, a dose-dependent cerebral vasoconstriction after cocaine


Fig. 7. Cocaine-induced intracerebral hemorrhage with intraventricular 

extension. 

administration in healthy human volunteers has been observed (242). Furthermore, 

a reduction of global CBF and cerebral perfusion deficits has been shown 

in human cocaine abusers receiving a single intravenous cocaine dose (204,243). 

The cerebrovascular symptoms that occur hours to days after cocaine abuse 

cannot readily be explained by the vasoconstrictive properties of cocaine because 

of its short plasma half-life of 60–80 minutes (213,219,222,244). Therefore, the 

longer half-life metabolites BE or CE have been considered to be responsible, 

as they induced significant vasoconstriction on cerebral arteries in animal experiments 

(187,189,244–246). Cardiac arrhythmia is another pathogenetic mechanism 

that can lead to secondary cerebral ischemia on embolic or hemodynamic 

basis (83,213,216,222,231). A cocaine-induced impairment of hemostasis, platelet 

dysfunction, and endothelium-dependent vasorelaxation have been described 

by other authors, but the studies have yielded conflicting results (247–250). 

In cocaine-associated intracerebral (Fig. 7) and subarachnoidal hemorrhage 

(Figs. 8A,B), underlying arteriovenous malformations or aneurysms are 

often observed, but in about half of the affected persons, there was no demonstrable 

lesion (90,182,186,213,216,218,219,221,223,225,227,229,230,235).


Fig. 8. Subarachnoidal hemorrhage due to rupture of an aneurysm of the 

middle cerebral artery in association with cocaine abuse. (A) Computed 

tomography scan. (B) Macroscopical view. 

Compared to non-drug-using persons, cocaine abuse has been shown to predispose 

to aneurysmal rupture at a significantly earlier age and in much smaller 

aneurysms (182,186,251). A sudden elevation of blood pressure is believed to 

be the likely cause, since the majority of cases become symptomatic within a 

few hours after cocaine abuse (88,186,213,215,217–221,225,229,235). 

Based on the angiographic observation of segmental stenoses and dilatations, 

a cocaine-induced cerebral vasculitis (Fig. 9) is considered to be the 

cause of the ischemic and hemorrhagic lesions (215,220,221,223,230,252–254). 

However, a vasculitis could be demonstrated by biopsy or autopsy only in rare 

cases (226,252,255–257). Experimentally, cocaine enhances leukocyte migration 

across the cerebral vessel wall and opens the BBB to HIV-1 invasion by a 

direct effect on brain endothelial cells and by the induction of pro-inflammatory 

cytokines and chemokines (258–260). Furthermore, brain capillary lesions were 

seen in rats after chronic administration of cocaine (261).


Fig. 9. Cocaine-induced vasculitis with destruction of the vessel wall and 

perivascular lymphocytic infiltration (hematoxylin and eosin, original magnification 

× 120). 

3.3. Seizures 

Cocaine-associated seizures have been reported in 2–10% of cocaine 

abusers (262–264). The majority of the cases show self-limiting generalized 

tonic-clonic seizures. However, status epilepticus and consecutive death have 

been reported in single cases (265). The pathogenetic mechanims are believed 

be due to a reduction of the seizure threshold or by induction of cardiac 

arrhythmia (265). 

3.4. Movement Disorders 

Movement disorders, for example, akathisia, choreoathetosis, dystonia, and 

Parkinsonism, are frequently observed in cocaine abusers, especially in “crack” 

abusers (“crack dancing”). The symptoms are explained by disturbances in the 

dopaminergic transmission in the nigrostriatal motor system (266–268). 


Receptors, and Gene Expression 

Marked reductions in the levels of enkephalin mRNA, µ-opioid receptor 

binding, and DA uptake site binding, concomitant with elevation in levels of


dynorphin mRNA and �-opioid receptor binding have been described in the 

striatum of human cocaine-related deaths (269). In chronic cocaine abusers, a 

decrease in the levels of DA was seen in the caudate nucleus and frontal cortex, 

but not in the putamen, nucleus accumbens, and cerebral cortex (270–274). 

This decrease was not paralleled by an increase of DA D 1 and D 2 gene expression 

in the nucleus accumbens, caudate nucleus, putamen, or substantia nigra 

(275). Simultaneously, there was an increase of cocaine binding sites on the 

DAT with a decrease of the DA D 1 -receptor density in the striatum and of D 1 

and D 3 receptor density in the nucleus accumbens (271–273,276–278). A 

marked reduction in vesicular monoamine transporter-2 (VMAT-2) immunoreactivity 

(270) and of the transcription factor NURR1 (279) in autopsy samples 

of human cocaine abusers might reflect damage to the dopaminergic system. 

An overexpression of �-synuclein in midbrain DA neurons in chronic cocaine 

abusers may occur as a protective response to changes in DA turnover and 

increased oxidative stress resulting from cocaine abuse (280). According to 

the authors, this accumulation of �-synuclein protein in long-term cocaine 

abuse may put addicts at increased risk for developing the motor abnormalities 

of Parkinson’s disease. Furthermore, an upregulation of � 2 -opioid receptors 

in the limbic system (281) and of CREB in the ventral tegmental area 

(282) has been described. In the serotonergic system, an increase of the 5-HT 

transporter in the striatum, substantia nigra, and limbic system has been demonstrated 

(283). The activity of phospholipase A 2 and phosphocholine 

cytidylyltransferase was selectively decreased in the putamen, a DA-rich brain 

area (284,285). 

4. CANNABIS 

Cannabis abuse represents a significant clinical forensic issue worldwide 

because it is the most common illicit drug in use today. � 9 -Tetrahydrocannabinol 

(THC), the major psychoactive component of cannabis, has a high abuse potential 

and leads to psychological dependency (286–292). Cannabis is thought to 

underlie its reinforcing and abuse potential by a still unknown mechanism that is 

most probably similar to that of other drugs of abuse that increase the activity of 

dopaminergic neurons in the mesolimbic dopaminergic system (293–297). 

4.1. Cannabinoid Receptors and Endocannabinoids 

Within the brain, THC is distributed heterogeneously, with its highest 

concentrations in neocortical, limbic, sensory, and motor areas (288). THC 

and other cannabinoids exert their effects by the interaction with specific


cannabinoid (CB) receptors (293,298–300). Two cannabinoid receptors, CB1 

and CB2, have been pharmacologically characterized and anatomically localized 

(298,301,302). CB1 receptors are found predominantly in the central and 

peripheral nervous system, where they have been implicated in presynaptic 

inhibition of neurotransmitter release. CB2 receptors are present on immune 

cells, where they may be involved in cytokine release (293,301,303). Both 

receptors are coupled through G proteins to signal transduction mechanisms 

that include inhibition of adenylyl cyclase, activation of mitogen-activated 

protein kinase, regulation of calcium and potassium channels (CB1 only), and 

other signal transduction pathways (293,298,301,303,304). The identification 

of specific receptors mediating the effects of cannabinoids soon led to the 

discovery of endogenous cannabinoid agonists (“endocannabinoids”). These 

lipid mediators of the eicosanoid class, notably arachidonoylethanolamide 

(anandamide), 2-arachidonoylglycerol and 2-arachidonylglyceryl, ether 

(noladin ether), bind to both cannabinoid receptor types. They have been implicated 

in various physiological functions, for example pain reduction, motor 

regulation, learning, memory, appetite stimulation, and reward (301,304,305). 

The CB1 receptors are distributed heterogeneously within the brain with the 

highest density in the substantia nigra, basal ganglia, hippocampus, and cerebellum 

(302,306–309). In the neocortex they are present with the highest density in 

the frontal cortex, dentate gyrus, mesolimbic dopaminergic system, and temporal 

lobe (302,307–309). This specific distribution of CB1 receptors correlates well 

with the effects of cannabinoids on memory, perception, and the control of movement. 

However, chronic exposure to THC fails to irreversibly alter brain cannabinoid 

receptors (310). The very low density of CB1 receptors in the brain stem and 

medulla oblongata explains the low acute toxicity and lack of lethality of cannabis 

(286,293,308). Nevertheless, the CNS toxicity of cannabis has been underestimated 

for a long time (311), since recent findings revealed THC-induced neuronal 

death (312–314). These studies demonstrated that THC has a time- and 

concentration-dependent toxic effect on cultured hippocampal, cortical, and neonatal 

neurons. The THC-induced generation of free radicals has been assumed to 

be the primary event that could lead to lipid peroxidation and subsequent neuronal 

apoptosis (312–314). These mechanisms are believed to be responsible for the 

cognitive deficits seen in chronic cannabis abusers (315). 

4.2. CNS Complications 

Besides cardiovascular complications, CNS complaints are the most common 

manifestations of acute cannabis toxicity (290). The latter include psychiatric 

symptoms such as panic attacks, anxiety, depression, or psychosis


(290,316,317). Furthermore, THC has been shown to affect cognition and 

impair verbal and memory skills (288,318–320). However, there is little evidence 

that such impairments in humans are irreversible, or that they are accompanied 

by cannabis-induced neuropathology (289). THC increases the 

depressive effects of alcohol, sedatives, and opiates, whereas its interactions 

with stimulants, for example, amphetamines or cocaine, are complex and can 

be either additive or antagonistic (291,321). 


Neuroradiological studies of the consequences after acute or chronic cannabis 

abuse demonstrated subtle CNS alterations. MRI studies failed to detect 

morphological brain changes in long-term cannabis abusers (322). However, PET 

and SPECT studies showed a transient vasodilatation with an increase of CBF and 

metabolism after acute cannabis abuse (323,324). In contrast, in chronic cannabis 

abusers a decreased cerebral metabolism and CBF has been described in the frontal 

lobe and cerebellum (325–329). The age at which exposure to cannabis begins 

seems to be important for the existence of CBF changes, with the early adolescence 

as a critical period (329). The cessation of chronic cannabis abuse is believed 

to lead to a decrease in the functional level of the frontal lobes (327). 


Neurological complications after cannabis consumption are rare and mainly 

consist of cerebrovascular events, for example, cerebral infarction (330,331) or 

transitory ischemic attacks (332). In all of these cases, cannabis was smoked in 

high doses over years and the abuse of other drugs has been denied or they were 

not detected in the acute phase of abuse. A cannabis-induced vasospasm or a 

cannabis-induced hypotension has been hypothesized to be the cause. 


Receptors, and Transcription Factors 

At the cellular level, abnormalities in the expression of transcription factors, 

NO formation and alterations in the brain dopaminergic system have been 

reported in animal experiments (333). The exact etiology of the different CNS 

alterations associated with cannabis abuse is still unclear. 

5. AMPHETAMINE AND METHAMPHETAMINE 

Over the past years, the illicit use of amphetamine and methamphetamine 

has significantly risen worldwide (3,20,334–341). Furthermore, in the context


of 3,4-methylenedioxymethamphetamine (MDMA) abuse, tablets sold as 

“ecstasy” often contain not only MDMA but other compounds such as amphetamine 

and methamphetamine (342). 

Amphetamine, methamphetamine, and cocaine comprise a subclass of 

psychostimulants that share a molecular site of action at monoamine transporters, 

in particular the DAT (3,146). Although they bind to the three major 

monoamine transporters, DA, 5-HT, and NE, it is the actions at DATs that 

are most central to both the motor-activating and reinforcing (rewarding) 

properties of these substances, but there are differences in the molecular 

mechanisms by which these drugs interact with DATs (343). Acute administration 

of psychostimulants enhance synaptic concentrations of DA and 

other monoamines. The potent sympathomimetic effects of amphetamine and 

methamphetamine include an elevation of pulse rate and blood pressure, an 

increased level of alertness, decreased fatigue, and suppression of appetite 

(146). The euphoric action and the reinforcing effect are related to their ability 

to release DA in the mesolimbic dopaminergic system and acetylcholine in 

the cerebral cortex (343–345). Adverse CNS events include seizures, agitation, 

and psychosis, often accompanied by aggressive behavior and suicidality 

(336,341,346–348). 


Amphetamines are the second most common cause (after cocaine) of 

ischemic or hemorrhagic stroke (Fig. 10) occurring largely in persons younger 

than 45 years (212). Besides stroke, subarachnoidal and intracerebral hemorrhages 

(Fig. 11) have been described after acute amphetamine and methamphetamine 

abuse (85,88,182,183,218,335,341,349–365). In the majority of 

cases there was no underlying brain lesion detectable. Only in single instances 

could an arteriovenous malformation (Fig. 12) be detected (357,362,364). The 

pathophysiology of cerebrovascular complications related to amphetamine and 

methamphetamine abuse may involve several mechanisms (88). A sudden elevation 

in blood pressure (336,354) or a cerebral vasculitis (341,349,358,365–369) 

are postulated as major underlying mechanisms. Amphetamine-induced 

cerebral vasculitis (Fig. 13) is described as a necrotizing angiitis closely resembling 

periarteritis nodosa, consisting of hemorrhages, infarctions, microaneurysms, 

and perivascular cuffing occurring in small- to medium-size arteries 

(88). Interestingly, a recent study indicated that methamphetamine might induce 

inflammatory genes in human brain endothelial cells (370). The vasoconstrictive 

effect of both substances may also lead to the development of ischemic 

stroke (360).


Fig. 10. Hemorrhagic stroke associated with amphetamine abuse. (A) Macroscopical 

view. (B) Microscopical view (hematoxylin and eosin, original magnification 

× 100). 

5.2. Neurotoxicity 

Throughout the brain, methamphetamine is heterogeneously distributed 

(371). The neurotoxic effects of amphetamine and methamphetamine on the 

dopaminergic system have been described in various animal species and in


Fig. 11. Amphetamine-induced intracerebral hemorrhage. 

humans by both neuroimaging and postmortem studies. These effects were 

characterized by desensitization of DA receptor function, and marked reduction 

of DA levels as well as other levels of dopaminergic axonal markers, for 

example, tyrosine hydroxylase, DATs, and VMAT-2 (372–410). Similar alterations 

have been reported in the serotonergic system (380,411-413). However, 

for most of these studies, the irreversibility of the neuronal deficits has 

not been established and it is still unclear whether the neurochemical alterations 

reflect neuroadaptation or neurotoxicity (414). 

Although these persistent deficits have been attributed to neurodegeneration, 

direct evidence for the loss of nerve terminals and/or their corresponding 

substantia nigra cell bodies has not been provided unequivocally (414), 

with the exception of a few studies in mice suggesting a methamphetamineinduced 

loss of dopaminergic cell bodies in the substantia nigra (415). Furthermore, 

a recovery phenomenon for the striatal DA system has also been 

reported (379,388,389,416). Based on animal studies, there is concern that 

thealterations in the dopaminergic system may predispose methamphetamine 

abusers to develop Parkinsonism as they age, at least the ones that survive 

their abuse (414,417,418). Neuroimaging and autopsy studies of human


Fig. 12. Intracerebellar hemorrhage associated with amphetamine abuse with 

an underlying arteriovenous malformation. 

Fig. 13. Cerebral vasculitis with perivascular lymphocytic infiltration (hematoxylin 

and eosin, original magnification × 120).


methamphetamine abusers, although much more limited, suggest changes in 

some but not all of the dopaminergic system markers (385,405,406,419). Therefore, 

the evidence from this human study is inconclusive regarding dopaminergic 

system degeneration. To define methamphetamine abuse as a risk factor 

in Parkinson’s disease, it is important to know whether these alterations in the 

dopaminergic system represent neurodegenerative changes or a drug-induced 

compensatory response to the disruption of neurochemical homeostasis. It 

should be noted that symptoms are expressed only when about 90% of DA 

neurons are lost. Thus, methamphetamine could destroy many dopaminergic 

neurons without leading to clinical symptoms (417). 

The mechanisms of methamphetamine-induced neurotoxicity are thought 

to be mediated by multiple mechanisms including the generation of free radicals 

and NO, excitotoxicity, disruption of mitochondria, and the induction of 

immediate early genes as well as transcription factors (380,419–430). Hyperthermia 

may be an additional mechanism (431,432). However, whether such 

neurotoxicity occurs in human methamphetamine and amphetamine abusers 

and is restricted to striatal DA neurons remains to be established. 

6. AMPHETAMINE AND METHAMPHETAMINE DERIVATIVES 

The abuse of amphetamine and methamphetamine derivatives is an emerging 

issue in current forensic medicine. Common substances include 4-methyl- 

2,5-dimethoxyamphetamine (DOM), 4-bromo-2,5-dimethoxyamphetamine 

(DOB), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine, 

“ecstasy,” “Eve” (MDE), 3,4-methylenedioxymethamphetamine, 

“Adam,” “XTC” (PMA), 4-methylthioamphetamine, “Flatliners,” 4-MTA, and 

4-para-methoxyamphetamine (PMA) (3,20,433–436). The street name “ecstasy” 

subsumizes different hallucinogenic amphetamine derivatives with 

MDMA and MDE being the main components (342,437). 

The most important difference between the European and the American 

experience of “ecstasy” is that whereas it tends to be taken alone or at parties, 

often combined with cocaine and opiates in the United States, it is used in 

Europe almost exclusively as a “dance drug” (438,439). Under the latter condition, 

the pharmacological effects of the drug may be compounded by physical 

exertion in overheated environments with scarce water supply (438,439). 

Tablets sold as “ecstasy” may contain not only MDMA but other compounds 

well known to cause neurotoxicity, such as methamphetamine and 

amphetamine (342,437). Furthermore, the consumption of “ecstasy” is often 

combined with the abuse of other drugs. Therefore, little is known about the 

effects of “ecstasy” abuse or the combination of “ecstasy” and amphetamine


abuse on neurons in the human brain. As MDMA is the most widely abused 

substance, this review will focus on CNS alterations associated with this drug. 

6.1. Receptor Interactions 

MDMA affects the peripheral and CNS by acting mainly on the serotonergic 

system. The drug has sympathomimetic properties and modulates psychomotor 

and neuroendocrine functions (18,433,440–444). The unique effect 

of MDMA is the feeling of intimacy and closeness, designated as “entactogenic” 

(445). MDMA acts as an indirect monoaminergic agonist and displays relatively 

high, similar affinities for �-adrenoceptors, 5-HT 2 receptors, M-1 muscarinic 

receptors, and H-1 histamine receptors. With less affinity MDMA 

binds to DA and NE uptake sites, M-2 muscarinic receptors, � 1 -adrenoceptors, 

ß-adrenoceptors, 5-HT 1 receptors, and D1 and D2 DA receptors. MDMA blocks 

5-HT reuptake and induces 5-HT release and, to a lesser extent, also causes 

DA and NE release (444,446–451). The 5-HT release appears to be related to 

MDMA action on the 5-HT transporter (452). In addition to its inhibition of 

monoamine reuptake, MDMA might also increase extracellular levels of 

monoamines by inhibiting brain monoamine oxidase activity (451). 

In human postmortem tissue, a distinct immunopositive reaction of 

MDMA and MDA was observed in the white matter, in all cortical brain 

regions and the neurons of the basal ganglia, in the hypothalamus, the hippocampus, 

and the cerebellar vermis, but in the brainstem relatively weak staining 

of neurons was seen (453). 

6.2. Neurotoxicity 

Exposure to MDMA can cause acute and long-term neurotoxic effects in 

animals and nonhuman primates (446,450,454–475). Nonhuman primates have 

been shown to be more sensitive to the neurotoxic effects of MDMA than rats. 

The serotonergic system seems to be mostly affected. Histological and immunohistochemical 

studies have also provided evidence for serotonergic 

neurodegeneration and axonal loss (455,457,462,463,468–472,476,477). 

Despite extensive studies, the mechanisms underlying MDMA neurotoxicity 

still remain to be fully elucidated (478–480). Current hypotheses of its damaging 

mechanisms include the formation of toxic MDMA metabolites with 

generation of free radicals as well as disturbances in the serotonergic, dopaminergic, 

GABAergic, glutamatergic, and NO system (481–483). Furthermore, 

hyperthermia seems to have an influence (484,485). 

Based on neuroimaging, clinical, and cell culture studies, there is a growing 

consensus that MDMA might also have acute and long-term neurotoxic


effects (465,467,486–517). Especially, impaired cognitive performance and 

an increased incidence of neuropsychiatric disorders have been reported 

(494,511,512,518,519). Nevertheless, it is still unclear how to extrapolate animal 

and nonhuman primate data to the human condition (479,481,504,520–522). 

6.3. Fatalities 

Besides serious long-term CNS effects, there is a risk of a fatal outcome 

after “ecstasy” consumption. Although death rates following MDMA abuse are 

low compared to the number of abusers, fatalities associated with MDMA have 

been reported worldwide (438,439,523–538). The cause of death may be a result 

of cardiovascular arrest, hyponatremia, or hepatic failure, whereas exertional 

hyperthermia or serotonin syndrome may lead to disseminated intravascular 

coagulation, rhabdomyolysis, and acute renal failure. Other victims sustained 

traumatic injuries, for example, traffic accidents (438,439,539). In these studies, 

detailed neuropathological examinations have not been performed. 

6.4. CNS Complications 

CNS complications after “ecstasy” consumption have been described occasionally 

and include ischemic as well as hemorrhagic cerebral infarction of 

unknown etiology (540–542). Further findings included intracranial hemorrhage 

(543,544), subarachnoidal hemorrhage (545), sinus vein thrombosis (546), hypersensitivity 

vasculitis (547), and leukoencephalopathy (548). In the globus 

pallidus, bilateral hyperintense lesions have been found (549,550). On neuropathological 

examination, necrosis of the globus pallidus and diffuse astrogliosis 

and spongiform changes of the white matter have been described (550). The 

authors pointed out that the globus pallidus is rich in serotonin-releasing neurons 

and that a local release of serotonin might have led to prolonged vasospasm 

and necrosis. This hypothesis has been substantiated by a SPECT study that 

demonstrated the vasoconstrictive properties of acute MDMA consumption via 

the excessive release of serotonin (413). Other neuropathological findings in 

deaths after “ecstasy” consumption were mainly owing to the complications of 

hyperthermia with DIC and consisted of cerebral edema, focal hemorrhages, 

and nerve cell loss, the latter being evident in the locus coeruleus (533). 

ACKNOWLEDGMENTS 

The help of Ida C. Llenos, MD, and Hans Sachs, PhD, in correcting the 

manuscript is highly appreciated. We thank Ms. Susanne Ring for her skillful 

technical assistance.


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Sudden Cardiac Death 137 

Sudden Death 

From Natural Causes

138 Fineschi and Pomara


5 

A Forensic Pathological Approach 

to Sudden Cardiac Death 

Vittorio Fineschi, MD, PhD and Cristoforo Pomara, MD 

But O heart! heart! heart! 

O the bleeding drops of red, 

Where on the deck my Captain lies, 

Fallen cold and dead 

—Walt Whitman, 

“O Captain! My Captain!” 

CONTENTS 

INTRODUCTION 

DEFINITION 

A METHODOLOGICAL APPROACH TO THE DISSECTION AND PREPARATION OF THE HEART 

CORONARY ANOMALIES AND STENOSIS 

THE MYOCARDIAL ALTERATION 

CONCLUSION 

APPENDIX: HEART MORPHOLOGY STUDY 

REFERENCES 

SUMMARY 

Sudden cardiac death is reported to occur in 70,000–100,000 individuals 

per year in Italy and is most prevalent in people between 40 and 65 years of 

age. In 1998, there were 719,456 cardiac disease deaths among U.S. residents 

aged 35 years or older, of which 456,076 (63.3%) were defined as sudden 

cardiac deaths. Sudden cardiac death is a death that is rapid (without any specific 

chronological limit) and unexpected or unforeseen, both subjectively and 

objectively, that occurs without prior clinical examination in apparently healthy 



139

140 Fineschi and Pomara 

people (“primary or unexpected or not foreseeable sudden death”) or in patients 

during an apparent benign phase in the course of a disease (“secondary or 

expected or foreseeable sudden death”). In children, adolescents, and young 

adults (21 years of age or younger) myocarditis, cardiomyopathies, and coronary 

artery anomalies are the most common causes of sudden cardiac death. 

Coronary atherosclerosis is the most common finding in sudden death in people 

older than 21 years. Almost all sudden cardiac death investigations require 

correlation of circumstantial data with autopsy and laboratory data. Relatively 

few causes of natural death are self-evident at autopsy. A complete autopsy, 

including detailed neuropathological and cardiovascular examination with toxicological 

studies, must be performed in the context of all available clinical 

information and of the circumstances of death, thus excluding noncardiac causes 

and discovering those that are cardiovascular in origin but not related to coronary 

causes. A detailed protocol is presented for a practical use in suspected 

cases of sudden cardiac death. Histology may offer structural details of the 

cardiac wall and coronary intraluminal changes, particularly when serial section 

studies are performed. Although some techniques have considerable merit 

in the research setting, many factors limit their application in daily forensic 

autopsy practice, particularly when autolysis is present. The possibility that 

immunohistochemical and biochemical methods, quantitative morphometry, 

and demonstration of apoptosis in the myocardium might enhance the detection 

of the early cardiac changes in sudden cardiac death is an exciting field of 

research. 

Key Words: Sudden cardiac death; coronary anomalies; coronary atherosclerosis; 

coronary plaque morphology; atonic death; myocardial contraction 

bands; colliquative myocytolysis. 


The forensic pathologist has a unique opportunity to study a wide range 

of sudden cardiac deaths resulting from all types of cardiac diseases (1). Usually, 

the forensic pathologist is the first professional to investigate these deaths 

as they are, by definition, sudden and often unexpected, and, therefore, fall 

under the jurisdiction of the medical examiner or coroner (2). As early as 

1707, in De Subitaneis Mortibus, prompted by an “epidemic” of sudden death 

in 1705, Lancisi clearly defined different types of death: 

Indeed, this absolutely complete cessation of animal movements and 

this departure of the soul from the body, even though it happens at 

all times more swiftly than thought itself, is nevertheless divided for 

the sake of common parlance and for greater clarity of teaching,


into natural, untimely and violent death, and those again individually 

into slow and sudden death, into those that are foreseen and 

forefelt and finally into such as are unforeseen, imperceptible and 

unexpected. 

Two basic notions pertain to sudden death: (a) its mystery from the clinical 

standpoint, and (b) its occurrence in apparently healthy people as well as in 

those in various phases of clinically recognized diseases, a distinction that any 

study of sudden death should consider to gain more precise knowledge of this 

phenomenon. In term of expectancy, sudden death in a healthy marathon runner 

during a race may be quite different from sudden death in a patient with chronic 

ischemic heart disease. In other words, a correct approach would distinguish 

between a first episode and a secondary event in which complications and/or 

iatrogenic effects may change the natural history of the disease process. 

2. DEFINITION 

On the basis that we as forensic pathologists prefer, the definition of 

sudden death is that of a death that is rapid (without any specific chronological 

limit) and unexpected or unforeseen, both subjectively and objectively, 

occurring without any prior clinical evaluation in apparently healthy people 

(“primary or unexpected or not foreseeable sudden death”) or in patients during 

an apparent benign phase in the course of a disease (“secondary or expected 

or foreseeable sudden death”). One should bear in mind that in the present 

etiologic and pathogenic uncertainty, any definition is only a working one that 

helps determine a better selection of case material to study. 

Sudden cardiac death is reported to occur in 70,000–100,000 individuals 

per year in Italy and is most prevalent in people between 40 and 65 years of 

age. In 1998, there were 719,456 cardiac disease deaths among U.S. residents 

aged 35 years or older, of which 456,076 (63.3%) were defined as sudden 

cardiac deaths (3). A variety of pathological conditions may lead to sudden 

cardiac death. In children, adolescents, and young adults (21 years of age or 

younger) myocarditis, cardiomyopathies, and coronary artery anomalies are 

the most common causes of sudden cardiac death. Coronary atherosclerosis is 

the most common finding in sudden cardiac death in people older than 

21 years (Table 1) (4). 

At present, unique objective data are postmortem findings and, in a selected 

group, changes detectable by electrocardiography in monitored patients 

or clinical follow-ups from resuscitated patients. Almost all sudden cardiac 

death investigations require a careful correlation of circumstantial data with 

autopsy and laboratory findings. Relatively few natural death causes are selfevident 

by themselves at autopsy.

Table 1 

Causes and Mechanisms of Sudden Cardiac Death 

Immediate cause Underlying cause Mechanisms 

Acute ischemia Coronary atherosclerosis, nonatherosclerotic Ventricular fibrillation, bradycardia, 

coronary diseases, aortic stenosis electromechanical dissociation 

(usually end stage or postresuscitation) 

Infiltrative diseases Inflammatory (myocarditis), scars (healed Ventricular fibrillation, bradyarrhythmias 

infarcts, cardiomyopathy) (uncommon a ) 

Cardiac hypertrophy Hypertrophic cardiomyopathy, systemic hypertension, Ventricular fibrillation, bradyarrhythmias 

idiopathic concentric left ventricular hypertrophy, (uncommon) 

aortic stenosis 

Cardiac dilatation Dilated cardiomyopathy, chronic ischemia, systemic Ventricular fibrillation, 

(congestive failure) hypertension, aortic insufficiency, mitral insufficiency bradyarrhythmias (uncommon) 

Cardiac tamponade Rupture myocardial infarct, aortic rupture Electromechanical dissociation 

Mechanical disruption Pulmonary embolism, mitral stenosis, left atrial Electromechanical dissociation, 

of cardiac blood flow myxoma ventricular fibrillation 

Global myocardial Severe ischemic heart disease, aortic stenosis Baroreflex stimulation with bradyarrhythmias, 

hypoxia ventricular tachyarrhythmias 

Acute heart failure Massive myocardial infarct, rupture papillary Electromechanical dissociation, 

muscle, acute endocarditis with chordal or ventricular fibrillation 

leaflet rupture, MVP with chordal rupture 

Generalized hypoxia Pulmonary stenosis, pulmonary hypertension Bradyarrhythmias 

Vasovagal stimulation Neuromuscular diseases Baroreflex stimulation with bradycardia 

Preexcitation syndrome Accessory pathways Atrial fibrillation � ventricular fibrillation 

Long QT syndrome Congenital and acquired states Ventricular fibrillation (torsades de pointes) 

Heart block AV nodal scarring, inflammation, tumor Bradycardia � ventricular fibrillation 

EMD, electromechanical dissociation; AV, atrioventricular; MVP, mitral valve prolapse. 

a Especially in the presence of infiltrative processes involving the conduction system. 

From ref. 6. 

142 Fineschi and Pomara


Davis has developed the following philosophical concepts concerning 

the investigation of sudden death (1): 

• Sudden death investigative opinions are dependent on circumstances as well as 

autopsy findings. 

• Circumstantial data is usually more important than autopsy findings. 

• What we call the “cause” of death does not answer the question why the affected 

individual died. 

• Autopsy findings of disease or injury may or may not be relevant to the cause of 

death. 

From this philosophical approach toward the investigation of sudden 

unexpected death derives the correct way as proposed by Cohle and Sampson 

in 2001 using four steps in sudden cardiac death investigation (5): 

1. Medical history and scene examination. 

2. Autopsy (gross examination and histology). 

3. Laboratory tests. 

4. Establishing the diagnosis. 

3. A METHODOLOGICAL APPROACH TO THE DISSECTION 

AND PREPARATION OF THE HEART 

A complete autopsy, including detailed neuropathological and cardiovascular 

examination with toxicological studies, must be performed in the 

context of all available clinical information and on the circumstances of death, 

thus excluding noncardiac causes such as subarachnoid hemorrhage or pulmonary 

embolism, and discovering those that are cardiovascular in origin but 

not related to coronary atherosclerosis (6). 

A properly performed examination of the heart is the basis of every forensic 

autopsy. When the heart is examined, it is very important that the method 

adopted is compatible between the exhausting and very often overwhelming 

work requested in an autopsy room and the time one can devote to it. The 

dissection of the heart can be practiced in different ways (7,8). The most common 

of all is the one proposed by Virchow and modified by Prausnitz: the cut 

follows the direction of the blood flow from the caval veins on the right side 

of the heart to the conum and pulmonary artery (inflow–outflow method). On 

the left side, the atrium is opened by cutting the pulmonary veins and the cut is 

continued with the dissection of the left side of the infundibulum and of the 

aorta. To examine the coronary arteries, different methods that are more or 

less complicated have been introduced, such as the postmortem chalk injection, 

injections of colored or transparent radiopaque fluids into opened or


undissected hearts, or plastic substances with the corrosion of the heart tissue and 

the resection of the tissue for a histological control before the corrosion (9). In the 

end, specific dissection plans have to be made to be compared with the 

echocardiographic images, if available. Each method has advantages and disadvantages 

because it is impossible to scrutinize simultaneously all possible changes. 

A long-standing method exists that (10) permits physicians to study groups of 

patients with quantitative and morphological changes of the heart structures that 

can be correlated with the previous medical history. This method can be adopted 

without waste of time and material, offering excellent diagnostic and scientific 

results. The heart is removed from the pericardium by cutting all the big vessels, 

all cavities are cleaned, and the heart is weighed and examined on the surface. The 

heart is left in a large container, containing a 10% formalin solution for 24 hours. 

Coronary arteries and each segment (main branches on the surface of the heart; 

extramural or epicardial coronary arteries or branches) are cross-sectioned at 

3-mm-thick intervals along their whole course by carefully avoiding any damage. 

The lumen reduction of coronary arteries must be expressed as a percentage of the 

lumen diameter calculated from plastic casts of normal vessels (11). Then, the 

whole heart is dissected into 1-cm-thick slices parallel to the posterior atrioventricular 

sulcus, taking care to proceed from the apex to the base. The last upper 

slice is cut on the plane of the left ventricular papillary muscles. The heart slices, 

the atrio-valve section, and the coronary segments are disposed in their anatomic 

sequence and color-photographed with a scale. In this way it is possible to obtain 

information on the thickness of the walls and the volumes of the cavities and to 

measure planimetrically the extension of a lesion in percentage of the body heart 

mass. After that, the end auricles, valves, and any other structures can be easily 

examined. Systematic sampling for histological and immunohistochemical investigations 

has to be undertaken from the specific parts. 

A histological examination of the entire ventricular wall (2 cm × wholewall 

thickness) at the apex and at the anterior, lateral, and posterior walls of 

left ventricle, anterior and posterior right ventricle, interventricular septum, 

and in each area with a macroscopically detectable lesion must be performed. 

When a more careful examination is necessary, instead of one slice, histological 

sections are made from the upper and lower parts of the slices. After further 

fixation in 10% formalin solution, the remaining tissue should be stored 

completely in hermetically sealed plastic bags. 

Each histological myocardial section (excluding epicardium and endocardium) 

should be measured by an image analysis system (e.g., Quantimet Leica, 

Cambridge, UK). Both the numbers of foci and myocardial cells with pathological 

alterations must be normalized to 100 mm 2 .


Fig. 1. Coronary congenital anomalies. 

A detailed protocol for practical usage in sudden cardiac death cases is 

presented in the appendix. 

4. CORONARY ANOMALIES AND STENOSIS 

Congenital coronary anomalies constitute a statistical incidence of 

0.3–0.8% and represent 0.1–2% of all congenital cardiac conditions worldwide. 

Congenital anomalies of the coronary arteries can present great difficulties 

in their diagnosis because these diseases can, at times, be absolutely 

asymptomatic and, although rarely, can manifest themselves with syncopal 

episodes or with a fading symptomatology leading to heart failure (9). However, 

the more serious the anomaly is, the more precocious is death (Fig. 1). 

Sudden cardiac death is most common when the origin of the left coronary 

artery is located in the right sinus of Valsalva. In such cases, several 

pathogenetic mechanisms have been proposed. These include compression by 

the pulmonary trunk, kinking, coronary artery spasm, or an acute ostial outlet 

resulting in a slitlike intramural course that allows diastolic compression, especially 

during exercise. Origin of both right and left coronary ostia in the left 

sinus is a less common and significant anomaly, even though a similar acutely 

angled outlet may be present. Another anomaly is the origin of the left main 

coronary artery from the pulmonary trunk (6).


The anomalous origin of the right coronary artery from the left Valsalva 

sinus has long been considered a mostly benign disease. In an earlier study, 

10 cases of sudden cardiac death were described that were attributed to this 

type of congenital anomaly (12). 

The origin of the right coronary artery from the left sinus may be an 

incidental observation during autopsy. Ischemia is usually precipitated by 

strenuous, prolonged effort, and this explains why a basal electrocardiogram 

(ECG) or even a stress test ECG may be negative. Syncopal episodes are the 

only prodromal symptoms. Repetitive ischemic episodes may cause patchy 

myocardial necrosis and fibrosis as well as ventricular hypertrophy, which 

eventually can elicit arrhythmias because of the malignant combination of 

acute and chronic substrates. This may explain why sudden cardiac death, 

associated with an anomalous origin of a coronary artery from the wrong sinus, 

may occur in adults even though the anomaly has been present since birth. 

An anomalous origin of the left circumflex artery from the left coronary 

sinus itself with a separate ostium has also been described in victims of unexpected 

arrhythmic sudden death. This anomaly was considered a benign condition 

until cases were reported, both clinically and pathologically, with 

evidence of myocardial ischemia in the absence of obstructive coronary atherosclerosis 

or causes other than the malformation itself. It should be noted 

that in children and young adults with coronary anomalies, sudden death often 

occurs during or following physical exertion (13–20). 

Coronary aneurysms are typical complications of Kawasaki disease in 

the healed phase. Coronarography studies found coronary artery aneurysms in 

more than 23% of Kawasaki patients that occurred in the initial tract of the 

coronary arteries, the right coronary artery being more frequently involved 

and occluded (21). Deaths from myocardial infarction in Takayasu disease are 

also described; a stenosing coronary arteritis is observed in such cases (22). 

The term “sudden coronary death” is in harmony with the classic pathogenetic 

viewpoint that any coronary arterial obstructive lesion leads to myocardial 

ischemia with consequent structural and functional damage to the 

cardiac pump. Any attempt to interpret the functional significance of coronary 

atherosclerotic plaques demands knowledge of their frequency and the degree 

of luminal reduction they cause in a healthy population. Pathologists are regularly 

consulted to assess coronary atherosclerosis at autopsy despite the difficulties 

inherent in the methods used to quantify stenosis. The preferred method 

is to cut multiple cross-sections at 2- to 3-mm-thick intervals along all the 

three major coronary arteries. Visual assessment can be made by the degree of 

stenosis seen at different sites. This method has very serious limitations when


used for correlation with angiography that was carried out during life or when 

used to indicate clinical significance. Pathologists will tend to overestimate 

the degree of narrowing. The explanation for this is the remodeling of the 

vessel wall. When comparing the lumen to the size of the vessel, the pathologist 

has to bear in mind the remodeling that occurs. The external size of the 

vessel at this time is larger than normal and the degree of stenosis will be 

overestimated. A second factor is that pathologists are examining collapsed 

and empty coronary arteries in which the lumen is often slitlike. In coronary 

arteries with eccentric plaques that are distended by blood flow, the lumen 

becomes round to oval, but when the lumen is bloodless it appears slitlike, 

thus causing a spurious impression of stenosis. The final factor is that calcification 

will hinder the cutting of cross-sections without completely distorting 

the lumen. A more sophisticated technique consists in decalcifying the coronary 

arteries before making the cross-sections. Segments of the major coronary 

arteries of several centimeters long can be removed from the heart and 

decalcified for 24 hours. In such segments, the degree of stenosis can be accurately 

assessed by comparing the vessel lumen at the narrowest point compared 

with the lumen at an area of the artery in which the wall appears relatively 

normal, thus giving an impression of the extent of stenosis that comes close to 

angiographic pictures in life (23). 

Histology may offer structural details of the wall and intraluminal changes, 

particularly when serial section studies are performed (Fig. 2). However, findings 

include aspects of events that occurred during the whole life of a plaque. 

We constructed a history of the coronary atherosclerotic plaque by studying 

many coronary sections and verifying the trend of morphological changes 

in relation to intimal thickening and lumen reduction in ischemic and clinically 

normal subjects (9). From the significant associations of first and second 

order of variables and the highest chi-square values obtained according to 

sensitive and specific codes, it was possible to outline a three-dimensional 

(radial, circumferential, and longitudinal) progression of the atherosclerotic 

plaque in patients with ischemic heart disease and in controls (Table 2). 

It is as follows: initially, a plaque is a nodular fibrous intimal thickening 

likely due to smooth muscle cell hyperplasia with subsequent fibrous 

tissue replacement. This early fibrous plaque is the only pattern occasionally 

seen in young people less than 20 years of age (24). The second stage is 

proteoglycan accumulation (basophilia) deep to the fibrous cap. Both fibrosis 

and basophilia are recurrent phenomena, being two basic elements in 

plaque progression. Subsequently, foam cells and cholesterol clefts and/or 

calcification appear in the proteoglygan pool, in keeping with the chemical


Fig. 2. Physiologic intimal thickening. (A) Smooth myocellular and (B) elastic 

fibre hyperplasia. (C,D) With increasing age this intimal thickening progressively 

loses myocellular and elastic components becoming (E,F) a fibrous intimal 

layer (hematoxylin and eosin and Gomori, original magnification × 50).


Table 2 

Schematic Presentation of the Progression of Atherosclerotic Plaques 

in Relation to Increasing Intimal Thickening and Lumen Reduction 

Intimal thickness (µ) Morphologic variables Lumen reduction (%) 

>300 Nodular smooth


Fig. 3. Typical atherosclerotic plaque without allograft vasculopathy changes 

showing lymphocytic perimedial infiltration (hematoxylin and eosin, original 

magnification × 50). 

regional contractility via nerve involvement, release of active substances 

resulting in coronary spasm, or myocardial asynergy (11). 

5. THE MYOCARDIAL ALTERATION 

In sudden cardiac death, the myocardial cell may stop functioning in 

irreversible relaxation, in contraction, or may progressively lose its force and 

velocity. Each situation produces a different morphological form of irreversible 

myocardial damage. 

Infarct necrosis is observed when myocytes lose their capability to contract, 

becoming passive and extensible elements. This loss of contraction can


Fig. 4. Schematic presentation of active plaque formation. 

be seen within a few seconds when experimentally occluding a dog’s coronary 

artery. The acutely ischemic myocardium becomes cyanotic and because 

of intraventricular pressure shows a paradoxical systolic bulging. The term 

“coagulation necrosis” seems inappropriate because of the lack of coagulation 

of structures in various phases. The term “infarct necrosis” seems more appropriate. 

The histological counterpart of this flaccid paralysis (with stretching 

and reduction in thickness of the infarcted wall) is a thinning of the mildly 

eosinophilic necrotic myocytes with elongation of sarcomeres and nuclei 

(Fig. 5). These changes are visible within 1 hour of experimentally induced 

coronary artery occlusion. Other histological changes in chronological sequence 

are seen in both animal experiments and human tissue: a centripetal polymorphonuclear 

(PMN) leukocytic infiltration from the periphery of the infarct 

occurs within 6–8 hours with minimal exudate of edema fluid, fibrin, and red 

cells. PMN leukocytes increase in number during the next 24 hours and disappear 

by lysis within the first week of onset, without evident destruction of 

necrotic myocytes. Large infarcts may show a central area where the sequence 

of changes described does not occur. Rather, the mildly eosinophilic, stretched, 

dead myofibers persist. This is due to a blockage of PMN leukocytic penetration 

caused by maximal stretching of the central part of the dead tissue. Furthermore,


Fig. 5. Early infarct necrosis. Stretching of flaccid paralyzed myofibers by 

intraventricular pressure with elongation of nuclei and sarcomeres, a change 

visible within 1 hour in experimental coronary occlusion. Note the absence of 

edema, hemorrhage, vacuolization, and pathological contraction bands 


if a marked PMN leukocytic infiltration develops at the edge of sequestered, 

dead myocardium, the overall appearance may resemble an abscess with myocyte 

destruction. Fibrin/platelet thrombotic occlusion of intramural vessels 

included in the infarcted zone occurs parallel to, but not before, PMN infiltration. 

The healing process, which starts 1 week after infarction, begins at the 

periphery by macrophagic digestion of necrotic material within sarcolemmal 

tubes and is followed by progressive collagenization. 

Three further findings and three comments complete histological observations 

in this type of necrosis. First, the registered order of sarcomeres may 

be maintained for a long time in remnants of dead myocytes in healed infarcts 

(>30 days) and if entrapped in a scar. Second, the lack of filling by postmortem 

injection of intramural arterial vessels is noticeable in an acute infarct 

(“avascular area”). Third, this type of necrosis usually presents as one focus. 

It may affect the subendocardial zone or a greater width of the ventricular wall 

and can be transmural. Its size ranges from less than 10% to more than 50% of


Fig. 6. Contraction band necrosis: markedly thickened Z-lines and extremely 

shortened sarcomeres (hematoxylin and eosin; original magnification × 80). 

the left ventricular mass. Very rarely it presents as small multiple foci in the 

subendocardium. 

A last comment concerns the so-called “wavy fibers,” undulated myocardial 

fibers proposed as an early sign of myocardial ischemia. When found, 

their lack of specificity does not permit, per se, a diagnosis of ischemia. In 

fact, wavyness of normal myocytes is usually observed around hypercontracted 

myocardial fibers. 

Contraction band necrosis presents an opposite pattern to infarct necrosis. 

