Skeletal Muscle Pathology after Spinal Cord Injury: Our 20 Year ...

Skeletal Muscle Pathology after Spinal Cord Injury: Our 20 Year
Experience and Results on Skeletal Muscle Changes in Paraplegics,
Related to Functional Rehabilitation
Roberto Scelsi
Department of Human and Hereditary Pathology, University of Pavia, Pavia, Italy
Abstract
The present review on 20-year-experience on paralyzed skeletal muscle in paraplegics after
traumatic spinal cord injury (SCI), reports changes in muscle fibres and microvasculature
seen after morphological, morphometric and ultrastructural studies on open and needle
biopsies. The changes were correlated with the time elapsed from SCI (1-17 months). Histopathological
and enzyme-histochemical changes in muscle fibres were seen first after 1
month and increased thereafter. In all stages post SCI, paraplegics showed myopathic alterations,
increase in the sarcoplasmic lipid contents and incidental denervation patterns. The
main ultrastructural changes regard the myofibrillar apparatus and mitochondria. Probably a
fibre type shifting to type 2 fibres occurs precociously, but only 7-8 months after SCI it is
well manifested. The blood vessel qualitative and quantitative changes in paraplegics regard
small vessels and capillaries and they may be important causes of the myopathic alterations
in paraplegics. The influence of disuse and spasticity on morphological fibre and
capillary modifications in paraplegics is reviewed and discussed. The knowledge of the
muscle condition and of plastic capacities for fibre type shifting in paraplegics is important
to oppose complications of SCI and to choice of an appropriate rehabilitative program directed
to prevention of changes associated to disuse, spasticity and vascular damage.
Key words: fiber types, microvasculature, mitochondria, MHC, pathology, skeletal muscle,
spinal cord injury.
Following spinal cord injury (SCI), upper motor neuron
paralyzed muscles show widespread disuse atrophy
and spasticity. In setting out a rehabilitation program of
patients with motor disease it is necessary to evaluate
the condition of the kinetic units, i.e. of the osteoarticular
segments and of the related skeletal muscle
groups. Experimental and clinical studies, and strategies
related to rehabilitation of paraplegics as the muscular
electric stimulation (FES) and the application of the mechanic
orthoses, are directed toward the recovery of the
muscle contractile properties and of the standing position
or walking. These conditions are important in the
preservation of the blood circulation in the paralyzed
limb, of the Ca content in bones, of the renal function
and for the reduction of spasticity and contractions in
paraplegic patients.
However, the results of the functional and morphological
changes of the muscle following SCI may condition
the choice of the rehabilitative program in paraplegics.
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Basic Appl Myol 11 (2): 75-85, 2001
In the last decades, many important experimental and
applied studies were performed on the skeletal muscle
in paraplegics following SCI, indicating marked
changes in the muscle morphology and in their metabolic
and contractile properties, and details on the plasticity
of the muscle in the present condition. These alterations
are well documented in animals, after experimental
cord lesion [18, 32], and in humans, generally after
traumatic cord lesions [3, 14, 15, 23, 31, 33, 50].
Our study group, in association with the Centre of
Functional Recovery of paraplegics of Villanova sull’Arda
(Pc), widely contribute to the morphological
documentation of changes in different skeletal muscles
and of related pathologies in paraplegics, as the microcirculatory
alterations and the heterotopic ossifications
[19-22, 38, 40, 42, 45, 46].
Currently, the main mechanism responsible for the
skeletal muscle atrophy in paraplegics is tought to be
disuse, but muscle fibres following SCI begin to change
their functional properties early post injury.

It is evident that other co-factors as spasticity and microvascular
damage, contribute to the induction of the
marked morphological and enzyme histochemical
changes seen in the paralyzed skeletal muscle.
The present review reports the results of our 20 year
experience on skeletal muscle morphology, on muscle
histochemical and metabolic profile and on muscle microcirculation
from paraplegics with SCI.
Skeletal Muscle Studies
Muscle fibre morphology and morphometry
Morphological and morphometric studies were performed
on different paralyzed muscles. Morphological
studies were performed on muscle transverse sections in
paraffine-embedded material with routine stains as
hematoxylin and eosin and Van Gieson. Quantitative
analysis of muscle fibre diameter was performed using an
automatic interactive image analysis system (IBAS I-II.
