The Autonomic Nervous System in Human SCI - Uniklinik Balgrist

The Autonomic Nervous
System in Human SCI
A Curt MD
Spinal Cord Injury Centre
University Hospital Balgrist
Schweizerisches Paraplegikerzentrum
Uniklinik Balgrist

Autonomic Nervous System
John Newport Langley introduced the term
“Autonomic Nervous System” in 1898
he was a lecturer from 1883 to 1903 and Professor of Physiology
from 1903 to 1925 at the University of Cambridge

Autonomic Nervous System
John Newport Langley introduced the term
“Autonomic Nervous System” in 1898
he was a lecturer from 1883 to 1903 and Professor of Physiology
from 1903 to 1925 at the University of Cambridge
• Langley, John Newport. 1921. The Autonomic Nervous System. Cambridge
• Langley, John Newport. 1898-1900. The Salivary Glands. In: Text-Book of
Physiology, edited by E. A. Schäfer, Edinburgh, London
• Langley, John Newport and Charles S. Sherrington. 1891. On Pilomotor Nerves.
Journal of Physiology 12: 278-291
• Langley, John Newport. 1898-1900. The Sympathetic and Other Related Systems of
Nerves. In: Text-Book of Physiology, 616-696. Edinburgh, London: E. A. Schäfer

What is special?
• Old part of the CNS
• No voluntary control
• No immediate distinct feedback
• Equilibrium system
– Balancing outputs (cardio-vascular system..)
– Indirect control and responses
– Hierarchical organization
• Specific anatomical organization

Autonomic Nervous System
• cardiac pacing
• blood pressure
• temperature
• sweating
• bladder
• bowel
• sexual

Spinal Cord Injury
Special model of autonomic dys-balance

Spinal Cord. 2009 Jan;47(1):36-43
International standards to document remaining
autonomic function after spinal cord injury
Alexander MS, Biering-Sorensen F, Bodner D, Brackett NL, Cardenas D, Charlifue S, Creasey G, Dietz V, Ditunno J, Donovan
W, Elliott SL, Estores I, Graves DE, Green B, Gousse A, Jackson AB, Kennelly M, Karlsson AK, Krassioukov A, Krogh K,
Linsenmeyer T, Marino R, Mathias CJ, Perkash I, Sheel AW, Schilero G, Schurch B, Sonksen J, Stiens S, Wecht J, Wuermser
LA, Wyndaele JJ.
Experts opinions consensus
… common strategy to document remaining autonomic neurological function following SCI.
… commissioned by ASIA and ISCoS
RESULTS: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic
function. ...
http://www.asia-spinalinjury.org/publications
/Autonomic_Standards_Assessment_Form_FINAL_2009.pdf

Steering Committee: Marcalee Sipski Alexander, Fin Biering-Sorensen, Susan Charlifue,
Volker Dietz, John Ditunno, Dan Graves, Michael Kennelly, Andrei Krassioukov, Ralph
Marino, Steven Stiens, Lynne Weaver
Urology Domain: Michael Kennelly, Diana Cardenas, Graham Creasey, Angelo Gousse, Bruce Green,
Todd Linsenmeyer, Brigitte Schurch, Jean-Jacques Wyndaele
Bowel Domain: Steve Stiens, Irene Estores, Klaus Krogh, Inder Perkash
Sexual Function Domain: Marcalee Sipski Alexander, Don Bodner, Nancy Brackett, Stacy Elliott,
Amie Jackson, Jens Sonksen
Cardiovascular, Sudomotor and Thermoregulatory Domain: Andrei Krassioukov, Ann-Katrin
Karlsson, Ralph Marino, Christopher J. Mathias, Jill Wecht, Lisa Wuermser

Klinik der autonomen Dysfunktion
urologisch
Inkontinenz (urgency/frequency)
Retention
a-hypokontraktiler Detrusor
Detrusorhyperreflexie
Schrumpfblase
Blasen-Nierensteine
Sphinkter-Detrusor Dyssynergie
Hydronephrose
vesicorenaler Reflux