Here the myocyte is unable to relax and its function arrests in contraction, 

or more precisely in hypercontraction, because of an extreme reduction in 

sarcomere length, much less than 1.5 µm as it is calculated for normal contraction. 

Histologically, this form of myocardial necrosis is characterized by 

irreversible hypercontraction of the myocyte with a breakdown of the whole 

contractile apparatus with markedly thickened Z-lines and extremely short 

sarcomeres (Figs. 6 and 7). This breakdown varies from irregular, pathological, 

and eosinophilic cross-bands consisting of segments of hypercontracted 

or coagulated sarcomeres to a total disruption of myofibrils, the whole cell 

assuming a granular aspect without visible clear-cut pathological bands (Figs. 8 

and 9). These deeply staining cytoplasmic bands in hematoxylin and eosin 

sections alternate with clear, empty spaces or with spaces filled by small dark


Fig. 7. Foci of about 10 hypercontracted sarcomeres without myofibrillar 

rhexis (hematoxylin and eosin, original magnification × 80). 

granules (9). Ultrastructurally, a transverse band appears as a small group of 

hypercontracted sarcomeres with highly thickened Z-lines or as amorphous, darkly 

electronmicroscopical dense material that is likely the result of coagulation of 

contractile proteins. The clear spaces are filled by normal or slightly swollen mitochondria 

containing dense, fine granules and occasionally showing rupture of their 

cristae. The sarcotubular system is totally disrupted whereas the basement membrane 

is essentially intact; only occasionally are interruptions seen in its continuity. 

Folding of the sarcolemma expresses the hypercontractile state of sarcomeres. 

Glycogen deposits disappear without evidence of intracellular or interstitial edema. 

There is no damage to blood vessels and hence no associated hemorrhage with the 

myocyte necrosis nor are platelet aggregates or platelet/fibrin thrombi to be found. 

It seems likely that the degree of fragmentation of the rigid, inextensible myocytes 

in irreversible hypercontraction is a consequence of the mechanical action of the 

normal contracting myocardium around them. Contraction band necrosis, as defined 

above, is reproduced experimentally by intravenous infusion of catecholamines, 

is not an ischemic change, and is observed in many human pathological entities 

such as pheochromocytoma, ischemic heart disease, electrocution, malignant hyperthermia, 

magnesium deficiency, psychological stress, and so on. It ranges from 

foci formed by one or a few myocytes to large zones in the absence of interstitial/ 

intermyocellular hemorrhage.


Fig. 8. (A,B,C,D,F) Clear paradiscal band (electron microscopy, original magnification 

× 3500). (E) Hypercontraction of relatively few sarcomeres adjacent 

to an intercalated disk produces a paradiscal lesion (phosphotungstic acid 

hematoxylin, original magnification × 640).


Fig. 9. (A,B) Evolving contraction band necrosis. (C) Progressive destruction 

of myofibrillar remnants associated with monocytes/macrophages leading to 

an alveolar pattern formed by empty sarcolemmal tubes infiltrated by macrophages 

loaded by lipofuscin. (D) A healing phase with progressive 

collagenisation ending in a fibrous scar. (E) Monocytic infiltration. (F,G) 

Hypercontraction produces a scalloped sarcolemma and wavyness of adjacent 

normal myocytes (hematoxylin and eosin, original magnification × 250).


Fig. 10. Contraction band necrosis. Diffuse early pattern without cellular 

infiltrate (hematoxylin and eosin, original magnification × 400). 

However, in many conditions, the frequency and extent of contraction 

band necrosis indicate an adrenergic role in its natural history, for example, in 

ischemic heart disease, intracranial hemorrhage and congestive heart failure— 

all diseases in which there is a general consensus for a sympathicomimetic 

overtone. In other words, sympathicotonic-prone individuals may have an 

“adrenergic crisis” any time a physical and/or psychological stress occurs, 

which explains the high variability among subjects of the same group. This 

concept is supported by the presence of all stages of the lesion (e.g., crossbands, 

alveolar healing) in the same heart, particularly in excised hearts deriving 

from transplantation surgery (Figs. 10–12). The latter is a unique model 

since agonal stimuli and reanimative, terminal therapeutic procedures are 

absent. It has to be stressed that in animal experiments, hearts excised from 

control animals did not show contraction bands of any type. The early contraction 

band necrosis in human hearts deriving from transplantation surgery 

may be related to presurgical adrenergic stress in patients with an already 

increased sympathetic overtone. Accordingly, the threshold for a diagnosis of 

sympathetic stress seems to be a number of foci and myocytes/100 mm 2 with 

the range of those found in the previously mentioned diseases and the presence 

of foci of contraction band necrosis of any stages. The significantly higher 

extent of this lesion in sudden, unexpected cardiac death cases with preceding 

resuscitation attempts seems more likely to be because of a longer survival 

rather than any iatrogenic effects. In fact, the frequency and extent of early


Fig. 11. Contraction band necrosis. Leukocytic infiltrate suggestive of a macrophagic 

reaction secondary to coagulative myocytolysis (hematoxylin and 

eosin, original magnification × 400). 

Fig. 12. Alveolar pattern of empty sarcolemmal tubes preceding collagenization 

(Movat, original magnification × 100). 

changes were similar in treated and nontreated subjects, all showing older 

phases of contraction band necrosis, a concept supported by intracranial hemorrhage 

and head trauma groups with a greater extent related to survival despite 

a terminal therapy in the former and no therapy in the latter. A last point 

is that multifocal and/or interstitial intermyocellular fibrosis may be owing to


Fig. 13. Colliquative myocytolysis in a case of acute myocardial infarction. 

The myocellular damage is limited to the (A) subendocardial and (B) perivascular 

regions. (C) Old myocardial infarction: preserved myocytes in the perivascular 

region C (hematoxylin and eosin; original magnification × 400). 

repetitive loss of myocytes with collagen substitution secondary to catecholamine 

myotoxicity with the false impression of a primary collagen matrix proliferation 

or reparative ischemic fibrosis. 

The evolving pathology of this necrosis can be distinguished as follows: 

(a) hypercontraction/cross-bands as an early change, (b) progressive destruction 

of myofibrillar remnants that is associated with infiltration by monocytes/ 

macrophages resulting in an alveolar pattern formed by empty sarcolemmal 

tubes loaded by lipofuscin, and (c) a healing phase with progressive 

collagenization ending in a fibrous scar. 

In the third pattern (colliquative myocytolysis), in contrast to the previously 

described types of myonecrosis, the cell maintains its function with a 

gradually reduced capacity to contract thus leading to heart insufficiency. The 

histological marker is a progressive loss of myofibrils associated with intracellular 

edema and with different degrees of damage from mild vacuolization 

(“moth-eaten pattern”) to total disappearance of myofibrils (Figs. 13 and 14). 

This produces an alveolar pattern but, in contrast to the other forms of


Fig. 14. Colliquative myocytolysis. Mild loss of myofibrils in a transverse 

section producing an alveolar pattern (hematoxylin and eosin, original magnification 

× 600). 

myonecrosis mentioned above, the alveolar pattern lacks macrophages or any 

other cell reaction. The impression is that of a colliquation or washout of myofibrils 

that leaves a sarcolemmal sheath with a clear alveolar appearance with 

a cytoplasm filled by edema and/or packed with small granules (mitochondria) 

(Fig. 15). 

Recently, we described a morphofunctional myocardial pattern linked 

with ventricular fibrillation defined as “myofiber break-up.” Myofiber breakup 

includes the following histological patterns: (a) bundles of myocardial cells 

in distension alternated with hypercontracted ones. In the latter, widening or 

rupture (segmentation) of the intercalated discs occurs. Myocardial nuclei in 

the hypercontracted cells assume a “square” aspect rather than the ovoid morphology 

seen in distended myocytes, (b) hypercontracted myocytes standing 

in line that are alternated with hyperdistended ones, often divided by a widened 

disk, and (c) noneosinophilic bands of hypercontracted sarcomeres alternated 

with stretched, often apparently separated sarcomeres. 

Each of the functional forms of myocardial damage described above has 

a distinct structural and biochemical nature. In irreversible relaxation, intrac-


Fig. 15. Colliquative myocytolysis: total disappearance of myofibrils in a 

transverse section (hematoxylin and eosin, original magnification × 100). 

ellular acidosis displaces Ca ++ from troponin. During irreversible hypercontraction, 

intracellular alkalosis induces a rapid loss of adenosine adenosine 

5'-triphospate with a lack of energy to remove Ca ++ from troponin and/or a 

massive intracellular influx of Ca ++ from increased membrane permeability. 

In the failing death of myocytes, the sarcotubular system and mitochondria 

have a reduced capacity to bind Ca ++ . 

The finding of contraction band necrosis, even if microfocal, could be an 

important histological signal for interpreting the cause of death and the natural 

history of a disease in any single patient. In particular, in a sudden death 

resulting from myocardial infarction that is otherwise not detectable histologically 

(26–28), the finding of contraction band necrosis could be the marker 

explaining cardiac arrest as secondary to adrenergic stress. However, one must 

remember that in people who die suddenly and unexpectedly, the frequency of 

a myocardial infarction is about 20% as shown in resuscitated and electrocardiographically 

monitored patients (9). Therefore, the finding of foci of catecholamine-induced 

damage in a case of sudden cardiac death that occurred 

within 6 hours after the onset of symptoms does not necessarily confirm the 

presence of an underlying myocardial infarction (29). The obvious need is to


discriminate between contraction band necrosis resulting from preterminal stimuli 

and its presence as a histological sign of adrenergic overdrive during the course 

of the disease. A significant variability of this lesion in different normal and 

disease patterns exists. For instance, contraction band necrosis is absent in carbon 

monoxide intoxication, whether accidental or suicidal, suggesting an 

antiadrenergic effect of lethal anoxia despite a longer survival period. Only if 

reoxygenation is restored, contraction bands lacking interstitial hemorrhage will 

be present (30). In other words, we need to know the frequency, extent, and 

stages of this lesion to interpret both the natural history of a disease and the 

mode of death. Beyond a histological threshold of 37 ± 7 foci and 322 ± 99 

myocytes/100 mm 2 , the lesion may indicate sympathetic overdrive in the natural 

history of a disease and associated arrythmogenic supersensitivity. 

6. CONCLUSION 

Knowledge of the many biochemical, functional, and morphological 

changes that occur in the heart in sudden cardiac death stimulated the development 

and refinement of techniques to aid in the postmortem diagnosis. 

Although some biochemical and functional abnormalities begin virtually 

immediately at the onset of severe ischemia (e.g., anaerobic glycolysis and 

loss of myocardial contractility occur within 60 seconds), other changes evolve 

over a more protracted interval, and loss of cell viability is not immediate 

(29). Although some techniques have considerable merit in the research setting, 

many factors limit their practical use in forensic pathology, particularly 

when autolysis is present. The possibility that immunohistochemical and biochemical 

methods, quantitative morphometry, and demonstration of apoptosis 

in the myocardium might enhance the detection of the early cardiac changes 

in cases of sudden cardiac death is an exciting field of research (31–33). With 

the recognition that there exists no highly specific and sensitive “gold standard” 

for the recognition of early myocardial pathological changes, the use of 

a combination of techniques in a standardized protocol might be appropriate 

in sudden cardiac death cases. Perhaps the most pressing issue related to the 

use of these techniques is how to select best those applicable to diagnostic 

purposes (34). At present, further studies are needed to confirm the best accuracy 

of these methods (35). 

In conclusion, progress to ultimate knowledge of cardiac morphology in 

sudden cardiac death cases requires to accredit facts and an intellectual challenge 

in which both agonistic and antagonistic ideas are needed. Also bear in 

mind that the value of any investigation may lie more in the questions it raises 

than in those it answers (9).


APPENDIX: HEART MORPHOLOGY STUDY 

Ord. N. ................... Source ................... Autopsy No. ................... 

Death-autopsy interval (hours) ...................... 

Last name ...................................................... First name .............................. 

Sex ................... Age (yrs.) ................... 

Body weight (kg) ................... Height (cm) ......... 

Interval first episode-death ................... minutes ................... hours 

Ischemic heart disease .............. 1. no 2. angina 3. infarct 4. unknown 

Cardiac failure ................... 1. no 2. yes 3. unknown 

Cardiac arrest ................... 1. ventric. fibrill. 2. asystole 3. failure 

4. elect. mech. diss. 5. unknown 

Other data ....................................................................................................... 

.............................................................................................................................. 

HEART GROSS EXAMINATION 

Weight (g) .......... body weight (kg) ..........% .......... 

Diameter longitudinal (mm) .......... 

transverse .......... 

antero-poster. .......... 

Wall thickness (mm) ANT/SUP POST/SUP 

LV .......... .......... 

RV .......... 

SPT .......... 

Other data ....................................................................................................... 

HEART HISTOLOGY 

CORONARY ARTERIES 

LM LAD LCX RCA RCA RCA RCA 

sup ant marg post 

Stenosis (%) ........ ........ ........ ........ ........ ........ ........ 

Stenosis type ........ ........ ........ ........ ........ ........ ........ 

1. nodular 2. semilunar 3. concentric 

Plaque ........ ........ ........ ........ ........ ........ ........ ........ 

1. Fibrous 2. +s.m.c. 4. basophilia 8. atheroma 

16. calcif. 32. hemorrhage 64. lymph-plasm. 

Thrombus 

mural 

1. no 2. yes 

........ ........ ........ ........ ........ ........ ........ ........


Thrombus 

occlusive 

........ ........ ........ ........ ........ ........ ........ ........ 

1. no 2. acute 3. recent 4. organized 

Other findings................................................................................................. 

.............................................................................................................................. 

MYOCARDIUM LV LV RV RV SPT 

ant post ant post 

Area mm2 ...... ....... ...... ...... 

Infarct necrosis % ...... ...... ....... ...... ...... 

Histological pattern ...... ...... ....... ...... ...... 

1. eosinoph+PMN 2. PMN exud. 3. macroph. 4. early fibr. 

5. fibr+necr tissue 

Wall location ...... ...... ...... ...... ...... 

1. subend. 2. intern. 4. subep. 

Base-apex 

location 

...... ....... ...... ...... ...... 

1. superior 2. middle 4. inferior 8. apex 

Coagulative myocytolysis 

No. foci ...... ...... ...... ...... ...... 

No. of myocytes...... ...... ....... ...... ...... 

Wall location ...... ...... ....... ...... ...... 


Type ...... ....... ...... ...... ...... 

1. monofocal 2. multifocal 3. confluent 4. massive 

Base-apex 

location 

...... ...... ....... ...... ...... 

1. superior 2. middle 4.inferior 8. apex 

Histological 

pattern 

...... ...... ....... ...... ...... 

1. hypercontr. + rhexis 2. holocytic 4. paradiscal 8. alveolar 16. organizing 

Associated 

monocytes 

...... ...... ....... ...... ...... 

1. no 2. micro 3. extensive 

Myofiberbreakup/VF 

1. no 2. yes 

...... ...... ....... ...... ......


LV LVP LV RV RV SPT 

ant ant post ant post 

Colliquative 

myocytolysis 

...... ...... ....... ...... ....... ....... 

Grade 0. 1. 2. 3. 

Base-apex 

location 

...... ...... ....... ...... ....... ....... 

1. superior 2. middle 4. inferior 8. apex 

Wall location ...... ...... ....... ...... ....... ....... 


Histological 

pattern 

...... ...... ....... ...... ....... ....... 

1. lysis 2. vacuolar 4. alveolar 

Fibrosis % ...... ...... ....... ...... ....... ....... 

Age ...... ...... ....... ...... ....... ....... 

1. old 2. recent 

Type ...... ...... ....... ...... ....... ....... 

1. monofocal 2. multifocal 4. confluent 8. perivasc/interfasc 16. intermyocellular 

Wall location ...... ...... ....... ...... ....... ....... 


Base-apex 

location 

...... ...... ....... ...... ....... ....... 

1. superior 2. middle 4. inferior 

Fibrosis 

endocardial 

...... ...... ....... ...... ....... ....... 

1. no 2. yes 4.+s.m.c. 8.+monocytes 16. s.m.c. sine end. fibrosis 

Type ...... ...... ....... ...... ....... ....... 

1. focal light 2. focal severe 3. diffuse light 4. diffuse severe 

Fibrosis 

epicardial 

...... ...... ....... ...... ...... ...... 

1. no 2. yes 4. + monocytes 8. + fibrin 

Type ...... ...... ....... ...... ...... ...... 

1. focal light 2. focal severe 3. diffuse light 4. diffuse severe 

Constrict. 

pericard. 

1. no 2. yes 

..........


Lymphocyte infiltrates 

LV LV RV RV SPT 

ant pos ant pos 

No. foci ...... ...... ....... ...... ....... 

perivascular ...... ...... ....... ...... ...... 

intramyocardial ...... ...... ....... ...... ...... 

intramyocardial ...... 

+ myoc. necr. 

Other infiltrates ......... 

...... ....... ...... ...... 

1. no 2. PMN 3. PMN+necrosis 4. Eosinophils 5. Eosinophils+necrosis 

Extension ...... ....... ...... ...... ...... 

1. focal light 2. focal severe 3. diffuse mild 4. diffuse severe 

Hypertrophy 

1. no 2. yes 

...... ...... ....... ...... ...... 

Disarray ...... ...... ....... ...... ....... 

1. no 2. focal 3. diffuse 

Other findings................................................................................................. 

.............................................................................................................................. 

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17. Taylor AJ, Rogan KM, Virmani R (1992) Sudden cardiac death associated with 

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Neonaticide 169 

Child Abuse, Neglect, 

and Infanticide

170 Byard


6 

Medicolegal Problems 

With Neonaticide 

Roger W. Byard, MBBS, MD 

CONTENTS 

INTRODUCTION 

MOTIVATION 

MATERNAL CHARACTERISTICS 

SCENE EXAMINATION 

ROLE OF THE PATHOLOGIST 

AUTOPSY EXAMINATION 

METHODS FOR DETERMINING LIVE BIRTH 

CAUSES OF DEATH 

CONCLUSION 

REFERENCES 

SUMMARY 

Neonaticide, or the killing of an infant within the first month of life, 

presents many difficulties for pathologists and courts. Births are often concealed 

and the victims’ bodies hidden. Pathological findings tend to be nonspecific, 

particularly where deaths have been caused by suffocation, drowning, 

or failure to provide adequate care and support of newly born infants. Determination 

of live or stillbirth may not be possible in cases of concealed births 

as independent witnesses are usually not available to verify mothers’ histories. 

Whereas changes of maceration indicate intrauterine death, a vital reaction 

in the umbilical cord stump with milk within the stomach indicates survival 

for some time after birth. The latter findings will not, however, be present in 

most deaths that typically occur soon after delivery. Failure to demonstrate 



171

172 Byard 

inflation of lungs or gas within the stomach does not exclude live birth, and 

conversely such aeration may occur from resuscitation or postmortem putrefaction. 

The flotation test is an unreliable indicator of prior respiration. Lack 

of precise pathological markers for live birth, and/or cause of death, often 

precludes definitive statements about the manner of death. Stillbirth cannot be 

excluded in cases where considerable doubts exist. 

Key Words: Concealed birth; homicide; infanticide; neonaticide; stillbirth. 


Although terminology differs slightly, neonaticide usually refers to the 

killing of young infants under 1 month of age, and infanticide to deaths before 

1 year. One month has been taken as 28 or 30 days, although on occasion, 

neonaticide has been used only for deaths resulting from inflicted injury or 

omission of adequate care within the first day of life, as these deaths generally 

occur very soon after delivery (1–3). Neonaticide has been separated from 

infanticide owing to the unique nature of the immediate postpartum period, 

and the typical features exhibited by many cases that differ from physical 

abuse in later infancy (4). 

2. MOTIVATION 

Reasons for killing newborn infants are varied and have differed among 

communities and over time. Community-sanctioned neonaticide has been practiced 

in many populations ranging from the Spartans of Ancient Greece to 

contemporary nomadic groups such as the Inuit. Infants were either smothered 

or drowned, or abandoned to die of exposure or animal attack. The justification 

for such practices was maintenance of a sustainable population in 

times of need, or the removal of physically or intellectually impaired infants 

who may have placed a burden on a community. Female infants were particularly 

at risk (5,6). Infants have been used as sacrificial offerings in religious 

ceremonies (7), a practice that may continue among certain modern cults (8). 

In more recent times, infanticide may be provoked by fears of shame or 

rejection by family members, particularly when pregnancy has occurred in 

young, unmarried women. Such pregnancies may have continued owing to 

failure to seek an abortion because of naïveté, denial, or strict religious, family, 

or societal restrictions against this procedure. Greater tolerance of pregnancy 

outside marriage has seen a reduction in numbers of such deaths, as 

have improvements in contraception and contraceptive advice. Infanticide may 

occur if a pregnancy has been the result of an extramarital affair, in an attempt


to hide the event from a spouse, or if there are financial concerns regarding 

the cost of another child, or the loss, or restriction of, employment (2,9). 

Although many mothers do not manifest psychiatric symptoms (10) depersonalization 

with dissociative hallucinations has been reported (11). Infanticide 

may be a manifestation of psychotic illness that has in some cases been 

triggered by pregnancy. The possibility of a puerperal association with mental 

illness has been long recognized and legislation in the United Kingdom has 

reflected this by stating that a mother’s mental state may be “disturbed by 

reason of her not having fully recovered from the effect of giving birth” (1,7). 

For this reason, a separate crime of infanticide has been maintained in some 

jurisdictions with lesser penalties than for murder. Repeated episodes of infanticide 

by some mothers over many years (12) with minimal attempts to either 

dispose of the bodies of the victims or disguise recent pregnancies also suggest 

mental disturbance. An example of the latter is the presentation of a mother 

to hospital with significant vaginal bleeding due to a retained placenta with 

complete denial of either the pregnancy or delivery. Carefully planned clandestine 

deliveries with complex methods of disposal of the body, such as 

encasement in cement and hiding within an attic, in other cases would seem to 

indicate an absence of incapacitating mental impairment or illness. 

3. MATERNAL CHARACTERISTICS 

Mothers are often young, poor, and unmarried with low levels of formal 

education (13). As noted previously, there may be evidence of underlying 

mental illness. Whereas in some cases pregnancies may have been concealed, 

occasionally mothers have simply not realized that they were pregnant (14). 

Spontaneous delivery into toilet bowls sometimes characterizes the latter group. 

Perpetrators usually do not have a criminal record. 

4. SCENE EXAMINATION 

The likely sequence of events may not be difficult to piece together if an 

infant and mother have been found soon after delivery. Copious amounts of blood 

within a bed or bathroom will indicate the place of delivery, and concealment of 

the body may show lack of forethought when a cupboard or container within the 

mother’s room or house has been used (Fig. 1). Attics, floor spaces, and garden 

beds may also be used as convenient and accessible hiding places (Fig. 2). 

Infants’ bodies may be thrown over fences into neighboring yards, or 

may be taken some distance from the mother’s place of residence and placed 

in rubbish dumpsters, left in public washrooms, or hidden in scrubland (Fig. 3).

174 Byard 

Fig. 1. Infant body wrapped in a towel and blanket found hidden in a cupboard 

following a concealed home delivery. No injuries were discernible at autopsy. 

Occasionally, garments of the mother are disposed with the body thus facilitating 

identification of the mother (Fig. 4). The placenta is often disposed of 

separately. The farther away from a mother’s residence that disposal takes 

place and when no personal items are present, the more difficult it may be to 

link an infant with a particular woman, unless problems associated with the 

delivery have resulted in medical attention and treatment. Different methods 

of disposal occur in different communities, with abandonment and disposal of 

infants in coin-operated lockers in railway stations being a method that has 

been utilized in Japan (15). In these cases, significant information may be 

obtained from station security cameras. 

Careful examination of a scene may produce significant information linking 

a particular infant and mother. For example, the presence of obvious injuries 

may indicate the type of weapon used, and material used to wrap or transport 

an infant, such as blankets or supermarket bags, may help to identify or locate 

the maternal residence. Adjacent household rubbish may also help in this regard. 

5. ROLE OF THE PATHOLOGIST 

Various questions need to be answered by a pathologist handling a 

case of suspected neonaticide. These include estimating the gestational age of


Fig. 2. Skeletal remains (mandibles and maxillae) from at least three infants 

were found beneath the floor of a house during renovations. Origin of the remains 

and causes of death could not be established. 

an infant, determining whether there are indications of live or stillbirth, checking 

for the presence of lethal underlying organic diseases, documenting lethal 

and nonlethal injuries, helping to establish the identity of the mother, and determining 

cause, mechanism, and manner of death if possible. 

Gestational age can most reliably be determined by comparing careful 

measurements of an infant to standard growth charts (16). Radiological evaluation 

will also be a useful adjunct by enabling ossification sites to be assessed 

against known developmental data. Although estimation of placental age by 

examination of chorionic villus maturation should be undertaken, this is a less 

reliable means of determining gestational age than morphometric measurements 

of an infant. 

Blood and tissue samples should be taken for possible matching with 

maternal blood groups and DNA if these become available. If a mother is

176 Byard 

Fig. 3. The body of a recently delivered infant wrapped in paper and poorly 

concealed in long grass (arrow). 

located, she can also be checked for various conditions that are associated 

with an increased risk of fetal demise including hypertension, diabetes mellitus, 

anemia, and renal or cardiac disease. A history of prolonged gestation 

(>42 weeks) and a high number of previous pregnancies may be 

significant. 

6. AUTOPSY EXAMINATION 

6.1. Examination of the Infant 

The autopsy examination of such infants should be undertaken by a 

pathologist with pediatric/perinatal experience and should follow standard 

guidelines (17), commencing with a full external examination with photography 

and radiology. Routine parameters that are measured include weight, 

crown-heel, crown-rump, and foot length. The presence of dysmorphic features 

should be documented, again with careful photographs, and karyotyping 

should be considered if significant abnormal features are noted, particularly if 

these correspond to known genetic conditions such as trisomy 21. If abnormal 

features are noted, attendance at the autopsy by, or consultation with, a medical 

geneticist may provide useful information regarding specific features that 

should be checked for on internal examination. Descriptions should include


Fig. 4. A mother’s garments that she was wearing prior to birth, which were 

disposed with the infant´s body in a plastic bag. Note the blood on the clothing. 

In this case, the clothing gave the first hint for a later identification of the 

mother. (Courtesy of Dr. Michael Tsokos, Hamburg, Germany.) 

the absence or presence of vernix caseosa and blood (Fig. 5) indicating recent 

delivery, or washing of the body before disposal. 

Any injuries should be examined and photographed. Injuries that may 

have been inflicted with the aim of killing an infant include: strangulation 

marks around the neck with bruising from hands, or parchmented abrasions 

from ligatures that may have been left in situ; craniocerebral trauma that may 

include bruising with subgaleal, extradural, and subdural hemorrhages, skull 

fractures and cerebral lacerations, and contusions from blows to the head with 

blunt objects; and stab wounds. Drowning and smothering may leave minimal 

findings; neither strangulation nor smothering are usually associated with facial 

petechiae in infants. Inflicted injuries should be carefully distinguished from 

injuries owing to birth trauma, normal anatomical features, and postmortem 

damage.

178 Byard 

Fig. 5. Clotted blood on the face and vernix caseosa on the left cheek, neck, 

shoulders, and upper chest indicating recent delivery. (Courtesy of Dr. Michael 

Tsokos, Hamburg, Germany.) 

The process of delivery may cause a number of characteristic injuries to 

infants such as hemorrhage and edema within the scalp (caput succadeum) 

and subperiostial hemorrhage (cephalhematoma). Fractures are uncommon and 

may involve the clavicles and long bones in breech deliveries or when there 

has been malpresentation or cephalopelvic disproportion. Internal injuries to 

the spleen and liver may also occur with obstructed labor. Separation of parts 

of the occipital bone, occipital osteodiastasis, may also be a feature of breech 

deliveries that causes cerebellar lacerations and tearing of dural venous sinuses 

with subdural bleeding (16). Precipitate delivery with excessive molding of 

the head may also cause intracranial hemorrhage. Unfortunately, assessment 

of the likely significance of certain of these lesions may be complicated by a 

lack of history of the delivery. 

Scratch marks or even a ligature around the neck may not necessarily 

indicate attempted strangulation, as these may be found if a mother has 

attempted to manually extract an infant, or has used a loop of cloth to assist 

with traction. Similarly, pressure from an umbilical cord wrapped around the 

neck may also leave circumferential grooving that should not be confused


Fig. 6. (A) Umbilical cord entanglement around the neck. (B) When the 

umbilical cord is removed prior to autopsy, circumferential grooving can be 

confused with ligature indentation. (Courtesy of Dr. Michael Tsokos, Hamburg, 

Germany.) 

with ligature indentation (Fig. 6A,B). Normal fat folds may also produce circumferential 

markings (18). 

Precipitate delivery may cause asphyxia in small infants, who can also 

sustain head injuries if a mother has delivered in a standing or squatting position 

with an umbilical cord long enough for an infant to strike the ground or 

floor. Asphyxia may also complicate obstructed labors from shoulder dystocia 

or cephalopelvic disproportion in larger infants. Evidence of acute asphyxia 

at autopsy includes thymic, pleural, and epicardial petechiae with intraalveolar 

hemorrhage, and meconium and shed fetal skin (squames) within distal air 

passages (16). More chronic stress may be manifested by evidence of growth 

retardation, decreased amounts of subcutaneous fat, and meconium staining 

of skin and fingernails. 

The body of an infant may also be damaged after death, particularly if it 

has been moved or compressed within a rubbish dumpster. Exposure of a body 

to animal and insect activity may also result in quite extensive soft-tissue trauma

180 Byard 

(19). Putrefactive and autolytic changes will be additional factors complicating 

assessment of the presence or absence of injuries. 

Another important aspect of the autopsy is to check for the presence or 

absence of lethal natural diseases. Certain conditions such as anencephaly and 

congenital diaphragmatic hernia with significant pulmonary hypoplasia should 

be readily identifiable, although subtle cardiovascular or metabolic abnormalities 

may be more difficult to diagnose. Full microbiological workup of both 

the infant and the placenta, if available, should be undertaken, along with 

histological examination of all major organs and tissues to check for sepsis. 

6.2. Examination of the Placenta 

Placental examination is a vital part of any perinatal autopsy, however, 

because of the unusual circumstance surrounding concealed deliveries and 

possible neonaticides the placenta may not always be available for pathological 

assessment. 

Various placental conditions may result in the stillbirth of otherwise completely 

normal infants (20). Premature separation of the placenta from its uterine 

attachments (abruptio placentae) may be associated with extensive 

retroplacental bleeding and compromise of placental and infant oxygenation. 

This may be manifested by persistence of clot adhering to the maternal surface 

of the placenta, or an indentation into the placental parenchyma indicating 

its position if it has become detached. Obstruction of the entrance to the 

birth canal by the placenta (placenta previa) may lead to massive hemorrhage 

once labor is initiated, with death of both mother and infant unless urgent 

medical intervention has occurred. Vasculopathy may result in extensive placental 

infarction and there may be evidence of sepsis in the form of acute 

chorioamnionitis and funisitis. 

Umbilical cord problems may also cause precipitate deterioration in an 

infant’s condition from a variety of mechanisms. Excessively long cords may 

cause blood flow obstruction if prolapse, torsion, or knotting occur. Long cords 

may also wrap around an infant’s neck. Conversely, blood flow in short cords 

may also be compromised if there is excessive traction during delivery. The 

average cord length is 54–61 cm with short cords measuring less than 30 cm 

and long cords measuring greater than 100 cm (16). Although possible twisting 

or knotting of cords may be difficult to assess, true knots should be tight, 

with congestion of vessels on one side and pallor on the other. There may be 

thrombi demonstrable histologically. 

Significant hemorrhage may occur during delivery if cord vessels overlie 

the entrance to the birth canal (vasa previa) or if vessels insert into the


Fig. 7. Incised end of an umbilical cord (arrow) in a case of neonaticide. 

more fragile membranes rather than the placental parenchyma (velametous 

insertion) where they are more likely to be traumatized. 

Examination of the ends of the cord must be undertaken macroscopically 

and microscopically. This will reveal whether the ends of the cord have been 

cut (Fig. 7), or have torn, possibly indicating a precipitate delivery. 

7. METHODS FOR DETERMINING LIVE BIRTH 


Determination of whether an infant was born alive or dead is one of the most 

difficult aspects of these cases. A further problem is that the definition of what 

constitutes “live birth” legally differs from jurisdiction to jurisdiction. Requirements 

have included complete expulsion from the birth canal with a heart beat and/ 

or respiratory efforts. Unfortunately, an autopsy examination simply cannot determine 

whether a heart has functioned or whether the body was completely expelled 

prior to death, and so pathological opinion relies on an assessment of the degree of 

pulmonary inflation, the presence or absence of a vital reaction in the tissues, or 

evidence of feeding. The age of viability also varies among jurisdictions with 24 

and 28 weeks being cited as the lower limits of potential survival (21).

182 Byard 

Signs of intrauterine death, caused by a process of sterile tissue breakdown 

or maceration, may be present indicating that live birth has not occurred. 

During this process the body undergoes a series of characteristic changes 

beginning with reddening, slippage, and peeling of the skin after 12 hours, 

followed by purple discoloration and blister formation after 24 hours, and the 

development of pleural, peritoneal, and pericardial effusions after 48 hours 

(16). After several days the body has lost tone, joints become hypermobile, 

and cranial bones have collapsed producing Spalding’s sign on radiography. 

An infant with changes of maceration has not been alive outside the uterus. 

The assertion that intraalveolar squames and/or meconium indicates stillbirth 

(22) is not correct as these findings merely indicate that some degree of fetal 

distress has occurred and may be found in living infants some time after birth. 

The most reliable evidence of live birth is an independent and reliable 

witness who has either seen the infant moving or heard the infant crying. Milk 

within the stomach indicates that the infant was alive long enough to feed and 

was capable of such activity. Drying and separation of the umbilical cord stump, 

which occurs after 24–48 hours, with histological evidence of a tissue reaction, 

may also be useful, but does not help with deaths in the immediate 

postdelivery period. 

7.2. Flotation Test 

One of the most time-honored tests used to assess the amount of pulmonary 

inflation that has occurred is the flotation test. This is based on the hypothesis 

that the lungs from an infant who has breathed will be expanded and filled 

with air and therefore will float in water, in contrast to the noninflated lungs 

of a stillborn infant, which will sink (4). Some authors suggest that it is better 

to attempt to float the lungs and heart en bloc to increase the sensitivity of the 

test (21). 

Unfortunately, interpretation of this test is fraught with difficulty as there 

are numerous false positives and negatives, making this test of dubious usefulness 

in isolation. For example, lungs from a stillborn infant may float if there 

has been attempted resuscitation, with forcing of air into distal airspaces, or if 

there has been generation of gas within lung tissues by putrefactive bacteria. 

Similarly, lungs from a live-born infant may not have been inflated sufficiently 

to float if respiratory efforts have been weak. It has even been asserted that 

moving a dead infant may cause air to be aspirated into the lungs (21). However, 

though considering these caveats it can certainly be said that salmon-pink 

spongy lungs that float in water, in the absence of resuscitation and putrefaction, 

are most in keeping with lungs from an infant who has breathed (Fig. 8).


Fig. 8. Aerated lungs floating in water in a case of alleged stillbirth without 

resuscitation. 

Radiographs may be used to assess the degree of pulmonary inflation 

and also to detect air within the stomach and upper gastrointestinal tract. If 

resuscitation or putrefaction have not occurred, it is assumed that air has reached 

the gut from swallowing. The stomach may also float in water if distended by 

air. The usefulness of attempting to demonstrate air within the middle ears is 

debatable and the relationship between the presence of pulmonary interstitial 

emphysema and possible live birth is yet to be clarified (23). 

7.3. Lung Weights 

Another measurement that has not proven of much use is comparison of 

lung to body weights. This was based on the observation that inflated and 

perfused lungs are heavier than lungs where respiration has not occurred. Again 

considerable inaccuracies occur. 

7.4. “Birth-Line” 

The so-called “birth-line” in teeth refers to a line caused by disturbance 

of ameloblast activity at birth that can be detected after several weeks. Although 

scanning electronmicroscopy has been used to identify this finding within several 

days of birth, its practical usefulness is not great given that most deaths 

occur earlier than this.

184 Byard 

8. CAUSES OF DEATH 

Deaths are most often a result of airway obstruction from smothering or 

strangulation. An infant’s nose and mouth may be blocked with a hand in an attempt 

to prevent the infant’s cries from being heard. Infants may also asphyxiate if placed 

in plastic bags and hidden while a mother cleans up after delivery and determines 

what she is to do. Drowning may occur if an infant is delivered into a toilet 

bowl and left there, or is held under water in a bath (24). Blunt head trauma 

may occur. Although stabbing is less common, occasionally a throat may be 

cut (2,9,10). 

Deaths may also occur from failure to provide appropriate care of a vulnerable 

newborn. Failure to tie off the cut umbilical cord may result in lethal 

blood loss, and airway occlusion from secretions may compromise respiration 

if not cleared. Failure to adequately clothe or place an infant in a warm environment 

may result in fatal hypothermia. 

9. CONCLUSION 

Given that the causes of death may not be found at autopsy in unexpected 

near-term stillbirths that occur in hospitals under highly controlled conditions, 

it is perhaps not surprising that determination of lethal mechanisms 

may not be possible in cases where infants have been found abandoned some 

days after delivery. In these cases, stillbirth must be assumed until there is 

firm evidence to the contrary. 

REFERENCES 

1. Marks MN, Kumar R (1996) Infanticide in Scotland. Med Sci Law 36, 299–305. 

2. Pitt SE, Bale EM (1995) Neonaticide, infanticide and filicide: a review of the literature. 

Bull Am Acad Psychiatr Law 23, 375–386. 

3. Adelson L (1991) Pedicide revisited. The slaughter continues. Am J Forensic Med 

Pathol 12, 16–26. 

4. Cohle SD, Byard RW (in press) Intentional trauma. In Byard RW, ed., Sudden death 

in infancy, childhood and adolescence, 2nd ed. Cambridge University Press, 

Cambridge. 

5. Ober WB (1986) Infanticide in eighteenth-century England. William Hunter’s contribution 

to the forensic problem. Pathol Annu 21, 311–319. 

6. Coon CS (1971). The hunting people. Little, Brown and Company, Boston. 

7. Kellett RJ (1992) Infanticide and child destruction—the historical, legal and pathological 

aspects. Forensic Sci Int 53, 1–28. 

8. Johnson CF (1990) Inflicted injury versus accidental injury. Pediatr Clin Nth Am 37, 

791–814.


9. Saunders E (1989) Neonaticides following “secret” pregnancies: seven case reports. 

Pub Health Rep 104, 368–372. 

10. Mendlowicz MV, Jean-Louis G, Gekker M, Rapaport MH (1999) Neonaticide in 

the city of Rio de Janeiro: forensic and psycholegal perspectives. J Forensic Sci 44, 

741–745. 

11. Spinelli MG (2001) A systemic investigation of 16 cases of neonaticide. Am J 

Psychiatr 158, 811–813. 

12. Funayama M, Ikeda T, Tabata N, Azumi J-I, Morita M (1994) Case report: repeated 

neonaticides in Hokkaido. Forensic Sci Int 64, 147–150. 

13. Overpeck MD, Brenner RA, Trumble AC, Trifiletti LB, Berendes HW (1998) Risk 

factors for infant homicide in the United States. N Engl J Med 339, 1211–1216. 

14. Wissow LS (1998) Infanticide. N Engl J Med 339, 1239–1241. 

15. Kouno A (2000) Coin-operated locker babies: murder of unwanted infants and child 

abuse in Japan. In Marvasti JA, Manchester CT, eds., Child suffering in the world. 

Child maltreatment by parents, culture and governments in different countries and 

cultures, Sexual Trauma Center Publication, Manchester, pp. 285–298. 

16. Keeling J (1987) Fetal and neonatal pathology, Springer, London. 

17. Bove KE and the Autopsy Committee of the College of American Pathologists 

(1997) Practical guidelines for autopsy pathology. The perinatal and pediatric 

autopsy. Arch Pathol Lab Med 121, 368–376. 

18. Byard RW (2004) Sudden infant death syndrome. In Byard RW, ed., Sudden death 

in infancy, childhood and adolescence, 2nd ed. Cambridge University Press, Cambridge, 

pp. 491–575. 

19. Byard RW, James RA, Gilbert JD (2002) Problems associated with cadaveric trauma 

due to animal activity. Am J Forensic Med Pathol 23, 238–244. 

20. Ito Y, Tsuda R, Kimura H (1989) Diagnostic value of the placenta in medico-legal 

practice. Forensic Sci Int 40, 79–84. 

21. Knight B (1996) Infanticide and stillbirth Ch 20. In Knight B, ed., Forensic pathology, 

2nd ed. Arnold Press, London, pp. 435–446. 

22. Bowen DAL (1989) Concealment of birth, child destruction and infanticide. In Mason 

JK, ed., Paediatric forensic medicine and pathology. Chapman and Hall Medical, 

London, pp. 178–190. 

23. Lavezzi WA, Keough KM, Der’Ohannesian P, Person TLA, Wolf BC (2003) The use 

of pulmonary interstitial emphysema as an indicator of live birth. Am J Forensic Med 

Pathol 24, 87–91. 

24. Mitchell EK, Davis JH (1984) Spontaneous births into toilets. J Forensic Sci 29, 

591–596.

SIDS 187 

SIDS

188 Byard and Krous

SIDS 189 

7 

Diagnostic and Medicolegal 

Problems With Sudden 

Infant Death Syndrome 

Roger W. Byard, MBBS, MD and Henry F. Krous, MD 

CONTENTS 

INTRODUCTION 

CHARACTERISTICS 

DEFINITION OF SUDDEN INFANT DEATH SYNDROME 

DIAGNOSTIC PROBLEMS 

PROBLEMS IN COURT 

CONCLUSION 

REFERENCES 

SUMMARY 

Although many cases of unexpected infant death have been attributed to 

sudden infant death syndrome (SIDS), it remains a contentious entity with 

arguments for and against it as a distinct “diagnostic entity.” Major problems 

exist owing to the lack of pathognomonic features at autopsy; however, there 

is no doubt that infants between the ages of 2 and 4 months have an increased 

risk of dying unexpectedly during sleep. This risk is exacerbated by sleeping 

face down, covering with bed clothes, and exposure to cigarette smoke. Difficulties 

arise in evaluating cases of infant death as there is no uniformity in 

approach to cases, or use of standard definitions, despite the ready availability 

of the National Institute of Child Health and Human Development (NICHD) 

definition for SIDS, the International Standardized Autopsy Protocol for Sudden 

Unexpected Infant Death, and the Sudden Unexplained Infant Death 



189

190 Byard and Krous 

Investigation Report Form. Similarities in the pathological findings at autopsy 

in infants whose deaths have been attributed to SIDS or to accidental or inflicted 

asphyxia emphasize the need for extensive background and scene information, 

with standard methods being utilized. Variations in approach make the assessment 

of cases even more difficult if they come to court. Although conflicting 

opinions, absence of requisite investigations, lack of pathognomonic findings, 

and the introduction of speculative research are certainly not unique to this 

area, they do feature particularly prominently. Courts attempt to deal with this 

tangle of complex causative mechanisms and theories, which are either not 

proven or are only poorly understood, by simplifying and summarizing. This 

sometimes results in loss of critical “gray” areas and important qualifiers, with 

resultant overstated and simplistic conclusions that are considered to be more 

easily understood by juries. Whereas researchers are better able to deal with 

the inconclusive results and uncertainties that beset this field, courts appear 

not as well equipped to do so. 

Key Words: Sudden infant death syndrome (SIDS); infant death; pathology; 

pediatric forensic pathology; court. 


Despite marked reductions in the incidence of infant deaths in communities 

where there has been active promotion of campaigns to inform parents 

and infant carers of risk factors, sudden infant death syndrome (SIDS) remains 

one of the major causes of unexpected, postneonatal infant death (1–3). The 

diagnosis of SIDS is still, however, controversial, with calls being made for 

the abandonment of the term based partially on cases of infanticide that had 

been ascribed initially to SIDS (4,5). This chapter deals with problems that 

arise in trying to separate SIDS from other causes of unexpected infant death. 

2. CHARACTERISTICS 

There is no doubt that SIDS is a useful term to use when infants die 

suddenly and unexpectedly during sleep and the cause remains unknown. The 

clinicopathologic profile of classic SIDS is characterized by recent antemortem 

good health, male gender, prone sleep position, maternal smoke exposure, 

and higher death rates during winter months. Other risk factors include 

premature birth, low birth weight, multiple births, lower socioeconomic status, 

minority ethnicity, bed sharing, being covered by blankets, and young 

maternal age (6–9). Unfortunately, similar features characterize many infants 

who have died of accidents, inflicted injuries, or definable natural diseases.

SIDS 191 

Thorough autopsies in SIDS infants do not, however, reveal significant underlying 

organic diseases or evidence of inflicted injury (10,11). 

3. DEFINITION OF SUDDEN INFANT DEATH SYNDROME 

Various different definitions of SIDS have been promulgated over the 

past decade. Definitions have variously required that death scene examinations 

and review of clinical history be performed, that there be a clear association 

with sleep, that the upper age limit should be 8 months, 1 year, or not 

specified, and that extensive ancillary postmortem investigations such as microbiological 

testing and toxicology should be undertaken (12–15). The significance 

of including minor pathological findings has been debated (16–18). Given 

this range of proposals, it is perhaps not surprising that there is confusion 

among pathologists and researchers regarding diagnostic requirements for SIDS 

and criteria for establishing other causes of death. 