Kontron, Bilanalyse, Munich). In the first study we analyzed
open biopsies of the rectus femoris muscle in 22
paraplegic patients aged 16-66 years in subsequent stages
(1-17 months) starting from the occurrence of SCI [38].
Next, our morphometric studies regarded open biopsies
from the gastrocnemius and soleus muscle (composed
predominantly of type 2 slow fibres) of 10 paraplegics
aged 16-54 years, grouped on the basis to the time
elapsed from SCI (1 to 10 months) [20, 21], and biopsies
from rectus femoris muscle in 10 young paraplegics aged
16-28 years, divided in 2 groups, 1-5 months and 6-14
months post SCI, respectively [45]. More recently, a
morphometric analysis on needle biopsies of quadriceps
femoris muscle was performed in 15 male paraplegics
aged 20-30 years, 7-14 months post SCI [41].
Skeletal muscle from healthy subjects is composed by
trophic fibres with multiple subsarcolemmal nuclei. The
histographic analysis of the normal vastus lateralis muscle
indicate a mean fibre diameter of 67.2 µm [37]. Fibres
are surrounded by a thin endomysium composed by re-
Paraplegia and muscle
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ticular connective tissue and by 4-8 capillaries. In Table
1, a summary of quantitative findings on rectus femoris
and quadriceps femoris fibres and capillaries (the fibre
atrophy grade, the fibre type percentage and the capillary
density and percentage) in different patient groups are
reported. Particularly, in a study on rectus femoris muscle
in paraplegics [38], in the early times post SCI (1-2
months) muscle fibre atrophy was evident with mean fibre
diameter 26 µm. The fibre diameter decreased progressively
after SCI and, at least in the first year after injury,
was directly proportional to the age of the cord lesion.
In this period denervation atrophy patterns with
small groups of angulated atrophic or targetoid fibres
were observed. 7-9 months post SCI the mean fibre diameter
was 20 µm, and at 10-17 months 16.5 µm.
The muscle atrophy in paraplegics is of central type
and depends on the disuse and loss of upper connections
of the lower motor neuron, sometimes associated to the
loss of anterior horn cells and transinaptic degeneration
[13, 28, 38]. The last alteration may be responsible for
the denervation changes seen in early stages post SCI
[42]. In the later stages of paraplegia (10-17 months
post SCI) diffuse muscle atrophy with reduction of the
muscle fascicle dimension is associated to fat infiltration
and endomysial fibrosis. In all stages post SCI, almost
all patients showed myopathic changes, as internal
nuclei, fibre degeneration and cytoplasmic vacuolation
due to lipid accumulation (see Figure 1).
Muscle fibre ultrastructure
Many different ultrastructural changes have been observed
in paralyzed muscle [38, 42]. The sarcolemma of
atrophic fibres frequently present irregular projections
containing many mitochondria, dilated sarcoplasmic reticulum
and glycogen granules. In the biopsies obtained
10-17 months after SCI, numerous fibres show vesicular
nuclei that sometimes migrate inside the fibres and
many sarcoplasmic glycogen granules and vacuoles
containing lipid osmiophilic material. These alterations
Table 1. Morphometric findings of muscle fibres and capillaries in rectus femoris and in quadriceps femoris muscles from
healthy subjects and from paraplegics (age 16-66) at various times post SCI. Mean ± standard error of the mean
(SEM). Statistical level of significance: * P < 0.25; ** P < 0.001.
Group Fibre diameter Fibre type percentage Capillary measures
(months post SCI) (µm) I IIA IIB C/F CD CAF
Rectus femoris m.
1 (1-5) 28* 49 28 23* 1.10* 340* 2.70*
2 (6-10) 22* 40 24 36* 1.00* 380* 2.10*
3 (11-17) 18* 30** 70**
Control 53 52 40 8 1.80 280 4.00
Quadriceps femoris m.
1 (7-14) 26** 45 20 38** 1.10* 340* 2.40*
control 54 54 30 18 1.80 270 4.10

Figure 1. Spinal cord injury.
are limited to the degenerating fibres and are considered
myopathic changes in the immobilized and hypoxiemic
muscle. The main ultrastructural alterations in paraplegics
regard the myofibrillar apparatus, mitochondria and
the sarcoplasmic lipid content of the muscle fibres.