Klinik der autonomen Dysfunktion
sexuell
gastrointestinal
sudomotorisch
Erektion/Emission/Ejakulation
Fertilität / Orgasmus
Paralytischer Ileus
Obstipation, Diarrhoe
An-/Hypo-/Hyperhydrosis
Thermodysregulation
Pupillomotorik
Hornersyndrom

Klinik der kardio-vaskulären
Dysfunktion
Bradykardie (Asystolie)
(Hypervagotonie)
Sympathetic failure
(Hyposympathonie)
Autonome Dysreflexie
(Dysregulation)
Nocturnale sympathische
Dysregulation
Intensivstation
temp. pacemaker
Mobilisation
Blutdruckkrisen mit
Bradykardie
24 RR-monitoring

Orthostatic hypotension = Sympathetic failure
Sympathetic (orthostatic) failure in acute and chronic SCI
Incompletely rebalanced in the chronic stage
probably by peripheral mechanisms

Approaches
• Midodrine (selective alpha-adrenergic agent)
• Fludrocortisone (mineralocorticoid)
• Dihydroergotamine (ergot alkaloids)
• Ephedrine (nonselective alpha-beta receptor agonist)
•
• Fluid & Salt
• Pressure Interventions (stockings)
• FES (physiological muscle pump)
• Exercise (treadmil, tilt tables)
Conclusion
…there is yet no gold standard
for the treatment of OH in SCI…
Arch Phys Med Rehabil 2009; 90: 876-85

Orthostatic hypotension in SCI
• orthostatic hypotension dependent on level of SCI
• SAP & DAP dysregulation from supine to upright
Claydon and Krassioukov J Neurotrauma 2006

Cardiovascular dysregulation
during activities in SCI
Abnormal cardiovascular responses to exercise and transient postexercise
hypotension common in cervical, but not thoracic SCI.
Claydon VE et al APMR 2006

Nocturnal autonomic regulation
Preserved in healthy controls and paraplegia

Nocturnal sympathetic dys-regulation
complete tetraplegia C6
multiple episodes of AD
successful treatment
of AD
Nitsche B, Perschak H, Curt A, Dietz V.
Loss of circadian blood pressure variability in complete tetraplegia. J Hum Hypentens 1996; 10: 311-317

Autonomic dys-reflexive episode
200
250
150
BP (mmHg)
100
HR (b/min)
50
200
150
100
EUS (cmH 2 O)
50
0
0
BLA (cmH 2 O)
induction of AD by electrical pudendal nerve stimulation in complete tetraplegia
Reitz A, Schmid DM, Curt A, Knapp PA, Schurch B.
Autonomic dysreflexia in response to pudendal nerve stimulation. Spinal Cord 2003; 41: 539-542

Assessment of the sympathetic level of lesion in patients with
spinal cord injury
JG Previnaire, JM Soler, W El Masri and P Denys
Study design: skin axon-reflex vasodilatation (SkARV) in SCI
Subjects: A total of 81 SCI patients ranging from C2 to L2.
Results: Above the lesion, SkARV was observed in all patients. In patients with a complete sympathetic
injury, the response below the lesion was either a vasoconstrictor response in upper motor neuron
lesions, or total absence of SkARV in lower motor neuron lesions.
.. excellent correspondence between complete somatic AIS A and complete sympathetic lesions…
.. whereas an incomplete somatic (ASIA B–D) lesion was often associated with a complete sympathetic lesion.
In 34% of complete ASIA A patients, a sympathetic zone of partial preservation was found, extending below the
lesion on sensory denervated dermatomes.
Conclusion: SkARV is a simple bedside test that allows the assessment of sympathetic completeness of
injury across the lesion as well as the excitability of the isolated spinal cord. …
Spinal Cord (2009) 47, 122–127

Assessment of the sympathetic level of lesion in patients with spinal cord injury
T3 AIS – A, SkARV normal to T3
but diminshed below
C4 AIS – B SkARV normal to C4
but diminished below