In 1991, a definition was formulated by an expert committee brought 

together by the National Institute of Child Health and Human Development 

(NICHD). This stated that SIDS refers to “the sudden death of an infant under 

one year of age which remains unexplained after a thorough case investigation, 

including performance of a complete autopsy, examination of the death 

scene and review of the clinical history” (19). Although the NICHD definition 

has not gained universal acceptance, most pathologists and researchers would 

recognize the value of the points that have been made, and although there is 

continued concern about the cutoff point of 1 year of age, it is acknowledged 

that unexpected deaths after infancy are very rare. More recently, Beckwith 

has proposed stratification of the definition with a graded classification ranging 

from SIDS cases that fulfill all of the required investigative steps to cases 

that are unclassifiable because of absence of significant information (20). 

Invited commentaries were in agreement with the need to redefine SIDS given 

the marked recent increase in knowledge in this area (21–26). 

4. DIAGNOSTIC PROBLEMS 

Unfortunately, SIDS is not so much a “diagnosis” as a conclusion that is 

reached by a process of exclusion. As a result, there is certainly no doubt that 

cases of infanticide and fatal accidents have been, and will continue to be, 

misdiagnosed as SIDS (10,27–29). This occurs in part because of the 

nonspecificity of postmortem findings in infants who have died of SIDS or of 

“soft” suffocation, and also because the standard of investigation of cases of 

infant death varies widely among jurisdictions (30).


In an attempt to reduce the numbers of these cases being misclassified, 

protocols have been devised that provide detailed guidelines for both death 

scene and autopsy examinations in cases of unexpected infant death (31,32). 

Although these protocols set a “gold standard” for the investigation of such 

cases, significant problems remain. For example, a major concern is that the 

diagnosis of SIDS is continually being made without fulfilling the criteria 

stated in the NICHD definition (30). 

In parts of Europe in the recent past, it has been stated that only 30–40% 

of cases of infants whose deaths were attributed to SIDS even had autopsies 

(1). In areas of Australia, cases may still be called SIDS with autopsies that 

are either incomplete or not performed by pathologists (30). Although conclusions 

are drawn on SIDS rates in isolated, indigenous, rural communities (33), 

it is difficult to believe that adequate examinations were always performed 

because of the logistical problems involved. 

Given this state of affairs, further dissemination and implementation of the 

Centers for Disease Control Guidelines and International Standardized Autopsy 

Protocol for sudden, unexpected infant death should be undertaken. It is noteworthy 

that these protocols have been endorsed by the Society for Pediatric Pathology 

and the National Association of Medical Examiners in the United States. 

The significance of misdiagnosis is far from academic. Other and future 

children in the family may be in jeopardy if rare inherited conditions are not 

characterized accurately. Failing to correctly diagnose accidental asphyxia due 

to an unsafe cot or cradle may result in a dangerous product being left in the 

marketplace, and lack of identification of infanticides may leave other children 

in the family at significant risk of injury or death. 

Research based on cohorts of infants or their families in whom inadequate 

investigations were undertaken must, therefore, be treated with circumspection. 

National or large multicenter studies are particularly vulnerable to this error as 

researchers often do not have control over the cases being passed to them, or 

complete understanding regarding the rigor with which other diagnoses were 

excluded. Papers that are now reporting SIDS research should always clearly 

specify not only the exact criteria followed to establish the diagnoses, but also 

the precise percentage of cases falling outside the NICHD definition. In addition, 

if research papers that were published before the current definition was 

formulated are being cited, this fact should be acknowledged. SIDS studies 

should also state whether the actual scene was investigated or whether scene 

information was collected only from questionnaires. It is time to re-evaluate 

SIDS research and possibly grade studies on the rigor with which diagnoses 

have been established. For example, cases would receive a high grading where

SIDS 193 

death scene, clinical history, and full autopsy examinations were conducted 

by members of an investigative team according to established and accepted 

definitions and protocols. Research based on cases diagnosed many years ago 

when scenes and clinical history were not considered important should carry 

less weight, and studies using a significant number of cases where autopsies 

were not done will in all likelihood be uninterpretable. 

The value of protocols can be seen in the increase in diagnoses of deaths 

owing to such entities as accidental asphyxia because of unsafe sleeping environments, 

with the portion of unexpected infant deaths resulting from other 

causes now reaching 25% in some communities. This means that as many as 

one in four unexpected infant deaths could be incorrectly labeled as SIDS 

without proper investigation (34). This also raises the possibility that conflicting 

data that abound in SIDS research may be partly a reflection of the lack of 

precision with which the initial characterization of cases was undertaken, rather 

than an inherent heterogeneity in the underlying mechanism. 

5. PROBLEMS IN COURT 

Dealing with cases of unexpected infant deaths in the court system adds 

yet another dimension of complexity. As many of these cases may have no, or 

only subtle pathological findings, it may be difficult to support or refute a 

diagnosis based purely on pathological findings. Cases that present particular 

difficulties concern families where multiple infant deaths have occurred. The 

concept of a third infant death in a family automatically representing a homicide 

is an extreme position as certain inherited conditions may be responsible 

for such a series of deaths. 

Examples of inherited conditions that may cause sudden and unexpected 

deaths in infants within a single family include prolonged QT syndrome and 

medium-length acyl-CoA dehydrogenase (MCAD) deficiency. Prolonged QT 

syndrome is caused by mutations involving genes that are involved in cardiac 

potassium and sodium channels resulting in lethal arrhythmias. MCAD deficiency 

is one of the most common inborn metabolic errors and has an estimated 

frequency of 1 per 20,000 newborns with a higher frequency among 

people of Northern European descent. The inheritance of the acyl-CoA dehydrogenase 

deficiencies is autosomal recessive and affected infants may die 

unexpectedly from metabolic disturbances. Mutations in both of these conditions 

can be detected by performing molecular studies on victims and close 

family members (1,35–37). 

Alternatively, problems may arise when hypothetical links to underlying 

findings in certain SIDS infants, such as inflammatory mediators like cytokines


(38,39), are given undue weight and used as “proof” in court that a particular 

infant death must be due to SIDS. It is important to recognize that such hypotheses 

are theoretical and unproven and cannot, therefore, be used as confirmatory 

“evidence” for a cause of death. 

Different problems also occur in different countries. For example, infant 

carers in certain jurisdictions have been charged with manslaughter when 

infants in their care have died while sleeping face down. The assumption has 

been made that there has been negligence in leaving such infants in a position 

where they are at risk of asphyxiation. The basis for this is, however, incorrect. 

As the majority of infants who sleep face down do not die, the mechanism 

of death is not simple asphyxia in most circumstances and must include 

a range of interactions involving diaphragmatic splinting, overheating, carbon 

dioxide rebreathing, in addition to possible airway occlusion, in an infant with 

inherent vulnerabilities (40–43). Death cannot, therefore, be attributed to suffocation 

purely on the grounds of an infant being found in the prone position. 

Other problems arise in cases of unexpected infant death when nonpediatric-trained 

forensic experts become involved in cases. For example, in 

a recent widely publicized case in the United Kingdom, retinal congestion 

was mistaken for antemortem retinal hemorrhage, leading to an incorrect 

diagnosis of shaken infant syndrome. In the same case, lacerations to the 

brain caused by postmortem removal were mistaken for inflicted antemortem 

trauma. Finally, isolation of the bacteria Staphylococcus aureus in pure 

growth from multiple sites, including the cerebrospinal fluid, was not regarded 

as significant. These errors led to a mother being convicted of the murder of 

two of her infants. The conviction was eventually overturned upon special 

review. 

The proffering of expert opinion by individuals who are peripheral to, or 

not actively involved in, pediatric forensic pathology often leads to confusing 

and conflicting information. Courts attempt to deal with masses of contradictory 

information by simplifying, which unfortunately often does not work. 

Attempting to summarize and categorize these extremely complicated cases 

into a series of questions with yes/no answers is akin to producing a one-page 

summary of a Russian novel. Although no one would disagree that the essentials 

of the plot could be captured by such an exercise, there is no doubt that 

important nuances conveying the true meaning and conclusions would be lost. 

Most would agree that such an exercise would be pointless. 

An example of incorrect expert opinion in the past has been the assertion 

that the bulk of cases attributed to SIDS have been homicides. This has been 

shown to be incorrect following the dramatic fall in numbers of SIDS deaths

SIDS 195 

following “reducing the risk” campaigns. Put simply, avoidance of cigarette 

smoke and prone sleeping are not preventative factors for murder. Certainly 

some cases of homicide have been misdiagnosed as SIDS; however, these 

undoubtedly represent a small percentage of overall cases of infant death. 

6. CONCLUSION 

A number of years ago, John Emery created a certain amount of controversy 

by asking whether the diagnosis of SIDS was being made too readily, 

resulting in a “diagnostic dustbin” into which a wide range of disorders were 

hastily placed (44). More recently, Meadow has asked whether the diagnosis 

of SIDS should be discontinued, given the number of misdiagnosed cases of 

homicide that were initially placed under the SIDS banner (4). 

Both of these papers highlighted inadequacies in the investigation of cases 

of unexpected infant death and there is no doubt that deaths have been attributed 

to SIDS in the past too readily and without due consideration of numerous 

pertinent facts (45,46). The “diagnosis” of SIDS cannot be made solely on 

the basis of autopsy findings and the 1991 definition clearly indicates this. 

The challenge, however, is to improve investigations into causes of infant 

death, including SIDS, rather than to revert to a situation where any complex 

or confusing case, or any case with potentially controversial diagnostic features 

is too readily relegated to an even larger “dustbin” of “undetermined” or 

“unascertained.” Although this may at times be the only conclusion possible, 

given the paucity of findings, it unfortunately does little to assist in the assessment 

and understanding of these complicated and emotive cases and should 

not be an excuse for incomplete investigations. 

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(2001) Postmortem molecular analysis of SCN5A defects in sudden infant death 

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Mycoplasma pneumoniae Pneumonia 199 

Infectious Diseases

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8 

Fatal Respiratory Tract Infections 

With Mycoplasma pneumoniae 

Histopathological Features, 

Aspects of Postmortem Diagnosis, 

and Medicolegal Implications 


CONTENTS 

INTRODUCTION 

ORGANISM, PATHOGENESIS, AND PATHOPHYSIOLOGY: A BRIEF OUTLINE 

HISTOPATHOLOGY 

POSTMORTEM DIAGNOSIS OF M. PNEUMONIAE INFECTION USING SEROLOGY AND PCR 

MEDICOLEGAL ASPECTS OF FATAL M. PNEUMONIAE INFECTIONS 

REFERENCES 

SUMMARY 

Mycoplasma pneumoniae is a prokaryotic microorganism that lacks a rigid 

cell wall and has a high affinity for respiratory epithelial cells. M. pneumoniae 

has been shown to be a major pathogen leading to severe, potentially lifethreatening 

respiratory tract infections. The organism itself is too small to be 

detected at light microscopy. Histopathological features of the disease include 

two patterns of injury represented by (a) circumscribed bronchiolitis and 

(b) organizing pneumonia, the latter corresponding to a generalized inflammatory 

process spreading from M. pneumoniae’s primary target zone, the bronchi 

and bronchioli. In M. pneumoniae-associated bronchiolitis, the mucosa of 

the upper and lower airways appear edematous and infiltrated by a dense pre- 



201

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dominantly mononuclear infiltrate accompanied by an intraluminal exsudate 

of neutrophils and, to a lesser extent, macrophages. Occasionally, plugs of 

granulation tissue within the lumen of bronchi and bronchioli corresponding 

to bronchiolitis obliterans can be seen. M. pneumoniae-organizing pneumonia 

is characterized by a dense mononuclear infiltrate in alveolar septa and alveolar 

spaces that is frequently accompanied by intraalveolar hemmorhages and 

edema. The lungs may additionally show features of diffuse alveolar damage 

including type II pneumocyte hyperplasia, squamous metaplasia, and hyaline 

membranes as well as occlusive venous thromboses. To enable etiopathogenetic 

conclusions concerning a causal relationship between M. pneumoniae infection 

and fatal outcome, for example, in cases of alleged medical malpractice, 

the forensic investigation should ensure postmortem blood sampling as early 

as possible with subsequent enzyme-linked immunosorbent assay-based serological 

determination of IgA and IgM antibodies as well as an immediate 

autopsy to obtain native lung specimens for direct detection of M. pneumoniae 

using standard polymerase chain reaction. Intrinsic and extrinsic risk factors 

predisposing to the development of fatal M. pneumoniae infection have to be 

considered carefully in the following expert witness. From the medicolegal 

point of view, the sudden, unexpected death of an individual occurring outside 

hospital as the sequel of a rapidly progressive course of M. pneumoniae 

infection will have to be regarded as unavoidable in most cases. However, 

data obtained from such instances are valuable since fatal respiratory tract 

infections with M. pneumoniae in individuals dying outside hospital are probably 

underestimated. 

Key Words: Mycoplasma pneumoniae; community-acquired pneumonia; 

organizing pneumonia; bronchiolitis obliterans; fatal infection; forensic 

histopathology. 


Mycoplasmas are prokaryotic microorganisms that lack a bacterial cell 

wall. Several mycoplasma species including Mycoplasma orale, Mycoplasma 

salivarium, Mycoplasma faucium and Mycoplasma buccale are encountered 

as part of the normal oropharyngeal human flora, but only Mycoplasma 

pneumoniae, which has a high affinity for respiratory epithelial cells, has been 

shown to be a major pathogen leading to severe, potentially life-threatening 

respiratory tract infections. M. pneumoniae infection is endemic in most regions 

of the world, although it is more common in temperate zones. M. 

pneumoniae is transmitted by respiratory droplet secretions (1). 

There are relatively few data on the pulmonary micromorphology of M. 

pneumoniae infections. The knowledge of the histopathological features of


the disease is based on a paucity of observations from open lung biopsy specimens 

(2–4), experimental studies (5,6) and rare fatal cases (7–10). 

After briefly reviewing the pathogenesis and pathophysiological properties 

of M. pneumoniae, the different histopathological features of respiratory 

tract infections with M. pneumoniae are presented. The role of postmortem 

diagnostic procedures such as serology and standard polymerase chain reaction 

(PCR) from native (fresh) lung autopsy material to provide evidence of 

M. pneumoniae as the etiological agent in question is also considered. In addition, 

medicolegal issues related to fatal outcome of the disease are discussed. 

2. ORGANISM, PATHOGENESIS, AND PATHOPHYSIOLOGY: 

A BRIEF OUTLINE 

Mycoplasmas are the smallest self-replicating organisms capable of causing 

infections in humans (11,12). These microorganisms lack a rigid cell wall 

and are bound by a single membrane, the plasma membrane. The lack of a cell 

wall is used to distinguish these microorganisms from ordinary bacteria and to 

include them in a separate class named Mollicutes. So far, 16 mycoplasma 

species have been identified in humans (13). The best studied is M. pneumoniae 

whose entire genome has been sequenced recently. It has a size of 816,394 

base pairs with an average G + C content of 40.0 mol% (14). 

M. pneumoniae is a rod-shaped organism that has a polar, tapered cell 

extension at one end. This structure, a specialized terminal filament that is 

termed the tip organelle, functions as an attachment organelle in cytadherence 

as well as gliding motility and cell division (15,16). Because of its size of 

10 × 200 nm, this Gram-negative organism escapes detection at light microscopy. 

M. pneumoniae adheres tenaciously to the epithelial lining cells of the 

respiratory tract. This adhesion of M. pneumoniae to the respiratory epithelium 

is a prerequisite for colonization and subsequent infection (17). Current 

theory holds that mycoplasmas remain attached to the surface of epithelial 

cells (18), although some mycoplasmas have evolved mechanisms for entering 

host cells that are not naturally phagocytic. The lack of a rigid cell wall 

allows direct and intimate contact of the mycoplasma membrane with the cytoplasmic 

membrane of the host cell. The receptors on host cell membranes 

responsible for mycoplasma attachment that have been identified so far are 

mostly sialoglycoconjugates and sulfated glycolipids (11,18). Most recent findings 

demonstrate that M. pneumoniae interacts in the respiratory system also 

with the surfactant proteins A and D and that primary determinants recognized 

on the organism are lipid components of the cell membrane (19,20). The

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attachment of mycoplasmas to the surface of host cells may interfere with 

membrane receptors or alter transport mechanisms of the host cell. The host 

cell membrane is also vulnerable to cytotoxic metabolites, cytolytic enzymes, 

and peroxide and superoxide radicals released by the adhering mycoplasmas 

causing ciliostasis, epithelial cell necrosis, and desquamation of mucosal cells 

into the airway lumen, the latter responsible for the cough that defines clinical 

presentation (1,16,21). M. pneumoniae infection is spread from one person to 

another by respiratory droplets produced by coughing. Spread of infection 

from person to person is very slow and a very close contact seems a prerequisite 

for infection (22). M. pneumoniae has an incubation period of 2–3 weeks 

(1,22) and epidemic outbreaks of M. pneumoniae pneumonia occur in 4- to 

5-year-cycles (23). Outbreaks of illness attributable to mycoplasmas commonly 

occur in closed or semiclosed communities (23). These outbreaks are difficult 

to contain because of delays in outbreak detection, and the long incubation 

period of the organism (24). 

3. HISTOPATHOLOGY 

A variety of pulmonary complications has been reported to occur with 

M. pneumoniae infection. These include organizing pneumonia, tracheobronchitis, 

obliterative bronchitis, bronchiectasis, pneumatocele formation, pleural 

effusions, interstitial fibrosis, lung abscess, and bronchiolitis obliterans 

(25–32). But because in a number of reports the affected individual suffered 

from severe underlying debilitating illnesses or immunological deficiencies 

that contributed to the onset of M. pneumoniae infection, it is tempting to 

speculate that the pathological features reported there may have been influenced, 

at least, to a certain degree by the pathophysiology and pathology of 

these underlying conditions. Furthermore, in most clinical cases reported, a 

detailed histopathological diagnosis is lacking. Therefore, this section focuses 

primarily on the pathological features of M. pneumoniae pneumonia that were 

observed in patients without immunocompromisation or co-existing lung diseases 

of other origin and were verified by histopathology. 

In a hamster model of M. pneumoniae infection, intratracheal inoculation 

of the organism produced a bronchiolitis characterized by peribronchiolar 

and perivascular lymphocytic infiltrates with neutrophils and macrophages 

within the bronchiolar lumen (6). 

At autopsy, infection with M. pneumoniae limited to bronchiolitis is 

merely characterized by patchy changes of the bronchioli, but this finding 

might escape macroscopical notice when the disease process is negligible. 

Widespread pneumonia caused by M. pneumoniae shows a patchy consolida-


Fig. 1. Bronchiolitis in Mycoplasma pneumoniae infection: edematous bronchiolar 

wall showing a dense inflammatory infiltrate of predominantly mononuclear 

cells and vascular congestion. Note the loss of mucosal integrity with 

subsequent epithelial cell necrosis and desquamation of mucosal cells into the 

airway lumen (hematoxylin and eosin). 

tion of one or more lobes of the lungs with confluent whitish-yellowish speckles 

on the cut surfaces. Vascular congestion is frequent. Depending on the 

presence and extent of pulmonary vessel thrombosis that usually escapes macroscopic 

examination, circumscribed pulmonary infarctions may be present. 

As with gross pathology, two distinctive pathological features of M. 

pneumoniae infection-associated pulmonary lesions can be distinguished on 

the micromorphological level, too. First, a bronchiolocentric pattern of injury 

reflected by a circumscribed bronchiolitis and second, a generalized inflammatory 

process spreading from M. pneumoniae’s primary target zone, the bronchi 

and bronchioli, to alveolar spaces and interstitium of one or more lobes of 

the lung. Referring to the histopathology of the bronchiolocentric pattern of 

injury, the mucosa of the upper and lower airways (primarily the terminal and 

respiratory bronchioles) appears edematous and infiltrated by a dense predominantly 

mononuclear infitrate. The release of cytotoxic and cytolytic substances 

by M. pneumoniae leads to loss of mucosal integrity with subsequent 

epithelial cell necrosis and desquamation of mucosal cells into the airway lumen 

(Fig. 1). This bronchiolitis is frequently accompanied by a dense intraluminal 

exsudate of neutrophils and, to a lesser extent, of macrophages (Fig. 2A,B). The 

organism itself is too small to be detected at light microscopy. The bronchiolar

206 Tsokos 

Fig. 2. Bronchiolitis in Mycoplasma pneumoniae infection. (A) Intraluminal 

exsudate of neutrophils and macrophages in a terminal bronchiolus. (B) Highpower 

view of excessive accumulation of neutrophils and macrophages within 

the lumen of a bronchiolus (hematoxylin and eosin). 

epithelium is frequently destroyed, but one has to be aware that this phenomenon 

may also be a sheer consequence of autolysis and consequently this finding 

can only be considered as a true sequel of infection when bronchiolar 

epithelium loss is partly replaced by a layer of granulation tissue (Fig. 3). In 

more rare cases, one may observe plugs of granulation tissue within the lumen 

of bronchi and bronchioli corresponding to bronchiolitis obliterans (Fig. 4A,B).


Fig. 3. Bronchitiolitis in Mycoplasma pneumoniae infection. The bronchial 

epithelium is destroyed and partly replaced by a layer of granulation tissue and 

capillary proliferation (hematoxylin and eosin). 

Ebenöther and coworkers recently investigated the cellular subtypes of 

the bronchiolar infiltrate in M. pneumoniae infection-associated bronchiolitis 

using immunohistochemistry (4). These authors found that the bronchiolar 

infiltrate consisted mainly of CD3-positive lymphocytes (accounting for 35% 

of mononuclear cells), CD8-positive lymphocytes (21%), and CD68-positive 

macrophages (30%) (Fig. 5A,B). Forty percent of nuclei within the bronchiolar 

wall tissue stained positive with MIB-1a. Because this antibody recognizes 

a nuclear antigen that appears in all phases of the cell cycle except the 

G0 phase, this observation indicates high proliferative activity of the mononuclear 

cells. 

Previously reported respiratory tract infections with M. pneumoniae 

associated with bronchiolitis obliterans have been described with and without 

organizing pneumonia (2–4,32–35). The term “organizing pneumonia” is 

defined pathologically by the presence of buds of granulation tissue progressing 

from fibrin exsudates to loose collagen containing fibroblasts that occur 

predominantly within the alveolar spaces but may also occupy the bronchiolar 

lumen (36,37). This pathological pattern, which is characterized by a remarkably 

preserved pulmonary architecture, has to be considered an unspecific 

inflammatory process resulting from a number of underlying etiologies. 

Organizing pneumonia can be regarded as a failure of resolution of acute pneumonia 

and as a kind of “limited wound healing reaction” of the lung parenchyma 

(38). Organizing pneumonia may be classified into three categories 

according to its cause: organizing pneumonia of determined cause (e.g., bacterial, 

viral, parasitic, and fungal infections, drug-induced, associated with 

radiation pneumonitis), organizing pneumonia of undetermined cause but 

occurring in a specific and relevant context (e.g., in association with connec-

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Fig. 4. Bronchiolitis obliterans in Mycoplasma pneumoniae infection. 

(A) Necrotic bronchiolar epithelium, lymphoplasmacytic infiltrate in the bronchiolar 

wall and a plug of granulation tissue occluding the bronchiolar lumen 

(hematoxylin and eosin). (B) Same visual field as before. Using phosphotungstic 

acid hematoxylin staining the fibrin network can be clearly distinguished. 

tive tissue disorders such as Wegener’s granulomatosis or rheumatoid arthritis), 

and cryptogenic (idiopathic) organizing pneumonia (38). Several possible 

causes and/or associated disorders may coexist in the same patient. Therefore, 

the histological finding of organizing pneumonia with or without bronchioli-


Fig. 5. (A,B) Mycoplasma pneumoniae-organizing pneumonia. High-power 

view of immunohistochemical staining of macrophages with CD68 within the 

intraluminal exsudate. Note the vacuolation of the cytoplasm (so-called “foam 

cells”) (CD-68). 

tis obliterans in autopsy cases of suspected fatal outcome of M. pneumoniae 

infection is highly unspecific. 

Severe, generalized lung injury in M. pneumoniae pneumonia is characterized 

by a dense mononuclear (lymphoplasmacytic) infiltrate in alveolar septa 

and alveolar spaces that is frequently accompanied by intraalveolar hemorrhages 

and edema (Fig. 6A–C).

210 Tsokos 

The lungs may additionally show features of diffuse alveolar damage 

including type II pneumocyte hyperplasia, squamous metaplasia, and hyaline 

membranes (Fig. 7). Occasionally, occlusive venous thromboses may be also 

present (Fig. 8A,B). Circumscribed microabscesses can be found only in cases 

of bacterial superinfection. 

M. pneumoniae has also been reported to exacerbate other respiratory 

disorders such as asthma (39,40) and chronic obstructive pulmonary diseases (41). 

4. POSTMORTEM DIAGNOSIS OF M. PNEUMONIAE 

INFECTION USING SEROLOGY AND PCR 

Serologic assays for immunoglobulin A and immunoglobulin M determination 

are mostly based on the enzyme-linked immunosorbent assay (ELISA) 

principle and various test kits are available from different companies. To 

achieve a conclusive diagnosis, separate detection of IgM or IgA antibodies is 

essential. IgM antibodies appear during the first week of the illness, and reach 

peak titers during the third week (42). In clinical practice, elevated IgM antibodies 

represent a reliable indicator of mycoplasma infection in children 

(43,44). IgM antibodies titer decline below the cutoff value of commercial 

assays within months. In a recent medicolegal investigation, using a highly 

specific enzyme immunoassay (Virion, Würzburg, Germany), our investigative 

group was able to detect an elevated IgM antibody titer (57 U/ml) against 

M. pneumoniae (normal range

Mycoplasma pneumoniae Pneumonia 211

212 Tsokos 

Fig. 7. Mycoplasma pneumoniae pneumonia. High-power view of diffuse 

alveolar damage with type II pneumocyte hyperplasia, squamous metaplasia, 

and thick PAS-positive hyaline membranes lining the alveolar wall (periodic 

acid-schiff). 

(46). A Western immunoblot technique for M. pneumoniae, enabling the detection 

of lower antibody levels than other assays, has been recently developed 

and is now commercially available (Virotech, Rüsselsheim, Germany). This 

method is currently probably the most specific technique for indirect detection 

of M. pneumoniae, but postmortem experience with this method within 

the forensic setting has not been established so far. 

To rule out the possibility that elevated antibodies are owing to past infection, 

standard PCR is currently the method of choice for direct detection of 

M. pneumoniae. PCR has replaced hybridization and direct antigen detection 

because of its higher sensitivity (45). In forensic autopsy practice, standard 

PCR for detection of M. pneumoniae from native (fresh) lung autopsy material 

is also a useful tool. 

5. MEDICOLEGAL ASPECTS OF FATAL M. PNEUMONIAE INFECTIONS 

The term and concept of atypical pneumonia derives from Reiman, who 

in 1938 described a series of cases in which patients had symptoms that differed 

from the typical symptoms of pneumococcal pneumonia (47). Differences 

included lack of response to penicillin, a longer duration of illness, and 

upper as well as lower respiratory tract symptoms. No bacterial pathogens 

were detected in these patients, and atypical pneumonia was attributed to pos-


Fig. 8. (A,B) Occlusive venous thrombosis with cellular debris and fibrin deposits 

in Mycoplasma pneumoniae pneumonia (phosphotungstic acid hematoxylin). 

sible viral infections. Finally, M. pneumoniae was identified as the etiological 

agent responsible for these cases of atypical pneumonia. Subsequently, atypical 

pneumonia became associated with other pathogens such as Chlamydia 

pneumoniae and Legionella that cause similar clinical presentations. 

M. pneumoniae accounts for 30–50% of community-acquired pneumonia 

and is one of the most frequent causes of pneumonia particularly among 

young adults (1,21,48–50). Approximately 20% of infected adult subjects are 

asymptomatic, the majority of cases (about 75%) develop minor respiratory

214 Tsokos 

tract diseases including pharyngitis and tracheobronchitis, and only 3–10% of 

infected subjects show serious clinical symptoms, mostly because of bronchopneumonia 

(49,51). 

In children under 5 years of age, M. pneumoniae infection is mostly 

nonpneumonic but in children between 5 and 15 years of age, the risk for M. 

pneumoniae pneumonia is highest (22). More than 30% of M. pneumoniae 

infections in this age group result in pneumonia (52). After a 2–3 week incubation 

period, the disease has an insidious onset composed of fever, malaise, 

headache, and cough. The latter, relatively constant and nonproductive, is the 

clinical hallmark of M. pneumoniae infection. The frequency and severity of 

cough increase over the next 1–2 days and the patient may become dyspnoic (1,22). 

As M. pneumoniae lacks a cell wall, this organism is not susceptible to 

penicillins or other antibiotics acting on this structure. The bacteriostatic antibiotics 

tetracycline and macrolides are effective in the treatment of M. 

pneumoniae infection (53,54). In children under the age of 8 years, tetracyclines 

are contraindicated and macrolides are the first choice (22). For detailed 

clinicopathological data on the symptoms and course of M. pneumoniae respiratory 

tract infections as well as diagnostic procedures and treatment, refer to 

the comprehensive clinical literature related to these topics. 

The forensic pathologist may be confronted with fatal M. pneumoniae respiratory 

tract infections presenting in the following constellations: (a) death of 

an individual who had consulted a physician prior to death but the correct diagnosis 

was not established because symptoms were misinterpreted for another 

disease and/or the applied diagnostic procedures were insufficient to achieve 

the correct diagnosis, (b) death of an individual who had consulted a physician 

prior to death and the correct diagnosis was established but treatment was inadequate, 

or (c) sudden, unexpected of an individual (usually occuring outside 

hospital) as the sequel of a rapidly progressive course of M. pneumoniae infection. 

To enable etiopathogenetic conclusions concerning the causal relationship 

between iatrogenic malpractice and fatal outcome of M. pneumoniae infection, 

the forensic investigation should ensure postmortem blood sampling 

as early as possible with subsequent serological determination of IgM or IgA 

antibody titers as well as an immediate autopsy to obtain native lung specimens 

for direct detection of M. pneumoniae using standard PCR. A thorough 

histological investigation as well as toxicological analysis is necessary to rule 

out concomitant diseases and/or intoxications, respectively, that may have 

contributed to fatal outcome. Intrinsic and extrinsic risk factors predisposing 

to the development of severe M. pneumoniae infection such as different kinds


of immunodeficiency syndromes, drug-induced immunosuppression, sickle cell 

disease, and pre-existing cardiopulmonary dysfunction (21,55,56) have to be 

considered carefully in the following expert witness. For the forensic examiner 

evaluating a questioned case of fatal M. pneumoniae infection, for example, 

under aspects of alleged medical malpractice, the most essential question is 

whether the fatal outcome could have been prevented in all probability by an 

early and right medical diagnosis and effective treatment. 

From the medicolegal point of view, the sudden, unexpected of an individual 

occuring outside hospital as the sequel of a rapidly progressive course 

of M. pneumoniae infection will have to be regarded as unavoidable in most 

cases. Nonetheless, data obtained from such instances are valuable because 

fatal respiratory tract infections with M. pneumoniae in individuals dying outside 

hospital are probably underestimated because testing for this organism is 

not often performed in the outpatient setting and such fatalities are probably 

highly underrepresented in the field of clinical pathology when compared to 

the forensic autopsy setting. 

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pneumoniaeantibodies in enzyme-linked immunosorbent assays and immunoblotting. 

J Clin Microbiol 23, 517–522. 

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Detection of specific IgM antibodies for the diagnosis of Mycoplasma pneumoniae 

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44. Waris ME, Toikka P, Saarinen T, Nikkaris S, Meurman O, Vainionpaa R, et al. 

(1998) Diagnosis of Mycoplasma pneumoniae pneumonia in children. J Clin 

Microbiol 36, 3155–3159. 

45. Sillis M (1990) The limitations of IgM assays in the serological diagnosis of Mycoplasma 

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pneumoniae infection. Clin Microbiol Infect 9, 263–273. 

47. Reiman HA (1938) An acute infection of the respiratory tract with atypical pneumonia. 

JAMA 26, 2377–2384.

218 Tsokos 

48. Mansel JK, Rosenow EC 3rd, Smith TF, Martin JW Jr. (1989) Mycoplasma 

pneumoniae pneumonia. Chest 95, 639–646. 

49. Clyde WA Jr. (1993) Clinical overview of typical Mycoplasma pneumoniae infections. 

Clin Infect Dis 17, Suppl 1: S32–S36. 

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Mycoplasma pneumoniae community-acquired pneumonia: a review of 101 hospitalized 

adult patients. Respiration 63, 261–266. 

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and azithromycin. Mayo Clin Proc 74, 613–634. 

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Med 12, 237–244.

Waterhouse–Friderichsen Syndrome 219 

9 

Pathological Features 

of Waterhouse–Friderichsen 

Syndrome in Infancy 

and Childhood 

Jan P. Sperhake, MD and Michael Tsokos, MD 

CONTENTS 

INTRODUCTION 

EXEMPLARY CASE STUDIES 

FATALITIES RESULTING FROM WATERHOUSE–FRIDERICHSEN SYNDROME 

MEDICOLEGAL ASPECTS 

CONCLUSIONS FOR THE PATHOLOGIST 

REFERENCES 

SUMMARY 

Between 1997 and 2002, five cases of fatal Waterhouse–Friderichsen 

syndrome (WFS) that occurred in infancy or childhood were investigated in 

our institute. The diagnosis of WFS was based on the following clinical as 

well as morphological criteria: (a) fulminant sepsis, (b) patchy purpura of the 

skin as a result of disseminated intravascular coagulation (DIC), and (c) bilateral 

hemorrhagic necroses of the adrenals. All cases had a very rapid clinical 

course of the disease (about 1 day or less). In two cases, postmortem microbiological 

examinations yielded meningococci as the infective agent. In both 

cases, the children examined underwent autopsy very early after death (5 hours 

and 24 hours, respectively) and did not receive antibiotics prior to death. In 

two other cases, meningococci were cultured in antemortem blood samples. 



219

220 Sperhake and Tsokos 

Macroscopically, the leptomeninges looked inconspicious in all five cases 

investigated. However, histology revealed meningitis to a mild or moderate 

degree in four cases. A previously clinically undiagnosed interstitial myocarditis 

was diagnosed in three cases by histological means, of which two 

cases showed Gram-negative diplococci in the myocardial lesions. For the 

pathologist investigating cases of WFS in infancy and childhood, the following 

points have to be emphasized: (a) when performing a medicolegal autopsy 

in a case of suspected WFS, the postmortem interval should be as short as 

possible (not longer than 24 hours) to provide the opportunity for an accurate 

microbiological examination of postmortem swabs; (b) in cases of WFS, meningitis 

does not seem to play a leading role for the clinical course of the disease 

or the actual cause of death; however, histologically a mild to moderate 

degree of meningitis is a frequent finding; (c) the presence of Gram-negative 

diplococci in myocardial lesions by histological means suggests that invasion 

of meningococci might be a causative factor for myocarditis in WFS; and (d) 

in accordance with the literature, myocarditis is often present in cases of WFS 

and therefore might be of importance for the clinical course. It is not certain 

yet if all children die from shock or DIC or rather, if myocarditis, leading to 

complete heart block, forward failure of the heart, or arrhythmia, is the actual 

cause of death. 

Key Words: Waterhouse–Friderichsen syndrome (WFS); infancy; 

childhood; Neisseria meningitidis; diplococci; meningitis; myocarditis; 

disseminated intravascular coagulation (DIC); postmortem microbiology; 

histopathology. 


Apoplexy of the adrenals in children was independently described by 

Waterhouse in 1911 and by Friderichsen in 1918 (1,2). The diagnosis of 

Waterhouse–Friderichsen syndrome (WFS) is mainly based on the combination 

of bilateral adrenal hemorrhage, purpura of the skin, and meningococcal 

infection (3). Cases with hemorrhage of only one adrenal have been reported, 

too (4). Various other germs, for example, pneumococci, Haemophilus 

influenzae, and streptococci, are also well-recognized as etiologic germs of 

WFS (5–14). Mortality of the syndrome is still considerably high. Whereas 

adult cases are rare, WFS occurs frequently in infancy and childhood. Because 

of the sudden onset of symptoms, short clinical course, and sudden, unexpected 

death, WFS is often a matter of medicolegal investigations. In this 

study, special focus is put on the pathology and postmortem microbiological 

findings as well as on medicolegal aspects of the disease.


2. EXEMPLARY CASE STUDIES 

2.1. Material and Methods 

Between 1997 and 2002, five cases of fatal WFS that occurred in infancy 

or childhood were investigated in our institute. The youngest child was 9 months 

old, the oldest 13 years of age. Three girls and two boys were affected. In all 

cases, diagnosis of WFS was based on the following clinical as well as morphological 

criteria: (a) fulminant sepsis, (b) petechial and/or patchy purpura 

of the skin as a result of disseminated intravascular coagulation (DIC), and 

(c) bilateral hemorrhagic necroses of the adrenals. 

The interval between death and autopsy ranged from a few hours to 6 days. 

Swabs for postmortem microbiological investigations were routinely taken 

from the leptomeninges, cerebrospinal fluid, and heart blood. In each case, all 

internal organs including the brain underwent a thorough histological examination 

using the following stainings: hematoxylin-eosin, perodic acid-schiff, 

Giemsa, Gram, and Elastica van Gieson. 

2.2. Case Reports 

2.2.1. Case 1 

A 9-month-old girl developed fever (40°C) and mild apathy 1 day before 

death. An antiphlogistic suppository was administered by the consulted pediatrician. 

In the early morning of the next day, a rash was observed by the mother. 

Death occurred shortly thereafter on the way to hospital. A medicolegal autopsy 

was performed 5 hours after death. Petechial and patchy hemorrhages in the 

skin (Fig. 1) and on the serous layers of the viscera as well as bilateral adrenal 

hemorrhage (Fig. 2) were present. Macroscopically, there were no signs of 

meningitis. At histological examination, mild meningitis with Gram-negative 

diplococci was observed. Postmortem swabs of the leptomeninges and postmortem 

blood cultures led to the cultural growth of Neisseria meningitidis 

serogroup B. The pediatrician was prosecuted but the proceeding was stopped 

because medical malpractice could not be proved against him. 

2.2.2. Case 2 

A 3-year-old boy fell ill with vomiting and fever up to 38.5°C. The consulted 

pediatrician prescribed an antiemetic. In the following night, the mother 

called the pediatrician on the phone because the boy developed red patchy 

spots on his trunk. On the phone, the doctor suspected urticaria and advised 

the mother to visit his consultation hour the following morning. One hour


Fig. 1. Case 1: 9-month-old girl with the typical rash of WFS that should not 

be confused with livores. 

Fig. 2. Case 1: In situ appearance of adrenal hemorrhage in the opened abdominal 

cavity after evisceration of liver, stomach, duodenum, pancreas, and spleen.


Fig. 3. Case 2: Cut surfaces of the adrenals showing diffuse hemorrhage. 

after the phone call, the worried mother brought the boy to a hospital where he 

died despite antibiotic therapy. Blood cultures grew meningococci (without 

subspecification). A medicolegal autopsy was conducted 6 hours postmortem. 

Major pathological findings were petechial and patchy hemorrhages of the 

skin of the trunk and the limbs (in part appearing like livores) and on serous 

layers, bilateral adrenal hemorrhage (Figs. 3 and 4), and lung edema. Macroscopically, 

there were no signs of meningitis. Histologically, the presence of 

mild meningitis could be established (Fig. 5). In cutaneous blood vessels, Gramnegative 

diplococci were detected. Microbiological investigations did not reveal 

the etiologic germ. Initially, the pediatrician was prosecuted but the legal 

measures were stopped later because it could not be ascertained beyond a reasonable 

doubt that the child could have been saved at the time of the consultation 

on the phone. 

2.2.3. Case 3 

A 13-year-old girl came home from school with fever up to 40°C. The 

family physician prescribed paracetamol. A few hours later, the mother recognized 

“red spots” all over the girl’s body. Shortly thereafter, the girl died 

despite resuscitation attempts. At autopsy, 24 hours postmortem, petechial 

hemorrhages on the girl’s skin and on the serous layers of the viscera were 

abundant. Both adrenals showed hemorrhagic necroses. Signs of circulatory 

shock were apparent. Histologically, interstitial myocarditis with phagocytized 

diplococci was detected (Fig. 6). There was no hint of any inflammatory


Fig. 4. Case 2: Panoramic view of an adrenal gland with fresh hemorrhagic 

necrosis of cortex and medulla (hematoxylin and eosin, original magnification 

× 20). 

Fig. 5. Case 2: Moderate meningitis showing a mixed cellular infiltrate 

(hematoxylin and eosin, original magnification × 100).


Fig. 6. Case 3: Interstitial myocarditis (hematoxylin and eosin, original magnification 

× 150). 

process in the leptomeninges neither by macroscopy nor by microscopical 

means. Postmortem swabs of the leptomeninges grew N. meningitidis 

serogroup C. 

2.2.4. Case 4 

A 2-year-old girl suffered from several episodes of vomiting that started 

1 day prior to death. Death occurred during sleep in the parental bed. On external 

examination, multiple hemorrhagic purpura of the skin were obvious. Autopsy 

was conducted 2 days postmortem. Autopsy revealed bilateral hemorrhages 

of the adrenals and patchy hemorrhages on the serous membranes. There were 

no macroscopical signs of meningitis. Histology showed interstitial myocarditis 

with focal necroses of muscle fibers. Gram-negative diplococci were abundant 

in the myocardial lesions, partly incorporated in macrophages (Fig. 7) 

and granulocytes. Mild meningitis with infiltration of granulocytes and lymphocytes 

and clusters of diplococci was also present. Postmortem microbiology 

failed to detect any germs. 

2.2.5. Case 5 

A 13-year-old boy was admitted to hospital with clinical signs of sepsis 

and DIC. A blood culture grew meningococi (without subspecification).


Fig. 7. Case 4: High-power view of myocardial lesions with arrows pointing 

at phagocytized diplococci (Giemsa, original magnification × 800). 

Despite antibiotic therapy, the boy died a few hours after admission. At medicolegal 

autopsy, performed 6 days postmortem, petechiae and purpura of the 

skin, bilateral adrenal hemorrhage, severe brain edema, and edema of the lungs 

were present. Histological examination revealed interstitial myocarditis and 

mild meningitis. Postmortem microbiology did not detect any germs. 

3. FATALITIES RESULTING FROM WATERHOUSE–FRIDERICHSEN 

SYNDROME 


WFS is a dramatic pediatric emergency that carries a high mortality. 

Whereas the mortality rate of meningococcal disease and meningococcemia 

(without WFS) ranges from 10 to 30% (15–18), the mortality rate rises up to 

95% in WFS (19–21). It has to be taken into account that mortality rates are 

often calculated on the basis of hospitalized children and do not consider those 

fulminant cases that never reach the hospital. The fatalities studied here have to 

be considered typical for the disease in many respects. All cases have in common 

that each individual presented with a fulminant clinical course of about 

24 hours or less. Only two of the children reached the hospital. Three out of the


five children saw a pediatrician or a family physician prior to death in an earlier 

state of the disease, a fact that led to legal repercussions in two of the cases. 

3.2. Specific Aspects 

3.2.1. Etiologic Germs 

According to the literature, more than 80% of the cases of WFS are caused 

by meningococci (22). It is likely that all of our cases were caused by meningococci. 

In Cases 1 and 3, postmortem microbiological investigations yielded 

meningococci as the infective agent. In Cases 2 and 5, meningococci were 

cultured in antemortem blood samples. In Case 4, Gram-negative diplococci 

were detected by histological means in the myocardium and leptomeninges. 

Taking a closer look at the cases with a positive outcome of postmortem microbiology, 

it becomes obvious that the individuals examined underwent autopsy 

very early after death (5 hours and 1 day, respectively) and did not receive 

antibiotics prior to death. The cases with negative postmortem microbiological 

results either did receive antibiotics prior to death (Cases 2 and 5) or the 

postmortem interval was 2 days or more (Cases 4 and 5), which is probably 

too long a time interval for the fragile and fastidious meningococci. This observation 

suggests the importance of an immediate autopsy, at least in cases without 

preceding antibiotic therapy. Postmortem swabs should be taken very 

carefully under sterile precautions (23). 

3.2.2. Meningitis 

Our results point to the leptomeninges as a promising tissue for the postmortem 

microbiological detection of meningococci. This was somewhat surprising 

because in none of the cases was meningitis diagnosed by gross 

examination at autopsy. However, histology revealed meningitis to a mild or 

moderate degree in all cases with the exception of Case 3. Regardless of this, 

postmortem swabs of the leptomeninges grew meningococci in this case. In 

three cases, diplococci were detected by histology in the leptomeninges. Therefore, 

the leptomeninges seems to be a regular target of meningococci in cases 

of WFS without having a major clinical significance. This corresponds to clinical 

observations of WFS cases (24,25). Meningococcemia without clinical 

signs of meningitis seems to carry a particularly high mortality (26). Encephalitis 

or intracerebral vasculitis was not observed in our cases. 