In Table 2, morphometric results of the analysis of
mitochondria (mean mitochondrial size and % of mitochondria
per fibre area) and of lipid droplet percentage
per fibre area are also reported.
Myofibrillar apparatus
Remarkable alterations in the myofibrillar apparatus
have been frequently observed in the medium and old
stage of the lesion, with loss and disruption of the myofilaments,
abnormalities of the Z line, including smearing
and streaming, and frequent formation of rods.
These alterations are generally considered as consequence
of muscle fibre degeneration.
Mitochondria
The mitochondria are generally small in size and
sometimes show swelling and intracristal inclusions.
The mitochondrial size and percentage significantly
decrease in paraplegics in comparison with normal
muscle [38]. Similar changes were observed in muscle
disuse in old aged subjects as result of low utilisation of
the lipid energy sources [30, 37]. In the immobilized
and atrophic muscle, the morphological mitochondrial
alterations are accompanied by impairment of the mitochondrial
oxidative enzyme activities [51]. Whereas
some authors described diffuse morphological damage
of mitochondria in disuse atrophy of skeletal muscle
Paraplegia and muscle
DISUSE SPASTICITY
MUSCLE FIBRE ATROPHY
CAPILLARY DECREASE
MYOPATHIC CHANGES
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FIBRE TYPE TRANSFORMATION
Satellite cells, myotubes FAST TYPE 2 FIBRE PREDOMINANCE
[51], in our studies these changes are confined to rare
interspersed fibres.
Lipid content
Interspersed round vacuoles either empty or filled with
osmiophylic lipid material, are seen in normal skeletal
muscle fibres. Lipids are normally utilized by mitochondria
to release energy for metabolism and muscle contraction.
They increase in the muscle with aging and are
expression of disuse and of abnormal mitochondrial
function [26, 37]. In paraplegics, the lipid droplets were
widely distributed in the cytoplasm, mainly in atrophic
fibres, and their percentage per fibre area significantly
increased (Table 3) [38]. This phenomenon may be related
to decrease in mitochondrial percentage and to the
less efficient utilisation of the lipid energy sources following
muscle inactivity [26, 38].
Previous reports on skeletal muscle fibre morphology
and composition have been performed on patients at different
times post SCI, using standard qualitative enzymehistochemical
methods. All authors reported increase
in the relative proportion of the fast type II fibres
in longstanding paralyzed muscles, if compared to normal
healthy control subjects. In some patients, this fibre
type transformation appears to be important, with rarefaction
of slow type I fibre in the biopsies [14, 15, 23,
31, 33, 50]. Morphological and morphometric analysis
of paralyzed muscle post SCI indicates a progressive
muscle fibre atrophy, with important structural alterations.
A 50% decrease in the fibre diameter was present
in the early stages of paraplegia. The disuse may be the
Table 2. Morphometric results of mitochondrial and lipid droplet content in quadriceps femoris muscle from young paraplegics
7-12 months post SCI and control healthy subjects (mean age: 25). Mean ± standard error of the mean (SEM).
Statistical level of significance: * P < 0.25; ** P < 0.001.
Mean mitochondrial size % mitochondria % lipid droplets
size (µm) per fibre area per fibre area
Controls 0.14 ± 0.09 2.53 ± 0.3 0.48 ± 0.20
Paraplegics 0.008 ± 00.4** 1.70 ± 0.5* 3.20 ± 1.00**

main cause of muscle atrophy in paraplegics. In the recent
cord lesion, the degree of muscle atrophy was evident
and denervation changes were also seen. In the
later stages of paraplegia the muscle atrophy degree increased
and myopathic changes with focal necrosis and
more extensive fibre degeneration in about 4% of fibres
were observed. The degenerative changes in paralyzed
muscle may be due to the vascular changes reported
below, and the denervation patterns might reflect the
presence of some coincidental alterations of the peripheral
nerve or trans-synaptic degeneration in the
lower motor neuron [13, 28, 38]. In advanced stages
post SCI, muscle atrophy and increase in the interstitial
endomysial connective tissues and perifascicular fatty
infiltration were evident. The significance of the ultrastructural
changes, particularly of the decrease in the
number of muscle mitochondria and of the increase in
cytoplasmic lipid vacuoles, are related to muscle inactivity
and degeneration.