Sympathetic skin response (SSR)
Otto Veraguth
1870 - 1944
Prof. for Neurology
Chair for Physical Medicine
EO 1918-1940
Spine Surgery with V. Horsley (London)
and Ch. Ellsberg (New York)

Sympathetic skin response (SSR)
One such early use of the galvanometer was in research published in 1890 by Jean De
Tarchanoff (1857–1927) in Russia entitled “Galvanic Phenomena in the Human Skin in
Connection with Irritation of the Sensory Organs and with Various Forms of Psychic Activity.”
The name Tarchanoff phenomenon was given to the effect.
In 1907, Frederick Peterson and Carl G. Jung published an article in the journal Brain based
on their research in Zurich. They used the galvanometer with normal and abnormal individuals
measuring galvanic skin changes in reaction to word associations. Jung mentioned the
research as early as 1906 in his Studies of Word Analysis.
Otto Veraguth (1870–1944) in Switzerland also published in 1907 a similar study using the
galvanometer in conjunction with word-association tests. He noticed that personally emotive
stimuli created larger fluctuations in the galvanometer readings from electrodes on the skin
than did neutral ones. This led to Veraguth to use the term “psychogalvanic reflex” for the
response.

Sympathetic skin response (SSR)
„wenn nicht der Gelehrtendünkel wäre“
Carl Gustav JUNG, Schweizer Psychiater und Psychologe, 1875–1961.
…über den Neurologen Otto Veraguth (1870–1944).
„... Ich bin neulich einmal angefragt worden, ob V. ein Analytiker sei, was ich
verneinte. V. hat ja alle Gelegenheit, das Märchen von der Exclusivität, das
unsere Gegner ersonnen haben, unwahr zu machen – wenn nicht der
Gelehrtendünkel wäre.“
lie detector test….
„Lügendetektor“

Sympathetic skin response (SSR)
Curt A, Weinhardt C, Dietz V.
Significance of sympathetic skin response in the assessment of autonomic failure in patients with spinal cord injury.
J Auton Nerv Syst 1996; 61: 175-180

Sympathetic skin response (SSR)
sympathetic failure
C1 - T3
autonomic dysreflexia
T4 - T9
Hand
reduced thermoregulation
internal
bladder sphincter
T10 - L2
Hand
Foot
bladder neck dyssynergia
Conus
Cauda
[mV]
[sec]
Hand
Foot
perineal
erectile dysfunction
Schurch B, Curt A, Rossier AB.
The value of the sympathetic skin responses in the assessment of the vesico-urethral autonomic system.
J Urol 1997; 157: 2230-2233

Neurorehabil Neural Repair. 2009 Jul-Aug;23(6):553-8
Sympathetic skin responses evoked by different stimuli modalities in
SCI patients
Kumru H, Vidal J, Perez M, Schestatsky P, Valls-Solé J.
OBJECTIVE: … sympathetic skin response (SSR) in SCI
METHODS: … SSR induced in the hand and foot in 50 SCI patients and 15 matched controls
by deep inhalation, unexpected acoustic stimuli, brisk hand muscle contraction, and median
and peroneal nerve electrical stimulation (PNS).
RESULTS: SSRs to any stimulus modality were absent in hand and foot in patients with
complete SCI above the T4 level. They were present in the hand and absent in the foot in
complete SCI patients at levels between T4 and T11 for all stimuli modalities except PNS.
CONCLUSION: SSR to various stimuli confirms the importance of supraspinal centers and the
integrity of sympathetic descending pathways. Simultaneous recording of the SSR in the hands
and feet provides information about the degree of sympathetic impairment possibly in the
efferent pathway.