3.2.3. Myocarditis 

A case report by Detsky and Salit described a 41-year-old man with meningococcemia 

who died of a complete heart block (27). The authors observed


myocarditis with focal necroses of the conduction system on the histological 

level. It has to be emphasized that we found prior clinically undiagnosed interstitial 

myocarditis in our series by histology in Cases 3, 4, and 5, a finding 

that is well in line with Böhm, who reported on 10 cases of WFS, 9 of which 

displayed interstitial myocarditis with vasculitis (22,28). With the exception 

of one case, myocarditis had not been diagnosed prior to death in the study by 

Böhm. He concluded that myocarditis (and not shock) might be the leading 

cause of death in many cases of WFS. He suspected endotoxinic vascular damage 

to be the cause of myocarditis rather than a direct invasion of meningococci 

into the myocardial tissue. According to the observations by Böhm, we 

found the infiltrate in the myocardial lesions to be composed of granulocytes, 

lymphocytes, and mast cells. These lesions were restricted to the left ventricle. 

However, we did not observe any hints toward an accompanying vasculitis 

in any of our cases. In contrast to Böhm, who emphasized that he did not 

find any bacteria in the myocardium, we detected Gram-negative diplococci 

in two of our cases. In both cases, intra- and extracellularly Gram-negative diplococci 

were visible by light microscopy. This finding shows that direct invasion 

of Gram-negative diplococci in the heart does play a role in the pathogenesis of 

myocarditis in WFS. Although to some extend this stands in contradiction to the 

clinical observations of other authors, who state that electrocardiogram changes 

are rare in cases of WFS (29), we agree with Böhm and Detsky (22,27) that 

myocarditis is responsible for the poor outcome in many WFS cases. 

4. MEDICOLEGAL ASPECTS 

In fatalities resulting from WFS in infancy and childhood, almost inevitably 

the question arises whether the child could have been saved if there was 

an earlier diagnosis (19). Especially if a physician has been consulted in the 

beginning of the disease, medical malpractice seems to be obvious for the 

parents. Because of the rapid clinical course of the disease and the rather 

unspecific findings in its beginning, it can be impossible even for the clinical 

professional to distinguish the disease from a common cold or an enteritis. 

Even if medical help is sought in an early stage of the disease, it is impossible 

to predict the outcome in an individual case (30). At the time when the rash is 

present, it is often too late to save the child’s life. However, in Case 2 the 

pediatrician felt comfortable with the diagnosis of urticaria without even having 

seen the child, which is definitely unacceptable from the medicolegal point 

of view. 

The (forensic) pathologist should not forget to protect her- or himself. 

Performing an autopsy on a child with WFS is a close contact and can put the


medical staff at a high risk for infection. Therefore, a mask and eye protection 

are obligatory. After autopsy, a postexposition chemoprophylaxis, for example, 

a single dose of 500 mg Ciprofloxacin, is strongly recommended by the Centers 

for Disease Control and Prevention (31). 

5. CONCLUSIONS FOR THE PATHOLOGIST 

When performing a medicolegal autopsy in a case of suspected WFS, the 

postmortem interval should be as short as possible (not longer than 24 hours) 

to provide the opportunity for an accurate microbiological examination of 

postmortem swabs. In cases of WFS, meningitis does not seem to play a leading 

role for the clinical course of the disease or the actual cause of death; 

however, histologically a mild to moderate degree of meningitis is a frequent 

finding. The presence of Gram-negative diplococci in myocardial lesions by 

histological means suggests that invasion of meningococci might be a causative 

factor for myocarditis in WFS. In accordance with the literature, myocarditis 

is often present in cases of WFS and therefore might be of importance 

for the clinical course; it is not certain yet if all children die from shock or DIC 

or rather if myocarditis, leading to complete heart block, forward failure of 

the heart, or arrhythmia, is the actual cause of death. 

REFERENCES 

1. Waterhouse R (1911) A case of suprarenal apoplexy. Lancet 1, 577. 

2. Friderichsen C (1918) Nebennierenapoplexie bei kleinen Kindern. Jahrb Kinderheilk 

87, 109. 

3. Harris P, Bennett A (2001) Waterhouse–Friderichsen syndrome. N Engl J Med 345, 841. 

4. Mühlig K, Theile J, Dalitz E (1995) Einseitige Nebennierenblutung–ein Waterhouse 

Friderichsen-Syndrom? Ultraschall Med 16, 293–296. 

5. Külz J, Kroll O (1984) Zur aktuellen Problematik des sogenannten Waterhouse– 

Friderichsen-Syndroms im Kindesalter. Kinderärztl Praxis 52, 3–15. 

6. Ryan CA, Wenman W, Henningsen C, Tse S (1993) Fatal childhood pneumococcal 

Waterhouse-Friderichsen Syndrome. Pediatr Infect Dis J 12, 250–251. 

7. Tsokos M (2003) Fatal Waterhouse–Friderichsen syndrome due to Ewingella 

americana infection. Am J Forensic Med Pathol 24, 41–44. 

8. Mirza I, Wolk J, Toth L, Rostenberg P, Kranwinkel R, Sieber SC (2000) Waterhouse– 

Friderichsen syndrome secondary to Capnocytophaga canimorsus septicemia and 

demonstration of bacteremia by peripheral blood smear. Arch Pathol Lab Med 124, 

859–863. 

9. Jacobs RF, Hsi S, Wilson CB, Benjamin D, Smith AL, Morrow R (1983) Apparent 

meningococcemia: clinical features of disease due to Haemophilus influenzae and 

Neisseria meningitidis. Pediatrics 7, 469–472.


10. Lineaweaver W, Franzini D, Dragonetti D, McCarley D, Rumley T (1986) 

Haemophilus influenzae meningitis and Waterhouse–Friderichsen syndrome in an 

adult. South Med J 79, 1034–1036. 

11. McKinney WP, Agner RC (1989) Waterhouse–Friderichsen syndrome caused by 

Haemophilus influenzae type b in an immunocompetent young adult. South Med J 

82, 1571–1573. 

12. Ip M, Teo JG, Cheng AF (1995) Waterhouse–Friderichsen syndrome complicating 

primary biliary sepsis due to Pasteurella multocida in a patient with cirrhosis. J Clin 

Pathol 48, 775–777. 

13. Agraharkar M, Fahlen M, Siddiqui M, Rajaraman S (2000) Waterhouse–Friderichsen 

syndrome and bilateral renal cortical necrosis in meningococcal sepsis. Am J Kidney 

Dis 36, 396–400. 

14. Karakousis PC, Page KR, Varello MA, Howlett PJ, Stieritz DD (2001) Waterhouse– 

Friderichsen syndrome after infection with group A streptococcus. Mayo Clin Proc 

76, 1167–1170. 

15. Busund R, Straume B, Revhaug A (1993) Fatal course in severe meningococcemia: 

clinical predictors and effect of transfusion therapy. Crit Care Med 21, 1699–1705. 

16. Cremer R, Leclerc F, Martinot A, Sadik A, Fourier C (1997) Adverse outcome in 

children with meningococcemia. J Pediatr 131, 649–651. 

17. Havens PL, Garland JS, Brook MM, Dewitz BA, Stremski ES, Troshynski TJ (1989) 

Trends in mortality in children hospitalized with meningococcal infections, 1957 to 

1987. Pediatr Infect Dis J 8, 8–11. 

18. Sørensen HT, Steffensen FH, Schønheyder HC, Nielsen GL, Hansen I, Madsen KM, 

et al. (1998) Trend in incidence and case fatality of meningococcal disease over 16 

years in Northern Denmark. Eur J Clin Microbiol Infect Dis 17, 690–694. 

19. Gradaus F, Klein RM, von Giesen H-J, Arendt G, Heintzen MP, Leschke M, et al. 

(1999) Klinischer Verlauf und Komplikationen der Meningokokkensepsis. Med Klin 

94, 633–637. 

20. Mok Q, Butt W (1996) The outcome of children admitted to intensive care with 

meningococcal septicaemia. Intensive Care Med 22, 259–263. 

21. Schroten H (2000) Meningokokkeninfektionen. In: Deutsche Gesellschaft für 

pädiatrische Infektiologie e.V., ed., Infektionen bei Kindern und Jugendlichen, 3rd 

ed. Futuramed, München, pp. 437–442. 

22. Böhm N (1982) Adrenal, cutaneous and myocardial lesions in fulminating 

endotoxinemia (Waterhouse–Friderichsen syndrome) Pathol Res Pract 174, 92–105. 

23. Tsokos M, Püschel K (2001) Postmortem bacteriology in forensic pathology: diagnostic 

value and interpretation. Legal Med 3, 15–22. 

24. Rosenberg H, Bortolussi R, Gatien JG (1981) Rash resembling anaphylactoid purpura 

as the initial manifestation of meningococcemia. Can Med Assoc J 15, 179–180. 

25. Vos GD, Wiegman A, Romijn JA, Meurs AM, Bruins-Stassen MJ, Bijlmer RP, et al. 

(1989) Not meningitis but septic shock is the killer in acute meningococcal disease. 

Ned Tijdschr Geneeskd 133, 772–775. 

26. Riordan FAI, Marzouk O, Thomson APJ, Sills JA, Hart CA (1995) The changing 

presentations of meningococcal disease. Eur J Pediatr 154, 472–474.


27. Detsky AS, Salit IE (1983) Complete heart block in meningococcemia. Ann Emerg 

Med 12, 391–393. 

28. Böhm N (1978) Waterhouse-Friderichsen-Syndrom: Morphologische Befunde und 

Aspekte zur Pathogenese. Verh Dtsch Ges Path 62, 449–455. 

29. Schütte B (1978) Waterhouse-Friderichsen-Syndrom—Klinischer Verlauf und 

Gerinnungsstatus. Verh Dtsch Ges Path 62, 442–448. 

30. Dashefsky B, Teele DW, Klein JO (1983) Unsuspected meningococcemia. J Pediatr 

102, 69–72. 

31. CDC (1997) Control and prevention of meningococcal disease. Recommendations 

of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm 

Rep 46 (No. RR-5), 1–10.

Accidental Autoerotic Death 233 

Death Scene Investigation

234 Seidl


10 

Accidental Autoerotic Death 

A Review on the Lethal Paraphiliac Syndrome 

Stephan Seidl, MD 

CONTENTS 

INTRODUCTION 

“PARAPHILIA” IN DSM–IV AND ICD–10 

PRACTICES OF AUTOEROTICISM 

A COMPARISON OF AUTOEROTICISM IN MALES AND FEMALES 

MEDICOLEGAL ASPECTS OF ACCIDENTAL AUTOEROTIC DEATH: THE DEMARCATION 

FROM SUICIDES AND HOMICIDES 

REFERENCES 

SUMMARY 

Accidental autoerotic death (AAD) is defined as a solitary, accidental 

death caused by a lethal paraphilia including hanging, strangulation, invert 

suspension, plastic-bag asphyxiation, electrophilia, and anesthesiophilia. Young 

white men comprise the largest group of victims, whereas the number of female 

AADs reported in literature is extremely small. In both sexes, AAD is 

most often seen in young to middle-aged adults. Practitioners tend to utilize a 

great range of elaborate devices and props, often designed to cause real or 

simulated pain, with pornographic material and evidence of cross-dressing 

and fetishism like intimate feminine garments. The absence of typical props 

in the majority of female AADs may impede the differentiation of AADs from 

suicides or homicides. To exclude the possibility of sexual homicide or suicide, 

investigators must establish the presence of key death scene characteristics 

before the death can be appropriately classified as an autoerotic fatality. 

The location elected for the autoerotic performance is usually secluded, often 

with evidence of repeated autoerotic behavior. Bondage is common, and death 



235

236 Seidl 

scene investigators must ensure that any bondage could have been secured by 

the deceased himself. Padding of the rope, especially in neck ligatures, to prevent 

subsequently detectable abrasions or bruises is regularly found. Because 

of the accidental nature of AAD, a failed rescue mechanism is usually evident. 

A lack of features of suicide with no antemortem evidence of suicidal 

ideation or depression is diagnostic for AAD; an overt suicide note is usually 

not present. Thorough investigations regarding life and environment of the 

victim and the circumstances of death may be effective in the determination 

of the manner of death in equivocal cases. Twelve general behavioral characteristics 

that investigators can look for to help them identify autoerotic death 

scenes are listed. 

Key Words: Accidental autoerotic death (AAD); autoerotic asphyxia; 

hypoxyphilia; lethal paraphiliac syndrome; paraphilia; asphyxiophilia; 

anesthesiophilia; electrophilia. 


Sexual “normality” and “deviancy” vary with the accepted moral attitudes 

of the particular society and with the particular times in which these 

societies are living. Inducing cerebral hypoxia for sexual gratification has been 

described by anthropologists and literates for centuries (1–6). Pressure on the 

neck during sexual activity was a common practice of Eskimos and Southeast 

Asians (1,4,5,7,8). Prostitutes have been experts in sexual asphyxiation for a 

long time, and during the Victorian era in London, men could satisfy their 

sexual urges through controlled hangings in the “Hanged Men’s Club” (6,9). 

Both the classical writer Peter Anthony Motteux and Frantisek Koczwara, 

composer of “The Battle of Prague,” died in the 18th century because of sexual 

asphyxia assisted by a prostitute (10,11). The death of Koczwara led to the 

suggestion of the term “Koczwarraism” for behavior utilizing asphyxial augmentation 

for the sexual response (2,12). Despite a strong tendency toward 

sexual repression in Western cultures, as early as in 1791, the year of 

Koczwara’s death, the Marquis de Sade described altered sexual behavior with 

self-induced asphyxia for the purposes of sexual gratification in his book 

Justine (4). 

Autoerotic behavior is any act that is sexually self-gratifying. An accidental 

autoerotic death (AAD) may occur during autoerotic behavior in which 

a device, apparatus, prop, chemical, or behavior that is engaged to enhance 

sexual stimulation causes death, if there is failure of the various self-rescue 

mechanisms that are specifically aimed at preventing such an occurrence 

(2,3,13–15). Scientific analyses of autoerotic deaths were not published in the


medicolegal literature until the 1920s (14,16–20). The first extensive series of 

50 AAD cases was published by Weimann (21). Forensic pathologists rapidly 

recognized the difficulty of distinguishing between AADs, suicides, and homicides, 

and an increasing number of case reports was published in the following 

decades. 

As the vast majority of autoerotic deaths are asphyxial deaths resulting 

from asphyxia due to hanging, strangulation, injurious agents, or other causes 

of asphyxia, autoerotic asphyxial deaths were categorized as typical cases in 

the 1960s and 1970s, and autoerotic deaths without asphyxia were denoted as 

atypical cases. Because of this definition and in contrast to the suggestions of 

Schwarz and Weimann (14,21), many cases that should have been classified 

as natural deaths during autoerotic activity were labeled and sometimes published 

as atypical autoerotic deaths, only because of the presence of associated 

unusual props (14,20,22–26). The case report “Vacuum Cleaner Use in 

Autoerotic Death” by Imami and Kemal, for example, deals with a natural 

death (myocardial infarction) during autoerotic activity and not with an AAD 

(22). Byard and Bramwell consequentially have issued a warning of an 

“overdiagnosis” of AADs and proposed to apply the broad term autoerotic 

death only to accidental deaths that occur during individual, usually solitary, 

sexual activity in which some type of apparatus that was used to enhance the 

sexual stimulation of the deceased caused unintended death (23). Furthermore, 

they suggested applying the term autoerotic asphyxial death to fatal episodes 

that result from asphyxia, thus maintaining the distinction from rarer cases 

involving other quite different mechanisms such as electrocution. In 1995, 

Behrendt and Modvig proposed a new classification of autoerotic deaths that 

focused less on the presence of asphyxiation but was built on the classification 

of paraphilias, an unusual act or bizarre imagery necessary for sexual 

gratification (27,28): persons who engage in paraphilic behavior may “overdo” 

the potentially lethal paraphilia needed for their sexual arousal and orgasm. In 

fatal cases, the lethal paraphilia, like asphyxiophilia, masochism, electrophilia, 

or anesthesiophilia, is the unintended and direct cause of death. Therefore, an 

AAD may be diagnosed if it is solitary, accidental, and caused by any lethal 

paraphilia (Table 1). According to this definition, the subclassification into 

typical and atypical AADs depends on the presence or absence of accompanying 

non-lethal paraphilia and/or props (29): in cases of typical AAD, nonlethal 

paraphilia and/or props like pornography, vibrators, or other phallic objects 

are present, but not in atypical cases. In this context, props are personal paraphernalia 

assumed to have been used actively or passively for sexual imagination 

and arousal and not for bondage, fetishism, or transvestism (Table 2) (27, 29).

238 Seidl 

Table 1 

Lethal Paraphilia 

Paraphilia Examples and variations 

Sexual asphyxiophilia Neck ligatures (hanging, strangulation) 

Invert suspension 

Complex ligatures 

Restrictive bondage (wrapping, cocooning) 

Face mask asphyxiation (gas, diving, anesthetic mask) 

Plastic-bag asphyxiation 

Mouth gag asphyxiation including sealing of the mouth 

Chest compression 

Immersion 

Sexual anesthesiophilia Nitrous oxide 

Ketamine 

Ether 

Chloroform and other halogenated hydrocarbons (i.e., 

fluorocarbons) 

Aerosols like glue spray (e.g., toluene) 

Gasoline, propane, butane sniffing 

Drugs (i.e., amphetamine, cocaine) 

Sexual electrophilia Direct electrical wiring from house current outlets, from 

electrical devices (television set, table lamp), or from 

low-voltage devices (e.g., toy train transformer) to penis, 

rectum, and/or nipples 

Sexual masochism Insertion of foreign bodies such as oversize or unclean 

fetishized objects into orifices. Apparatus to induce 

peritoneal pain with knifes. 

Note. Modified according to ref. 44 

The definitions of Byard and Bramwell as well as Behrendt and Modvig both 

seem to be well qualified for the distinction between fatal cases during autoerotic 

practice and autoerotic deaths, thus avoiding an overdiagnosis of autoerotic deaths. 

2. “PARAPHILIA” IN DSM–IV AND ICD–10 

As early as in the year 1886, the psychiatrist von Krafft-Ebing published 

his phenomenology of sexual behavior called Psychopathia sexualis (30). He 

classified homosexuality, sadism, and masochism as well as fetishism as 

“paresthesias” of sexual perception and as “perversions” of the sex drive. In 

1940, the psychologist Clifford Allen eschewed the pejorative term “perver-


Table 2 

Nonlethal Paraphilia (NLP) and Props Occurring in Typical AADs 

NLP/prop Example 

Nonlethal Fetishism Plastic, rubber, or leather attire, etc. 

paraphilia Transvestism Cross-dressing, cosmetics 

Bondage (physically bound 

or restrained with handcuffs 

or chains) 

Props Oral fetish Female underwear placed on or in 

(personal the mouth 

paraphernalia) Penis fetish Female undergarments 

Other fetishes Anal stimulation devices, vibrators, 

and other phallic objects; 

horsewhip, etc. 

Pornography Photographs, videotapes 

Mirror 

Video camera 

Note. Modified according to ref. 27. 

sion” and called sexualities departing from ordinary heterosexuality “paraphilias” 

(31). The most recent fourth edition of the handbook of the American Psychiatric 

Association, the Diagnostic and Statistical Manual of Mental Disorders 

(DSM–IV) (32), defines “paraphilia” as recurrent, intense sexual urges, fantasies, 

or behaviors that involve unusual objects, activities, or situations and cause 

clinically significant distress or impairment in social, occupational, or other 

important areas of functioning. Eight numerically coded paraphilias are listed: 

pedophilia (302.2), transvestic fetishism (302.3), exhibitionism (302.4), fetishism 

(302.81), voyeurism (302.82), sexual masochism (including automasochism, 

302.83), sexual sadism (302.84), frotteurism (302.89), and “paraphilia not otherwise 

specified” (302.9). Autoerotic asphyxia is discussed under 302.83 

Hypoxyphilia involves sexual arousal such that the person produces 

oxygen deprivation by means of a noose, ligature, plastic bag, mask, 

chemical (often a volatile nitrite that produces temporary decrease 

in brain oxygenation by peripheral vasodilatation), or chest compression, 

but allows him/herself the opportunity to escape asphyxiation 

prior to the loss of consciousness (6,32). 

The 10th revision handbook of the World Health Organization, the International 

Classification of Mental and Behavioral Disorders (ICD–10), does

240 Seidl 

not use the term “paraphilia,” but paraphrases sexual deviations with the term 

“Disorders of Sexual Preference” (33). In this classification, seven numerically 

coded disorders are listed: fetishism (F 65.0), fetishistic transvestism 

(F65.1), exhibitionism (F 65.2), voyeurism (F65.3), pedophilia (F65.4), and 

sexual sadism and masochism (F65.5). F 65.6 allows one to code the combination 

of several disorders in one person. F 65.8 (“Other disorders of sexual 

preference”) subsumes disorders like frotteurism, zoophilia (sodomism), telephone 

scatologia, necrophilia, and coprophilia, and the use of (self-)strangulation 

for intensifying sexual excitement. Regarding autoerotic practices, it is 

exemplified that “masturbatory rituals of various kinds are common, but the 

more extreme practices, such as the insertion of objects into the rectum or 

penile urethra, or partial self-strangulation, when they take the place of ordinary 

sexual contacts, amount to abnormalities.” As many cases of autoerotic 

deaths show combined aspects of masochism, transvestism, or transvestic 

fetishism, which disclose different degrees of sexual identification that are 

fundamental in reaching orgasm, the correct grading of AADs is difficult in 

both classifications, DSM–IV and ICD–10 (3,34). For these combined paraphilic 

cases, the term “multiplex paraphilias” was suggested (28, 35). 

3. PRACTICES OF AUTOEROTICISM 

3.1. Sexual Asphyxia (Asphyxiophilia) 

Most cases of sexual asphyxiophilia occur with both heterosexual and 

homosexual partners and not in solitary sexual activity (2,36). However, the 

vast majority of autoerotic accidents and deaths are of an asphyxial nature 

(4,5,27,37). Of 46 AAD cases in Denmark, 38 were asphyxial deaths, 53% of 

these a result of hanging, 5% each owing to strangulation and invert suspension, 

and 37% resulting from plastic-bag asphyxiation (27). In accordance with this 

study, most authors reported a preponderance of hanging (17,20–22,38–41). 

The basic mechanism of all sexual asphyxias is the production of cerebral 

hypoxia in order to induce a semihallucinogenic and euphoric state and 

thus to heighten the sexual response (5,14,21,28,42,43). The three general 

categories of asphyxial autoerotic deaths are strangulation, suffocation, and 

chemical asphyxia by anesthetic agents and volatile substances (36,44). The 

most common technique to gain cerebral hypoxia is strangulation including 

hanging (6). Unconsciousness may be produced in less than 10 seconds with 

only 7 pounds of pressure on the common carotid artery (45,46). Independent 

of the particular technique, the practitioners often use protective padding like 

scarfs or towels to avoid abrasions or grooves. In some cases of hanging, the


rope, dog collar, or chain is attached to some overhead support like ceiling 

joists, pipes, or perches, and the tension of the noose is gained by bending the 

legs and plumping against the pull of the rope (4,5,23,47,48). 

According to the definition as an accident, an intended free hanging (“typical 

hanging”) without contact of any part of the body with various objects like 

floor, bed, or chair is never seen in AADs, whereas all variations of so-called 

atypical (incomplete) hanging were portrayed. In one case reported by 

O’Halloran et al., the rope was hooked on the raised shovel of a backhoe tractor. 

The practitioner had constructed a kind of remote control with a broom 

stick, and thus was able to raise or lower the hydraulic shovel (49). The loss of 

consciousness secondary to cerebral hypoxia can result in a loss of balance, 

loss of the control position, and, finally, partial or complete suspension. Risse 

and Weiler communicated a case in which the fatal outcome of an autoerotic 

hanging was videotaped by the practitioner himself (50). The man wore a long 

nightgown, a bra, earrings, and a woman’s wig. He sat down on an office 

chair, sealed his mouth with six strips of duct tape, tied his feet to the chair, 

put his head in an open loop mounted at the ceiling, and tied his hands behind 

his back. During the next 25 seconds, the loop was tightened by turning the 

head and moving the chair, and then the practitioner tightened the rope again 

by pressing the hand lever of the seat height adjustment. During the next 

55 seconds, the man got more and more agitated, head and body were moved 

back and forth jerkily. Having acquitted himself of the handcuffs, he tried to 

grab at the hand lever of the seat height adjustment again, but abruptly lost 

consciousness. The unconscious victim reared up in a cramp, and in the following 

2 minutes deep inspiratory movements occurred, whereby the body 

repeatedly abutted upon the chair. During the following 6 minutes until the 

exitus, several motionless phases occurred, each lasting 10–45 seconds, with 

an intermediate rearing-up of the body. The video underlines impressively the 

abrupt loss of consciousness, which makes it impossible to use existing selfrescue 

mechanisms. 

Other practitioners pass the rope over a support and either attach a weight 

to the free end, which produces tension (36), or join the free end to their wrists 

or ankles and tighten the rope by movement of their extremities (4,51). In 

many more cases, fixed nooses are placed around the neck, often joined to one 

or both wrists or ankles, sometimes with additional bondage that encircles the 

genitals (3,21,29,42,52,53). If the legs or the arms are extended, the noose 

around the neck is tightened and the genitals are stimulated. On the other hand, 

the compression will cease as soon as muscular tension on the free end of the 

noose is relaxed (3,36). However, the ability of the practitioner to escape injury

242 Seidl 

or death may be seriously impaired by his already altered euphoric and hypoxic 

state of mind (3,23,34,52). Moreover, a sudden exaggerated bilateral pressure 

on the carotid sinuses may result in an immediate loss of consciousness (3). In 

one of this author’s cases, a 44-year-old man who suffered from epilepsy with 

approximately one attack per week was found dead on the floor of the living 

room (Fig. 1A,B). The apartment was locked from inside. The man was wearing 

a brassiere and a slip with traces of an obvious emission of semen. He had 

placed an open noose of a silken scarf around his neck, and the free ends were 

joined to his wrists. The scarf decussated anterior and made it possible for the 

practitioner to open the noose simply by moving his wrists each to the opposite 

side. Next to the body, a pair of scissors was found on the floor. The skin 

of the head and the neck above the scarf showed a massive congestion. Autopsy 

revealed the typical signs of an asphyxial death. Because of the autopsy finding 

of a tongue bite, it was discussed that the man might have suffered an 

epileptic attack during his autoerotic activity and, therefore, was not able to 

relax the noose or to grab at the scissors. 

The frequent presence of self-rescue mechanisms like knives show that 

the practitioners are usually well aware of the possibility of accidental injury 

or death (23,40,54). Nevertheless, many deaths occur, usually as a result of an 

accidental fall while suspended from the neck during sexual arousal, or an 

overzealous application of neck ligatures (42). In one of our cases, a 43-yearold 

man was found naked on the floor of his living room, which was locked 

from inside. Some pornographic material as well as female underwear was 

found around the body. The man wore two necklets and had a studded leather 

belt around his neck. The belt buckle was locked and no rescue mechanisms 

were present. At autopsy, a single horizontal rope mark was seen, reflecting 

exactly the studs of the belt (Fig. 2A,B). Because of the signs of death from 

suffocation and the absence of natural diseases, it has to be assumed that the 

victim lost consciousness during his autoerotic activities and was no longer 

able to open the belt buckle. 

Besides neck ligatures, and sometimes combined with them (21,46), there 

is a great variety of devices to induce hypoxia such as mouth gags, anesthetic 

masks, adhesive tapes, or plastic bags with or without additional anesthetics 

like ether or aerosols (see Subheading 3.2., Anesthesiophilia). In another of 

our cases, a 39-year-old man was found dead in his locked bedroom, lying 

supine in his bed. The man wore a respirator mask, which was firmly fixed to 

his head by elastic bands. A rubber balloon was attached to the free end of a 

tube, which was connected with the mask (Fig. 3A,B). The man wore a red


Fig. 1. (A,B) AAD of a 44-year-old man who suffered from epilepsy. Around 

the neck is a silken scarf with an open noose; the free ends are joined to the 

wrists. The vasculature of the skin of head and neck above the scarf is congested. 

Autopsy revealed an asphyxial death. The autopsy finding of a tongue 

bite led to the assumption that an epileptic attack might have foiled the escape 

mechanisms in this case.

244 Seidl 

Fig. 2. AAD of a 43-year-old man by strangulation with a studded leather 

belt. (A) Belt. (B) Single horizontal rope mark, reflecting exactly the studs of 

the belt. 

rubber pinafore tied up with a rubber band. A massage vibrator located by the 

rubber band above the genitals, was still running when the man was found. 

Another technique of asphyxiophilia is to wrap the body tightly in sheets 

of plastic (Fig. 4A,B), blankets, or chains (2,3,7,40,55–58). One of the first 

AAD cases portrayed by Weimann involved a 49-year-old man who died due 

to body compression by chest and abdominal ligatures (19). A lethal compression 

of the body with a high abdominal ligature, involving a suspension apparatus, 

has been described by Thibault et al. (40,59). Madea portrayed the AAD


Fig. 3. AAD of a 39-year-old man. (A) The man wore a respirator mask, 

which was firmly fixed to his head by elastic bands. (B) A rubber balloon was 

attached to the free end of a tube, which was connected with the mask. The 

man wore a red rubber pinafore tied up with a rubber band. A massage vibrator 

was located by the rubber band above the genitals.

246 Seidl 

Fig. 4. (A,B) AAD of a 38-year-old man who was found dead hanging in a 

plastic sack. The rope for hanging was fixed to a permanent hook on the ceiling. 

The cause of death was atypical strangulation owing to a neck ligature 

which was actually a dog collar. (Courtesy of Dr. Michael Tsokos, Hamburg, 

Germany.) 

of a 56-year-old man who was found dead in a head-down position, hanging 

in a sack (60,61). Death was caused by asphyxia owing to compression of the 

chest and by insufficient blood supply to the heart caused by the head down 

position. Minyard communicated an AAD of a 34-year-old security guard who 

had wrapped his complete body with clear adhesive tape (7). A snorkel apparatus 

protruded from one end of the wrapping. Within his cocoon, the victim 

was found nude except for a rubber hat on his head. The snorkel device had 

become detached from the face and mouth area where it had been inserted. In 

the left hand of the victim, a pocket knife for use as an escape mechanism was 

found. The knife blade protruded through the wrapping over the man’s left 

hand. O’Halloran and colleagues (49) reported an interesting case, where the 

victim had tied his ankles to a segment of pipe so that his legs were spread. A


yoke was attached to the center of the pipe, which was attached by a chain 

above the front loader bucket of a tractor. Fully raising the hydraulic bucket 

caused complete suspension of the inverted body by the ankles. Two ropes led 

from the victim to the control lever on the tractor for raising and tilting the 

bucket. The man had placed a piece of lumber next to his body under the tractor 

scoop as a safety measure to prevent it from drifting down. When the victim 

was found, the tractor engine was stalled, the board was snapped, and the 

scoop rested on the back of the body. The man died of positional asphyxiation 

by chest compression. 

Another bizarre case of a fatal chest compression was reported by 

Rothschild and Schneider (62). A 19-year-old man was found dead in his room, 

tied to his bed, and wearing a compressed-air overall as used by jet-fighter 

pilots to improve the venous blood flow (Fig. 5A,B). The overall was connected 

to a 12-V-compressor by a flexible pressure tubing. The man wore a 

motorbike helmet, and under his overall had on an unitard and several face 

masks. The cause of death was an extensive chest compression by the overall, 

which was overfilled with air. Schwarz (14) and Sivaloganathan (63) reported 

cases of autoerotic submersion, and Du Chesne communicated a case of drowning 

during autoerotic activity, where the water might have taken the role of a 

fetish (20). 

3.2. Anesthesiophilia and AAD by Other Chemical Agents 

The inhalation of anesthetics, inhalants, and solvents mostly occurs in 

combination with plastic-bag asphyxiation, and sometimes with other appropriate 

devices like gas masks, anesthetic masks, diving masks, or even anesthetic 

machines. Similar to so-called “glue sniffing” of solvents for adhesives 

like toluene, the practitioners may simply inhale the substances (21) or often 

soak a rag with a solvent, and then insert the rag in the mouth to inhale the 

fumes, which is consistent with a practice known as “huffing” (64). In these 

cases, the oral prop becomes the lethal paraphilia (27). The substances that are 

used, like glue spray, butane, propane, xylene, benzene, or gasoline, are obtainable 

at most everywhere, and the inhalation of anesthetic gases such as ether 

or chloroform for their euphoric and narcotic effects has been described for 

many years (14,21,22,54,65). Jones et al. reported an AAD with plastic-bag 

asphyxiation in combination with inhaled glue spray (55), and Gowitt and 

Hanzlick described two cases with an involvement of 1-1-1-trichloroethane, a 

compound commonly found in typewriter correction fluid (65). Weimann and 

Schellmann reported AADs involving other halogenated hydrocarbons like 

ethyl chloride (21) and carbon tetrachloride (54), and Hazelwood as well as

248 Seidl 

Fig. 5. Fatal asphyxiophilia of a 19-year-old man who wore a compressedair 

overall as used by jet-fighter pilots to improve venous blood flow. 

(A) Front view. (B) Back view. (Courtesy of Prof. Markus Rothschild, 

Cologne, Germany.)


Gowitt and Hanzlick presented fatal AADs owing to inhalation of the fluorocarbon 

dichlorodifluoromethane (Freon 12) (65,66). 

Isenschmid et al. reported an interesting case where the victim was found 

in a conversion van with a plastic bag around his head that was tightly secured 

with a piece of panty hose (64). The plastic bag contained a folded towel and a 

pressurized can of Fix-A-Flat tire repair, containing chlorodifluoromethane 

(FC-22), tetrachlorethylene (perchloroethylene), and a “trade secret,” was found 

close by the deceased. The man was clad in a nylon body stocking, which 

contained an opening in the crotch exposing his genitals. His penis was tied 

with an additional piece of stocking material, and his waist was bound loosely 

with a buckled leather belt. Concentrations of tetrachlorethylene, obtained by 

GC-ECD analysis, were 62 mg/L in blood, 341 mg/kg in liver, 47 mg/kg in 

lung, and negative in urine and were consistent with an acute lethal 

tetrachlorethylene intoxication. 

Sometimes, elaborate techniques are found in anesthesiophilia. One of 

the first AADs involving nitrous oxide was portrayed by Schwarz in 1933 

(18). The practitioner had used a complicated system of tubes, valves, and 

rubber balloons to apply laughing gas, which he had stolen from his father’s 

medical practice. Rothschild and Schneider communicated a case of a lethal 

anesthesiophilia owing to nitrous oxide from cream dispenser cartridges (62). 

The nitrous oxide was applied by a homemade closed system of anesthetic 

tubes, plastic bags, and an anesthetic face mask. Enticknap published the case 

of a 19-year-old female dental receptionist who was found in the surgery with 

the anesthetic face piece of a Walton No. 2 anesthetic machine in position 

over the nose (67). The woman died as a result of accidental nitrous oxide 

poisoning. Leadbeatter reported an AAD of an antiques dealer, who sat in a 

chair in front of which a Walton anesthetic machine was placed (56). Anesthetic 

tubing connected this machine to a firmly fixed anesthetic face mask. 

The setting of the machine indicated delivery of a gas mixture of 95% nitrous 

oxide and 5% oxygen; the indicator on the face mask attachment was in the 

“no valves” position. Although the toxicological analysis revealed just traces 

of nitrous oxide in blood as a consequence of the long time interval between 

death and autopsy, the death could be ascribed to hypoxia resulting from inhalation 

of nitrous oxide. 

Breitmeier et al. reported a bizarre autoerotic accident owing to multiplex 

paraphilia involving a fatal combination of asphyxia by suffocation and intoxication 

with ketamine, which was self-administered by an intravenous catheter 

(39). The toxicological analysis of blood taken from the femoral vein revealed a 

ketamine concentration of 2.5 µg/ml, which is well within the therapeutic range.

250 Seidl 

The death occurred as a result of the dual effects of the mouth gag (rubber ball) 

and a drug-induced respiratory depression combined with cerebral edema (39). 

Drugs like cocaine, lysergic acid diethylamide (LSD), cannabis, or amphetamines 

are also used to enhance sexual excitement, sometimes combined 

with unusual application modes. Schwarz, for example, communicated an AAD 

owing to a lethal intoxication with rectally administered cocaine (14). 

3.3. Electrophilia 

Compared to asphyxiophilic deaths, reports on autoerotic deaths resulting 

from electrophilia are rare and, apart from one case communicated by Weimann 

(21), comprise exclusively men, if the published cases (14,24,38,68–74) are 

scrutinized according to the AAD definitions of Byard and Bramwell as well 

as Behrendt and Modvig (23,27). Autoerotic electrocutions usually involve 

low-voltage alternating current, and a variety of devices is used to gain direct 

autoerotic stimulation, most of which involved household or homemade electrical 

devices like electrical wiring from a television set, a table lamp, or a 

defective toy train transformer (2,13,22,49,68–70). Sometimes practitioners 

simply use Y-shaped cables with a plug for house current (220 V) at one end 

and self-made electrodes at the other ends (own case and ref. 38). In both of 

these cases, one electrode was introduced in the anus, whereas the other electrode 

was applied to the penis. Rectal application of electricity is a common 

practice for obtaining semen from bulls (“electroejaculation”) (21,38) and might 

be the idea behind this uncommon method of masturbation. 

Another favored location for the placement of electrodes are the nipples. 

One of the first electrophilic AADs that involved house current (220 V) applied 

to the nipples was reported by Schwarz (14). As a rescue mechanism, the 27-yearold 

electrical-engineering technician had integrated in the circuit a preset potentiometer 

(dropping resistor), but seems to have oversized the dosage applied 

to the electrodes. Schott and colleagues reported an AAD of a 18-year-old 

man who was wearing two brassieres (13). Underlying each brassiere cup were 

two wet folded terry cloths, with a metal washer loosely adhered to the outer 

cloth. The washers were wrapped in exposed wires from the two short ends of 

a Y-shaped electrical cord. The long end of this cord was connected to a functional 

electrical outlet (110 V) via a two-pronged plug. Autopsy disclosed 

patterned second- and third-degree burns of the bilateral mammary regions. 

The authors attributed death to acute cardiac dysrhythmia secondary to lowvoltage 

electrocution. A similar case was portrayed by Hazelwood et al. where 

a 30-year-old man wore a brassiere and wet terry cloth towels that were attached 

via tin foil and rotisserie to the house current (66).


Sometimes the circuits are elaborate and comprise several body parts. 

Weimann reported a case of a 15-year-old electrician apprentice, who connected 

a teaspoon in his rectum, aluminum around his penis, and a glow lamp 

mignon holder in his mouth with the house current in such a way that he was 

able to control the strength of the current with his lips by fastening or unscrewing 

the bulb similarly to a potentiometer (21). The death occurred because of 

the bad insulation of the glow lamp cables, leading to an exclusion of the glow 

lamp from the circuit. 

In cases of electrophilia with fatal outcome, pornographic literature or devices 

for deviant sexual gratification are regularly found (38,75), whereas the death 

scenes seem to be of a less bizarre imagery than in asphyxiophilic cases (20). 

3.4. Other Practices of Autoeroticism 

The practices discussed in this section regularly comprise techniques that 

extravagate to sexual masochism. The insertion of foreign objects into the 

mouth, penis, vagina, or rectum is a known and dangerous autoerotic practice. 

Death may result particularly from bleeding or peritonitis, especially if perforations 

occur that lead to an opening of the abdominal cavity (43). Byard et al. 

reported a septic autoerotic death where a pencil was found in the peritoneal 

cavity (76). The perforation of the bladder led to the suggestion that the pencil 

had been introduced through the penile urethra. A similar case in which death 

occurred owing to massive abdominal hemorrhage secondary to bladder rupture 

was communicated by Diggs (77). In this case, the foreign body used to 

inflict the traumatic injuries was a chopstick. Sivaloganathan portrayed the 

death of a 23-year-old man resulting as a late complication of autoerotic practice 

(78); the man died of bronchopneumonia as a sequel of renal failure 

(bilateral pyelonephritis) following a bladder calculus that had formed around 

a coiled plastic tube with an entire length of 20–30 cm. 

Schmeling et al. communicated an AAD of a 23-year-old man who was 

found dead in his room, wearing female underwear (79). The man had constructed 

an apparatus to induce peritoneal pain, consisting of a wooden slat 

that was attached by a hinge to the wall unit beside the bed. A vise with two 

inserted knives was affixed to the other end of the slat. Lying back on his bed, 

the man was able to move the slat up and down by an electric motor that was 

operated by remote control. The drive train was performed by a cord with a 

counterweight. The length of the cord was adjusted in such a way that the 

knives contacted the abdominal skin in the “down” position of the slat. When 

the cord twitched, the knifes penetrated the abdominal wall and death occurred 

as a result of internal bleeding.

252 Seidl 

4. A COMPARISON OF AUTOEROTICISM IN MALES AND FEMALES 

Whereas approximately 50 AAD cases per year were estimated in 1972 

(4), conservative estimates suggest now that 500–1000 AADs occur annually 

in the United States alone (3,6,80,81,82). The age range of male and female 

victims is wide, from 9 to 80 years in men (2,4,27,41), and from 17 to 68 years 

(2,29) in women. In both sexes, however, AAD is most often seen in young to 

middle-aged adults. 

Whereas young white men comprise the largest group of victims 

(23,32,40,80,81), the number of female AADs reported in the literature is 

extremely small (2,4,20,51,82). In the 1950s, Schwarz explained the nonexistence 

of female AADs with the presumption that women were less active in 

erotic matters and would get by with simple means for masturbation instead of 

elaborate apparatus (14). Although Meixner had reported a female AAD case 

as early as 1952 (21,83), Resnick stated as late as 1971 an absolute absence of 

AAD in females (1). In the same year, Henry published the first case of a 

typical female AAD in the English medicolegal literature (84), and, to our 

knowledge, in the following decades up to now only 62 cases have been communicated. 

Omitting identical cases and cases that do not fulfill the criteria 

for AAD according to the definition of Behrendt and Modvig (27), there remain 

just 15 published typical female AAD cases (29). Gosink and Jumbelic quoted 

a male to female ratio of more than 50:1 (41). 

Males tend to utilize a great range of elaborate devices and props, often 

designed to cause real or simulated pain, with pornographic material and evidence 

of cross-dressing and fetishism like intimate feminine garments (Fig. 6) 

(2–6,28,41). Frequently, the paraphernalia associated with the practice becomes 

more elaborate as the participant ages and becomes more experienced (41). In 

the largest published series to date, 26 (20.5%) of 127 males dying of autoerotic 

asphyxiation were cross-dressed at the time of death, 5 of whom had 

been observed by others to have repeatedly cross-dressed in the past, and another 

5 who had sizable or diverse collections of women’s clothing or makeup 

(49,85). Additionally, mirrors are often placed by male practitioners to enable 

them to observe their activities (2,4,5,36,86). In contrast, the female AAD 

seems to have a less obvious presentation (5,52). As just one case was published 

until 2002 where a woman was wearing unusual “harem-style” clothing 

with an elaborate system of rope bindings (84), it was thought for a long time 

that females are usually found without unusual or bizarre equipment, naked 

with only a single ligature, tightened either by lowering the body or by pulling 

an attached cord tied to the hands or legs (2,40,42,87). The four cases published 

by Behrendt et al., however, confirm that females may be as elaborate


Fig. 6. AAD (positional asphyxia) of a 19-year-old man who wore feminine 

garments and high-heeled shoes. (Courtesy of Dr. Wolfgang Huckenbeck, 

Düsseldorf, Germany.) 

with nonlethal paraphilias and props as are known to be men (29). Besides 

bizarre equipment like a horsewhip, pornographic material, a plastic bag with 

ether, and elaborate bondage encircling the limbs and/or the vulva, there was 

one case in which the bondage with chains was similar to a typical homicide 

ritual of the Italian mafia called “incaprettamento” (29,88). Therefore, it has 

to be stated that female AADs may very closely resemble a typical male AAD 

(29). In the majority of female AADs, however, the absence of typical props 

like pornographic material, cross-dressing, or elaborate and often bizarre equipment, 

as it is nearly regularly used by men, may impede the identification of a 

female AAD (42). 

5. MEDICOLEGAL ASPECTS OF ACCIDENTAL AUTOEROTIC DEATH: 

THE DEMARCATION FROM SUICIDES AND HOMICIDES 

AADs may very closely resemble a sadistic and/or ritualistic homicide 

or suicide (2,5,14,17,18,21,29,48,76,89–91). Madea portrayed the case of a 

homicide by throttling and strangulation that was first considered an AAD 

(89), and Naeve discussed the possibility of feigning an AAD in both suicide 

and homicide (90). To exclude the possibility of sexual homicide or suicide, 

the investigators have to establish the presence of key death scene characteristics 

before the death can be appropriately classified as an autoerotic fatality 

(1,2,4,6,21,41,44,48,52,55,80,92). 