Muscle fibre type composition
Normal quadriceps femoris muscle is composed of two
major types of fibre characterized by enzymehistochemical
methods (myofibrillar ATPase pH 9.6 and 4.6): type 1
and type 2 fibres, and numerous sub-types. In our studies
the normal type 1 fibre diameter measures 52.2 µm and
the type 2 fibre diameter 48.2 µm [20]. Type 1 fibres are
often of smaller diameter, contain many mitochondria
and do not stain histochemically for myosin ATP-ase activity.
Type 2 fibres are often broad and possess few mitochondria
but they stain intensely for myosin ATP-ase
activity [8]. In Table 1 and 3, morphometric findings on
the fibre diameter and on the fibre type percentage in
rectus femoris, quadriceps femoris, soleus and gastrocnemius
muscle biopsies from paraplegic patients at times
ranging over 1-17 months post SCI are reported. In significantly
early time periods post injury (1-4 months post
SCI) evident preferential atrophy of type 2 fibres was observed,
but no changes in the relative percentage of type 1
and 2 fibres were remarked.
Paraplegia and muscle
Table 3. Mean muscle fibre type diameter in soleus and gastrocnemius muscles of paraplegics (age 16-54) and healthy control
subjects.
Group Soleus muscle Gastrocnemius muscle
(months post SCI)
Fibre type Fibre type
I IIA IIB I IIA IIB
1 (1-2) 30 24 26 28 22 24
2 (3-4) 28 22 24 28 24 24
3 (5-6) 28 24 22 26 24 22
4 (7-8) 26 24 24 24 22 20
5 (9-10) 16 21 20 14 20 18
Control 50 48 44 48 46 46
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Biopsies performed 4-9 months post SCI showed atrophy
of both fibre types with a reduction in the relative
percentage of type 1 fibres. Following long term SCI
(10-17 months post SCI), upper motor neuron paralysed
muscles lose the normal type 1 and 2 type mosaic pattern
and become predominantly composed of type 2 fibres.
Interesting results have been obtained from the
study of the paretic soleus muscle, that normally is predominantly
composed by slow type 1 fibres. A significant
shift of type 1 fibres to type 2B was observed in the
7-10 months post SCI patient group [20, 21, 38, 42].
The above described results support the presence of
progressive changes in paralyzed muscles probably occurring
early after cord injury, but most evident 4 months
post SCI. The main interesting change in the contractile
properties of paralyzed muscle after SCI is the fibre type
transformation phoenomenon, with type 1 fibre change to
type 2, representing down-regulation of the slow MHC
isoform and upper-regulation of the fast isoform in those
fibres. The shift to type II fibres was more evident in
quadriceps and rectus femoris, and in soleus muscle,
while in the gastrocnemius muscle the fibre type conversion
was less remarkable. Moreover, the plastic modifications
of the fibre types was more evident in young
paraplegics than in older subjects. This result is probably
related to modifications in muscle morphology and in
their contractile properties described in the normal sedentary
aging man [30, 37]. The fast type II predominance
in longstanding paraplegia may explain the problem of
muscle fatigability encountered during rehabilitation exercise
using FES. Studies on experimental spinal cord
transaction showed changes in the rat and cat skeletal
muscle, with almost complete type I to type II fibre transformation
[18, 52]. These changes are different from
those seen in immobilisation in which large increase in
the ratio for fast resistant and slow units are seen [24]. It
may be suggested that in long term paraplegia the loss of
the upper motor neuron control and the spasticity may
induce phoenomena of fibre type transformation. The described
muscular changes in paraplegics are reversible

after FES and electrically induced training, with partial
recovery of the muscle atrophy and with modification in
the fibre type transformation [25].
Myosin heavy chain isoform profile
Studies on myosin heavy chain (MHC) content in
muscle fibres from parapegic patients are very scarce.