Functional SSR recordings during micturition
subjective sensation
first desire to void
SSR hand
SSR foot
1 mV
EMG pelvic floor
0.1 mV
1 sec
Time

Functional SSR recordings during micturition
subjective
sensation
SDV SDV SDV SDVSDV SDV
Hand
SSR
1 mV
EMG
Foot
Pelvic floor
0.1 mV
10 sec
Time

Functional SSR recordings during micturition
subjective
sensation
SDV
Short relief of SDV
SDV
Hand
SSR
Foot
EMG
1 mV
0.1 mV
Pelvic floor
Voluntary pelvic floor contraction
10 sec
Time

Functional SSR recordings during micturition
subjective
sensation
SDV
Disappearing desire to void after onset of micturition
SSR
1 mV
Hand
Foot
EMG
0.1 mV
10 sec
Micturition
Time
Pelvic floor

Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H668-78
Clinical correlates of frequency analyses of cardiovascular control after
spinal cord injury
Claydon VE, Krassioukov AV.
International Collaboration on Repair Discoveries, Vancouver, Canada.
… evaluation of cardiovascular autonomic dysfunction after SCI
… frequency analyses of heart rate and blood pressure variability (HRV and BPV) after SCI in 26
subjects with chronic cervical or thoracic SCI
SCI results in reduced sympathetic drive to the heart and vasculature, and increased baroreflex
delay in cervical SCI subjects and reduced cardiac vagal tone in thoracic SCI subjects.
… useful non-invasive clinical tools with which to assess autonomic completeness of injury
following SCI.

Heart Rate Variability: An Objective Measure of Autonomic Activity and
Bladder Sensations During Urodynamics
Ulrich Mehnert, Peter A. Knapp, Nicole Mueller, Andre´ Reitz, and Brigitte Schurch
Spinal Cord Injury Center, Balgrist University Hospital, Zürich, Switzerland
Aims: … cardiac autonomic activity during standard filling cystometry (FC) using heart rate variability (HRV)
Results: in 12 healthy subjects the LF/HF ratio showed a reproducible activation pattern with a stable sympathovagal balance
until FDV.
Before SDV was indicated, the sympathovagal balance started to shift towards sympathetic activation and caused a significant
increase in LF/HF.
Conclusion: HRV analysis seems to be a useful indicator for the general activation pattern of the sympathovagal balance during
FC, correlating the intensity of the bladder filling sensation to stress and sympathetic activation.
Neurourol. Urodynam. 28:313–319, 2009

Restor Neurol Neurosci. 2005;23(5-6):331-9
The ability of physiological stimuli to generate the sympathetic skin
response in human chronic spinal cord injury
Nicotra A, Catley M, Ellaway PH, Mathias CJ.
PURPOSE: … in chronic SCI .. if recording the sympathetic skin response (SSR) provides
evidence of integrity of the spinal component of the sympathetic pathways.
METHODS: Thirty subjects with chronic SCI and 15 healthy normal subjects were studied. The
SSR was elicited using two physiological (auditory and inspiratory gasp) stimuli. In addition,
electrical (median and peroneal nerve) stimulation was also performed.
RESULTS: Palmar and plantar SSRs could be readily elicited in all control subjects by all stimuli.
In the majority of SCI subjects, the presence or absence of the SSR was related to the ASIA
impairment scale. The exceptions indicated preserved (or damaged) sympathetic spinal cord
pathways.
CONCLUSIONS: .. SSR using either physiological or electrical stimuli, may be a reliable, noninvasive
method of determining integrity of sympathetic cholinergic pathways in SCI

SSR due to pudendal nerve stimulation in
healthy controls
Stimulation
hand
SSR
1 mV
foot
EMG
pelvic floor
0.1 mV
1 sec
Time
Fig. 1

SSR due to pudendal nerve stimulation in
complete SCI
Stimulation
hand
SSR
1 mV
foot
EMG
pelvic floor
0,1 mV
1 sec
Time
Fig. 2

SSR below the level of SCI
Interrupted Somatosensory Pathway
Complete SCI on cervical or thoracic level
T10-L2
SSR Foot
BCR
Spinal Sympathetic Sudomotor Pathway
S2-S4
Pudendal Nerve
Schurch B, Curt A, Rossier AB.
The value of the sympathetic skin responses in the assessment of the vesico-urethral autonomic system.
J Urol 1997; 157: 2230-2233

Autonomic Nervous System
• Frequently underestimated
• Interdisciplinary diagnostics
• Clinically relevant to patients
• Treatment available

END
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