Because of the desire for secrecy and privacy, the location for the performance 

of the activity is usually a secluded place, often with evidence of

254 Seidl 

Fig. 7. Permanent hooks on the ceiling facilitating repetition of hanging for 

autoerotic behavior. (A) Note the pornographic pictures on the wall on the left 

side. (B) This construction was used as a block and pulley. (Courtesy of Dr. 

Michael Tsokos, Hamburg, Germany.) 

repeated autoerotic behavior, for example, permanent hooks on the walls or 

ceiling (Fig 7A,B) to facilitate repetitive hanging (1–4,14,21,44,52,81,93). The 

victims are found alone, often in isolated areas outdoors but mostly, however, 

in rooms locked from inside. Mirrors that allow the practitioner to observe his 

activities (2,4,21,86) are no secure criterion for an AAD, as this finding has 

also been described in cases of suicide (94). Bondage (Fig. 8) is common, 

with often elaborate and bizarre methods of restriction and a variety of ropes 

and cords tied to and around the genitals (1,2,4,23,34,36,42). The death scene 

investigators have to ensure that any bondage could have been secured by the 

deceased himself (36,41,44). A further important piece of evidence against 

suicide is padding of the rope, especially in neck ligatures, to prevent subsequently 

detectable abrasions or bruises (2,4,5,36,41,80,81). Because of the 

accidental nature of AAD, one or sometimes several failed escape mecha-


Fig. 8. AAD with deliberate bondage around ankles and legs. The practitioner 

is wearing female underwear. 

nisms are usually evident (2,3,21,46,49). The emission of semen is compatible 

with, but does not necessarily confirm sexual activity in itself, since a 

near-terminal reflex neurophysiological response to hypoxia is common, as is 

postmortem discharge of semen from the meatus, in any type of death, not 

only in asphyxia (1–3,36). 

Abrasions and bruises are no definite sign of homicide, as body movements 

occur especially in asphyxiophilia and electrophilia, and the body may 

repeatedly bump against surrounding structures (50). A lack of features of 

suicide with no antemortem evidence of suicidal ideation or depression is diagnostic 

for AAD; an overt suicide note is usually not present (2,4,23,36,86). 

Turvey, however, discussed the possibility that a suicide note might be present 

as a prop, a part of a victim’s masochistic fantasy (44). 

In some cases, the differentiation between AAD and suicide remains 

impossible: although the death scene with sexual attributes suggests an AAD, 

predictable fatal autoerotic techniques and insufficient rescue mechanisms make 

it inevitable that the victim must have been aware of the fatal outcome (9,20,56). 

Knight assumed a mixed motivation in these infrequent cases (36), and Byard 

and Botterill warned that in certain cases suicide or undetermined might be 

more appropriate conclusions regarding the manner of death (93). Contostavlos 

argued as well that at least some of these cases (suspension or extremely restrictive 

bondage) were similar in nature to Russian roulette, and were more properly 

labeled “manner undetermined” (95). Thorough investigations regarding 

life and environment of the victim and the circumstances of death, sometimes 

referred to as “psychological autopsy,” may be effective in the determination 

of the manner of death in equivocal cases (28,59,77,96,97). Jobes et al. showed

Characteristic Explanation 

Table 3 

Twelve Characteristics for a Determination of Autoerotic Death 

1* Location Secluded or isolated area with a reasonable expectation of privacy; rooms locked from inside. 

Evidence of solo sexual activity. 

2 Body No free hanging in asphyxial hanging deaths: the victim’s body may be partially supported by the 

position ground, or the victim may even appear to have simply been able to stand up to avoid strangulation. 

3 High-risk Potentially lethal devices, apparatus, or chemicals brought in to the autoerotic activity that enhance 

elements physical or psychological pleasure and increase the risk of death. 

4 Self-rescue Any provision that allows the victim to voluntarily stop the effect of the high-risk element (e.g., slip 

mechanisms knot, knife). 

5 Bondage Use of special materials or devices that physically restrain the victim and have a psychological/fantasy 

significance to the victim. It is important that any bondage could have been secured by the deceased 

himself. 

6 Masochistic Inflicting physical or psychological pain on sexual areas of the body, or other body parts: indicators of 

behavior current use (e.g., genital restraints, ball-gag, nipple clips, or suspension) and/or healed injuries 

suggesting a history of autoerotic behavior. 

256 Seidl

7 Attire The victim may be dressed in fetishistic attire or in one or more articles of female clothing/cross-dressing. 

Both may be absent! The victims may be fully dressed, nude, or partially undressed. 

8 Protective To avoid visibility to others, injuries may be inflicted only to areas that are covered by clothing, and/ 

padding or protective padding like scarfs or towels are used to prevent abrasions or grooves. 

9 Sexual Items found on or near the victim that assist in sexual fantasy (vibrators, dildos, mirrors, erotica, 

paraphernalia diaries, photos, films, female undergarments, etc.). 

and props 

10 Masturbatory Absence and presence of semen from the scene are no reliable indicators of autoerotic death. 

activity Masturbation may be suggested by the presence of semen on hands and towels. 

11* Evidence of Evidence of behavior similar to that found in scene that predates the fatality, e.g., permanently affixed 

prior autoerotic protective padding, plastic bags with repaired “escape” holes, complex high-risk elements, complex 

activity escape mechanisms, healed injuries, grooves worn in a beam (from repeated ligature placement), etc. 

12* No apparent The victims have made plans for future events in their life (e.g., plans to see friends or go on trips). 

suicidal intent Absence of a suicide note is not always an indication of an autoerotic event. If one is present, it must 

be determined that it was written around the time of death, and is not a prop. 

Note. Modified according to refs. 1, 44, and 66. Characteristics marked with an asterik are mandatory; unmarked features are facultative. 

Accidental Autoerotic Death 257

258 Seidl 

that a standardized psychological autopsy technique in these cases may lead to a 

shift toward suicidal death (96). Finally, the death scene investigator should 

be alert to the fact that family members or acquaintances could have removed 

female clothing and props in an attempt to disguise the manner of death with 

its attendant social stigma (2,3,6,38,76). For example, Garza-Leal and Landron 

reported a case where the father of the victim admitted to having removed 

pornographic pictures from the scene (3). 

In continuation of Resnick’s criteria (1), Hazelwood (66) and Turvey 

(44) established general behavioral characteristics that investigators can look 

for to help them identify autoerotic death scenes (Table 3). It has to be mentioned 

that not all of these criteria need to be present. At least the following 

characteristics, however, are obligatory: (a) reasonable expectation of privacy, 

(b) evidence of solo sexual activity, (c) evidence of prior high-risk autoerotic 

practice, and (d) no apparent suicidal intent (44). 

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Lethal Hypothermia 263 

11 

Lethal Hypothermia 

Paradoxical Undressing and Hide-and-Die 

Syndrome Can Produce Very Obscure Death Scenes 

Markus A. Rothschild, MD 

CONTENTS 

INTRODUCTION 

PARADOXICAL UNDRESSING 

HIDE-AND-DIE SYNDROME 

REFERENCES 

SUMMARY 

Hypothermia is a relatively rare cause of death in temperate climate zones. 

In most cases of lethal hypothermia, elderly and mentally ill persons are affected 

as well as persons under the influence of alcohol or other substances. Although 

most cases of death from hypothermia are accidental, they, more often than 

other types of death from environmental conditions, produce a death scene 

that is at first obscure and difficult to interpret. The reason for this frequent 

obscurity is mainly because of the phenomenon of the so-called paradoxical 

undressing as well as the hide-and-die syndrome. In many cases, the bodies 

are found partly or completely unclothed and abrasions and hematomas are 

found on the knees, elbows, feet, and hands. The reason for the paradoxical 

undressing is not yet clearly understood. There are two main theories discussed: 

one theory proposes that the reflex vasoconstriction, which happens 

in the first stage of hypothermia, leads to paralysis of the vasomotor center 

thus giving rise to the sensation that the body temperature is higher than it 

really is, and, in a paradoxical reaction, the person undresses. The other theory 



263

264 Rothschild 

says that it seems to be the effect of a cold-induced paralysis of the nerves in 

the vessel walls that leads to a vasodilatation giving an absurd feeling of heat. 

In 20% of cases of lethal hypothermia, the phenomenon of the so-called hideand-die 

syndrome also can be observed. Some of these bodies are situated in a 

kind of “hidden position,” for example, located under a bed or behind a wardrobe. 

Apparently, this finding is the result of a terminal primitive reaction 

pattern, which is probably an autonomous behavior triggered and controlled 

by the brain stem. It shows the characteristics of both an instinctive behavior 

and a congenital reflex. 

Key Words: Lethal hypothermia; paradoxical undressing; hide-and-die 

syndrome; death scene investigation; terminal burrowing behavior. 


Hypothermia is a relatively rare cause of death in temperate climate zones. 

In most cases of lethal hypothermia, infants, elderly, and mentally ill persons 

are affected as well as persons under the influence of alcohol or other substances 

(1–5). 

The dangerous effects of cold do not necessarily develop only at temperatures 

below 0°C (32°F). Hypothermia can even occur at ambient temperatures 

of around 21°C (70°F). Cases of lethal hypothermia are found in about 

1% of all autopsy cases examined in Institutes of Legal Medicine that are 

situated in bigger cities of Germany (6), whereas those institutes situated in 

smaller cities and with rural environment observe these cases in about 2% of 

all their autopsy cases. Approximately 50% of all victims of lethal hypothermia 

are under the influence of alcohol. 

Hypothermia is the result of an imbalance between an increased loss of 

body heat and an insufficient production of body heat. Hypothermia means all 

states with a core temperature of the body under 35°C (95°F). A prolonged 

process of hypothermia leads to a cold-induced diuresis and leaking of plasma 

into extracellular spaces and therefore results in an increase of blood viscosity 

and a decrease of blood circulation. With further progression, anuria occurs. 

If the body’s temperature decreases further, potassium will transfer from the 

extracellular to the intracellular compartments, whereas the sodium concentrations 

remain stabile. These changes in the ratio of potassium/sodium and 

the increased affinity of oxygen to hemoglobin can result in fatal ventricular 

fibrillation, acidosis, and edema of the brain. 

Although most cases of death from hypothermia are accidental and collectively 

amount to only a relatively small number of deaths encountered in 

the forensic pathologist’s or medical examiner’s practice, they more often than


other types of death from environmental conditions produce a death scene that 

is at first obscure and difficult to interpret (7). The reason for the frequent 

obscurity of the death scene in cases of lethal hypothermia is mainly because 

of the phenomena of the so-called paradoxical undressing (1,8–12) and the 

hide-and-die syndrome (13,14). In many cases, the bodies are found partly or 

completely unclothed and abrasions and hematomas are seen on the knees, 

elbows, feet, and hands (8,11). Some of these bodies are found in a kind of 

“hidden position” (e.g., located under a bed or behind a wardrobe [14]). At 

first sight, these observations will strongly indicate a crime, as very often a 

naked female body raises the suspicion of a preceding sexual attack. As a 

consequence, the public prosecutor will, in such cases, demand an autopsy to 

clarify the cause of death. Similar to autopsy cases of death from asthma, 

epilepsia, or drowning, the gross autopsy findings may be nonspecific or any 

pathological features may be even totally absent. Therefore, it is very important 

for the forensic pathologist and medical examiner, respectively, to visit 

the death scene to get as many clues and hints toward the case as possible. 

However, in a large number of cases of death from lethal hypothermia, the 

autopsy shows a typical group of findings such as cherry-red or pink livores 

mortis, swelling and red-purple spots and sometimes abrasions over the joints, 

Wischnewski spots in the gastric mucosa, pancreatitis, high levels of acetone 

in blood and/or urine, and basal lipid accumulations in the epithelial cells of 

renal proximal tubules. Outcome of autopsy together with the results of the 

death scene investigation then very often obviously show that the police are 

dealing with a case of hypothermia without any hints for a preceding crime. 

2. PARADOXICAL UNDRESSING 

The phenomenon of paradoxical undressing in cases of lethal hypothermia 

(Fig. 1) can be observed more often at moderately cold ambient temperatures 

from –5° to +5°C (23–41°F) and in a slow decrease of body temperature 

than in cases with very cold ambient temperatures and a rapid decrease of 

body temperature. The bodies are found inadequately clothed or completely 

naked. In cases of paradoxical undressing, two-thirds of the bodies are partially 

unclothed and one-third is totally naked (11,14,15). 

In the overwhelming number of cases, the clothes are strewn on the ground 

beside the body, sometimes forming a trail of scattered clothing over a distance 

of some meters. But cases where the clothes are scattered all over the 

place can also be observed. Although there seems to be no homogenous pattern 

of undressing, it seems that undressing in most cases had started with the 

lower half of the body. One reason for this could be linked with the well-known


Fig. 1. Paradoxical undressing. This 51-year-old man was found dead on the 

floor of his flat in which heat and electricity had been switched off for weeks 

because the man was overdue with his fees. The ambient temperature in the 

flat was 10°C (50°F) and the outside temperature ranged between –4°C and 

–12°C (10–25°F) for several days. Except for underpants, the man was completely 

undressed. Note the spots (that were red-purple colored and attributed 

to hypothermia) and abrasions on the right knee. The blood alcohol concentration 

was 110 mg/dL. The finding situation and the results of the forensic autopsy 

indicated that the man had died of lethal hypothermia. (Courtesy of Dr. Michael 

Tsokos, Hamburg, Germany.) 

phenomenon of cold-induced diuresis, where possibly the hypothermic person 

removes the urine-wet clothes. Another explanation could be a different 

number of heat receptors in the lower and in the upper half of the body thus 

resulting in different heat sensations. However, this is still unclear and further 

investigations are needed. 

The paradoxical undressing obviously happens in a state of severe mental 

confusion. Otherwise, why these persons behave like they do would not be 

understandable. In the case presented in Fig. 2, the 37-year-old mentally ill 

woman was walking around when she saw an open door leading to the basement 

of a building of a cleaning company. She entered the basement and accidentally 

was locked in. When she was found dead partly naked a few days 

later, she was lying on the lowest shelf of a steel storage shelving unit that was 

filled with a large number of frocks (an example of the so-called hide-and-die


Fig. 2. Hide-and-die syndrome. This 37-year-old mentally confused woman 

was found dead lying on the lowest shelf of a steel storage shelving unit in the 

basement of a building. During the weekend, when she was accidentally locked 

in the building, the ambient temperature in the basement was between 12 and 

15°C (54–59°F). Outcome of toxicology was negative. According to autopsy and 

circumstances at the death scene, the woman had died from lethal hypothermia. 

syndrome; see next section). The ambient temperature in the basement was 

between 12 and 15°C (54–59°F). It would have probably saved her life if she 

had put on some of these frocks instead of taking her own clothes off. 

The reason for the phenomenon of paradoxical undressing is not yet 

clearly understood. We know that cold causes a reflectory vasoconstriction 

and opening of arteriovenous shunts. As a result, the temperature of the skin 

decreases and if the body stays in the cold environment, the body temperature 

will decrease as well. It is not clear what is happening then and two main


theories are discussed (16–20): the first theory proposes that the reflex vasoconstriction, 

which happens in the first stage of hypothermia, leads to paralysis 

of the vasomotor center in the hypothalamus thus giving rise to the sensation 

that the body temperature is higher than it really is and, in a paradoxical reaction, 

the person undresses. The second theory says that paradoxical undressing 

is an effect of a cold-induced paralysis of the nerves in the vessel walls 

that leads to a vasodilatation thus giving an absurd feeling of heat. 

3. HIDE-AND-DIE SYNDROME 

In cases of lethal hypothermia, the phenomenon of the so-called hideand-die 

syndrome can be also observed (13). We observed the hide-and-die 

syndrome in an earlier study of 69 cases of death from lethal hypothermia in 

20% of the cases (14). In 80% out of the cases showing a paradoxical undressing, 

there seems to be a link with the hide-and-die syndrome and there seems 

to be no hide-and-die syndrome without paradoxical undressing (14). 

In the hide-and-die syndrome, the bodies are found in a position that at 

first raises suspicion of an attempt to hide the body (Fig. 3). But after a thorough 

investigation, including death scene investigation and autopsy, it is evident 

in most cases that no other person was involved and a crime will be 

excluded. 

Obviously, the strange positions in which the bodies are positioned are 

the result of a (pre-)terminal behavior. The situation in which the bodies are 

found and their positions always give the impression of a protective “burrowlike” 

or “cave-like” situation, as the bodies are found under the bed, behind 

the wardrobe, on a shelf, etc. The clothes are always strewn on the ground in 

front of the final position, sometimes forming a trail. In every case, the paradoxical 

undressing had obviously happened before this self-protective phenomenon 

occurred, which for good reasons is called hide-and-die syndrome 

(13). This is sustained by the fact that the removed clothing was never found 

directly at the final position where the body was found and some of the victims 

had obviously been crawling around (8,15,21,22). In most cases, the final 

position in which the bodies were found could be reached only by crawling on 

all fours or flat on the body, resulting in abrasions on the knees and elbows 

(8,11) (Fig. 4A,B). This crawling to the final position seems to have happened 

after the paradoxical undressing as there were abrasions to the skin but no 

damage to the corresponding parts of the removed clothing. 

Apparently the hide-and-die-syndrome is not a result of conscious acting 

but of a terminal primitive reaction pattern that is probably an autonomous 

behavior triggered and controlled by the brain stem. It shows the characteris-


Fig. 3. Paradoxical undressing and hide-and-die syndrome. The bodies of 

two men, 34 and 52 years old, were found lying in a public park in a prone 

position on the ground, one in front of and one underneath a park bench. Both 

men were under considerable influence of alcohol (280 and 300 mg/dL, respectively). 

On the morning the men were found, the ambient temperature was 9°C 

(38°F). Forensic autopsy showed the typical findings of lethal hypothermia. 

(Courtesy of Prof. Klaus Püschel, Hamburg, Germany.) 

tics of an instinctive behavior and a congenital reflex. This phenomenon gives 

the impression of a final program of the archencephalon. It seems to be an act 

of getting out of harm’s way and into safety. Furthermore, a state of severe 

mental confusion, which obviously plays a role in cases of hypothermia 

(1,16,21), seems to be a promoting factor. This behavior probably occurs with 

the objective of reaching a state of common safety rather than specifically to 

bring the body into warmth. Otherwise it is not understandable why the victims 

of hypothermia prefer to lie naked on a stone-cold floor rather than putting 

their clothes on again. 

As in other findings of hypothermia (3,22,23), this phenomenon also 

seems to be dependent on how rapid the body temperature decreases. Moderately 

cold ambient temperatures and a slow decrease of the body temperature 

induce a hide-and-die syndrome more often than environmental temperatures


Fig. 4. Death from hypothermia. (Red-purple) spots attributable to hypothermia 

showing superficial abrasions on (A) knees and (B) elbows, most probably 

originating from crawling on all fours or flat on the body in a final state of 

mental confusion. (Courtesy of Dr. Michael Tsokos, Hamburg, Germany.) 

far below 0°C (32°F) with a sudden state of severe hypothermia. Interestingly, 

there seems to be no significant relation between alcohol or other substances 

and the occurrence of paradoxical undressing or hide-and-die 

syndrome (14). 

There are many publications concerning hypothermia but hardly any specifically 

describe the hide-and-die syndrome only. Kinzinger et al. (11) reported 

on two completely undressed males who died in a public park due to hypothermia. 

Both men were found in a prone position with the arms close to the 

body, one directly under a bench, the other just in front of it. This clearly 

shows the situation of the hide-and-die syndrome, but the authors did not elaborate 

on this. Therefore, one can assume that this phenomenon occurs more 

often than it is described in the literature. 

Following the assumption that the hide-and-die syndrome is a primitive 

response pattern of the brain stem, there should be some parallels in the animal 

world. Unfortunately there are hardly any publications about animals dying 

because of hypothermia, but there exist numerous papers on hibernation. 

Various mammals encounter the problem of increased thermoregulatory 

energy demands by means of deep hibernation or daily torpor (24,25,27) in 

which they reduce their energy requirements to a fraction of their euthermic


metabolic rate (24–27). Hibernators retreat into their hibernaculum, for 

example, a frost-protected cave or burrow, and relinquish most of their behavioral 

and territorial activities (28). 

REFERENCES 

1. DiMaio DJ, DiMaio VJM (1989) Forensic pathology. CRC Press, Boca Raton, 

London, New York, Washington. 

2. Drese G (1984) Unterkühlung—Todesursache oder wesentlicher Nebenbefund? 

Kriminal Forensische Wiss 55/56, 184–189. 

3. Hirvonen J (1976) Necropsy findings in fatal hypothermia cases. J Forensic Sci 8, 

155–164. 

4. Kortelainen ML (1987) Drugs and alcohol in hypothermia and hypothermia-related 

deaths. J Forensic Sci 32, 1704–1712. 

5. Krjukoff A (1914) Beitrag zur Frage des Todes durch Erfrieren. Vjschr Gerichtl Med 

47, 79–101. 

6. Lignitz E (2003) Kälte. In Madea B, ed., Praxis Rechtsmedizin. Springer, Berlin, 

Heidelberg, New York, pp. 181–186. 

7. Hirvonen J (1977) Local and systemic effects of accidental hypothermia. In Tedeshi 

CG, Eckert WG, Tedeshi LG, eds., Forensic medicine, Vol. 1. Saunders, Philadelphia, 

pp. 758–774. 

8. Dreifuß H (1977) Tödliche Unterkühlung: Unfall oder Verbrechen? Kriminalistik 

31, 205–206. 

9. Duguid H, Simpson G, Stowers J (1961) Accidental hypothermia. Lancet 2, 1213–1219. 

10. Goremsen H (1972) Why have victims of death from the cold undressed? Med Sci 

Law 12, 201–202. 

11. Kinzinger R, Riße M, Püschel K (1991) “Kälteidiotie”—Paradoxes Entkleiden bei 

Unterkühlung. Arch Kriminol 187, 47–56. 

12. Wedin B, Vanggaard L, Hirvonen J (1979) Paradoxical undressing in fatal hypothermia. 


13. Knight B (1997) Forensic pathology, 2nd ed. Edward Arnold, London, Melbourne, 

Auckland, pp. 414–415. 

14. Rothschild MA, Schneider V (1995) “Terminal burrowing behaviour”—a phenomenon 

of lethal hypothermia. Int J Legal Med 107, 250–256. 

15. Sivaloganathan S (1986) Paradoxical undressimg and hypothermia. Med Sci Law 

26, 225–229. 

16. Buris L (1993) Forensic medicine. Springer, Berlin, Heidelberg, New York, pp. 

146–148. 

17. Hirvonen J, Huttunen P (1982) Increased urinary concentration of catecholamines in 

hypothermia deaths. J Forensic Sci 27, 264–271. 

18. Molnár GW (1946) Survival of hypothermia by men immersed in the ocean. JAMA 

131, 1046–1050. 

19. Paton BC (1983) Accidental hypothermia. Pharmacol Ther 22, 331–377.


20. Prescott LF, Peard MC, Wallace JR (1962) Accidental hypothermia, a common 

condition. BMJ 2, 1367–1370. 

21. Reuter F (1933) Lehrbuch der gerichtlichen Medizin. Urban & Schwarzenberg, 

München, Wien, Baltimore. 

22. Unterdorfer H (1977) Statistik und Morphologie des Unterkühlungstodes. Ärztl 

Praxis 29, 459–460. 

23. Schneider V, Klug E (1980) Tod durch Unterkühlung. Gibt es neue Gesichtspunkte 

zur Diagnostik? Z Rechtsmed 86, 59–69. 

24. Ruf T, Heldmaier G (1992) The impact of daily torpor on energy requirements in the 

djungarian hamster, Phodopus sungorus. Physiol Zool 65, 994–1010. 

25. Ruf T, Klingenspor M, Preis H, Heldmaier G (1991) Daily torpor in the djungarian 

hamster (Phodopus sungorus): interactions with food intake, activity, and social 

behaviour. J Comp Physiol [B] 160, 609–615. 

26. Heldmaier G, Ruf T (1992) Body temperature and metabolic rat during natural 

hypothermia in endotherms. J Comp Physiol 162, 696–706. 

27. Heldmaier G, Steinlechner S (1981) Seasonal pattern and energetics of short daily 

torpor in the djungarian hamster, Phodopus sungorus. Oecologia 48, 265–270. 

28. Heldmaier G (1993) Seasonal acclimatization of small mammals. Verh Dtsch Zool 

Ges 86, 67–77.

HELLP 273 

Maternal Death in Pregnancy

274 Tsokos

HELLP 275 

12 

Pathological Features 

of Maternal Death 

From HELLP Syndrome 


CONTENTS 

INTRODUCTION 

MATERNAL COMPLICATIONS ASSOCIATED WITH HELLP SYNDROME 

DIFFERENTIAL DIAGNOSES 


REFERENCES 

SUMMARY 

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome 

is a life-threatening complication of preeclampsia during pregnancy or postpartum. 

Serious complications occur in 12.5–65% of cases of HELLP syndrome 

and are associated with a maternal mortality between 1.1 and 3.4%. 

Despite active research for many years, the etiology of this disorder exclusive 

to human pregnancy has not been sufficiently clarified. In clinical practice, 

disseminated intravascular coagulation (DIC) is found in 4–38% of cases with 

HELLP syndrome. Despite the apparent correlation between the marked degree 

of DIC in laboratory tests and the extent of laboratory changes in HELLP syndrome 

and the rate of maternal complications, the manifestation of DIC is neither 

an initial nor a principal symptom of HELLP syndrome but rather reflects 

a secondary pathophysiological process of the primary disease state that can be 

regarded as a result of preeclampsia that was diagnosed and/or treated too late. 

Hepatic rupture as a sequel of subcapsular liver hematoma in the course of 



275

276 Tsokos 

DIC, occurring in 1–1.8% of cases, is considered the most serious and lifethreatening 

maternal complication in HELLP syndrome. Hepatic rupture is located 

predominantly in the anterior-superior region of the right hepatic lobe 

and can occur both antepartum and postpartum. The main autopsy findings in 

HELLP syndrome are petechiae and suffusions in conjunctivae, skin and on 

mucous and serous surfaces of internal organs, cerebral edema, signs of acute 

respiratory distress syndrome (ARDS), edema of the lower extremities, hyperemia 

of the spleen, hydropericardium, and shock kidneys. Since these findings 

may be initiated by a variety of underlying pathologic conditions, they are 

highly unspecific. In contrast, liver pathology is a hallmark in the postmortem 

diagnosis of HELLP syndrome. At autopsy, the liver shows a rigid consistence 

with yellow-brown cut surfaces and confluent hemorrhagic foci on cross-sections 

of the liver parenchyma and occasionally subcapsular liver hematoma or 

hepatic rupture. The histopathological features of hepatic alterations in HELLP 

syndrome are periportal hepatocellular necrosis, hemorrhages sharply demarcated 

by an extended fibrin network from the surrounding unaffected liver parenchyma, 

and leukostasis in the liver sinusoids. In the kidneys, the glomeruli 

are primarily affected. They are enlarged and appear bloodless as a result of 

obliteration of the capillary lumina by swollen, vacuolated, and occasionally foamy 

endocapillary cells. In most cases, two characteristic capillary loop patterns of 

the glomeruli can be distinguished: (a) the cigar-shaped loop type presenting 

elongated, stretched, and obstructed loops, and (b) the pouting loop type showing 

enlarged glomerular tufts filling Bowman’s space with herniation of capillary 

loops into the proximal tubules. Relevant to medicolegal implications of a 

fatal outcome of HELLP syndrome is the point that the presenting symptoms of 

patients are generally highly unspecific. As a result, many of the patients are 

initially misdiagnosed with other medical or surgical disorders such as gastroenteritis, 

hepatitis, pyelonephritis, appendicitis, acute fatty liver of pregnancy, 

(AFLP), idiopathic thrombocytic purpura, and hemolytic uremic syndrome (HUS). 

Delay in diagnosis or expectant management of HELLP syndrome is implicated 

in a considerable number of cases with fatal outcome. 

Key Words: HELLP syndrome; pregnancy; maternal death; preeclampsia; 

eclampsia; disseminated intravascular coagulation (DIC); acute respiratory 

distress syndrome (ARDS); acute fatty liver of pregnancy (AFLP); 

thrombocytopenia; renal pathology. 


In 1954, Pritchard et al. recognized the association between hemolysis, 

elevated liver enzymes, and thrombocytopenia in the setting of pregnancy (1).

HELLP 277 

In 1982, Weinstein coined the term HELLP syndrome to describe the clinical 

manifestations in a group of preeclamptic/eclamptic patients with the finding 

of hemolysis (H), elevated liver enzymes (EL), and a low platelet count (LP) 

(2). Notwithstanding the fact that since then a large number of studies and 

case reports dealing with the search for predictive factors, diagnostic improvements, 

and clinical management of HELLP syndrome has appeared in the literature, 

the disease is still a severe complication of preeclampsia during 

pregnancy or postpartum tainted with a high risk of maternal and perinatal 

mortality and morbidity (3–10). Since the proposal of more strict criteria for 

the diagnosis of the “true” HELLP syndrome (11), it has been observed that 

many women with severe preeclampsia may have laboratory abnormalities 

such as isolated hemolysis, low platelet count, or elevated liver enzymes without 

the complete HELLP syndrome. This has been referred to as “partial” 

HELLP syndrome (10,12). 

The HELLP syndrome occurs in 0.2–0.6% of all pregnancies. Approximately 

10% of patients with HELLP develop hypertension and proteinuria, 

and meet criteria for preeclampsia. Despite their similarities, HELLP is associated 

with a higher rate of maternal and fetal morbidity and mortality than 

preeclampsia (13). The incidence of the syndrome among patients with severe 

preeclampsia is 9.7% and is significantly higher in patients with delayed diagnosis 

of preeclampsia and/or delayed delivery (3). 

2. MATERNAL COMPLICATIONS ASSOCIATED WITH HELLP SYNDROME 

2.1. Clinical Presentations/Causes of Death 

Despite active research for many years, the etiology of this disorder exclusive 

to human pregnancy has not been sufficiently clarified. Recent evidence 

suggests that there may be several underlying causes or predispositions leading 

to the signs of hypertension, proteinuria, and edema (14). Current theories 

suggest altered prostaglandin synthesis, inappropriate sensitivity to angiotensin 

II, and immunologic factors as etiologies of preeclampsia (15) as well as an 

association of factor V and factor II mutations with preeclampsia (16). 

In most cases, HELLP syndrome is assumed to be initiated by inadequate 

placental vessel development with subsequent placental ischemia, leading to 

the release of circulating vasoconstrictors such as thromboxane A2, angiotensin, 

prostaglandin F2, and endothelin-1. The ischemic placenta also produces 

fewer vasodilators, such as prostacyclin, prostaglandin, E2, and nitric 

oxide. The ensuing imbalance in vasoactive substances causes intense systemic 

vasospasms and endothelial damage in multiple organs (17).

278 Tsokos 

Serious complications occur in 12.5–65% of cases of HELLP syndrome 

(6) and are associated with a maternal mortality between 1.1 and 3.4% (4,18). 

In 1993, Sibai et al. published the largest prospective cohort study of maternal 

complications in HELLP syndrome so far, including clinical data from 442 

pregnancies with HELLP syndrome (4). The presenting symptoms of the 

patients were abdominal pain (65%), nausea or vomiting (36%), headache 

(31%), visual changes (10%), hemorrhage (9%), jaundice (5%), diarrhea (5%), 

and shoulder or neck pain (5%). As a result of the unspecifity of these symptoms, 

many of the patients were initially misdiagnosed with other medical or 

surgical disorders such as gastroenteritis, hepatitis, pyelonephritis, appendicitis, 

acute fatty liver of pregnancy, idiopathic thrombocytic purpura, and 

hemolytic uremic syndrome. In the series by Sibai et al., which can be regarded 

as representative for the disease, serious maternal complications were disseminated 

intravascular coagulation (DIC) (21%), abruptio placentae (16%), 

acute renal failure (8%), ascites (8%), pulmonary edema (6%), pleural effusions 

(6%), cerebral edema (1%), retinal detachment (1%), laryngeal edema 

(1%), subcapsular liver hematoma (1%), and acute respiratory distress syndrome 

(ARDS) (1%). In three out of four maternal deaths in this study, multiple 

organ failure lead to hypoxic brain damage as the immediate (clinical) 

cause of death. The remaining death was stated as multiple organ failure in a 

patient who had a ruptured subcapsular liver hematoma. However, the authors 

do not comment on whether these diagnoses were verified by autopsies. 

In a more recent clinical series conducted by Isler et al. in 1999, including 

54 maternal deaths from HELLP syndrome, the clinical causes of death 

were stated as follows (19): cerebral hemorrhage (45%), cardiopulmonary arrest 

(40%), DIC (39%), ARDS (28%), renal failure (28%), sepsis (23%), hepatic 

hemorrhage (20%), and hypoxic ischemic encephalopathy (16%). From a pathophysiological 

viewpoint, this clinical classification is highly unsatisfactory 

for several reasons. First, one is tempted to speculate that cerebral hemorrhage 

may have occurred as a result of DIC. Second, cardiopulmonary arrest 

is, strictly speaking, the final cause of death in each fatality, for example, as a 

result of DIC or ARDS, and third, sepsis may have been the underlying cause 

of DIC in some cases where the diagnosis of sepsis was clinically missed. 

In a series of 14 fatal cases of HELLP syndrome from 150 maternal deaths 

encountered in Bavaria, Germany (population approximately 11.5 million persons), 

between 1983 and 1992, the clinical causes of deaths were intracerebral 

hemorrhage (n = 8), ruptured subcapsular liver hematoma (n = 2), and, in one 

case each, thrombosis of sinus cavernosus, acute renal failure, pulmonary insufficiency 

(not further specified), and myocardial infarction (18). In all eight

HELLP 279 

cases of intracerebral hemorrhage, the diagnosis was made clinically by computed 

tomography. In this series, the clinical cause of death was verified by 

autopsies in six cases. 

In 2002, Soh et al. reported a case of fatal cerebellar infarction in a 39-yearold 

primipara with postpartum HELLP syndrome (20). 

DIC can be found in 4–38% of cases with HELLP syndrome (21). Despite 

the apparent correlation between the marked degree of DIC in laboratory tests 

and the extent of laboratory changes in HELLP syndrome and the rate of 

maternal complications (22), the manifestation of DIC is neither an initial nor 

a principal symptom of HELLP syndrome but rather reflects a secondary pathophysiological 

process of the primary disease state that can be regarded as a 

result of preeclampsia that was diagnosed and/or treated too late (6). 

Hepatic rupture as a sequel of subcapsular liver hematoma in the course 

of DIC is considered the most serious and life-threatening maternal complication 

in HELLP syndrome responsible for a maternal mortality between 50–77% 

(6,23–24). Hepatic rupture in HELLP syndrome has been reported to be located 

predominantly in the anterior-superior region of the right hepatic lobe (26–28) 

and can occur both antepartum and postpartum in 1.5–1.8% of cases with 

HELLP syndrome (23,24). In a Medline search covering the years 1990–1999, 

Reck et al. found 49 cases with HELLP syndrome-associated liver rupture 

published within this period (25). 

2.2. Autopsy Features 

Although a considerable number of case reports dealing with fatal HELLP 

syndrome has appeared in the medical literature during the last decades, autopsy 

features have only been reported sporadically, leading to a primarily anecdotal 

rather than systematic approach toward the true pathology of the disease. 

The main gross pathology findings can be summarized as follows (29): 

petechiae as well as more widespread hemorrhages (suffusions) attributable 

to DIC in conjunctivae, skin, on mucous surfaces and serous coats of internal 

organs, and in the gray and white matter of the brain (purpura cerebri), cerebral 

edema, signs of ARDS such as fixed, edematous and congested lungs, 

edema of the lower extremities, hyperemia of the spleen, hydropericardium, 

and shock kidneys (Fig. 1). Because the aforementioned pathological features 

can be initiated by a variety of underlying pathologic conditions, these findings, 

when present, have to be considered as highly unspecific. In contrast, 

liver pathology appears to be one of the hallmarks in the postmortem diagnosis 

of HELLP syndrome (29,30). At autopsy, multiple blackish-reddish patches 

are a striking finding after opening of the abdominal cavity (Fig. 2). The liver

280 Tsokos 

Fig. 1. Maternal death from HELLP syndrome in the late third trimester. 

Uterus and pelvic organs after evisceration. Note the marked shock kidneys. 

(Courtesy of Prof. Franz Longauer, Koˇsice, Slovak Republic.) 

Fig. 2. Maternal death from HELLP syndrome. Opened abdominal cavity: 

multiple blackish-reddish patches are present on the surface of the liver. (Courtesy 

of Dr. Friedrich Schulz, Hamburg, Germany.)

HELLP 281 

Fig. 3. Maternal death from HELLP syndrome. Cross-section of the liver 

parenchyma showing confluent hemorrhagic foci. (Courtesy of Dr. Friedrich 

Schulz, Hamburg, Germany.) 

shows a rigid consistence with yellow-brown cut surfaces and confluent hemorrhagic 

foci on cross-sections of the liver parenchyma (Fig. 3). Occasionally, 

subcapsular liver hematoma or even rupture of the liver may be present. In 

such cases, the immediate cause of death has to be considered hemorrhagic shock. 

In the remaining cases, lacking a clear-cut cause of death such as hepatic 

encephalopathy verified antemortem by clinical and laboratory means, the fatal 

outcome will have to be attributed to multiple organ failure (a combination of 

renal and hepatic failure, and ARDS), mainly as a result of DIC. 

2.3. Histopathology 

Liver pathology is a hallmark for the postmortem diagnosis of HELLP 

syndrome. The histopathological features of hepatic alterations in HELLP syndrome, 

which can be considered pathognomonic for the disease especially 

when found combined, can be summarized as follows: (a) periportal hepatocellular 

necrosis and hemorrhages sharply demarcated by an extended fibrin 

network from the surrounding unaffected liver parenchyma (Fig. 4A,B), (a) 

leukostasis in the liver sinusoids; (c) bile stasis with swelling of Kupffer’s 

cells, and (d) absence of inflammatory cellular infiltrates and lack of fatty 

transformation of hepatocytes (29).

282 Tsokos 

Fig. 4. Maternal death from HELLP syndrome. (A,B) Periportal hepatocellular 

necrosis and hemorrhages sharply demarcated by an extended fibrin network 

from the surrounding unaffected liver parenchyma (phosphotungstic acid 

hematoxylin). 

In the kidneys, preeclampsia primarily affects the glomerulus. The characteristic 

and diagnostic features of preeclamptic nephopathy are a combination 

of glomerular alterations rather than a single lesion. The glomeruli are 

enlarged and appear bloodless as a result of obliteration of the capillary lumina 

by swollen, vacuolated, and occasionally foamy endocapillary cells (29,31–33) 

(Fig. 5). The lack of intraglomerular cell proliferation (hypercellularity) and

HELLP 283 

Fig. 5. Maternal death from HELLP syndrome. Enlarged glomerulus with 

capillary loops virtually devoid of erythrocytes. The capillary lumina are for 

the most part obliterated by swollen, vacuolated, and occasionally foamy 

endocapillary cells (periodic acid-schiff). 

inflammatory changes in the glomeruli in HELLP syndrome is essential in 

differentiating acute glomerulonephritis (33). In most cases, two characteristic 

capillary loop patterns of the glomeruli (which may appear next to each 

other in one visual field) can be distinguished: a cigar-shaped loop type presenting 

elongated, stretched, and obstructed loops, and the pouting loop type 

showing enlarged glomerular tufts filling Bowman’s space with herniation of 

capillary loops into the proximal tubules (Fig. 6A,B). In both types, the loops 

are virtually devoid of erythrocytes, the mesangial cells appear swollen, and 

the endocapillary cells are vacuolated. Ballooning (dilatation) of the tips of 

the loops is another characteristic feature of preeclampsia (31). The most characteristic 

light microscopical features of liver and kidneys associated with 

HELLP syndrome are given in Table 1. 

Gerth et al. recently reported on a 26-year-old primigravida who developed 

HELLP syndrome 3 days after delivery of a healthy male infant. A renal biopsy 

performed on Day 12 postpartum showed partial obstruction of glomerular

284 Tsokos 

Fig. 6. Maternal death from HELLP syndrome. In the kidneys, two characteristic 

capillary loop patterns of the glomeruli can be distinguished: (A) the cigarshaped 

loop type with elongated, stretched, and obstructed loops, and (B) the 

pouting loop type showing enlarged glomerular tufts filling Bowman’s space 

with herniation of capillary loops into the proximal tubules (periodic acid-schiff). 

capillaries by fibrin deposits. On Day 60 postpartum, a thrombotic 

microangiopathy of arterial vessels with narrowing of the vascular lumen and 

mononuclear cell infiltration of the vessel layers was seen (34). 

Controversy persists concerning the pathogenesis of the histopathological 

alterations of the renal structures. Some authors favor the theory that the

HELLP 285 

Table 1 

Histomorphological Alterations of Liver and Kidneys Found in HELLP Syndrome 

Liver • Periportal hepatocellular necrosis (coagulation necrosis) and hemorrhages 

sharply demarcated by an extended fibrin network from the surrounding 

unaffected liver parenchyma 

• (Focal) leukocyte sticking (leukostasis) in liver sinusoids 

• Bile stasis with swelling of Kupffer’s cells 

• Lack of inflammatory cellular infiltrates in liver plates 

• Lack of fatty transformation of hepatocytes 

Kidneys • Bloodless glomeruli with swollen, vacuolated, and occasionally foamy 

endocapillary cells 

• Elongated and obstructed (“cigar-shaped”) capillary loops and enlarged 

glomerular tufts filling Bowman’s space with herniation of capillary 

loops (“pouting”) into the proximal convoluted tubules 

• Ballooning (dilatation) of the tips of the loops 

• Swelling of mesangial cells 

• Thrombi formation in glomerular capillaries and the vasa recta in cases 

with severe DIC 

Note. Modified from ref. 29. 

pathological changes of the glomeruli are, at least to a certain degree, a direct 

result of DIC (35,36). On the other hand, the occurrence of DIC is not specific 

for HELLP syndrome since DIC is a complication of preeclampsia in 

general that positively correlates in its intensity with the severity of preeclampsia 

(37). The frequency of DIC in HELLP syndrome depends not least 

on the presence and extent of placental abruption (4). However, signs of 

DIC on the micromorphological level such as microthrombi composed of 

fibrin and platelets can be seen infrequently in glomerular capillaries and 

vasa recta of the medulla as well as in smaller vessels and capillaries in 

various internal organs, for example, the lungs and intestinum (29). In addition, 

intraalveolar edema, activated alveolar macrophages and fibrin deposits 

covering the alveolar epithelium as hyaline membranes as a result of ARDS 

may be seen in the lungs. 

In the myocardium, focal contraction band necrosis without any accompanying 

inflammatory changes can be found frequently. Although an earlier 

study revealed the presence of contraction band necrosis in 35% of cases of 

fatal eclampsia in contrast to only 3% in controls and the authors attributed 

the frequent occurrence of myocardial contraction band necrosis in eclampsiaassociated 

deaths to preceding coronary artery spasms (38), myocardial

286 Tsokos 

contraction band necrosis is a well-known phenomenon to the forensic 

pathologist because it can be frequently observed not only in autopsy cases 

with myocardial ischemia of coronary origin but also in a variety of underlying 

pathologic conditions prior to death such as protracted agony, prolonged 

resuscitation attempts, preceding head trauma, repeated defibrillations with 

automatic implantable cardioverter-defibrillators, and in the sequel of administration 

of catecholamines during intensive care or before operation (39–44). 

For that reason, the finding of myocardial contraction band necrosis adds nothing 

to a definite postmortem diagnosis of preeclampsia or HELLP syndrome 

in specific autopsy cases in question. 

3. DIFFERENTIAL DIAGNOSES 

When examining fatalities that occurred during pregnancy or postpartum, 

the forensic pathologist has to be aware of an underlying HELLP syndrome 

irrespective the preceding clinical course (because this may have been 

atypical) and regardless of whether the syndrome was clinically suspected or 

not. For clinical characteristics and laboratory findings and their interpretation 

in the light of suspected HELLP syndrome in the living as well as the 

controversy concerning the definition, diagnosis, cause, and management of 

the syndrome, refer to the comprehensive clinical literature on this topic (e.g., 

3–6,9–12,15). Concerning the autopsy finding of intrahepatic hemorrhage 

and/or liver rupture, the (forensic) pathologist has to aware of possible differential 

diagnoses, especially liver rupture of traumatic origin. Underlying pathological 

conditions predisposing to spontaneous, nontraumatic liver rupture are 

malignant or benign liver tumors, hepatic amyloidosis, or peliosis hepatis 

(45–52).Because these conditions are difficult to diagnose in vivo and opportune 

life-saving surgery often fails, the definitive diagnosis is mainly established 

at autopsy in such cases. 

Another differential diagnosis is acute fatty liver of pregnancy (AFLP) 

characterized by microvesicular fatty infiltration of the liver, hepatic failure, 

and encephalopathy typically developing in the third trimester of pregnancy 

(53). DIC may be present in up to 75% of cases. Up to 50% of patients with 

AFLP also meet clinical criteria for preeclampsia (13). Fetal mortality remains 

at 15%, though maternal mortality occurs in less than 5% of cases (54). 