Paraplegia and muscle
Figure 2. A. Fascicular atrophy with increase of perimysial fatty tissue in the rectus femoris muscle. 15 months post
SCI. Giemsa. X 60. B. Pattern of denervation in groups of angulated atrophic fibres in the rectus femoris muscle.
1 month post SCI. DPNH diaphorase. X 250. C. Numerous lipid vacuoles in the muscle fibre cytoplasm. 6
months post SCI. H & E. X 250 D. Normal type I and type II (dark) fibre distribution in the quadriceps femoris
muscle. 18 days post SCI. Myosin ATPase pH 9.4. X 150. E. Some areas of type 2 fibre predominance in the
rectus femoris muscle. 9 months post SCI. Myosin ATPase pH 9.4. X 150. F. Diffuse type II fibre predominance
in the soleus muscle. 17 months after SCI. Myosin ATPase pH 9.4. X 150.
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The adult normal skeletal muscle fibres express only
one MHC isoform. Type 1 fibres have the slow MHC
isoform, type 2 fibres have the fast MHC isoform and
type C fibres co-express both MHC isoforms. In our
studies, the expression in MHC isoform content of the
whole biopsy was analyzed with an electrophoretic separation
technique [6] on medial gastrocnemius and soleus
muscles in paraplegics 1-10 months post SCI.

The results indicated in the early period post SCI (1-6
months) a predominant type 2 muscle fibre atrophy,
without changes in the relative percentage of fibre types
and MHC content. Eight months post injury, we remarked
atrophy of both fibre types with increase in the
relative percentage of type 2 fibres and fast MHC content.
However, the shift of the type 1 to type 2 fibres was
evident 7-8 months post SCI [42]. Fibre type transformation
of type 1 to type 2 fibres goes through a transitional
phase where they co-express slow and fast myosin isoforms.
Data presented by Burnham et al [3], by means of
immunofluorescence determination of single fibre MCH
isoform, suggest that the onset of fibre shifting to type 2
fibres in paraplegics may to be earlier than previously described,
probably occurring about 1 month post SCI. This
study was performed on vastus lateralis muscle biopsies
from 12 paraplegics with SCI over a period of 1-219
months after SCI. Thus, following long term SCI induced
paralysis, fibres in the quadriceps femoris and vastus lateralis
muscle take on a new state profile defined by a shift
in the MHC expression to the fast isoform.
Paraplegia and muscle
Figure 3. A. Normal capillary distribution in a paraffin embedded transverse section of muscle fibres from an healthy subject.
Rectus femoris muscle. Immunohistochemical reaction for CD 36. X 60. B. Reduction in the number of capillaries
and marked dilatation of the lumen of small blood vessels in gastrocnemius muscle. 12 months after SCI. Immunohistochemical
reaction for CD36. X 60.
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FES and electrically induced training determine in the
paralyzed muscle expressing a majority of MHC isoform
II B fibres, a fibre type transformation towards the
more fatigue resistant MHC isoform II A [25].
Interesting results on paralyzed muscle derive from
the characterization of fibre type profile with enzymehistochemistry
and from the study of the MHC isoforms
over a wide range of post SCI periods. The findings
support the concept of progressive stages of change in
muscle from paraplegics, suggesting that the earliest alterations
post SCI are confined to the morphological
muscle aspects (fibre atrophy, focal fibre degeneration
with changes in the ultrastructural profile and capillary
dilatation). The onset of the fibre type shifting to type 2
fibre probably occurs 1 month after SCI, but only 7-8
months after injury the shift of the type 1 to type 2 fibres
is well manifested. This fibre type conversion is
related to muscle plasticity, defined as a functional fibre
remodeling after different normal and pathological conditions,
inducing important changes of the subcellular

structure, of the enzyme content, of the metabolic and
biochemical characteristics, and of the contractile properties
of muscle fibres [10, 34]. The spasticity causes
pathological changes in refex function, such as loss of
reciprocal inhibition, cocontraction of agonist and antagonist
muscles and the loss of activity in the inhibitory
pathways. These alterations, together with disuse and
other co-factors, are undoubtedly an appropriate opportunity
for the development of the plastic changes in the hypertonic
paralyzed muscle [4].