Other differential diagnoses that should be kept in mind in autopsy cases 

of suspected HELLP syndrome are thrombotic thrombocytopenic purpura 

(TTP) and hemolytic uremic syndrome (HUS), both pregnancy-associated 

thrombocytopenias that are traditionally considered the main entities of thrombotic 

microangiopathies (55).

HELLP 287 


When giving a medicolegal expertise in suspected cases of medical malpractice 

related to HELLP syndrome (e.g., under aspects of delayed diagnosis 

or stillbirth following expectant management of maternal symptoms) one has 

to bear in mind that the presenting symptoms of patients with HELLP syndrome 

are generally highly unspecific. As a result, many of the patients are 

initially misdiagnosed with other disorders (4). Delay in diagnosis of HELLP 

syndrome was implicated in 22 of 43 patients’ deaths (51%) in a study by Isler 

et al. (19). 

Management of HELLP is generally supportive, with the goal of medically 

stabilizing the patient prior to delivery (56). Conservative management 

has the primary goal and its only indication to gain time for further fetal lung 

maturation after administration of betamethasone or methylprednisolon. However, 

the effects of corticosteroids on the pathophysiological mechanisms in 

HELLP syndrome are still unknown (6). As shown recently in a large 

multicenter study, severe maternal complications in HELLP syndrome are significantly 

lower when the patient is delivered promptly after diagnosis, in contrast 

to expectant management (57). DIC requires immediate delivery by 

cesarean section before the manifestation of life-threatening maternal or fetal 

complications (6). Despite appropriate general and obstetric management, a 

subset of patients displays prolonged thrombocytopenia and multiple organ 

dysfunction with potential fatal outcome following delivery. 

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thrombocytopenia and other hematologic abnormalities associated with severe 

toxemia of pregnancy. N Engl J Med 250, 89–98. 

2. Weinstein L (1982) Syndrome of hemolysis, elevated liver enzymes, and low platelet 

count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 

142, 159–167. 

3. Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC, Ryan GM (1986) Maternalperinatal 

outcome associated with the syndrome of hemolysis, elevated liver enzymes, 

and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol 

155, 501–509. 

4. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA (1993) Maternal 

morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, 

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249–260.

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(1998) Maternal and perinatal outcome after expectant management of the HELLP 

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management in 254 consecutive patients with severe pre-eclampsia remote from 

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Partial HELLP Syndrome: maternal and perinatal outcome. Sao Paulo Med J 120, 

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11. Sibai BM (1990) The HELLP syndrome (hemolysis, elevated liver enzymes, and low 

platelets): much ado about nothing? Am J Obstet Gynecol 162, 311–316. 

12. Audibert F, Friedman SA, Frangieh AY, Sibai BM (1996) Clinical utility of strict 

diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) 

syndrome. Am J Obstet Gynecol 175, 460–464. 

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pathogenesis and management. Blood 80, 2697–2714. 

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considerations. Obstet Gynecol Surv 57, 598–618. 

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V Leiden and factor II G20210A in preeclampsia and HELLP syndrome. Acta Obstet 

Gynecol Scand 81, 1095–1100. 

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1983–1992. Zentralbl Gynakol 116, 202–206. 

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Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and 

low platelets) syndrome. Am J Obstet Gynecol 181, 924–928. 

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infarction with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. 

Gynecol Obstet Invest 53, 240–242. 

21. Reubinoff BE, Schenker JG (1991) HELLP syndrome—a syndrome of hemolysis, 

elevated liver enzymes and low platelet count—complicating preeclampsiaeclampsia. 

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23. Hüskes KP, Baumgartner A, Hardt U, Klink F (1991) Doppelseitige, mehrzeitige 

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25. Reck T, Bussenius-Kammerer M, Ott R, Muller V, Beinder E, Hohenberger W 

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28. Sheikh RA, Yasmeen S, Pauly MP, Riegler JL (1999) Spontaneous intrahepatic 

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in pregnancy from HELLP syndrome. A report of three medicolegal autopsy cases with 

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Gynecol Obstet 255, Suppl 2: S245–S254. 

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changes in the renal glomerulus and the juxtaglomerular apparatus in human 

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33. Gaber LW, Spargo BH, Lindheimer MD (1994) The nephropathy of preeclampsiaeclampsia. 

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defibrillation. Am J Forensic Med Pathol 8, 3–8. 

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and treatment. Forensic Sci Int 54, 181–189. 

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contraction bands. Definition, quantification and significance in forensic pathology. 


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human hearts. A morphometric study. Int J Cardiol 88, 267–278. 

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rupture of the liver associated with amyloidosis. J Clin Gastroenterol 11, 85–87. 

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54. Bacq Y (1998) Acute fatty liver of pregnancy. Semin Perinatol 22, 134–140. 

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Resuscitation Injuries 291 

Iatrogenic Injury

292 Darok


13 

Injuries Resulting From 

Resuscitation Procedures 

Mario Darok, MD 

CONTENTS 

INTRODUCTION 

POSSIBLE INJURIES DURING RESUSCITATION PROCEDURES 


REFERENCES 

SUMMARY 

Life-threatening situations deserve fast medical intervention but resuscitation 

procedures may have considerable effects on the patient’s health 

condition because (additional) trauma may occur. Additionally, these accidentally 

caused iatrogenic injuries might by themselves be life-threatening 

for the patient. The main injurious resuscitation measures include standard 

cardiopulmonary resuscitation (Std-CPR), active compression-decompression 

cardiopulmonary resuscitation (ACD-CPR), defibrillation, tracheotomy, 

coniotomy, tracheal intubation, puncture of veins or pericardium, and decompression 

of tension pneumothorax or mediastinal emphysema. In particular, 

injuries as a result of CPR are commonly encountered at autopsy and often 

not unexpected for the forensic pathologist. The most common cardiac 

resuscitation-related injuries are fractures of the ribs and sternum in 40–70% 

of cases. Above all, elderly patients are prone to such injuries. Trauma related 

to CPR is a rare complication in children. When encountering pediatric rib 

fractures, the forensic pathologist has to be aware of the differential diagnosis 



293

294 Darok 

of child abuse since rib fractures, especially when of different ages and affecting 

multiple adjacent ribs, are a hallmark of nonaccidental injury in children. 

CPR may lead to severe injuries of internal organs. Main factors 

influencing frequency and severity of injuries resulting from resuscitation 

procedures include length of resuscitation time, age of the patient, and degree 

of qualification of the medical personnel. From the medicolegal point of 

view, complications and accidental iatrogenic injuries will never be completely 

avoidable but their possibility has to be taken into consideration 

throughout further medical treatment. An undetected injury may result in 

impairment or even death of the patient and the responsible physician runs 

the risk of being prosecuted. To give a correct opinion, especially in cases of 

questioned medical malpractice, it is essential that forensic medical experts 

are familiar with resuscitation-related injuries and are able to distinguish 

them from the sequels of a natural disease process or trauma that occurred 

prior to resuscitation procedures. 

Key Words: Resuscitation; iatrogenic injury; medicolegal aspects; 

adverse effect; complication; expert opinion. 


During resuscitation procedures the physician will always give priority 

to clearing the life-threatening condition. Nevertheless, as some resuscitation 

procedures consist of massive manipulations, they hold a high risk of injury to 

the patient. Physicians should be aware of these risks to avoid additional danger 

for the patient. 

Howard is said to have caused the first recorded injury resulting from 

resuscitation procedures. In 1860, he performed a kind of thorax compression. 

While presenting his new method in front of police officers, he fractured several 

ribs of a well-known personality. Thereupon, external cardiac massage 

was not performed for decades (1). 

Being of highest relevance for the outcome of the patient, injuries owing 

to resuscitation procedures also have a great importance in forensic medicine 

as they have to be distinguished from lesions of different origin, for 

example, in cases of polytrauma. Finally, there is an increasing number of 

autopsies taking place against the background of questioned medical malpractice 

associated with resuscitation procedures preceding death (2). A good 

knowledge of resuscitation procedures and related adverse effects is therefore 

essential for the forensic pathologist in order to give a correct medical 

expert opinion.


2. POSSIBLE INJURIES DURING RESUSCITATION PROCEDURES 

2.1. Resuscitation Procedures on the Airways 

2.1.1. Intubation 

Tracheal intubation is one of the most common interventions in the treatment 

of life-threatening situations. Because securing of the patient’s airway 

deserves fast intervention, unintentional injuries cannot always be avoided. 

Even the assistance for intubation, namely traction and hyperextension of the 

neck, may lead to injury of the cervical soft tissue. The unconscious patient is 

incapable of showing any pain-elicited defense. If the patient’s neck is put in 

an extreme reclination by the assistant, a maximal straightening and, in consequence, 

a high tension load of the cervical column will occur, which might 

result in lesions of small vessels and retropharyngeal hemorrhage, respectively. 

According to autopsy data, the frequency of retropharyngeal hemorrhage as a 

sequel of resuscitation procedures is 9.2% (3). In a series of 65 primary 

atraumatic autopsy cases, Saternus and Fuchs found lesions of the carotid intima 

in 3 cases and explained this finding with the aforementioned maneuvers during 

tracheal intubation (3). 

Besides tracheal lesions, especially as a sequence of multiple attempts of 

intubation (4), tracheal intubation itself might result in further injury of cervical 

soft tissue, basically as a result of mechanical damage during the manipulations. 

These lesions include abrasion and hematoma of lips, tongue, and 

pharyngeal arch. According to an earlier autopsy study, the frequency of mucosal 

injury of the pharynx and larynx, respectively, is 18% (5). 

Fracture and dislocation of teeth, superficial injuries of the vocal cords, 

and pharyngeal hemorrhage are further intubation-related injuries. Although 

being a well-known complication to each physician, rupture of the stomach 

because of erroneous tube positioning into the esophagus and inflation of the 

stomach may occur (6–8). Other authors reported tube-induced esophageal 

perforation, especially in resuscitation of newborns (9,10). Lesions of the recurrent 

nerve, perforation of the piriform sinus, subluxation of the arytenoid cartilage, 

and tears of the vocal cords are exceptional findings in forensic autopsy 

practice, although they are possible from the anatomic point of view. 

In some cases, lesions of the trachea occur that result in pneumothorax 

and emphysema of subcutaneous tissue. Tracheal lesions are significantly more 

frequent in females than in males and more frequent in children than in adults. 

Lesions from tracheal intubation are always located in the membraneous part 

and situated in the longitudinal axis of the trachea (11).

296 Darok 

2.1.2. Tracheotomy/Coniotomy 

Tracheotomy or coniotomy are classical resuscitation measures. These 

iatrogenic wounds are indispensable to improving the life-threatening condition. 

The extent of this wound might accidentally exceed that which is necessary 

and thus threaten the life of the patient. Because of frequent complications, 

this method has a rigorous indication nowadays, after being performed generously 

in earlier decades. 

Mucosal lesions may derive from the tracheal incision and insertion of 

the cannula. Normally, these lesions would not lead to functional disorder and 

would heal without consequences. A “stab wound” of the dorsal tracheal wall 

might occur by accident resulting in local hemorrhage, mediastinal emphysema, 

subcutaneous parapharyngeal emphysema, or even pneumothorax. 

With coniotomy, the ramus of the superior thyroid artery, which is located 

at the lower margin of the thyroid cartilage, might be injured leading to hemorrhage 

(12). 

In the past few years, percutaneous needle cannulation of the trachea 

gained in importance for being a less invasive intervention because there is no 

surgical wound, unlike in tracheotomy, and tracheal cartilages are thought to 

remain untouched. The primary trauma of tissue is hence decreased but, nevertheless, 

iatrogenic injuries may occur. 

A postmortem study of 12 patients who had undergone percutaneous tracheotomy 

prior to death revealed fracture of at least one tracheal cartilage in 

11 cases (13). Additionally, in two cases a fracture of the cricoid cartilage was 

seen. Other studies reported cases of tension pneumothorax, accompanied by 

subcutaneous and mediastinal emphysema, as a result of tracheal rupture following 

percutaneous tracheotomy (11,14). 

2.2. Resuscitation Procedures on the Heart 

2.2.1. Cardiopulmonary Resuscitation 

To the forensic and clinical pathologist the most common and well-known 

sign of external heart massage are superficial dermal abrasions above the sternum 

stemming from the hands of the person performing cardiac massage. 

Although these minor injuries of course do not have any forensic relevance, 

fractures of ribs and/or sternum cannot always be avoided during cardiac massage, 

particularly in elderly patients having a rigid thorax. The most common 

regions of fractures are ribs 2–7 on the left and 2–6 on the right side, respectively 

(15). According to the literature, the frequency of rib fractures as a 

sequel of cardiac massage varies from 19 to 80% and that of sternal fractures


from 0 to 47%. In persons of higher age, an increase of fracture frequency is 

described unanimously. These thoracic fractures may lead to lung contusion 

or, in some cases, even to more severe lesions of the lung (16). As a result, a 

pneumothorax might develop, possibly leading to pneumoperitoneum when 

the gas escapes into the peritoneum through the epiploic foramen, primary 

lesions of the gastrointestinal tract, or the diaphragm (17,18). 

The location of resuscitation-related rib fractures is mainly in the 

medioclavicular line, thus close to the sternal joint, whereas sternal fractures 

are located horizontally in the lower two thirds. These sharp-edged bone fragments 

can be located close to the heart. Continued heart massage in combination 

with inward bone dislocation may result in lesions of the pericardium or 

even lead to life-threatening injury of the heart with pericardial tamponade 

(19). In cases of polytrauma, ruptures of aorta or vena cava are facilitated 

because of traumatic distortions and/or tears of the vessel wall (20). 

Rupture of the stomach or diaphragm might also be an effect of heart 

massage but are also a possible complication of the Heimlich maneuver. With 

artificial respiration, inflation and distension of the stomach can occur. In this 

case, additional compression during external heart massage can result in injuries 

to the gastric mucosa (16). A case of Mallory–Weiss syndrome with 

hematemesis following cardiopulmonary resuscitation (CPR) has been reported 

(21). Other rare complications of CPR include gastrointestinal hemorrhage 

(22) and aspiration (23). Injuries to sanguine internal organs like liver and 

spleen are also rare but much more dangerous (16,20,24) since in most cases 

intraabdominal hemorrhage will develop resulting in hypovolemic shock and 

death if the internal hemorrhage remains undetected. Too low positioning of 

thorax compression at the costal arch level in conjunction with violent pressure 

application is considered to be the cause of abdominal organ contusions 

(20). On the other hand, pre-existing organic damage like cavernous hemangioma 

and abnormal fragility of the liver owing to sepsis may worsen outcome 

(16). In the literature, some cases of CPR resulting in pulmonary 

barotraumas have been reported (25,26), thus possibly leading to massive fatal 

air embolism of cerebral vessels (27). 

2.2.2. Active Compression-Decompression 

Cardiopulmonary Resuscitation 

Active compression-decompression cardiopulmonary resuscitation (ACD- 

CPR) is one of the recent developments in emergency medicine. A plungerlike 

suction device, the so-called CardioPump ® , has been developed and is commercially 

available. In particular, the decompression phase improves venous

298 Darok 

return and cardiac output as well (28). The typical sign of CardioPump ® usage 

is a reddish ring on the skin at the sternum corresponding to the rubber suction 

cup of the CardioPump ® . 

Several postmortem studies have been undertaken to assess the risk of 

injuries in ACD-CPR. The results showed a higher frequency of thoracic bone 

fractures using ACD-CPR than using standard CPR (Std-CPR). This frequency 

was even exceeded by those patients who had undergone ACD-CPR subsequent 

to Std-CPR (29). In two cases, massive injuries of the heart as a result of 

fractured sternal bone fragments were observed that were attributed to the use 

of the CardioPump ® (30). In another case, massive laceration of the recently 

infarcted heart was observed after combined Std-CPR and incorrectly attempted 

ACD-CPR (31). In conclusion, possible injuries because of Std-CPR and ACD- 

CPR are very similar but in principle there is no higher risk of being injured if 

ACD-CPR is performed correctly. However, in a study in cadavers, females 

were found to have a higher risk of sternal fractures, whereas elderly patients 

seem to have a higher risk of rib fractures (32). Another study reported that 

consequences of ACD-CPR are less severe than those of Std-CPR (33). Frequency 

and severity of injuries is significantly higher if Std-CPR and ACD- 

CPR are applied in combination (29–31). 

2.2.3. Defibrillation 

Apart from temporary erythema, no relevant injuries are observed as a 

sequel of defibrillation (15). One case study describes a case of a primary 

successful CPR lasting for 90 minutes, including 14 cardioversions, resulting 

in rhabdomyolysis of the thoracic musculature, myoglobinuria, and, finally, 

renal failure (34). 

2.2.4. Intracardial Injection/Pericardiocentesis 

Intracardial injection is by itself an injury to the heart. Erroneous paracentesis 

of the heart or a coronary vessel may lead to pericardial hemorrhage 

and tamponade (15). Adjacent organs like lungs, liver, and mammarian 

artery and vein are also at risk of being damaged (12). Pericardiocentesis 

comprises the risk of myocardial lesions and the complications mentioned 

above. 

2.3. Resuscitation Procedures on Other Thoracic Organs 

2.3.1. Decompression of Mediastinal Emphysema 

Main complications include lesions of cervical organs like thyroid gland 

and large vessels with resulting retrosternal hemorrhage (12).


2.3.2. Decompression of Tension Pneumothorax 

In pneumothorax, the lung is retracted from the thoracic wall and therefore 

out of risk from injury. Merely the lesion of intercostal vessels might 

cause a circumscribed hemorrhage, which is of no mayor consequence. 

2.4. Resuscitation Procedures on Vessels 

2.4.1. Puncture of a Vein 

In peripheral veins, paravenous positioning of a needle or catheter 

becomes apparent almost immediately and has no consequences. However, 

puncture of central veins holds many dangers. Erroneous puncture of the subclavian 

vein with puncture of the pleura will result in accumulation of air, 

blood, or infusion of fluid inside the thoracic cavity. Even if the catheter is 

positioned correctly inside the subclavian vein, a perforation of the vessel can 

occur, leading to soft-tissue hemorrhage of possibly large extent. If the catheter 

is pushed forward excessively, injuries of the heart valves or even atrial 

perforation and pericardial tamponade are possible. Incorrect positioning of 

the catheter might even result in embolic vascular occlusion. Possible injuries 

from jugular vein puncture include lesions of the carotid artery with the effect 

of soft-tissue hemorrhage, air embolism, and injuries of the heart valves. 


According to unanimous reports from the literature, length of resuscitation 

time, age of the patient, and degree of qualification of the emergency 

personnel are the main factors influencing frequency and severity of injuries 

resulting from resuscitation procedures (15,16). 

Most of the methodical or accidental injuries due to resuscitation procedures 

are relatively minor as they have no relevant influence on the clinical 

outcome of the affected patient. On the other hand, even lethal injuries of 

internal organs can result. 

External cardiac massage is per se a blunt thoracic trauma with defined 

localization and dose (15). In accordance, most injuries are located on the 

thorax. CPR shows the highest frequency of injuries. According to data from 

the literature, the rate of complications in cardiac resuscitation is 20–55% 

(15,35). Injuries of ribs and/or sternum amount to 40% of cases, if the thorax 

is elastic, and to 70% of cases with a barrel-shaped thorax (36). Interestingly, 

a major study showed that resuscitation-related fragility of ribs 2–7 is dependent 

on age whereas fragility of ribs 3 and 4 is also dependent on the duration 

of the preceding cardiac massage (37). Fractures of ribs 1, and 8–12 are very

300 Darok 

rare after CPR (37,38) whereas abdominal visceral complications are noted in 

30.8% of cases. (35). 

The frequency of intubation-related injuries is said to be 13% (16). Cervical 

injuries after intubation and thoracic injuries after CPR have a similar 

frequency (36). 

In a most recent study of 204 fatalities of children, injuries attributable 

to resuscitation procedures were detected in 42.5% of children who underwent 

resuscitation procedures (39). All but two of these injuries were of a 

minor nature consisting principally of bruises or abrasions. Two significant 

injuries were identified, both occurring as a result of readily identifiable resuscitation 

procedures. The likelihood of injury increased with the length of 

resuscitation: in children resuscitated for less than 60 minutes, the incidence 

of injury was 27% compared with 62% for children resuscitated for longer. 

Another report also indicates that trauma related to CPR is a rare complication 

in children (40). However, when encountering pediatric rib fractures, the forensic 

pathologist has to be aware of the differential diagnosis of child abuse 

since rib fractures, especially when of different ages and affecting multiple 

adjacent ribs, are a hallmark of nonaccidental injury in children. 

Basically, percental results should be responded to skeptically. The great 

majority of statistical studies is based on data from autopsy cases after unsuccessful 

resuscitation. Regarding the age distribution of the analyzed cases, it 

should be taken into consideration that not only morbidity and mortality 

increase with age but also the probability of an unsuccessful resuscitation 

attempt. In addition, the thoracic skeleton of the elderly patient shows a highly 

increased vulnerability because of degenerative alterations. Another contributory 

effect to high injury frequency is the fact that, in cases of multiple futile 

resuscitation attempts, a less experienced helper is likely to force his or her 

efforts excessively. In consequence, the physiological threshold might be 

exceeded resulting in massive injuries. Finally, an unsuccessful resuscitation 

will probably take more time than a successful one and thus the likelihood of 

injuries will increase. 

Complications and accidental iatrogenic injuries will never become completely 

avoidable in medicine in general nor in first aid. From the medicolegal 

point of view, problems arise if the possibility of a complication has not been 

taken into consideration and remains undetected, leading to impairment of 

health condition or even death of the patient. In this case, there might be repercussions 

on the physicians in charge: the responsible physicians might be 

prosecuted and/or civil action could be brought against them. A detailed and 

complete documentation is strongly recommended to prove the sequence of


events as other evidence will most probably not be available months or years 

after the incident when the trial takes place. 

For the forensic medical expert, it is of great importance to have a good 

knowledge of injuries resulting from resuscitation procedures as they have to 

be distinguished from other trauma to give a correct opinion. Of course, this 

cannot always be decided with certainty, for instance, if trauma and/or preexisting 

organic disorders are present (31,41). 

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a sequence of multiple attempts of endotracheal intubation in the course of a preclinical 

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Anästh Intensivmed 29, 42–49. 

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9. Eldor J, Ofek B, Abramowitz HB (1990) Perforation of oesophagus by tracheal tube 

during resuscitation. Anaesthesia 45, 70–71. 

10. Topsis J, Kinas HY, Kandall SR (1989) Esophageal perforation—a complication of 

neonatal resuscitation. Anesth Analg 69, 532–534. 

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tracheobronchial tree. Chest 112, 774–778. 

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Med Wochenschr 118, 567–572. 

13. Van Heurn LWE, Theunissen PHMH, Ramsay G, Brink PRG (1996) Pathologic 

changes of the trachea after percutaneous dilatational tracheotomy. Chest 109, 

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14. Malthauer RA, Telang H, Miller JD, McFadden S, Inculet RI (1998) Percutaneous 

tracheostomy. Chest 114, 1771–1772. 

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302 Darok 

16. Pracht U, Schulz E (1987) Befunde nach erfolgloser kardiopulmonaler Reanimation. 

Notarzt 3, 187–189. 

17. Hargarten KM, Aprahamian C, Mateer J (1988) Pneumoperitoneum as a complication 

of cardiopulmonary resuscitation. Am J Emerg Med 6, 358–361. 

18. Hartoko TJ, Demey HE, Rogers PE, Decoster HL, Nagler JM, Bossaert LL (1991) 

Pneumoperitoneum—a rare complication of cardiopulmonary resuscitation. Acta 

Anaesthesiol Scand 35, 235–237. 

19. Noffsinger AE, Blisard KS, Balko MG (1991) Cardiac laceration and pericardial 

tamponade due to cardiopulmonary resuscitation after myocardial infarction. J Forensic 

Sci 36, 1760–1764. 

20. Umach P, Unterdorfer H (1980) Massive Organverletzungen durch Reanimationsmaßnahmen. 

Beitr Gerichtl Med 38, 29–32. 

21. Norfleet RG, Smith GH (1990) Mallory–Weiss syndrome after cardiopulmonary 

resuscitation. J Clin Gastroenterol 12, 569–572. 

22. McGrath RB (1983) Gastroesophageal lacerations. A fatal complication of closed 

chest cardiopulmonary resuscitation. Chest 83, 571–572. 

23. Lawes EG, Baskett PJ (1987) Pulmonary aspiration during unsuccessful cardiopulmonary 

resuscitation. Intensive Care Med 13, 379–382. 

24. Adler SN, Klein RA, Pellecchia C, Lyon DT (1983) Massive hepatic hemorrhage 

associated with cardiopulmonary resuscitation. Arch Intern Med 143, 813–814. 

25. Hillman K, Albin M (1986) Pulmonary barotrauma during cardiopulmonary resuscitation. 

Crit Care Med 14, 606–609. 

26. Shulman D, Beilin B, Olshwang D (1987) Pulmonary barotrauma during cardiopulmonary 

resuscitation. Resuscitation 15, 201–207. 

27. Yamaki T, Ando S, Ohta K, Kubota T, Kawasaki K, Hirama M (1989) CT demonstration 

of massive cerebral air embolism from pulmonary barotrauma due to cardiopulmonary 

resuscitation. J Comput Assist Tomogr 13, 313–315. 

28. Guly UM, Robertson CE (1995) Active decompression improves the haemodynamic 

state during cardiopulmonary resuscitation. Br Heart J 73, 372–276. 

29. Rabl W, Baubin M, Broinger G, Scheithauer R (1996) Serious complications from active 

compression-decompression cardiopulmonary resuscitation. Int J Legal Med 109, 84–89. 

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compression-decompression cardiopulmonary resuscitation (ACD-CPR). Analysis 

of iatrogenic complications and their biomechanical explanation. Forensic Sci Int 

89, 175–183. 

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active compression-decompression cardiopulmonary resuscitation. Int J Legal Med 

111, 93–96. 

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compression-decompression cardiopulmonary resuscitation (ACD-CPR) in cadavers. 

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aktiven Kompression-Dekompressions-Technik (ACD) im Rahmen der präklinischen 

Reanimation. Anesthesiol Intensivmed Notfallmed Schmerzther 29, 492–500.


34. Minor RL Jr, Chandran PK, Williams CL (1990) Rhabdomyolysis and myoglobinuric 

renal failure following cardioversion and CPR for acute MI. Chest 97, 485–486. 

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Rechtsmed 86, 161–174. 

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Schäden nach der äußeren Herzmassage. Zbl Rechtsmed 20, 8. 

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Anästh Intensivther Notfallmed 18, 199–203. 

39. Ryan MP, Young SJ, Wells DL (2003) Do resuscitation attempts in children who die, 

cause injury? Emerg Med J 20, 10–12. 

40. Price EA, Rush LR, Perper JA, Bell MD (2000) Cardiopulmonary resuscitationrelated 

injuries and homicidal blunt abdominal trauma in children. Am J Forensic 

Med Pathol 21, 307–310. 

41. Zhu BL, Quan L, Ishida K, Taniguchi M, Oritani S, Kamikodai Y, et al. (2001) Fatal 

traumatic rupture of an aortic aneurysm of the sinus of Valsalva: an autopsy case. 

Forensic Sci Int 116, 77–80.

Postmortem Alcohol Interpretation 305 

Toxicology

306 Hunsaker and Hunsaker


14 

Postmortem Alcohol Interpretation 

Medicolegal Considerations Affecting 

Living and Deceased Persons 

Donna M. Hunsaker, MD 

and John C. Hunsaker III, MD, JD 

CONTENTS 

INTRODUCTION 

CONSUMPTION OF ETHYL ALCOHOL AND ITS PATHOLOGICAL EFFECTS ON THE BODY 

THE INTERPRETATION OF ETHYL ALCOHOL RESULTS: MEDICOLEGAL ASPECTS 

REFERENCES 

SUMMARY 

Ethyl alcohol (EA), the psychoactive ingredient in “alcoholic beverages,” 

is ubiquitous globally, and intemperate consumption is commonly associated 

with violence and disease. The most frequently detected drug by toxicology 

laboratories, it is the leading cause of drug-associated death and nonfatal 

trauma. As a central nervous system depressant, it acutely impairs human function 

and produces consistently documented, measurable neurophysiologic 

changes at advancing stages of intoxication. The pharmacokinetics of EA 

(absorption, distribution, elimination) is subject to multiple variables. Tolerance 

to EA from habitual consumption critically impacts the evaluation of 

both behavioral change and biochemical features. Toxicity from chronic consumption 

causes multiorgan pathology with considerable morbidity and mortality. 

Toxicologists have quantified EA in virtually all bodily organs, tissues, 

and secretions. Whole blood from the femoral or subclavian veins is the 

analytical “gold standard” for EA in official medicolegal death investigation. 



307

308 Hunsaker and Hunsaker 

Many studies have established the comparative ratio of blood EA concentration 

(BAC) to matrices from extravascular compartments. Postmortem decomposition 

spuriously increases blood EA owing to endogenous production by 

overgrowth of normal, fermentative flora in the gut with substantial (~0.20%) 

artifactual elevations. Vitreous humor, typically sterile, is a reliable comparison 

medium to differentiate antemortem consumption from postmortem production. 

Fluids from embalmed bodies may be utilized selectively to estimate 

the antemortem BAC by comparison with constitutive volatiles in embalming 

fluid. Characteristic gross and histological pathology in various organ systems 

may be diagnostic of chronic alcoholism even without established history. 

Progressive toxic effects are commonly expressed in the liver, heart, 

pancreas, and the central nervous system. Clinically, many non-alcohol-related 

medical or drug-related conditions may mimic acute EA intoxication. The 

medicolegal investigator may be required to interpret analytical results in 

specimens from a survivor responsible for deaths in vehicular collisions. For 

this reason this review also addresses issues related to the collection and processing 

of specimens from living persons. Application of retrograde analysis 

and extrapolation to estimate the BAC at a time prior to collection may be 

cautiously considered only when the subject is clearly in the elimination phase. 

These estimations rely not only on the type and timing of collected specimens, 

but also on factors such as the individual’s physiology, the type of alcoholic 

beverage consumed, and the length and circumstances of the drinking period. 

In all medicolegal investigations, biochemical specimens invariably have future 

evidentiary relevance and materiality. Strict observance of the legal chain of 

custody in specimens obtained from both the deceased and survivors is mandatory 

to guarantee the reliability and integrity of the analysis on which the 

forensic pathologist as interpretative toxicologist relies. Properly recognized, 

obtained, packaged, transmitted, analyzed, and stored specimens facilitate 

admissibility of results and valid expert interpretation in court. 

Key Words: Blood ethyl alcohol concentration; pharmacokinetics; neuropsychological 

effects of alcohol; retrograde extrapolation; postmortem decomposition; 

forensic toxicology; forensic pathology; legal chain of custody. 


Ethyl alcohol (EA) is the most commonly used and abused drug in the 

world (1,2). It is the most frequently detected drug in deaths from all causes, 

having the highest incidence in trauma (3). In the United States, EA use and 

abuse are responsible for around 100,000 deaths and well over $100 billion in 

economic costs annually (4). Not only is EA a toxin that contributes to natural


disease (5), it is associated with a vast number of preventable, often fatal injuries 

(6–15). 

A comprehensive review of alcohol in medicolegal settings appears in the 

multiauthored text Medical-Legal Aspects of Alcohol edited by James Garriott 

(16). Body fluid EA levels can be reliably quantitated in blood, vitreous humor, 

urine, breath, cerebrospinal fluid, saliva, and bile. The “gold standard” in testing 

postmortem fluid EA levels for medicolegal purposes is whole blood (from 

the femoral or subclavian veins) by headspace gas chromatography (17–19). 

The blood alcohol content (BAC), which devolves from collection and analysis 

of the specimen at specific, discrete points in time, is dependent on the 

individual’s unique absorption, distribution, and metabolism of the drug (20). 

Correlation of the BAC to the level detected in a particular body fluid from one 

or more other body compartments is one of the most important components in 

the evaluation of a specific case (21,22). Consideration of the acute and chronic 

drinking status of the individual in question—ranging from naïve drinker to 

“social consumer” (23) to alcoholic (24)—aids in the overall interpretation of 

the neuropathophysiological effects of the BAC on the subject. The clinical 

stages of acute alcoholic influence and intoxication developed by Dubowski 

constitute a workable guideline for correlation of such measurable behavioral 

alterations with the whole-blood EA levels (25–27). The Widmark equation, conceived 

by the Swedish physiologist Erik M. P. Widmark (1889–1945), is a useful 

construct to provide retrograde and anterograde calculations for BAC estimations 

at a time different from the time of sample collection (28,29). This review also 

underscores the necessity of, and specifies the procedures for, maintaining the 

appropriate chain of custody for medicolegal purposes. 

2. CONSUMPTION OF ETHYL ALCOHOL AND ITS PATHOLOGICAL EFFECTS 

ON THE BODY 

2.1. Characteristics of Alcoholic Beverages 

An hydroxylated aliphatic hydrocarbon, the simple chemical or drug, 

EA (C 2 H 5 OH; molecular weight 46), itself is a clear colorless, odorless, flammable 

liquid with a warm burning taste. Chemically, it is only slightly polar, 

so that it easily passes through lipid cell membranes. For millennia it had been 

accepted as a social drug consumed in alcoholic beverages (30). A beverage 

that contains a least 0.5% EA is considered an alcoholic drink. Alcoholic beverages 

are numerous and varied. The availability and type of EA in beverages 

and other commodities depend on local customs, traditions, agricultural products, 

and industrial technology within a given cultural, social, or political setting.


Overall, the most common means of EA exposure is by oral consumption. 

With wide industrial use of EA as a solvent or as an offshoot of many 

manufacturing processes, exposure from either inhalation of the vapor or 

cutaneous touching of the liquid may occur. At present, regulation prescribes 

the threshold for exposure in industry at 1000 ppm (1900 mg/m 3 ) (31). Intravenous 

injection of EA, the fastest route of entry, is used uncommonly to 

treat methyl alcohol (32) or ethylene glycol poisoning, or to occasionally 

detoxify trauma patients under the influence of EA (33). Significant quantities 

of EA are commonly incorporated into medications including mouthwashes, 

over-the-counter drugs, and prescription medications or elixirs (1). 

Approximately 10–18% EA may be mixed in some mouthwashes and health 

tonics. Sundry cold medicines may contain up to 4–10% EA. The elixir of 

terpin hydrate, a prescriptive antitussive, may have EA content of 40% (34). 

A detailed list of these commercially available EA-containing products is 

referenced in Winek and Esposito’s chapter on antemortem and postmortem 

alcohol determination (1) and Garriott’s text (16). Calculation of the BAC 

after consumption of these products rests on determining the percent alcohol 

content within the medication and quantitating the established volume 

of the medication consumed (1). 

Methanol (wood alcohol), isopropanol (rubbing alcohol), and ethylene 

glycol (most commonly in antifreeze) may be ingested in desperation or confusion, 

particularly by alcoholics without a readily available source of EA, as 

a substitute for EA. In these cases, toxicity can be achieved at low blood levels 

(34). Fatalities attributed to ingestion of common household products containing 

EA are also described (35). 

EA for consumption (drinking alcohol) is prepared by fermentation of 

sugars and starches from various sources in the presence of yeast. Fermented 

beverages have a maximal alcohol content of 14–15% by volume. Corn and 

molasses, fruit juices, grain, rye, and barley are common raw materials for 

starting the fermentation process (1,36). Ordinary alcoholic beverages may be 

divided into three general classes, depending on the manufacturing process 

and the types of agricultural products used to make them (1). These products 

include wines, fermented malt beverages, and distilled “hard” liquors. Wines 

are essentially fermented juices of fruits, berries, and flowers. The final product 

is either artificially sweetened or fortified with additional alcohol. The 

average alcohol content in wines ranges between 10 and 20%. Fermented malt 

beverages, such as beer, ale, porter, and stout, typically have alcoholic contents 

ranging between 3 and 8%. Distilled or hard liquors with alcoholic contents 

ranging between 40 and 50% include rye, bourbon, blends of brandy,


scotch, gin, vodka, and rum, to name a few. Manufacturers of whiskey, rum, 

brandy, gin, and other alcohol products use distillation, the process of superheating 

a mixture of alcohol and water with capture and cooling of the steam 

thus formed, to increase the percent alcohol concentration by volume (1,36). 

The EA content of a beverage may be stated in several ways. The most 

commonly used terminology is percent composition by weight (e.g., in the 

United States beer contains 3.2% EA by weight, which is equivalent to 4% 

EA by volume) (37). “Proof “is the quantity of alcohol in wines and distilled 

liquors expressed in the United States. The proof equals twice the percentage 

of EA by volume (i.e., 1 oz of 80 proof whiskey contains 40% EA by 

volume, which amounts to


2.2. Pathophysiological and Pharmacodynamic Effects of Ethanol 

An individual who is drinking EA cannot control or predict the type of 

social behavior or psychomotor changes he or she will experience during or 

within minutes to hours after the act of consumption (27). Lack of muscular 

coordination even at low BAC is coupled with increased reaction time to environmental 

stimuli. Cutaneous vasodilatation causes an increased blood supply 

to the venous plexus of the skin and results in cutaneous flushing (41). The 

person also feels warmer despite the insensible loss of body heat. Such peripheral 

dilatation accounts for the phenomenon observed in very cool or cold 

environmental conditions whereby a person under the influence of alcohol 

tends to become hypothermic, and even freeze to death, more quickly than 

one who is sober. Increased urine output from drinking alcoholic beverages is 

attributed to both greater water intake (water diuresis) and the inhibitory effect 

of EA on antidiuretic hormone, with resultant increased renal excretion (27). 

The principal pharmacodynamic actions of EA are attributable to its primary 

action as a central nervous system (CNS) depressant (27,41). The higher 

CNS centers (neocortex) are initially affected and, as the blood level rises 

sufficiently, EA interferes with the function of lower centers controlling respiration 

and circulation. As a CNS depressant, it acts as a sedative, a hypnotic, 

and an anesthetic. The depressant effect on individual neurons is directly proportional 

to the amount of intra- and perineuronal EA, which is reflected in 

the BAC, so that there is progressive deterioration of body functions as the 

blood level increases. The early effects produced by a relatively low BAC 

include reduction of tension, relaxation, release of inhibition, a sense of wellbeing, 

poor judgment, and mild euphoria (1, 27). These combined effects often 

lead to false courage and diminished ability to adjudge danger in a given situation. 

Such early effects create the common misconception by the uninitiated 

that EA is a stimulant. This phenomenon of apparent stimulation, more properly 

termed “pseudo-stimulation,” is a result of its ability at the very early 

phase of EA consumption to repress psychological inhibitory mechanisms that 

typically are controlling factors in behavior (26). 

Progressive psychomotor effects are well delineated in the adaptation of 

K. M. Dubowski’s Table of Stages of Alcohol Intoxication (1,25,27,41) 

(Table 1). 

The physiologic effects of alcohol are considerably more pronounced 

when the blood level is rising relative to levels attained at peak or plateau, or 

when the level is falling. This phenomenon is coined the Mellanby Effect 

(42). An extreme example is that reported of a 23-year-old comatose female 

following a single-driver motor vehicle collision (43). Shortly after the event


Table 1 

Modification of Dubowski’s Stages of Alcohol Intoxication 

Subclinical or sobriety (0.00–0.04%): The functional changes occur in the high cerebral 

cortex and affect perception and processing of information received by the special 

senses. Learned motor responses are spared. 

Euphoria (0.05–0.14%): This stage, considered to be “under the influence” of EA, is 

characterized by a diminished attention span, judgment, and control with incremental 

loss of motor response. There is mild euphoria, increased self-confidence, and 

sociability. 

Stimulation or excitement (0.15–0.24%): EA is to most observers demonstrably a central 

nervous system depressant. Personality and behavioral changes are unpredictable, 

with decreased inhibition and poor judgment. There is impairment of memory 

and comprehension. Decreased sensory response with increased motor reaction time 

and muscular incoordination supervene. 

Confusion (0.25–0.34%): This stage is associated with slurred speech and stumbling 

gait. There is decreased pain sense, impaired balance, and disturbance of perception 

of color, form, dimensions, and motion. Increased mental confusion with exaggerated 

emotional states (fear, anger, and grief) is very characteristic of this stage. 

Stupor (0.35–0.4%): The individual is apathetic with markedly decreased response to 

stimuli, impaired consciousness coexistent with arousable sleep. 

Coma (>0.40%): Complete unconsciousness without arousal; death ensues in 95% of 

cases where coma lasts greater than 12 hours. 

Death (0.45–0.60%): Forensic pathologists and other specialists agree that the minimum 

lethal level of alcohol is subject to many variables, such as the underlying 

health of the consumer or the rapidity of intake, and may be found at levels from 

0.30 to 0.45% secondary to respiratory depression. 

Note. According to ref. 25. 

her BAC was 780 mg/dL on hospital admission, and declined to a BAC of 190 

mg/dL at discharge to police authority 11 hours later. At that time, she fulfilled 

the criteria for sobriety upon thorough neurological examination: full 

consciousness without any signs of neuropsychological impairment. 

In summary, the progressive effects, which become more pronounced 

with steadily increasing BAC, consist of intellectual deterioration, followed 

by impairment of motor coordination, loss of consciousness, respiratory depression, 

circulatory collapse, and death. EA acts selectively as a CNS depressant 

at low doses and initially affects the most sophisticated parts of the brain (i.e., 

the cerebral cortex), which control judgment and morals. At increasingly higher 

levels, EA is a more generalized depressant and triggers progressive dysfunction 

of the oldest portion of the brain, most importantly the brainstem, which


regulates homeostatic control of autonomic body functions (27,41). Each person 

reacts differently at measured equivalent BAC levels secondary to individual 

psychomotor variability in response to EA as a drug. The physical effects 

of EA, which are subject to objective analysis, are dependent predominantly 

on the amount consumed. In contrast, the subjective intellectual and emotional 

effects are strongly influenced by the “set” and “setting.” The “set” is 

defined as the mood and attitudes of the individual at the time of consumption, 

that is, the individual’s underlying personality traits, which may become 

unmasked (“In vino veritas”). The “setting” refers to the external circumstances 

in which the consumption occurs (37). 

In assessing the effects of EA on human behavior, the forensic specialist 

must be aware of many other drugs and conditions—with or without the added 

presence of EA—that produce signs and symptoms similar or identical to those 

caused by EA (34). Factors comprising the differential diagnosis of causes of 

acute EA intoxication include nonalcoholic medical conditions with similar 

clinical manifestations such as diabetic ketoacidosis, hypoglycemia, craniocerebral 

trauma or neurodegenerative diseases, and spontaneous cerebrovascular 

events (stroke) (34,37). 

In view of the contemporary pharmacopeia and epidemic of substance abuse, 

the forensic investigator must be aware of the phenomenon of drug–drug interactions 

to reach sound medical conclusions about the effects of any drug on individual 

behavior. Certain non-alcohol-based therapeutic drugs such as anticonvulsants, 

narcotics, antihistamines, sedatives, analgesics, tranquilizers, hypnotics, and rarely 

antibiotics, such as streptomycin or sulfonamides, can alone create physical or 

mental changes in susceptible individuals, which may mimic the effects produced 

by EA (37). The combination of EA and many of these drugs usually creates 

either an accumulative or a synergistic effect that promotes higher levels of CNS 

depression. The difference between additive effect and synergistic effect may be 

summarized, as follows: the additive effect is essentially a one-to-one relationship 

whereby each chemical contributes equally to the resultant enhanced stage of 

impairment (1 + 1 = 2), whereas the synergistic (or superadditive) effect is greater 

than that expected in an individual by the combination of the two or more drugs (1 

+ 1 = 3). The synergism in turn exaggerates the combined ability of such drugs to 

cause deterioration in alertness, coordination, and concentration. A very common 

example of synergism reported in the United States is the combination of EA and 

cocaine. Cocaine ingested in concert with EA produces the metabolite through 

hepatic transesterification, cocaethylene (ethyl benzoylecgonine), which is longer 

acting, enhances the cocaine-induced euphoria, and is more toxic than the parent 

drug, cocaine, alone (44).


Reduced effects, or antagonism, occur through interactions with drugs such 

as naloxone and naltrexone, both narcotic antagonists, which have been used in 

the clinical setting to treat effects of acute and chronic alcoholism (27). Individuals 

treated with disulfiram (Antabuse ® ) (45) or metronidazole (Flaygl ® ) (46), 

and who then ingest even small quantities of alcohol, may experience severe 

toxic reactions and, in some cases, death without prompt treatment. 

Rapid or continual consumption of EA resulting in a nonfatal but relatively 

high BAC may cause serious toxic biologic effects. Immediate toxic 

effects include dizziness and drowsiness, mental confusion, slurring of speech, 

excessive sweating, incoordination, nausea, headache, cardiac dysrhythmias, 

coma, acidosis, and circulatory collapse. Some individuals may sense eye irritation, 

narcosis, and vertigo (27). 

A BAC between 0.35 and 0.45% is generally reported by most investigators 

to represent the minimal lethal level. Caution in interpretation is mandatory 

in light of the great variation of human response to any substance 

introduced into the body, which unarguably includes EA. Considerably lower 

levels of BAC, for example, may trigger a lethal cardiac dysrhythmia in a 

susceptible person (41,47). The presence of a pre-existing disease or gastrointestinal 

surgeries may hasten death at a considerably lower BAC. On the other 

hand, a chronic alcoholic or otherwise habituated drinker who has developed 

marked tolerance may survive an extremely higher BAC (e.g., >0.50%), which 

would be deemed lethal in a nontolerant person (48–50). 