Muscle microcirculation studies
Blood vessels
The first studies on microvasculature from human
skeletal muscle concerned normal healthy adults, athletes
and normal subjects trained in endurance or strength [1,
2, 7]. They demonstrated a close relationship among the
muscle fibre diameter, fibre type and capillary number.
The greatest number of capillaries surrounds the type 1
slow fibres. Literature data on normal muscle microcirculation
concern qualitative and quantitative analysis of
capillaries. In our studies on muscle microcirculation in
paraplegics, microscopic qualitative studies were performed
using histological and ultrastructural methods.
More recently these studies utilized the immunohistochemical
characterization of capillaries by mean of antibodies
as endotheline and CD 36.
The quantitative evaluation of capillaries was performed
with an automatic Interactive Image Analysis
Sistem- IBAS I,II (Kontron-Bildanalyse Munich, Germany)
on histological sections, the number of capillaries
per fibre (C/F), capillaries surrounding a single fibre
(CAF), and the capillary density per square millimeter
(CD) were determined (Table 1). The clinical and morphological
evidences of vascular alterations in paraplegics,
as vasomotor disturbances and decrease in the venous
distensibility and capacity [16] and structural alterations
in the muscle blood vessels [45] may be important
causes of the degenerative myopathic changes in paralyzed
muscle fibres. These alterations are similar to those
seen in patients with chronic venous insufficiency, who
develop microangiopathy of cutaneous blood and lymphatic
capillaries [11]. In recent SCI (1-4 months post
injury), when paralysis with profound hypotonic flaccidity
is evident, marked capillary dilatation and interstitial
vasogenic oedema were seen. In later stages of paraplegia
(10-17 months post SCI), when spasticity becomes evident,
paraplegics showed thickening of the arteriolar wall
with reduplication of the basal lamina of capillaries and
Paraplegia and muscle
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of capillary wall associated to reduction in the capillary
number [20, 38, 42, 45]. The above mentioned microvascular
changes are also present in the skin of paralyzed
muscle and may be expression of a microangiopathy in
paraplegics after SCI [11, 20, 42]. These alteration are
important and similar changes, as the reduplication and
thickening of the capillary basal lamina, have been described
in diabetes mellitus, in dystrophia myotonica and
in other different microvascular diseases [36, 48]. Human
and experimental studies on skeletal muscle inactivity
which causes muscle atrophy, showed reduction of capillaries
as well as the long standing denervation atrophy
that cause reduction and damage of mitochondria and of
capillaries [5, 35, 51].
On the basis of these observations, the capillary
qualitative and qualitative changes in paraplegics may
be due to interaction of different factors: disuse fibre
atrophy, reduction in muscle volume, incidental overimposed
denervation, loss of type 1 fibres that are normally
surrounded by a great number of capillaries, and
shift to the type 2 muscle fibres. Moreover they could
be interpreted as a negative phoenomenon inducing the
ischemic degenerative myopathic changes described in
muscle fibres in long term paraplegia [42].
The results of a study on young paraplegics after use
of gait orthoses (HGO,ORLAU Parawalker), the period
after supply ranging from 5-6 months [41, 43] support
the latter hypothesis.
In Table 4, overall capillary and fibre morphometry in
rectus femoris muscle from untrained and Parawalker
trained paraplegics were reported. After orthotic walking
training there was a discrete preservation of the
muscle fibre diameter and increase of the muscle capillary
supply in comparison with untrained paraplegics.
These results are in agreement with those described in
experimental spinal cord lesions in animals in which
favourable exercise-induced changes in biochemical and
contractile properties of muscle fibres and in muscle
capillarity were observed [9, 17].
Lymphatics
In paraplegics, immobilization, prolonged bed rest and
loss of muscle contraction are main causes of venous stasis
in the lower extremities. The venous stasis is frequently
associated to microlymphatic changes of the skin
of the paralyzed leg and it is an important cause of thromboembolic
disease in paraplegics. In the patients, the increase
of the deep venous resistance and the venous stasis
determinate microangiopathic alterations in the skin, in-
Table 4. Overall capillary and fibre morphometry in rectus femoris muscle from healthy control subjects, untrained paraplegics
and Parawalker trained paraplegics. Mean ± standard error of the mean (SEM). P < 0.0001.