With chronic consumption of EA, various degrees of physical dependence 

and tolerance will develop. Chronic tolerance is a consequence of decreased 

effectiveness of the desired effects at a given amount of EA after prolonged, 

uninterrupted consumption of large quantities, as compared to the occurrence 

of acute tolerance developing after intake of a very large dose during a single 

episode (51). With cessation of use, the chronically tolerant subject characteristically 

experiences withdrawal symptoms (52). There are three types of tolerance 

(27,53). Metabolic tolerance is present when a variety of “activated” 

hepatocellular enzymes accelerate the rate of alcohol metabolism (elimination) 

by as much as 30%. Pharmacodynamic tolerance refers to the adaptive 

response to EA by the brain’s neurotransmitters (54). Behavioral tolerance, or 

accommodation, is evident when the chronic alcoholic psychologically and/or 

physically functions better than a nontolerant individual at a given or expected 

BAC (1). 

When increased quantities of EA are chronically consumed, delayed toxic 

biological effects ensue and include poisoning at the cellular level with resultant 

clinically obvious functional disturbances in various organ systems (53,55).


Significant pathologies with pathophysiological sequelae may involve the liver 

(fatty liver, acute hepatitis, cirrhosis with liver failure, hepatocellular carcinoma), 

heart (alcoholic cardiomyopathy, secondary hypertension), brain 

(Wernicke–Korsakoff encephalopathy [vitamin B 1 {thiamine} deficiency], 

superior cerebellar vermal atrophy, Marchiafava–Bignami disease, elevated 

risk for stroke, and seizure disorders), esophagus (submucosal varices, Mallory– 

Weiss syndrome, rupture, carcinoma), stomach and duodenum (alcoholic gastritis, 

gastric atrophy, peptic ulcer disease, carcinoma), pancreas (acute and 

chronic pancreatitis with pseudocysts), and genitourinary (diminution of testosterone 

production, dysfunctional penile tumescence, infertility in both sexes). 

EA toxicity occurs in pregnancy as well (fetal alcohol syndrome, spontaneous 

abortion, fetal EA withdrawal, teratogenesis). Concomitant poor nutritional 

intake leads to general malnutrition (56). 

Characteristic pathological clues at the autopsy allow the pathologist reasonable 

inferences about the chronicity of EA usage in many cases, even in 

the absence of supportive history. Most notably, micronodular cirrhosis without 

infectious hepatitis or intrinsic liver disease is very specific for chronic 

EA intake (53,55). An enlarged, fatty liver suggests the habitual use of alcohol 

in an established drinker of EA as first on the list of differential etiologies 

rather than a single act of EA consumption or binge (34). Various endstage or 

severe disease conditions primarily involving the liver, such as micronodular 

cirrhosis or “alcoholic hepatitis,” eventually cause inefficient, depressed alcohol 

metabolism and eventuate in impaired elimination (55). Clinically apparent 

sequelae include a variety of seizure disorders (57,58), among which delirium 

tremens ( “D-Ts” or “rum fits”) is the most serious clinically (59). This manifestation 

along with others constitutes complex withdrawal symptoms that may 

occur upon cessation of EA use by the binge drinker or alcoholic (53,55). 

2.3. Pharmacokinetics of Ethyl Alcohol 

Pharmacokinetics refers to the fate of EA in the body after consumption. 

Although EA can enter the body through inhalation, injection, direct insertion 

per rectum, or absorption by direct skin contact, it typically is swallowed and 

travels from the mouth through the esophagus to the stomach (60). Negligible 

amounts of EA may be absorbed through the lining of the oral cavity, but the 

fluid leaves the mouth rapidly so it is free of alcohol after about 15–20 minutes. 

Easily miscible with water, EA requires no physical disintegration or 

digestion before entering the blood and capillaries of the upper gastrointestinal 

tract. When EA enters the upper gastrointestinal tract, it passes through 

the membranes of the gut by simple diffusion. A small percentage (


Table 2 

Hepatic Alcohol Dehydrogenase Pathway 

ADH 

1) [EA] CH 3CH 2OH + NAD + � [acetaldehyde] CH 3CHO + NADH + H + 

ALDH 

2) CH 3CHO + NAD + � [acetic acid] CH 3COOH + NADH + H + 

via Krebs cycle 

3) CH 3COOH [acetate � acetyl CoA] � CO 2 + H 2O 

EA is absorbed through the wall of the stomach, but upon entry into the proximal 

small intestine approximately 80% of the ingested substance is quickly 

absorbed and then distributed in the circulatory system without being bound 

to plasma proteins or forming complexes with other intravascular transport 

systems. The rate of flow from the stomach to the small intestine depends on 

various factors, including the amount and kind of food in the stomach, pathological 

conditions or prior surgery of the stomach or small intestine, or both, 

concentration, composition and amount of EA ingested, and the temperature 

of the alcoholic beverage. Once in the circulation, EA distributes rapidly 

throughout the compartments of body according to the water content: the corporeal 

concentration of EA is proportional to the water content in that fluid or 

compartment (34). 

More than 90% of EA is metabolized to carbon dioxide (CO 2 ) and water 

(H 2 O) in the liver by the chemical process of oxidation, primarily via the alcohol 

dehydrogenase (ADH) pathway in the cytosol (61). Chemically, EA is 

metabolized through a series of well-understood enzymatic reactions: first, 

the hepatic enzyme ADH converts EA to acetaldehyde via an oxidation reaction. 

Acetaldehyde is further oxidized to acetate by acetaldehyde dehydrogenase 

(ALDH). Acetyl coenzyme forms as acetate combines with coenzyme A 

and enters the Kreb’s cycle, as a result of which H 2 O, CO 2 , and calories are 

generated (Table 2). 

As a carbohydrate EA yields approximately 7 calories per gram, yet has 

no nutritional value (1). At least two other metabolic pathways of lesser import 

are the microsomal ethanol-oxidizing system (MEOS) within the endoplasmic 

reticulum and the perioxidase-catalase system of the peroxisomes (P 450 - 

dependent system). The MEOS is of import when the hepatic EA concentration 

rises because the K m Michaelis velocity constant of the Michaelis–Menten


kinetics is four to five times higher than for the ADH system (62). The hepatic 

microsomal P 450 -enzyme-oxidation-system pathway appears to be increased 

with chronic EA intake and is regarded as a likely candidate responsible for 

the development of tolerance in habitual consumers (34). 

3. THE INTERPRETATION OF ETHYL ALCOHOL RESULTS: 


3.1. Physiology of Ethyl Alcohol and Widmark Equations 

Consideration of the absorption of EA after intake is the most difficult 

aspect of interpreting EA concentrations in the body because the absorption 

profile is dependent on an unruly, large number of variables, many of which 

may not be either discoverable or quantifiable in a specific case (63). The rate 

of absorption of EA is susceptible to both intraindividual and interindividual 

variation. The bioavailability of alcohol is considerably greater in women than 

men because of the relatively lower concentration of gastric ADH in women, 

which yields a lesser degree gastric first-pass metabolism (64). In general for 

a fasting person, most EA is absorbed in the stomach and small intestines 

within 20–30 minutes after a single dose. In contrast, with a full stomach of a 

fatty meal, the complete absorption may be greater than several hours because 

of delayed gastric transit to the bowel (65,66). Intrinsic or additional extrinsic 

factors promoting a relatively rapid rate of absorption in the gut include the 

following: an empty stomach: cholinergic agents, parasympathomimetic agents, 

gastric resection (67), the percent carbonation of beverage, gastric ulcers, gastritis, 

H 2 -receptor antagonists, (68), aspirin (acetylsalicylic acid) (69), erythromycin, 

and femaleness (64). Factors that decrease the rate of gut absorption 

include: a full stomach, anticholinergic agents, sympathomimetic agents, malignant 

gastric neoplasm, pyloric stenosis, stimulants such as nicotine or caffeine, 

opiates, tricyclic antidepressants, antidiarrheal agents, malnutrition/ 

starvation, fatty foods, emotional upset, extreme fear or pain, major injury or 

shock, very high or very low EA concentrations within the beverage ingested, 

nausea, strenuous exercise, or maleness (1,34). 

Absorption of EA via the stomach wall is slow. Any substance that may 

delay the emptying time of the stomach will retard the absorption of EA. Greasy 

foods will coat the gastric lining and retard absorption of alcohol (1,27). Fatty 

foods such as milk, cream, and butter will slow the stomach-emptying time. In 

these cases, absorption of EA will be delayed. Eating food products during or 

shortly after consumption of EA will delay the presentation of EA to the small 

bowel and thereby extend the absorption time. Therefore, on a full stomach as


compared to an empty stomach, blood peak values will be lower and there will 

be a slower rise of the BAC. In other words, it requires a longer period of time 

and greater consumption of alcoholic beverages to reach an equivalent BAC 

for a person who is eating than for a person who is consuming an alcoholic 

beverage on an empty stomach. 

The absorption rate of EA depends on the amount, the dilution (concentration), 

and type (composition) of EA ingested. The maximal absorption rate 

of alcohol occurs with solutions that are approximately 20% EA. In beverages 

such as champagne with carbonation, absorption will be enhanced. Absorption 

is slower in very dilute and very strong alcohol beverages. The slower 

absorption rate observed in “strong” drinks is secondary to irritation of the 

gastric mucosa and delayed gastric emptying. Therefore, maximum absorption 

of EA occurs in those who partake of in moderate amounts (1). In the vast 

majority of cases (90%), peak BAC is reached during the first 60 minutes of 

ingesting a single dose EA (34). In the majority of fasting persons, the gastrointestinal 

tract will absorb most EA consumed orally within 20–30 minutes. 

Peak BAC levels may be delayed when several drinks are consumed 

rapidly approximately 45 minutes after the last ingested drink. Therefore, a 

BAC curve can be constructed based on incrementally elevated levels of blood 

EA that increases with each drink. The concentration curve will eventually 

plateau and decline from the maximum level after the maximum BAC is 

reached (1). 

Upon entering the circulation, EA is distributed throughout the entire 

organism passing from the portal vein to the liver then to the heart, the lungs, 

and then returns to the heart with generalized distribution throughout the body. 

When equilibrium is reached, EA is present in all compartments in proportion 

to their water content. The speed at which various organs reach equilibrium 

depends on the degree of their blood supply. The rates of attainment of 

alcohol equilibrium following distribution are variable among different individuals, 

between the sexes, and under different drinking conditions (37). Oral 

intake at a slow steady rate allows distribution to keep pace with absorption. 

Large volumes of strong alcoholic beverages that are rapidly consumed may 

cause distribution to body organs or compartments to lag behind the absorption 

rate. 

EA is not stored in the tissues; once it enters into the blood stream, the 

body almost immediately begins to eliminate alcohol by two simultaneous 

physiologic processes, metabolism and excretion. Excretion, as a form of elimination, 

of EA is relatively negligible and unimportant in terms of overall disposal 

of it. The major portion of the small fraction is lost to expired air, urine,


tears, saliva, breast milk, sweat, and feces (1,27,60). Precisely because the 

relative amount excreted is so small, therapeutic efforts to lower the BAC 

short of extracorporeal or peritoneal dialysis have little effect. Accordingly, 

the combination of excretion and metabolism determines the rate at which EA 

is eliminated from the body. The rates vary from person to person and even 

from day to day in the same individual. Most studies conclude that alcohol is 

metabolized in a linear fashion or zero-order kinetics. This means that the 

dissipation in a given case is linear (X amount per Y period of time) and independent 

of the dose of EA in the body. For virtually all purposes impacting 

expert medicolegal evaluation, first-order kinetics, meaning that the rate of 

elimination nonlinearly increases as the concentration of EA increases, does 

not apply (70). However, investigators have reported rare exceptions to these 

approximations at the extremes of BAC, where first-order pharmacokinetics 

applies: BAC greater than 0.02% (71) or at “very high” BAC levels (43,72). 

Within these parameters the BAC curve can be constructed through reliance 

on the combination of excretion and metabolism rates. The BAC curve is a 

hypothetical construct graphically depicting the fate of absorbed EA in the 

body over time and is heavily dependent on multiple variables, as discussed 

above. It is composed of three parts: (a) absorption phase; (b) equilibrium or 

plateau phase, indicating the maximum BAC; and (c) elimination phase. 

Elimination rates reported in the medical literature are variable, typically 

ranging from the average of 0.015–0.018%/h (27). The rates at the lower 

level of the scale are generally associated with naïve drinkers, in contrast to 

higher rates typically found among the more experienced drinkers, which some 

studies report as high as 26.6 ± 7.0 mg/dL/h (70). In yet another set of controlled 

studies, investigators have reported ranges of EA elimination demonstrating 

a fourfold difference, from the slowest in a healthy male yielding a 

ß-slope of 9 mg/dL/h to the fastest, a male chronic alcoholic, at 36 mg/dL/h 

(70,73). Certainly, many factors, including dose of EA consumed, drinking 

patterns, and relation to kind and timing of food intake, alter the shape and 

maximum height of the BAC curve. As discussed above, the consumption of 

strong or diluted beverages delays the absorption of EA reflected by the gradual 

sloping and plateauing of the curve. It is obvious that the more EA a person 

consumes, the higher the BAC will become. However, both body size and 

relative adiposity determine the distribution of alcohol. A heavier lean person 

has higher water content and greater capacity for the generalized distribution 

of EA within the body. Therefore, a person whose body weight is 200 pounds 

will have a lower BAC after complete consumption of the identical amount of 

EA over the same time period than that of a person weighing 150 pounds or


less. This notion is expressed mathematically by Widmark’s general equation, 

which will be described later in this chapter (1). 

Widmark developed several equations that helped explain the metabolism 

of EA in various individuals. Applications of the Widmark equation are 

threefold: (a) calculation of the amount of EA consumed for known BAC, (b) 

back calculation of BAC at a previous time based on a measured subsequent 

BAC, and (c) forward calculation to estimate an expected BAC based on the 

amount of EA consumed (34). The Widmark equation is based on the slope of 

a linear elimination phase � seen in the BAC curve. This mathematically derived 

linear phase � is equal to a mean of 0.0025 mg/gm/min or 0.0158 gm/dL/h 

with a range of 0.012–03.019 gm/dL/h as previously discussed. Interindividual 

values for adults may vary greatly. Intraindividual values are relatively stable 

and can be reproduced over time. The � value does not change with the type of 

beverage, the amount of beverage consumed, or the rate of consumption (34). 

Extrapolation of the � slope back to the Y intercept at T 0 (or the time drinking 

began) yields C 0 , which represents the expected BAC after complete absorption 

of the entire dose. 

The Widmark equation begins with 

C = C – � t t 

where C equals a previous estimated BAC based on C (specific or measured 

t 

BAC obtained at time t during the absorptive phase). The Widmark factor is 

designated as “r” (p or rho), which equals the ratio of percent EA in the body 

to the percent of EA in the blood. EA is soluble in water but not in fat. The r 

factor is a stable factor with interindividual variation based on body type. The 

ratio helps to equalize the BAC with the concentration of EA in the body and 

takes into account the relative proportion of fat to lean tissue mass. This is 

designed to allow for differentiation between large, obese individuals or thin 

individuals, and inherently distinguishes males from females. The average male 

r factor is 0.68 (range 0.51–0.85) and for females 0.55 (range of 0.49–0.76). 

The r value is lower in obese and higher in thin individuals. Children will 

have an r value that is up to 0.75. The r factor is also elevated in chronic 

alcoholics. The general Widmark equation is expressed as 

A/pr = C . 0 

where A is the amount of EA consumed, p is the body weight, r is the Widmark 

factor (see above), and C is the expected maximum BAC (assuming 100% 

0 

absorption and no metabolism). 

Medicolegal forensic science experts, including toxicologists and pathologists, 

are frequently requested to determine whether the BAC of a person cor-


responds to the reported quantity of EA ingested or to the estimate of the 

quantity of EA consumed based on a measured blood level at a given time. 

The minimal essential information necessary to make such estimations includes 

the individual’s body weight, percent of EA in the drink, the number of alcoholic 

beverages consumed, the length of the drinking period, and a given 

individual’s dissipation rate. Various formulas have been employed to answer 

such questions. Some of the formulas are geared to predict a BAC based on X 

number of drinks, their alcoholic percentage, and the weight of the individual. 

The following practical equation has been adapted from Widmark’s general 

equation: 

D = (C + � t ) wr (0.389) 

where D is the number of drinks consumed, C equals to the BAC in percentage 

(gram percent), � is the metabolic rate (0.015%/hr), t is the time since 

drinking began in hours, w is the body weight in pounds, r is the Widmark 

factor (0.68 for men, 0.55 for women), and 0.389 represents the conversion 

factor (based on one drink of 0.50 fluid ounces of absolute alcohol). 

The conversion factor will help convert the body weight into pounds, the 

alcohol into volume, and the volume into number of drinks. The equation can 

be rearranged to calculate the expected BAC based on the number of drinks 

consumed as follows (34): 

C = D/wr (0.389) – � t . 

Retrograde calculations to estimate the amount of EA in the individual’s body 

obtained from a given BAC can also be performed. When EA is lost by metabolism, 

time must be additionally calculated within the general Widmark equation. 

Thus, the calculation is: 

A = pr (C t + � t ). 

This calculation is used for the maximum amount of EA consumed (A) based 

on a person’s later BAC at time t (time, in hours, since drinking began) (34). 

Widmark’s calculations and hypotheses, first developed in 1932, have limitations 

and drawbacks, but overall have gained considerable acceptance in many 

medicolegal applications. 

In circumstances in which there is a delay between collection of the sample 

of material containing EA and the actual occurrence (such as a motor vehicle 

collision), the process of retrograde extrapolation may be invoked for medicolegal 

purposes. Such a back calculation is permissible and accurate only 

when the individual is in the elimination phase of the blood alcohol curve. 

Because it is often difficult to quantify the variables in the mathematical for-


mulas, this still remains a controversial extrapolation (74). As U.S. state legislatures 

continue to enact per se laws, where the BAC at the time of collection, 

as remote as 4 hours after the motor vehicle event, is the determinative factor, 

courts of final jurisdiction have held back extrapolation is unnecessary (75). 

Potential risks for erroneous application of this kind of extrapolation and 

sources of error may arise in the medicolegal arena. These confounders should 

be appreciated by all medical examiners facing expert testimony on blood EA 

in court: (a) retrograde extrapolation to determine earlier BAC assumes that 

the individual is in the postabsorptive phase—if only one BAC level is reported, 

one may be unsure whether or not blood EA is rising or falling at collection: 

(b) the � and r values in the Widmark equation are averages for a population 

of individuals and not individually specific—reference to several � and r values 

tend to eliminate this error, (c) specific time intervals since first to last 

drink cannot be determined unless strict observation of the individual is performed, 

and (d) equations, which are derived from experiments on individuals 

drinking under carefully controlled laboratory conditions and on empty stomachs, 

do not well represent real-life situations of hectic consumption patterns 

of a variety of alcoholic beverages over variable periods while eating all kinds 

of foods (34). 

3.2. Antemortem and Postmortem Collection 

and Testing for Ethyl Alcohol: Interpretative Toxicology 

Logically, because the level of alcohol in the CNS directly affects behaviorand 

activity, the best sample for measurement of EA concentration is brain 

(21). Obviously, this is not feasible for living individuals. Although brain tissue 

is usually readily available at autopsy, it is not the specimen of choice for 

several reasons: (a) blood from the vascular compartment is usually easier to 

obtain and process, (b) the BAC adequately reflects the effect of EA on the 

brain, and (c) it is more practical, technically efficient, and economically sound 

to analyze blood regularly when such high volumes are involved. 

Accordingly, the common test specimens collected by law enforcement 

agencies and medicolegal investigators to determine EA levels are blood (whole 

blood, plasma, and serum), breath alcohol content (BrAC), and urine alcohol 

content (UAC) (76–78). In contrast to the practices of clinical laboratories, 

which analyze either serum or plasma from living subjects for BAC, most 

toxicology laboratories evaluating postmortem samples report BAC from whole 

blood preserved in sodium fluoride. In death investigation, whole blood is the 

“gold standard” for measurement of BAC (21,79). Yet, because most forensic 

experts are frequently called upon to either interpret results from or analyze


these antemortem serum or plasma samples, it is incumbent on the expert to 

appreciate the meaning of the different results from various analytes. Under 

most physiological conditions serum or plasma contains about 10–12% more 

water than the same volume of whole blood, so that the EA levels are correspondingly, 

but only slightly higher in these samples. The average EA ratio of 

whole blood to serum or plasma is approximately 1:1.8, with a reported range 

of 1.12–1.17. The following EA ratios obtain for conversion of these blood 

components to whole blood: serum = 1.12–1.17; plasma = 1.10–1.35 (21,79). 

EA is the most frequently analyzed drug by the toxicologist collaborating 

in consultation with coroners and medical examiners. Optimal specimens 

are required for accurate analysis by the laboratorian as practitioner of analytical 

toxicology, as well as for evaluation and interpretation of the analytical 

results by the forensic pathologist, the practitioner of interpretative toxicology. 

Specific analytical methods are necessary because of the potential interference 

by a variety of volatile substances in postmortem specimens (78,80). 

Gas chromatography is the “gold standard” for BAC analysis, affording specific 

identification and quantification of EA (81). Headspace chromatography 

is completely specific for EA. It is the only test method acceptable in most 

courts of law granting admissibility of analytical results on which to base expert 

testimony (34,78,80). The gas chromatograph separates volatile compounds 

on a column by a carrier gas, which is passed through a detector designed for 

either flame ionization or thermal conductivity. EA is initially separated, based 

on the appropriately calibrated gas chromatograph parameters and columns, 

and subsequently quantified. Headspace gas chromatographic methods use 

vapor samples in a closed system for injection. The headspace procedure 

employs blood samples placed in small, capped bottles from which the extracted 

vapor is injected into the chromatograph. Separation and detection of volatiles 

occurs upon this injection. 

Hospital and clinical laboratories commonly employ an enzymatic method 

to determine BAC (21,78), and resort to such methodologies because gas chromatographs 

are not universally available in the clinical laboratory (78). The 

coenzyme, nicotinamide adenine dinucleotide, is reduced as a byproduct of 

the oxidation reaction of EA to acetaldehyde. The resultant reduction product 

is measured by a spectrophotometer. This is a quick, easy, and automated 

method to detect EA; however, it lacks the specificity of headspace gas chromatography 

because the presence of other alcohols such as isopropanol may 

interfere chemically and yield an inconclusive, false-positive, or spurious result. 

Unlike head space chromatography, antigen–antibody reactions are subject to


cross reaction with other substances within the blood and for that reason are 

not regarded as a reliable method for testing BAC in a medicolegal or juridical 

context (1,27,77). Clinical toxicologists regard serum as an easier medium to 

analyze, pointing to extensive surveys in which precision and span of values 

derived from serum are better than those recorded for whole blood (82). The 

researchers conclude, however, that using either serum or whole blood produces 

essentially equivalent results for clinical and forensic purposes, as long 

as the final report of analytical results clearly specifies the analyte (serum, 

plasma, whole blood). 

In most postmortem cases, there is greater opportunity to collect a variety 

of specimens for laboratory analysis. Utilizing multiple specimens from 

various compartments and subcompartments of the body is beneficial because 

the analysis of more than one sample tends to ensure accuracy in a given quantitative 

result and thereby facilitate optimal interpretation. 

In postmortem sampling, whole blood continues to be the sine qua non 

for analysis. At autopsy it is more desirable to collect at least two samples of 

blood, one from the heart region (central) and one from the peripheral vasculature 

(83). It is nevertheless necessary to specify unequivocally the source of 

the sample or the site of collection of whole blood. Arterial BAC may be at 

least 40% higher than venous BAC in the absorptive phase. Bloody fluid (which 

is not blood!) recovered from extravascular body cavities, from body surfaces, 

or from the relevant scene, especially in trauma, is a less reliable toxicological 

specimen to quantitate EA for various reasons (1). The bloody fluid may have 

either a higher or lower level of EA than that in intravascular blood per se 

(central or peripheral), and accordingly may make meaningful interpretation 

of the reported “BAC” virtually impossible. In collecting blood samples at 

autopsy, there are factors influencing the concentration of EA that are not 

pertinent to antemortem sampling techniques. Diffusion of significant amounts 

of EA out of the esophagus or stomach into the surrounding pericardial cavity 

and heart is likely to occur, and becomes increasingly significant as the postmortem 

interval increases with the time of delay between death and autopsy 

(84). Yet, if there is a great period of time, measured in hours, between the last 

drink and death, diffusion of EA from the gut to the “heart blood” will not be 

substantial. Under such circumstances where the autopsy is performed within 

48 hours of death, diffusion of alcohol from the gut to the heart is fairly insignificant. 

Femoral and subclavian venous (peripheral) blood sites are preferable 

to central heart blood, but these may be difficult to obtain secondary to 

insufficient volume and in cases of traumatic hypovolemia (“empty heart sign”)


(22,85). Taking a “blind” sample at autopsy via precordial percutaneous 

pericardiocentesis, to collect blood is indisputably flawed and to be avoided. 

Blood must be drawn from the chambers of the heart, or the great vessels 

exiting or entering the heart, as heart blood. In summary, external chest puncture 

is not considered an acceptable procedure for the collection of a blood 

sample for subsequent EA analysis (1,27,34). False elevations of EA in bloody 

fluid collected by external chest puncture can be confirmed by analysis of 

postmortem UAC (1). 

As a quality control measure, concomitant comparative quantitation of 

EA in the postmortem vitreous humor (vitreous alcohol content or VAC) is an 

excellent means for interpreting the reported BAC, whether central or peripheral. 

Because the intact, relatively avascular globe in the orbit is anatomically 

isolated from other tissues or fluid, it serves as an excellent compartment to 

obtain unadulterated vitreous humor for quantitation of EA. Characteristically, 

VAC lags approximately 1–2 hours behind BAC at the phase of equilibrium 

(86,87). Therefore, BAC in the absorptive phase is higher than VAC. At the 

plateau or equilibrium phase, the reported average ratio of BAC:VAC is 

1.0:1.05 to 1.3. Logically, in the postabsorptive or elimination phase, VAC is 

higher than the BAC. Such comparative analysis is helpful in establishing 

whether or not the deceased was in the absorptive or elimination phase at the 

time of death. Given the well-documented BAC:VAC ratios, reference to the 

VAC is also very useful in inferring the probable BAC at death when intravascular 

blood or other body fluids are not readily available (1). As in all extrapolations 

drawing upon EA levels in other body compartments, caution is always 

prudent in estimating the BAC from the VAC at autopsy, as the EA distribution 

ratio (VAC/BAC) (femoral blood) exhibits wide variation in light of recent 

research encompassing 706 forensic autopsies (88). These authors recommend 

a conservative approach by dividing the postmortem VAC by 2.0 to arrive an 

estimate of the equivalent (femoral) BAC, which, although lower than the 

“true value,” may then be offered with a high degree of confidence in the 

medicolegal arena. 

In cases where vitreous humor is not available, such as in decomposition 

or trauma, other aqueous body tissues may be used to quantitate EA, because 

of its ready miscibility in water. Other tissues and samples (89) used for blood 

alternatives are bile (90), urine, gastric contents, bone marrow (91), solid 

organs, for example, liver, kidney, brain, spleen, and lung, cardiac, smooth, or 

skeletal muscle (92), intracerebral and paradural hematomas (93,94), synovial 

fluid (95), and cerebrospinal fluid (96). Many researchers have reported an


established range and ratio of EA in these various specimens to BAC (21,97). 

These tabulations are helpful and afford reasonable inferences with respect to 

BAC when intravascular blood is unavailable (21,85). 

With qualification, urine is potentially an acceptable medium to estimate 

BAC and to determine the pharmacokinetic phase the subject is in at the time 

of collection. The preferred sample is ureteral urine in which excreted EA 

from the renal circulation is virtually identical to the BAC in that vascular 

compartment. Under most circumstances at autopsy, collection of ureteral urine 

is not practical. The urinary bladder acts as a storage container for the eliminated 

urine waste until the urine is voided (1). Pooled urine, which continuously 

enters and collects in the urinary bladder and thereby contains variable 

time-and-volume-dependent amounts of EA, is not an accurate medium for 

comparison to the BAC. There are collection problems inherent in the measurement 

of UAC. In living subjects, the stored urine must be voided and a 

subsequent urine specimen collected over time (30–60 minutes) during which 

consumption of EA does not occur. Voided urine should be used only as a 

qualitative test for EA. Toxicological analysis of urine may be done in a given 

situation, but generally it is of little or no value when used alone to estimate an 

individual’s BAC at a given time. At autopsy, UAC represents the cumulative 

or integrated sum of different BAC’s intra vitam over time, during which the 

individual may be or is passing through various phases of EA metabolism and 

the urinary bladder continuously receives urine from the kidneys as an excrement. 

Such pooled urine does not reflect a BAC at any particular point in 

time, but merely estimates an average urine concentration for that period of 

collection time and may be used for rough estimates of BAC in that time frame. 

The reported average UAC:BAC ratio is 1.33, but the experimentally determined 

range is great, reportedly from 0.21 to 2.17 to 2.44. (21,34). UAC:BAC 

comparisons can help delineate the stage of metabolism the individual is in at 

the time of specimen collection: absorptive phase—UAC:BAC 1.3 (21,76). 

Because of the intimate association between alveolar air and the pulmonary 

circulation, EA is presumed to migrate from the pulmonary vessels by 

simple diffusion and suffuse the intraalveolar gas, which becomes laden with 

EA molecules. Alveolar air forcefully exhaled from these sites becomes breath, 

suitable as such for EA quantitation. Breath EA analysis is noninvasive and 

affords quick results. According to many experiments based on Henry’s law, 

EA distributes between pulmonary blood and the alveolar air (BrAC) on average 

at a fixed partition ratio of 1:2100. One milliliter of blood contains the


same weight of alcohol as 2100 mL of alveolar air. The reported ranges, indicative 

of significant time-dependent intraindividual and interindividual variation, 

extend from 1:1142 to 1:3478 (1). In this regard, researchers point out 

the 1:2100 ratio undervalues the actual ratio for 86% of the population (falsely 

low) while overstating it for 14% (falsely high) (98,99). When employed properly, 

breath analysis, reported as BrAC, has been supported by investigators 

(100) and accepted in most jurisdictions, either as an independent determinant 

of intoxication or as a means of arriving at the BAC via the conversion ratio. 

Understandably, the assumptions involved in converting very low levels of 

EA in alveolar air to levels in the blood are subject to critical scrutiny, especially 

when individual may be subject to conviction of a given criminal offense 

based on a measured level as low as 0.001% BAC (60). 

With the dynamic evolution of the interface of science and law in regard 

to the question of driving under the influence of alcohol, some of the issues 

discussed above have become moot in the wake of enactment of per se statutes 

by many state legislatures. No conversion from BrAC to BAC is required. 

Before 2000, the state of Kentucky, for example, defined “alcohol 

concentration” as follows: . . .”either grams of alcohol per 100 milliliters of 

blood or grams of alcohol per 210 liters of breath” (101), which the legislature 

amended recently by lowering the minimal BAC (or breath equivalent) 

to 0.08%. In regard to expert testimony on retrograde extrapolation, the same 

statute made back calculation virtually unnecessary. Under defined conditions 

the statutory formulation focuses on the time of collection (102), not the 

BAC at the time of the traffic event: “ [a] person shall not operate . . . a motor 

vehicle . . . [h]aving an alcohol concentration of 0.08 or more as measured by 

a scientifically reliable test or tests of a sample of the person’s breath or blood 

taken within two (2) hours of cessation of operation . . . of a motor vehicle . . 

. [w]hile under the influence of alcohol. . . .” The Kentucky Supreme Court 

has upheld this language (103). 

Whenever fluids or analytes other than blood are submitted for EA analysis, 

a number of factors that influence the distribution ratio must be considered. 

The most critical factor influencing the distribution ratio is the stage of 

alcohol distribution in the body when samples are collected. The optimal specimen 

is one collected after a blood EA maximum is reached and begins the 

elimination phase. If the specimen is collected on the absorption side of metabolism 

curve, then total body distribution has not been achieved so that analysis 

of that sample will not properly reflect the BAC (1).


3.3. Decomposition and Embalming: 

Confounders in Interpreting BAC 

Thorough intravascular embalming procedures render blood an unsuitable 

medium for specific BAC. Vitreous humor may serve as a suitable substitute. In 

such cases, the toxicologist requires a sample of the embalming fluid to compare 

with the analytical results of analysis of the vitreous humor. In general, 

many embalming fluids either do not contain EA or have relatively low levels 

compared to other volatiles (21,79). Embalming fluid is usually composed of 

formaldehyde. Other volatiles in the commercially manufactured embalming 

fluid may include acetone, methanol, isopropanol, and occasionally EA. Typical 

formulas distinguishing the components of embalming products, including 

various alcohols, are readily available. Another technical difficulty with analysis 

of EA in exhumed/embalmed bodies arises when dehydration of tissue or 

postmortem synthesis of alcohol is present after prolonged burial (1). 

Postmortem decomposition, even at an early stage, factitiously elevates 

BAC and is a confounding factor for the interpretative toxicologist. Fermentative 

bacteria, predominantly entering the vascular compartment after death 

and metabolizing glucose or protein, produce endogenous EA chemically identical 

to that in alcoholic beverages. Because of relative isolation from the 

putrefactive processes, urine from the urinary bladder and intraocular vitreous 

humor, as relative sterile compartments, are sometimes spared of this phenomenon. 

Zumwalt et al. report postmortem BAC as high as 0.22% attributable 

to endogenous production (104). In this study, the authors conducted 

simultaneous analysis of vitreous humor or urine, which contained no measurable 

levels of EA in 23 moderate to severely decomposed bodies. Bodies 

that have been stored in cold environments generally will have minimal 

endogenous alcohol production (104). This applies as well to victims of drowning, 

who frequently undergo severe decompositional change even in temperate 

climates. Dilutional factors may occur especially in freshwater drownings. 

Therefore, the BAC quantified from postmortem samples may actually be lower 

than the true level. Specific variations are not known at this time because of 

the lack of research in this area (1). 

Of note is that the endogenous generation of EA from glucose by microorganisms, 

primarily fungi and bacteria, is not unique to the postmortem period. 

Such considerations are also relevant to the living, particularly exemplified by 

subjects with multiple metabolic complications of diabetes mellitus and urinary


Table 3 

Embden–Meyerhof (EM) Glycolytic Pathways 

1) EM pathway: �� CO 2 + Pyruvic acid 

2) Pyruvate decarboxylase: Pyruvic acid � Acetaldehyde 

3) Alcohol dehydrogenase: Acetaldehyde � EA 

tract infections. Discrepancies between BAC and UAC, where the latter demonstrates 

abnormally elevated amounts of EA, are attributable to urinary retention 

and incontinence (105–107) whereby intravesical glucose fermentation occurs 

via the Embden–Meyerhof glycolytic pathways (Table 3). As a result of this 

phenomenon, postmortem UAC in diabetics is unreliable (108). 

3.4. Establishing Legal Chain of Custody: Procedures 

for Preserving Chemical Evidence 

All personnel (e.g., pathologists or other physicians, nurses, toxicologists, 

biochemists, laboratorians, and police) handling or possessing any kind 

of physical evidence have a legal duty to maintain the evidentiary chain of custody 

(109). Preservation of the integrity of physical evidence undergoing subsequent 

analysis affords admissibility of test results at trial. The results may then 

be entered as proof of an issue in question by establishing credibility in the 

minds of the court and jury (77). This axiom applies particularly to specimens 

of biological or chemical evidence, which as a class may be consumed in analysis 

and are susceptible to tampering, contamination, or spoilage. The law requires 

written documentation reflecting positive identification and the absence of significant 

alterations or tampering of chemical specimens from the time of collection 

through laboratory analysis. Such documentation comprises not only the 

laboratorian’s reports and work sheets but also written notes, forms, or computer 

printouts establishing an uninterrupted chain of custody. 

To properly collect and preserve chemical evidence, a clearly detailed 

hierarchical chain of command must be designated. In the hospital setting, a 

physician, nurse, phlebotomist, or laboratory technician working under the 

direction of a physician is required to collect the samples. Specifically designed 

sterile collections tubes must be utilized. Depending on the design, these collection 

tubes may contain sodium fluoride (gray top in the United States), 

heparin or another anticoagulant (green or lavender top in the United States), 

or no additives at all (red top in the United States). The anticoagulant and 

bacteriostatic actions of sodium fluoride are optimal for preservation and storage 

of whole blood (34).


In contrast to sample collection at autopsy, there are advantages and disadvantages 

related to the collection of each type of fluid specimen, that is, 

blood and urine, in the clinical setting. A specimen of blood, the “gold standard” 

for determination of the BAC, is unquestionably the most desirable 

sample to collect. In the clinical or hospital environment, however, such a 

sample may be difficult or impossible to obtain from living persons because 

of the unavailability of an appropriate phlebotomist or lack of consent from 

the individual whose BAC is in question. As noted above, the standard practice 

in the hospital of clinical laboratory is to centrifuge or otherwise separate 

whole blood, and then to analyze the plasma or serum for quantification of EA. 

Standard phlebotomy procedures involve percutaneous puncture of the 

antecubital vein as the usual location of a venipuncture site. If this location is 

inaccessible, a vein from the hand or leg may be entered. In selected instances, 

withdrawal from a central venous or other intravenous catheter is appropriate. 

The location of the source of blood must be documented. The specimen container 

must as a minimum have a legible notation of the individual’s name, the 

date and time drawn, the individual’s identification number, and the clear identity 

of witnesses observing and of the person drawing the specimen. Additional 

medicolegal information should be documented by the hospital or the 

police agency involved (77). In addition to the same information indicated on 

the specimen tube, the individual’s age and the type of disinfectant used in 

location of vena puncture should be documented in the medical report. Contamination 

of a blood specimen using a rubbing-alcohol cotton swab (70% EA) 

prior to the blood collection may cause erroneous elevation of the blood alcohol 

levels. The results of various controlled studies testing this confounding 

issue are contradictory (110). It is recommended that butadiene (aqueous 

povidone-iodine) or other non-alcohol-containing disinfectants are used in the 

collection of blood. A police official’s request for the blood and a consent form 

for established blood withdrawal must be completed prior to sample collection. 

When the custody of the blood specimen leaves the hands of one official 

to another, proper documentation of this transfer of evidence is legally mandatory. 

The person collecting the specimen initiates the legal chain of custody. 

Upon collection, the official first labels the container(s) with data 

identifying the subject, case number, time and date of collection, body site of 

collection, character of description of sample, and then legibly affixes his or 

her name or initials. A similar process applies mutatis mutandis to sample 

collection at autopsy. Contemporaneous with those notations, the initial collector 

of the sample enters the same data on a specially designed standard 

form consisting of a master sheet and duplicates.


If the chemical evidence is not immediately transferred to a subsequent 

custodian, the collector then preserves the specimen in locked storage or 

refrigeration with clearly established limited access in preparation for transfer 

of custody to the next official in the chain for final delivery to the analyst. 

Transportation of the body fluid specimens should be performed in an expedient 

manner (1). It is mandatory that this evidence with proper documentation 

be secure at all times. If transportation delays are anticipated, refrigeration of 

the specimen is recommended. The best storage temperatures are between 

–20°C and –4°C (34). In cases of relatively short intervals between collection 

and analysis, refrigeration, though desirable, is not always necessary. Studies 

have been performed to compare any significant changes in BAC between 

stored room temperature blood specimens preserved in sodium fluoride and 

refrigerated specimens. These comparisons were performed over several days 

(2–14 days), and insignificant differences were found. Even with the absence 

of the storage preservative sodium fluoride, insignificant differences of analyzed 

blood alcohol levels were recorded after 14 days (1). 

Every person involved in the evidentiary escort of the physical evidence 

records similar data on the prepared form upon taking possession, and keeps a 

copy—not the original accompanying the evidence—for future reference in 

court. This procedure may involve few or many custodians. Ultimately, the 

clearly identified receiving analyst at the end of the chain records all data as to 

condition of seals on containers, date and time of receipt, time and type of 

analysis and report, and also notes whether and how any retained sample is 

stored. This paper trail of documentation may then be referred to at trial by 

any official witness in the chain as a means of establishing the integrity of the 

specimen (111,112). The results of analytical studies of samples collected clinically 

are inadmissible at trial without clear proof of the legal chain of custody 

(113). In summary, to avert legal challenges, the forensic pathologist of 

necessity must adhere to all of the following stages of evidence processing: 

“recognition, obtainment, preservation, transport and submission, and analysis” 

(114). 

ACKNOWLEDGMENT 

The authors thank Carol Bibelhauser for excellent clerical support. 

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Iliopsoas Muscle Hemorrhage 339 

Forensic Differential Diagnosis

340 Türk


15 

Iliopsoas Muscle Hemorrhage 

Presenting at Autopsy 

Elisabeth E. Türk, MD 

CONTENTS 

INTRODUCTION 

CAUSES OF ILIOPSOAS MUSCLE HEMORRHAGE 

CLINICAL ASPECTS 

POSTMORTEM FINDINGS AND THEIR INTERPRETATION 

FORENSIC MEDICAL ASPECTS OF ILIOPSOAS MUSCLE HEMORRHAGE 

REFERENCES 

SUMMARY 

Iliopsoas muscle hemorrhage presenting at autopsy can result from a 

variety of underlying pathological conditions. Such conditions include primary 

(hemophilia) or secondary (disseminated intravascular coagulation, anticoagulant 

drugs) coagulation disorders, hypothermia, trauma, iatrogenic 

damage, and other, rare causes. Iliopsoas hemorrhage can be extensive and 

through the massive blood loss may account for fatal outcome, but the bleeding 

can also be small and carry only diagnostic relevance. In many cases of 

hypothermia, sepsis, or coagulation disorders, additional macroscopically visible 

pathological findings are discrete or completely absent, making it necessary 

to perform further investigations such as histology and laboratory tests to 

establish the right diagnosis. In some autopsy cases, however, the cause of the 

muscle hemorrhage cannot be made out. The clinical picture of iliopsoas muscle 

hemorrhage can vary from no symptoms at all over slight pain in the groin to 

life-threatening hemorrhagic shock. In the living, imaging techniques like ultrasound 

and computed tomography are needed for establishing the diagnosis. 



341

342 Türk 

Because of the great differences in clinical presentation, as well as the rare 

occurrence of iliopsoas muscle hemorrhage, the disorder is sometimes overlooked 

in the clinical setting until severe and sometimes fatal complications 

develop. Thus, from the medicolegal point of view, questions concerning medical 

malpractice may arise in cases of iliopsoas muscle hemorrhage. 

Key Words: Iliopsoas muscle hemorrhage; medicolegal autopsy; differential 

diagnosis; surgery; medical malpractice. 


Iliopsoas muscle hemorrhage is not rarely found at medicolegal autopsies, 

but frequently does not receive much attention from the forensic pathologist 

or is considered a finding of minor relevance. In some cases, however, the 

bleeding can have a certain diagnostic value for establishing the cause of death. 

This is especially true for causes of death where other characteristic features 

are only irregularly present, for example, Wischnewski spots of the gastric 

mucosa or frostbite-like lesions of exposed skin areas in hypothermia. In such 

cases, the presence of iliopsoas muscle hemorrhage can be one piece of the 

puzzle that in the end allows to establish the right diagnosis. On the other 

hand, the bleeding itself can account for fatal outcome resulting from massive 

blood loss and hemorrhagic shock, especially when the diagnosis is delayed 

in the clinical setting. 

2. CAUSES OF ILIOPSOAS MUSCLE HEMORRHAGE 

2.1. Anticoagulant Therapy 

Anticoagulant therapy can be considered the most frequent cause of iliopsoas 

muscle hemorrhage. The iliopsoas muscle is a relatively rare site for 

bleeding complicating anticoagulant therapy (1–3), and thus the hemorrhage 

may easily be overlooked. All kinds of anticoagulant drugs potentially bear 

the risk of spontaneous bleeding. Most cases appear to occur owing to anticoagulation 

with heparin (4). In patients receiving heparin, the overall bleeding 

complication rate has been reported to be 0.4% for fatal bleedings, 6% for 

major, and 16% for minor bleedings, respectively, with the iliopsoas muscle 

being a rare bleeding site (1). The risk of bleeding complications has been 

shown to increase in a dose-dependent manner, but individual parameters also 

seem to play a role (5,6). Although iliopsoas muscle hemorrhage can be one 

manifestation of heparin-induced thrombocytopenia (HIT), in most cases 

described in the literature it occurred in patients without evidence of HIT and 

with coagulation parameters within the therapeutic range of heparin (7,8).


In patients receiving oral anticoagulant drugs, fatal, major, and minor 

bleeding complications have been reported to occur with average frequencies 

of 1%, 5%, and 17%, respectively (1). These bleeding complications 

most often occur because of accidental overanticoagulation (1,9). Additional 

risk factors include wrong diet, change of medication involving drugs that 

interact with oral anticoagulants, advanced age, and renal failure (6). Still, 

voluminous and even fatal iliopsoas hematoma can develop if anticoagulant 

levels are within the therapeutic range, even in the absence of additional risk 

factors (10). 

Antiplatelets therapy, for example, ticlopidine, may also be complicated 

by iliopsoas muscle hematoma (11). However, data on the frequency of this 

complication of antiplatelets drugs are missing in the literature. 

2.2. Disseminated Intravascular Coagulation 

Disseminated intravascular coagulation (DIC) can result from different 

pathological conditions, for example, bacterial sepsis, massive trauma, or 

malignancies. Because of the release of thrombogenic factors, small thrombi 

are deposited throughout the microvasculature in the early phase of DIC. This 

leads to a consumption of coagulation factors and platelets, resulting in diffuse 

hemorrhage in the later phase of DIC. Thus, bleeding can develop virtually 

everywhere in patients with DIC. How frequently iliopsoas muscle 

hemorrhage occurs in these patients is undetermined. Major or even lifethreatening 

hemorrhage appears to be relatively rare, as the literature lacks 

reports on such cases. A case of massive bilateral iliopsoas hemorrhage has 

recently been reported in septic DIC (12), the blood loss accounting for fatal 

outcome together with septic multiple organ failure. It should be noted that 

the blood loss in major iliopsoas hemorrhage will lead to an increased consumption 

of coagulation factors and platelets as well as to volume depletion, 

and may thus aggravate the vicious circle of shock and DIC. 

2.3. Iatrogenic Causes 

The most frequent iatrogenic cause of iliopsoas muscle hemorrhage is 

undoubtedly overanticoagulation, which is discussed separately above. There 

are, however, a few diagnostic and therapeutic interventions that may, though 

very rarely, be complicated by iliopsoas hematoma and should be considered 

if the respective symptoms are present. In orthopedic physical maneuvers, 

namely lumbar spinal decompression procedures, iliopsoas hematoma can occur 

as a rare complication even in patients without any evidence of coagulation 

disorders (13,14). Likewise, iliopsoas hematoma can occur after aortic vascular

344 Türk 

surgery (15) or even special coronary stenting procedures (16). Basically, any 

kind of surgical intervention in the retroperitoneal cavity bears the risk of this 

complication. As patients undergoing surgery regularly receive anticoagulant 

drugs, they are at high risk of developing major iliopsoas hemorrhages. 

2.4. Trauma 

Trauma with hyperextension in the hip joint, like in a fall, can lead to 

symptomatic iliopsoas muscle hemorrhage resulting from the traumatic rupture 

of small blood vessels. This does not necessarily have to be a fall from a 

height; instead, a slip on the flat is sufficient to cause major hematoma (17). 

The bleeding can also result from muscle rupture in massive hyperextension 

(18). Rare cases of iliopsoas muscle bleeding due to hyperextension in athletes 

have been reported (19). 

2.5. Hypothermia 

In hypothermia deaths, iliopsoas muscle hemorrhage has been suggested 

to be a characteristic pathological finding by some authors (20,21), but this is 

discussed controversially as the finding occurs only irregularly in hypothermia 

deaths and, therefore, has to be considered nonspecific (22–24). The underlying 

pathophysiological mechanism of the development of iliopsoas 

hemorrhage in hypothermia is yet unknown. An increased capillary permeability 

owing to hypoxic damage has been discussed (20). Major bleedings do 

generally not occur, and accordingly, the blood loss does not contribute to 

fatal outcome in these cases. 

2.6. Miscellaneous Causes 

Any kind of noniatrogenic coagulation disorder predisposing for bleedings 

can also result in iliopsoas hematoma. The most common of these disorders is 

undoubtedly hemophilia. Thirty percent of all bleeding complications in hemophilic 

patients have been reported to occur within skeletal muscles (25). Iliopsoas 

muscle hemorrhage is often voluminous in these patients, frequently 

causing muscle function inhibition. Recurrent iliopsoas hemorrhages seem to 

occur in approximately 14% of these cases (25). Liver cirrhosis is another 

common disease associated with impaired coagulation, but has only once been 

reported to result in iliopsoas hematoma (26). Rare causes of iliopsoas 

hematoma resulting from impaired coagulation include thrombocytopenia in 

Gaucher’s disease (27) and leukemia (28). Finally, bone metastases of solid 

malignant tumors can cause coagulopathy and thus result in iliopsoas 

hematoma (29).


Other causes of iliopsoas hematoma are very rare. Single case reports 

exist about iliopsoas hemorrhage secondary to rupture of abdominal aortic or 

iliac artery aneurysms (30,31). Iliopsoas hemorrhage has furthermore been 

reported to occur spontaneously, without any history of coagulopathy or 

trauma (32). 

A summary of the pathological conditions that might result in iliopsoas 

muscle hemorrhage is given in Table 1. 

3. CLINICAL ASPECTS 

3.1. Presentation 

Table 1 

Potential Causes of Iliopsoas Muscle Hemorrhage 

Coagulation disorders iatrogenic: overanticoagulation 

noniatrogenic: DIC, hemophilia, liver cirrhosis, inherited disease 

with thrombocytopenia (e.g., Gaucher’s disease), leukemia, 

bone metastases of solid malignancies 

Rare iatrogenic causes orthopedic physical maneuvers, aortic surgery, coronary 

stenting procedures 

Trauma hyperextension in the hip joint 

Hypothermia 

Miscellaneous causes ruptured retroperitoneal aneurysms, spontaneous hematoma 

Depending on the source of the bleeding and on the patient’s coagulation 

parameters, symptoms can develop within a dramatically short period of time 

(10). In minor bleedings, symptoms are not necessarily present at all (31). 

Patients with iliopsoas muscle hemorrhage might present with pain in the loins 

(4,9), which can vary from mild to violent, depending on the volume of the 

bleeding as well as on the patient’s individual susceptibility to pain. As extension 

of the hip joint makes the pain worse, patients might present a “psoas 

position” with the hip joint flexed (13,33). Patients receiving analgesic therapy, 

or patients with a reduced sensitivity to pain, for example, owing to diabetic 

polyneuropathy, might not complain about pain even when major bleeding is 

present (10). In some patients, abdominal pain or pain in the back is present 

rather than pain in the loins (7,11) which may lead to diagnostic problems. A 

lower abdominal mass might be palpable depending on the size of the 

hematoma.

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Because of the close topographical proximity of the iliopsoas muscle to 

the femoral nerve, femoral neuropathy or even complete femoral paralysis 

might develop in patients with major bleedings causing femoral nerve compression 

(4,11,13,14,33). Voluminous hemorrhage can even cause lumbosacral 

plexopathy (15,34). Early symptoms of nerve compression might be 

quadriceps muscle fasciculation (14), which might progress into complete quadriceps 

muscle paralysis or paralysis of the whole leg together with an incomplete 

or complete loss of sensibility (15,34). It can take several days for 

symptoms to become so severe that further diagnostic steps have to be undertaken 

(34). Usually, these symptoms are fully reversible after successful treatment 

of the iliopsoas muscle hematoma (17,34). Hematuria has been described 

to occur in some patients (35). Anemia is present in patients with major blood 

loss. Some patients just complain about being unwell without any specific 

symptoms, and others do not have any recognizable symptoms at all unless 

severe or even fatal complications develop (10). 

3.2. Complications 

The iliopsoas muscle can accumulate up to 10 times its own volume (36), 

making major blood loss quite likely, sometimes resulting in life-threatening 

and sometimes fatal hemorrhagic shock. In patients with a high degree of 

comorbidity, especially in patients with severe coronary artery sclerosis, even 

smaller hematoma can cause fatal internal blood loss. 

Owing to a compression of large veins by the hematoma, deep venous 

thrombosis in the leg or pelvis with the risk of subsequent pulmonary embolism 

complicates iliopsoas muscle hemorrhage in some patients, even if they 

receive anticoagulant drugs (37). Withdrawal of anticoagulants, which is 

often necessary in order to control the bleeding, increases the risk of thrombus 

formation. 

A possible urological complication is ureteral obstruction that might result 

in hydronephrosis if the hemorrhage is not treated in time (35). In rare cases, 

fistulas between the bleeding and the large bowel can develop, with subsequent 

infection of the iliopsoas muscle and the risk of sepsis (38). 

3.3. Differential Diagnosis 

A plethora of diseases, many of them much more common than iliopsoas 

muscle hemorrhage, can cause the same or similar symptoms as iliopsoas bleeding, 

in some cases leading to a misdiagnosis in the first place. When taking the 

patient’s medical history, questions concerning bleeding disorders and prior 

trauma are indispensable.


The differential diagnosis of iliopsoas muscle hemorrhage includes all expansive 

pathological conditions that involve the iliopsoas muscle such as neoplasms 

and infectious processes. Neoplastic lesions in the iliopsoas muscle are 

usually metastases of malignancies; primary tumors are very rare (39,40). Infection 

can occur as a direct extension from contiguous structures, or as pyogenic 

abscesses in bacterial sepsis. Pyomyositis, a bacterial infection with abscess formation 

in the skeletal muscles most frequently caused by Staphylococcus aureus, 

is difficult to diagnose as the symptoms are often nonspecific, but the disease 

should also be taken into consideration as otherwise the outcome is often fatal 

(41). In very rare cases, primary iliopsoas abscesses can be found (42). 

Retroperitoneal expansive pathological processes that do not involve the 

iliopsoas muscle can also mimic symptoms of iliopsoas muscle hemorrhage. 

Such processes include all kinds of tumors, infectious lesions, or hemorrhages 

in the retroperitoneal cavity, for example, kidney tumors or retroperitoneal 

abscesses (17,43). 

In patients with femoral neuropathy, the symptoms might easily be misinterpreted 

as signs of a spinal process, for example, a lumbar disc prolapse. 

Many patients do in fact have a lumbar disc prolapse visible in computed 

tomography (CT) or magnetic resonance tomography (MRT) scans, which is 

then mistaken to be the source of the patient’s symptoms. However, many 

lumbar disc prolapses are chronic, asymptomatic processes. One clinical diagnostic 

criterion is that in iliopsoas muscle hemorrhage, in contrast to a chronic 

asymptomatic lumbar disc prolapse, severe femoral neuropathy or lumbosacral 

plexopathy might develop within a very short period of time, for example, 

hours up to a few days. Another orthopedic differential diagnosis would be 

acute arthritis of the hip joint, which might also cause symptoms very similar 

to those of iliopsoas muscle hemorrhage (17). 

When anemia or hemorrhagic shock are the only symptoms of iliopsoas 

muscle hemorrhage, other bleeding sources than the iliopsoas muscle 

are often suspected in the first place, for example, a ruptured abdominal 

aortic aneurysm (10). 

If the patient presents with abdominal pain, there is a great number of 

diseases that might be suspected before the diagnosis of iliopsoas muscle hemorrhage 

is established, including splenic rupture after a trauma, gastrointestinal 

disease such as acute appendicitis, and many others (17). 

3.4. Diagnosis and Treatment 

Clinical signs like a flexed hip joint, a palpable lower abdominal mass, 

or symptoms of femoral neuropathy may arise the suspicion of iliopsoas muscle

348 Türk 

hemorrhage. As the lesions are often undetectable by physical examination, 

the definite diagnosis has to be made by imaging techniques. Possible ways of 

detecting the bleeding are ultrasound, CT, and MRT. Ultrasound is, however, 

a poor tool for differentiating between different kinds of iliopsoas muscle pathology 

(44). MR imaging is most accurate in most cases, and often CT and 

MRT have complementary roles in establishing the diagnosis (44). Valuable 

criteria for the differentiation between a neoplasm, a hemorrhage, and an 

abscess by CT are irregular margins and accompanying bone destruction for 

neoplasms, low attenuation for abscesses, and diffuse involvement of the whole 

muscle for hemorrhages (45,46). Although these rather reliable features exist 

for each of the three diseases, it has been shown that in many cases it is impossible 

to distinguish between different diseases involving the iliopsoas by radiological 

imaging techniques alone (45,46). In these cases, it becomes necessary 

to perform a muscle biopsy, which allows the most accurate diagnosis of all 

diagnostic options (39,40,45,46). In active bleedings, spiral CT has been proven 

to be an especially valuable tool as it allows a better evaluation of vascular 

extravasation of contrast, and the examination time is markedly shorter than 

in conventional CT investigations (7). Some authors suggest that if an active 

bleeding site is documented in spiral CT to directly perform selective catheterization 

of the iliopsoas supply arteries, which is of diagnostic as well as of 

therapeutic value (7). 

In many cases, conservative management of the bleeding is possible. 

Bed rest with flexion in the hip joint should be applied, and deregulated anticoagulant 

drugs should be corrected (8,17). Some cases will require a temporary 

complete cessation of anticoagulant therapy to stop the bleeding (17). 

Ultrasound-guided percutaneous decompression using a pigtail catheter has 

proven to be an effective treatment for iliopsoas muscle hemorrhage (8). When 

active bleeding is present, selective transcatheter arterial embolization has been 

shown to be an effective, less invasive alternative to surgical decompression 

(7). In some cases of active bleeding, and in cases of severe femoral neuropathy 

with symptom progression, as well as in major traumatic damage to the 

iliopsoas muscle, early surgical intervention is still considered the therapy of 

choice for many authors (4,17,33,47). 

Complications often require treatment on an intensive-care unit. Septic 

complications must be treated with antibiotics. Deep venous thrombosis resulting 

from vein compression by the iliopsoas hematoma is a therapeutical problem, 

as anticoagulation to treat the thrombosis would increase the risk of further 

bleeding. However, guidelines on how to treat these patients are still missing 

in the literature.


4. POSTMORTEM FINDINGS AND THEIR INTERPRETATION 

Morphological differences will in most cases not concern the bleeding 

itself, but rather additional autopsy findings associated with the respective 

underlying pathological condition. 

Depending on the size of the hematoma, small or larger parts of the iliopsoas 

muscle can be completely destroyed. In voluminous hematoma, the 

fascia might tear and blood might be found in the retroperitoneal cavity (12). 

If the bleeding has developed slowly, organized or partly organized hematoma 

can be found, making it possible to comment on the time of the onset of bleeding 

and on survival time. This can be elucidated in greater detail if histopathological 

investigations are performed. If questions concerning the wound age 

are aroused, Prussian Blue staining should be performed to allow a more 

accurate assessment of the age of the hematoma. 

In cases of fatal iliopsoas muscle hemorrhage, signs of internal blood 

loss, namely sparse postmortem lividity, pallor of the inner organs, and subendocardial 

hemorrhages can be expected (10). When DIC is the underlying cause 

of iliopsoas muscle bleeding, hemorrhages might be found throughout the body, 

especially in the mucosae (12). In sepsis, there are only unspecific macroscopical 

signs at autopsy, and even on the microscopical level, there is no specific 

finding to confirm the diagnosis. Thus, if sepsis is suspected, measurement of 

serum procalcitonin should be performed, as this marker has been shown to be a 

reliable parameter for the postmortem diagnosis of sepsis (48). In iliopsoas muscle 

hemorrhage as a complication of anticoagulant drugs, additional bleeding sites 

might be found, but in many cases described in the literature, iliopsoas muscle 

hemorrhage was the only manifestation of anticoagulant-related bleeding 

(7,8,10,11). In cases where anticoagulation with coumarin plays a role, it makes 

sense to perform toxicological analyses to address the question if serum coumarin 

levels were within the therapeutic range (0.16–3.6 µg/mL) (49). Coagulation 

parameters like international normalized ratio and partial thromboplastin 

time are, unfortunately, not reliable in postmortem casework. 

If the iliopsoas bleeding is traumatic, features characteristic of the sustained 

trauma will be present at autopsy. In most of these cases, the underlying 

trauma will be a fall from a height, and death will be a result of head or 

internal organ injuries. Iliopsoas muscle hemorrhage will, in most cases, not 

be relevant for fatal outcome. Still, the finding might carry a certain diagnostic 

value for the reconstruction of the fall, as a hyperextension in the hip joint 

can be suspected if iliopsoas muscle bleeding is found. This is especially true 

if inguinal tears of the skin are also present. In these cases, a feet- or knee-first 

impact is likely.

350 Türk 

In hypothermia deaths, extensive or streaky iliopsoas muscle hemorrhage 

might be found (20). On the microscopical level, fragmentation of skeletal 

muscle fibers as well as segmental or discoid fiber degeneration have also 

been described (20,21). Other autopsy features characteristic of hypothermia, 

namely Wischnewski spots of the gastric mucosa and frostbite-like reddish 

discoloration of exposed skin areas, are often absent. In these cases, an 

early death scene investigation with determination of the rectal temperature is 

highly desirable to confirm the diagnosis. In cases of fatal hypothermia, iliopsoas 

muscle hemorrhage is as such not sufficient to confirm the diagnosis. It 

might only further corroborate the diagnosis if other features suggestive of 

fatal hypothermia are present. 

5. FORENSIC MEDICAL ASPECTS OF ILIOPSOAS 

MUSCLE HEMORRHAGE 

Above all, iliopsoas muscle hemorrhage potentially gains forensic medical 

relevance if it leads to fatal outcome and questions of medical malpractice 

are aroused. In a patient treated with anticoagulant drugs, the first questions 

will be if there has been an iatrogenic overanticoagulation and if the monitoring 

of the patient’s coagulation parameters has been performed tightly enough. 

This cannot be clarified by autopsy alone, and thus the careful evaluation of 

the patients’ medical records is necessary to elucidate such cases. Another 

important question concerning medical malpractice in cases of iliopsoas muscle 

hemorrhage is whether the diagnosis has been established in time, or if there 

was a delay that might have caused fatal outcome. In most cases, this can also 

be clarified only by carefully scrutinizing the patient’s medical records to 

answer if the patient had any of the characteristic symptoms mentioned earlier, 

which diagnostic steps had been undertaken, and if there had been any pathological 

findings that were overlooked. Sometimes, histological investigations 

are advantageous in such cases as they allow to estimate the age of the bleeding 

and thus give insight into how long the bleeding had not been diagnosed. 

In other iatrogenic causes of iliopsoas muscle hemorrhage, the questions will 

be (a) if the cause of the bleeding had been malpractice during the respective 

procedure, and (b) if the patient had been informed about the possibility of 

this complication before the procedure. However, irrespective of the exact 

wording of the question concerning medical malpractice, the responsible persons 

will very rarely be sentenced in criminal law, even if malpractice can be 

proven. This is because it will in most cases not be possible for the medical 

expert witness to state with almost complete certainty (the criminal standard


“beyond a reasonable doubt”) that the bleeding would not have occurred or 

fatal outcome could have been avoided if the responsible medical staff had 

acted lege artis. 

In conclusion, the forensic pathologist should be aware of the differential 

diagnoses of iliopsoas muscle hemorrhage, as the disorder might carry a 

high forensic medical relevance in some cases. 

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neuroectodermal tumor of the kidney manifested as a spontaneous hematoma. J 

Radiol 8, 237–240. 

44. Daly BD, McPhillips M, Leung AW, Evans RM, Metreweli C (1992) Ultrasound, 

computed tomography and magnetic resonance in the investigation of iliopsoas 

compartment disease. Australas Radiol 36, 294–299. 

45. Lenchik L, Dovgan DJ, Kier R (1994) CT of the iliopsoas compartment: value in 

differentiating tumor, abscess, and hematoma. AJR Am J Roentgenol 162, 83–86. 

46. Yeh PH, Jaw WC, Wang TC, Yen TY (1995) Evaluation of iliopsoas compartment 

disorders by computed tomography. Zhonghua Yi Xue Za Zhi 55, 172–179. 

47. Kumar S, Anantham J, Wan Z (1992) Posttraumatic hematoma of the iliacus muscle 

with paralysis of the femoral nerve. J Orthop Trauma 6, 110–112. 

48. Tsokos M, Reichelt U, Nierhaus A, Püschel K (2001) Serum procalcitonin (PCT): 

a valuable biochemical parameter for the post-mortem diagnosis of sepsis. Int J Legal 

Med 114, 237–243. 

49. Schulz M, Wischhusen F, Schmoldt A (1991) Therapeutische und toxische 

Plasmakonzentrationen sowie Eliminationshalbwertszeiten gebräuchlicher Arzneistoffe. 

Anästhesiol Intensivmed Notfallmed Schmerzther 26, 37–43.

Index 355 

Index 

A 

Accidental autoerotic death (AAD), 235– 

262 

Abdominal wall, 

rupture of, 14 

Acetaldehyde dehydrogenase, 317 

Acute coronary syndromes, 149, 150 

Acute fatty liver of pregnancy, 286 

Adam, 102 

Adenylyl-cyclase subtype I, 88 

ADH. See Alcohol dehydrogenase 

Adrenals, 

apoplexy of, 220 

hemorrhage, 220 

necroses of, 221 

Adrenergic crisis, 157 

AFLP, See Acute fatty liver of pregnancy 

Alcohol, 

absorption, 318, 319 

bioavailability, 318 

blood alcohol concentration, 

analysis, 324–325 

arterial, 325 

calculation of, 321–323 

confounders in interpreting, 329, 

330 

curve, 319, 320 

absorption phase, 320, 326 

elimination phase, 320, 326, 

328 

determining, 311 

interpretation of, 325 

355 

maximum height, 320 

measurement of, 323–328 

peak, 319 

plateau, 319, 320 

specimens for, 325–328 

breath analysis, 327, 328 

and cocaine, 314 

congeners, 311 

contamination of specimen, 331 

conversion factor, 322 

decomposition, 329, 330 

distillation, 311 

distribution ratio, 328 

driving under the influence, 328 

effects on, 

behavior, 314 

elimination, 

impaired, 316 

embalming, 329, 330 

endogenous generation, 329, 330 

ethyl alcohol, 308–330 

diffusion out of the esophagus or 

stomach, 325 

physiology of, 318–323 

ethylene glycol, 310 

excretion, 319 

gastric first-pass metabolism, 318 

intoxication, 

differential diagnosis of, 314 

isopropanol, 310 

lethal hypothermia, 264 

lethal level, 315

356 Index 

metabolism, 317–323, 326 

methanol, 310, 329 

pathological effects, 309–318 

pharmacodynamic effects, 312–316 

pharmacokinetics, 316–318 

first-order, 320 

postmortem interpretation, 307–338 

storage temperatures, 332 

tolerance, 315 

toxicity, 

in pregnancy, 316 

UAC:BAC ratio, 327 

urine alcohol content (UAC), 323, 

326, 326, 330 

vitreous alcohol content (VAC), 326 

Alcohol dehydrogenase, 317 

ALDH. See Acetaldehyde dehydrogenase 

Alteration, 

myocardial, 150–162 

Alveolar pattern, 159, 160 

Alzheimer´s disease, 64 

Amphetamine 

abuse, 

cerebrovascular complications of, 

98 

effects, 

reinforcing, 98 

sympathomimetic, 98 

derivates, 102–104 

neurotoxicity, 99–102 

Amputation, 

of extremities due to burning, 14 

Anesthesiophilia, 247–250 

Angiitis, 

necrotizing, 84, 98 

Animal activity, 179, 180 

Anticoagulant therapy, 342, 343 

iatrogenic overanticoagulation, 343, 

349, 350 

oral, 

bleeding complications, 343 

Apolipoprotein E, 65 

Apoptosis, 

in the myocardium, 162 

Arteritis, 

cerebral, 84 

Artifacts, 

due to heat, 10–22 

Asphyxia, 

accidental, 193 

autoerotic, 240–247 

caused by kneeling on the thorax, 34 

chemical, 240. See also 

Anesthesiophilia 

compression of the chest, 246 

homicidal, 36 

neonaticide, 179 

plastic-bag, 240, 246 

sexual, 240–247, 255 

Asphyxiation. See Asphyxia 

Asphyxiophilia. See Asphyxia, sexual 

Astrocytes, 60, 64, 84 

adult, 62, 

fibrous, 62 

GFAP-positive, 62, 64 

immature, 64 

protoplasmatic, 62 

reactive, 61, 62, 64 

Autoeroticism. See also Autoerotic death 

females, 252, 253 

Autoerotic death, 235–262 

death scene characteristics, 253–258 

demarcation from suicides and homicides, 

253–258 

drowning during, 246 

electrocutions, 250 

escape/(self-) rescue mechanisms, 

242, 250, 254, 255, 256 

practices, 240–251 

septic, 251 

Avascular area, 152 

Axonal injury, See Diffuse axonal injury 

B 

BAC. See Alcohol, blood alcohol concentration 

Benzodiazepines, 89 

Benzoylecgonine, 89

Index 357 

Birth line, 183 

Bleeding. See Hemorrhage 

Blister, 

of the skin, 7 

Blood alcohol concentration. See Alcohol 

Blood–brain barrier, 57, 89, 93 

in fire victims, 21, 22 

Blood vessels, 

formation of, 

following traumatic brain injury, 65 

Blunt force, 

biomechanical mechanisms, 32 

skin lacerations due to, 35 

Bondage, 241, 253–255 

Bones, 

changes in burning, 18 

Boxer´s attitude. See Pugilistic attitude 

Burned bodies, 

destruction of, 12 

morphological findings in, 3–27 

Burning, 3–27 

postmortem, 9, 17, 18 

signs of vitality, 9, 15, 16, 17, 21 

Burns, 

direct, 15 

of the skin, 6–8 

degrees, 6, 7,13,14 

Brain, 

abscess, 85 

damage, 60 

hyperthermic, 20–22 

hypoxic, 278 

experimental, 57 

septic foci, 85 

Brain injury. See Brain, damage 

Bronchiolitis obliterans. See Mycoplasma 

pneumoniae 

C 

Calcination, 14 

Cannabis. See also Tetrahydrocannabinol 

toxicity, 

acute, 96, 97 

chronic, 97 

Caput succadeum, 178 

Carbon monoxide, 

hemoglobin, 5 

intoxication, 82, 162 

Cardiac death, 139–168 

among U.S. residents, 141 

with preceding resuscitation attempts, 

157, 158 

Cardiac diseases, 140. See also Cardiac 

death 

Cellular response, 

inflammatory, 56–58 

late, 

in the brain, 57 

Central nervous system, 

alterations in drug abuse, 79–136 

in thermal trauma. See Brain damage, 

hyperthermic 

proliferative processes in, 65 

Cephalhematoma, 178 

Cephalopelvic disproportion, 178 

Cerebral blood flow, 80 

CGS. See Crow–Glassman Scale 

Charring, 

of a body, 7, 11, 14, 19 

Chasing the dragon, 86, 87 

Chemical evidence, 

procedures for preserving, 330–332 

Chest compression, 247 

Chlamydia pneumoniae, 213 

Club drugs, 80 

CNS. See Central nervous system 

Coagulation necrosis, 151 

Cocaine, 

abuse, 89–95 

autopsy findings in, 91, 93 

cerebral vasospasm in, 91 


90 

movement disorders in, 94 

neuroimaging in, 90 

potential of, 90 

and alcohol, 314 

neurotransmitters,

358 Index 

alterations of, 94, 95 

rectally administered, 250 

Codeine, 89 

Combustion, 18 

spontaneous human, 8 

Contraction band necrosis, 153–162, 

285, 286 

Contusion. See also Lesion, cortical 

cortical, 56, 62, 65 

Convection, 6 

Coprophilia, 240 

Coronary artery, 

aneurysms, 146 

anomalies, 145–150 

occlusion, 151 

spasm, 145, 149 

stenosis, 145–150 

Coronary atherosclerosis, 141, 146 

Coumarin, 349 

Crack dancing, 94 

Cremations, 14, 15 

Cross-dressing, 252, 253 

Crow–Glassman Scale, 13 

Crow´s feet, 9 

Crumbling point, 15 

D 

DAI. See Diffuse axonal injury 

Damage, 

thermal. See Burned bodies, Burns, 

Blister 

Dance drug, 102 

Death scene, 251 

Decomposition, 329, 330 

Defense injuries. See Injuries 

Designer drugs, 80 

DIC. See Disseminated intravascular 

coagulation 

Diffuse alveolar damage, 210 

Diffuse axonal injury, 56 

Disseminated intravascular coagulation, 

221, 229, 278–281, 286, 343, 349 

Dissociative hallucinations, 173 

Disulfiram, 315 

Diuresis, 

cold-induced, 266 

Down syndrome. See Trisomy 21 

Drug abuse. See also Cannabis, Cocaine, 

Opiates, 

changes in gene expression, 81 

genetic risk factors for, 81 

Drug dependence. See Drug abuse 

E 

Ecstasy, 80, 98, 102, 104 

Electroejaculation, 250 

Electrophilia, 250, 251, 255 

Embalming, 329, 330 

Embden–Meyerhof glycolytic pathways, 

330 

Endocannabinoids, 95, 96 

Endocarditis, 85 

Eosinophilia, 

cytoplasmic, 82 

Erythema, 6, 7 

Erythrophages, 59 

Ethyl alcohol. See Alcohol 

Eve, 102 

Exposure, 

of intestinal loops due to fire, 15 

External findings, 

in burned bodies, 6–14 

F 

Ferruginated neurons. See Red neurons 

Fetishism, 239, 240, 252 

Fibrosis, 

myocardial, 146, 158 

reparative, 159 

Fire. See also Burned bodies, Burns, 

Burning 

annual deaths related to, 4 

complete consumption by, 13 

consumption by, 7,8 

deaths, 3–27 

fumes, 

inhalation of, 15 

scene of, 13,14

Index 359 

smoldering, 8 

victims, 

morphology of, 3–27 

brain in, 20–22 

Flatliners, 102 

Flotation test, 182, 183 

Forensic wound age estimation. See 

Wound age 

Fracture, 

calvaria, 34 

facial bones, 34 

ribs, 39 

skull base, 34 

sternum, 39 

throat skeleton, 36 

Fragmentocytes, 17 

G 

Gastrointestinal tract, 

in burning, 18 

GFAP. See Glial fibrillary acidic protein 

Glial fibrillary acidic protein, 61–64 

Glue sniffing, 247 

H 

Haemophilus influenzae, 220 

Hair, 

singeing of, 8 

Hanging, 237, 240, 241 

repetitive, 254 

Head-down position, 246 

Healing phase, 159 

Healing process. See Wound, healing 

process 

Heart, 

dissection of, 143–145 

methods, 

inflow–outflow method, 143 

postmortem chalk injection, 143 

insufficiency, 159 

Heat, 

changes of hair, 8 

effects of, 3–27 

prolonged exposure to, 9, 19 

HELLP. See Hemolysis, elevated liver 

enzymes, low platelet count syndrome 

Hematoidin, 59 

Hematoma, 

epidural, 19, 20 

iliopsoas, 343, 344, 346, 349 

liver, 

subcapsular, 278, 279, 281 

Hemolysis, 17 

Hemolysis, elevated liver enzymes, low 

platelet count syndrome, 275–290 

acute respiratory distress syndrome 

(ARDS), 278, 285 

autopsy features, 279–281 

causes of death, 277–279 

clinical presentations, 277–279 

contraction band necrosis, 285, 286 

differential diagnosis, 286, 287 

disseminated intravascular coagulation 

(DIC), 278–281, 285, 286, 

287 

hepatic encephalopathy, 281 

histopathology, 281–286 

hypoxic ischemic encephalopathy, 

278 

kidneys, 282–285 

liver pathology, 279–281 

liver rupture, 279, 281, 286 

maternal complications associated 

with, 277–286 

maternal mortality, 279, 286 

medicolegal aspects, 287 

petechiae, 279 

placental abruption, 285 

sepsis, 278 

Hemophilia, 344 

Hemorrhage, 

adrenal, 220 

cortical, 55 

diapedetic, 55 

epidural, 19, 20, 35 

intraabdominal, 297 

intraalveolar, 179, 209

360 Index 

intracerebral, 90, 91, 92, 98, 104, 158, 

178, 278 

intracranial. See intracerebral 

intrahepatic, 286 

petechial, 10 

postmortem, 20 

retropharyngeal, 295 

retroplacental, 180 

retrosternal, 298 

subarachnoid, 35, 85, 90, 92, 98, 104 

subdural, 35, 177, 178 

subendocardial, 349 

subgaleal, 177 

subperiostal, 178 

Hemorrhagic shock, 346 

Heparin, 342 

Heparin-induced thrombocytopenia, 342 

Hepatic failure, 104 

Heroin, 

impure, 84 

intoxication, 82–84, 87. See also 

Opiates 

maintenance treatment, 89 

Hibernation, 270, 271 

Hide-and-die syndrome, See Hypothermia 

HIT. See Heparin-induced thrombocytopenia 

HIV. See Human immunodeficiency 

virus-1 

Homicide, 

sadistic, 253 

Homosexuality, 238 

Huffing, 247 

Human immunodeficiency virus-1, 93 

Hypothermia, 87, 184, 263–272 

core temperature, 264 

hide-and-die syndrome, 268–271 

iliopsoas muscle hemorrhage, 342, 

344, 350 

mental confusion in, 269 

paradoxical undressing, 265–268 

vasoconstriction, 267, 268 

ventricular fibrillation, 264 

Hypoxia, 

autoeroticism, 242 

cerebral, 82, 83, 87 

secondary to respiratory depression, 

84 

Hypoxyphilia, 239. See also Autoerotic 

Death, Asphyxia 

I 

Iliopsoas muscle hemorrhage, 341–353 

causes, 342–345 

disseminated intravascular coagulation, 

343 

hypothermia, 344 

iatrogenic 343, 344 

trauma, 344 

complications, 345 

diagnosis, 346, 347 

delay in, 350 

differential diagnosis, 346 

femoral paralysis, 346 

forensic medical aspects, 350, 351 

medical malpractice, 350, 351 

presentation, 345, 346 

recurrent, 344 

trauma, 344, 349, 350 

treatment, 346, 347 

Infanticide, 172, 190–192. See also 

Neonaticide 

repeated episodes of, 173 

Infarction. See Myocardial infarction 

Inflammatory cellular response. See 

Cellular response 

Inhalation, 

of hot gases, 15 

of hot steam, 16, 17 

Injury pattern, 

analysis of, 

in kicking and trampling, 31–47 

three-dimensional documentation of, 

42 

Injuries, 

from defensive action, 42–45 

kicking,

Index 361 

to head, 35, 36 

to inner organs, 39–42 

to neck, 3–39 

to thorax, 39–42 

Intubation. See Resuscitation procedures 

Ischemic heart disease, 147 

Isopropanol. See Alcohol 

K 

Karyotyping, 176 

Kawasaki disease, 146 

Ketamine, 249 

Kicking, 31–49 

Killing, 

by burning, 4 

Kupffer´s cells, 281 

L 

Laceration, 

of the skin, 35 

Laminin, 65 

Legal chain of custody, 330–332 

Lesion, 

cortical, 59, 60, 62, 64 

ischemic, 90 

Leukoencephalopathy, 104 

Ligature, 

indentation, 178, 179 

strangulation, 36 

Lipofuscin, 159 

Live birth, 175 

methods of determining, 181–183 

Liver, 

cirrhosis, 344 

micronodular, 316 

rupture. See Hemolysis, elevated liver 

enzymes, low platelet count 

syndrome 

M 

Maceration, 182 

Macrophages, 

cerebral, 59, 60 

pigment laden, 84 

MAP. See Microtubule associated protein 

Masochism, 238, 256 

sexual, 239, 251 

Masochistic behavior, See Masochism 

Mellanby Effect, 312, 313 

Meningitis, 85, 227 

Meningococcal infection. See Meningococcemia 

Meningococcemia, 220, 226–229 

Meningococci. See Meningococcemia 

MEOS. See Microsomal ethanol-oxidizing 

system 

Methadone, 89 

Methamphetamine. See Amphetamine 

Methanol. See Alcohol 

Metronidazole, 315 

Microglia, See Microglial cells 

Microglial cells, 59, 60, 84 

Microsomal ethanol-oxidizing system, 

317, 318 

Microtubule associated protein, 56 

Mollicutes, 203 

Moth-eaten pattern, 159 

Mycoplasma pneumoniae, 201–218 

bronchiolitis obliterans, 204, 206–209 

histopathology, 204–210 

infection, 

iatrogenic malpractice related to, 

214, 215 

incubation period, 204 

spread of, 204 

treatment of, 214 

pneumonia, 204, 207 

postmortem diagnosis using serology 

and PCR, 210–212 

thrombosis in, 205, 210 

Myocardial infarction, 146, 150–162 

Myocardial ischemia. See Myocardial 

infarction 

Myocardial necrosis. See Myocardial 

infarction 

Myocarditis, 141, 227–229 

Myofiber break-up, 160

362 Index 

N 

Necrophilia, 240 

Necrosis, 

hepatocellular, 281 

myocardial. See Myocardial infarction 

Neonaticide, 171–185 

autopsy, 176–183 

causes of death, 184 

examination of the placenta, 180, 181 

maternal characteristics of, 173 

motivation of, 172, 173 

role of the pathologist in, 174–176 

scene examination in, 173, 174 

Nephropathy, 

preeclamptic, 282 

Nerve cell damage, 104 

hypoxic, 81, 82 

Nerve cell loss. See Nerve cell damage 

Nerve injury, 

response to, 59 

Neuron-specific enolase, 64, 65 

Neuronal cell, 

cloudy swelling of, 55 

damage, 81 

Neuronal damage, 

after traumatic brain injury, 55, 56 

primary, 84 

Neuronal degeneration. See Neuronal 

damage 

Nitric oxide, 97, 102 

NO. See Nitric oxide 

Nuclear pyknosis, 55 

O 

Opiates, 

abuse, 81–89 

autopsy findings in, 81, 82 

cerebral atrophy in, 81 


82–84 

infections associated with, 85 

neuroimaging in, 81 

effects on the central nervous system, 

87–89 

hypoxic-ischemic leukoencephalopathy 

due to, 84 

intoxication, 

hypoxia during, 82 

neurotransmitters, 

alterations of, 87 

Opioid receptors, 87 

P 

Paradoxical undressing. See Hypothermia 

Paralysis, 

cold-induced, 268 

Paraphernalia, 252, 257 

Paraphilias, 237, 238–240. See also 

Autoerotic death 

multiplex, 240 

nonlethal, 252, 253 

Parkinson´s disease, 64, 95, 100, 102 

Parkinsonism. See Parkinson´s disease 

PCR. See Polymerase chain reaction 

Pedophilia, 240 

Petechiae, 179, 279 

Phospholipase A2, 95 

Placenta, 

abruptio, 180 

infarction, 180 

previa, 180 

velametous insertion, 181 

Plaque, 

active, 149 

atherosclerotic, 147, 

eccentric, 147 

fibrous, 147 

progression of, 147 

vascularized, 149 

Pleura sign, 16 

PMN. See Polymorphoneuclear leukocytes 

Pneumonia. See also Mycoplasma 

pneumoniae 

atypical, 212, 213 

community-acquired, 213 

Pneumothorax. See Resuscitation procedures

Index 363 

Polymerase chain reaction, 56, 210–212 

Polymorphoneuclear leukocytes, 

infiltration, 151 

Polysubstance abuse, 80 

Postmortem effects, 

of heat, 

on the skin, 7 

Postmortem microbiological investigations, 

221–229 

Preeclampsia, 282, 283, 286 

Procalcitonin, 349 

Protective padding, 

autoeroticism, 240, 257 

Psoas position, 345 

Pugilistic attitude, 10–12 

Puppet organs, 15 

Pyomyositis, 347 

Q 

QT syndrome, 193 

R 

Reactive gliosis. See Traumatic brain 

injury 

Recovery phenomenon, 100 

Red neurons, 55, 56 

Respiratory failure, 

primary, 84 

Respiratory tract, 

changes, 

in burning, 15–17 

Resuscitation procedures, 

airways, 295–296 

cardiopulmonary, 296–298 

active compression–decompression, 

297, 298 

rate of complications, 299 

coniotomy, 296 

esophageal perforation, 295 

fracture of, 

cricoid cartilage, 296 

ribs, 296 

tracheal cartilage, 296 

injection, 

intracardial, 298 

S 

injuries resulting from, 293–303 

intubation, 295 

frequency of related injuries, 300 

lung contusion, 297 

mediastinal emphysema, 296, 298 

medical malpractice associated with, 

294 

medicolegal aspects, 299–301 

pneumothorax, 295–297 

puncture of vein, 299 

retropharyngeal hemorrhage, 

frequency of, 295 

stomach, 

inflation of, 295, 297 

rupture of, 295, 297 

tracheotomy, 296 

Sadism, 238 

Scratch marks, 178 

Seizure, 

cocaine-associated, 94 

Self-immolation. See Self-incineration 

Self-incineration, 7 

Sepsis, 221, 278, 343, 349 

Sexual deviancy, 236 

Sharp force, 

traces of, 

in burning, 19 

Shoe, 

describing the sole pattern using 

special classification codes, 42 

imprint of the sole of, 39 

Shrinkage. See Tissue 

Siderophages, 59 

SIDS. See Sudden infant death 

syndrome 

Sinus vein thrombosis, 104 

Skin, 

splitting of by heat, 8, 9 

Smooth muscle cell hyperplasia, 147 

Smothering, 184 

Soft tissue. See Tissue 

Spalding´s sign, 182

364 Index 

Species, 

determination of, 12 

Spectrin, 56 

Spheroids, 56 

Spider´s web fracture, 19 

Spongiform leukoencephalopathy, 86, 87 

Stab wound, 64, 65, 177, 184. See also 

Wound 

Stabbing. See Stab wound 

Staphylococcus aureus. See Pyomyositis 

Stillbirth, 175, 182–184 

Strangulation, 177, 178, 184, 237, 240, 

253 

Stroke, 

associated with, 

cocaine abuse, 90–93 

amphetamine abuse, 98 

in heroin addicts, 82–84 

Subendocardial hemorrhage. See Hemorrhage 

Sudden cardiac death. See Cardiac death 

Sudden death, 

definition of, 140, 141 

following physical exertion, 146 

inherited conditions causing, 193 

investigation of, 143 

Sudden infant death syndrome, 189–198 

definition, 191 

diagnostic problems, 191–193 

risk factors, 190 

Suffocation, 191, 194, 240, 249. See also 

Asphyxia 

Surfactant proteins, 203 

Syncopal episodes, 145, 146 

Sympathicomimetic overtone, 157 

T 

Takayasu disease, 146 

TBI. See Traumatic brain injury 

Tenascin, 62, 64, 65 

Tetrahydrocannabinol, 

abuse, 95–97 

complications, 96, 97 

neuroimaging, 97 

neurotransmitters, 

alterations of, 97 

receptors, 95, 96 

THC. See Tetrahydrocannabinol 

Tissue, 

brain, 

damage, 60 

cervical soft, 

injury of, 295 

destruction, 59 

healing phase after, 60 

fluid, 

loss due to burning, 4,12 

shrinkage due to burning, 6, 8, 9, 15, 

18, 19, 20 

Trampling, 31–49 

Transverse myelitis, 85 

Traumatic brain injury, 53–75 

in rats, 59, 60 

inflammatory cellular response to, 

56–58 

reactive gliosis, 60–65 

Trisomy 21, 176 

U 

Umbilical cord, 178, 179, 180, 181, 184 

Urine alcohol content (UAC). See Alcohol 

V 

Vaporization of body fluids, 15 

Vasculitis, 84, 93, 98, 228. See also 

Angiitis, Arteritis 

Vessel, 

wall, 

remodeling of, 147 

Vimentin, 21, 59, 60, 62 

Virchow–Robinson spaces, 21 

Vitality, 

in burning, 9, 15, 16, 17, 21 

Vitreous alcohol content (VAC). See 

Alcohol 

Voyeurism, 239, 240

Index 365 

W 

Washerwoman´s skin, 

differential diagnosis of, 7 

Waterhouse–Friderichsen syndrome, 

219–231 

diagnosis, 220 

etiologic germs, 227 

medicolegal aspects, 228, 229 

meningitis, 227 

mortality rate, 226 

Wavy fibers, 153 

WFS. See Waterhouse–Friderichsen 

syndrome 

White matter, 

brain, 

spongiform changes of, 104 

Widmark, 

equations, 318–323 

factor, 321, 322 

Wischnewski spots, 265, 342 

Wound. See also Stab wound 

healing process, 

in human brain tissue, 60–65, 65 

penetrating, 9 

Wound age, 

estimation of, 54, 59, 60, 349, 350 

in cortical contusions, 53–75 

morphological parameters for, 54, 

65–68 

Z 

Z-lines, 153, 154

About the Editor 

Dr. Michael Tsokos is a Lecturer of Forensic Pathology 

and Legal Medicine at the University of Hamburg, Germany, 

and the Police Academy of the City of Hamburg, Germany. He 

is the primary or senior author of more than 90 scientific 

publications in international journals, the editor of a monograph 

on external examination before cremation (in German) and the 

editor of one book on sudden, unexpected death (in German). 

In 1998 and 1999, he worked for a time with the exhumation 

and identification of mass grave victims in Bosnia-Herzegovina 

and Kosovo under the mandate of the UN International Criminal 

Tribunal for the former Yugoslavia. He is a member of the 

International Academy of Legal Medicine and the German 

Identification Unit of the Federal Criminal Agency of Germany. He is a member of the 

Editorial Board of Legal Medicine and Assistant to the Editor-in-Chief of Rechtsmedizin 

(the official publication of the German Society of Legal Medicine). In 2001, Dr. Tsokos 

was honored with the national scientific award of the German Society of Legal Medicine 

for research on micromorphological and molecularbiological correlates of sepsis-induced 

lung injury in human autopsy specimens.

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