Untrained paraplegics 26.0 ± 4.2* 47.0 ± 4.0 1.10 ± 0.12 340 ± 8 2.70 ± 0.1*
Parawalker users 33.0 ± 5.4* 50.0 ± 5.6 1.46 ± 0.6* 300 ± 8 3.60 ± 0.4*
Normal adults 53.3 ± 7.4* 52.0 ± 4.2 1.80 ± 0.1* 280 ± 18 4.00 ± 0.2

Paraplegia and muscle
Figure 4. A. Disorganized myofibrils with smearing and streaming of the Z line. Rectus femoris muscle. 7 months post
SCI. Electron micrograph. X 7,000. B. Extensive myofibrillar degeneration and vacuolation with presence of lysosomal
bodies in the cytoplasm of two adjacent muscle fibres. Rectus femoris muscle. 17 months post SCI.
Electron micrograph. X 6,000. C. Two adjacent muscle fibres with subsarcolemmal lysosome accumulation and
two small vessels with thickening of the basal lamina. 4 months post SCI. Soleus muscle. Electron micrograph. X
6,000. D. Thickened intramuscular capillary with reduplication of the basal lamina. Soleus muscle. 10 months
post SCI. Electron micrograph. X 10,000.
- 82 -

volving blood and lymphatic vessels and eventually leading
to skin dystrophic changes and oedema (phlegmasia
alba dolens). The morphological identification of lymphatic
vessel in the skeletal muscle is difficult. However,
in a study, we analyzed lymphatic vessels in the skin of
the lower extremities from young male paraplegic patients
with and without thromboembolic disease (TED) [44, 46].
In paraplegics with TED of deep veins, skin lymphatic
vessels of paretic legs showed dilated lumen and distended
wall. The endothelial cells were attenuated and
numerous channels among endothelial cells were present.
Perivascular collagen and elastic fibres were dissociated
by oedema and by the presence of granular material. In
paraplegics without TED similar but more rare microlymphatic
changes are present.
These morphological changes demonstrated a lymphatic
microangiopathy in paraplegics, with lymph stasis
and an increased transcapillary diffusion of the
lymph material into perivascular dermic tissues, clinically
resulting in oedema and reduced removal of tissue
catabolites. These leg terminal lymphatic changes and
the blood cutaneous microangiopathy probably determinates
the extent of the trophic disturbances and the ulcer
formation in paraplegics. The microangiopathy is the
basis for reduction of PO2 and of for destruction of the
lymphatic capillary network, seen respectively after
transcutaneous PO2 measurements and by fluorescent
microlymphography in long term paraplegia and in patients
with chronic venous insufficiency [11, 46].
Conclusions and Perspectives
From a rehabilitation perspective it is necessary to
evaluate the conditions of the motor unit and the muscle
fibre plastic potentialities and reversibility in paraplegics
after SCI. The results from the present studies
demonstrated changes in the fibre morphology and in
their contractile properties, and in the muscle capillarity
of paralyzed muscle fibres after SCI. There is a number
of rehabilitative programs that are able to modify muscle
atrophy and to prevent some clinical complications, by
means of physical training, FES, aerobic exercise trainers
and bio-mechanic orthoses. In numerous reports, prevention
of muscle disuse and improvement in the fibre
oxidative capacities after muscle electric stimulation in
paraplegics were demonstrated [12, 49]. In adult paraplegics,
FES induce changes of morphological, biochemical
and histochemical profile, and of contractile
properties of muscle fibres and improve the muscle
capillarity [31], as well as the use of bio-mechanic orthoses
[27, 41, 43] and of aerobic exercise trainers [29].
The muscle fibre atrophy and the fibre type transformation
process in paraplegics was partially normalized after
electrical induced cycle training [25]. These supports
for paraplegic locomotion require high energy cost and
may be utilized in patients without cardiovascular and
respiratory diseases [27]. The knowledge of the muscle
Paraplegia and muscle
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condition and of plastic capacities for fiber type shifting is
not only important in attenuating the adverse muscle impact
and complications of SCI, but it is also crucial in the
choice of an appropriate rehabilitative program directed to
preventing the changes associated to disuse and to retrain
contractile properties associated to spasticity and microvascular
damage. In fact, it is well known that the therapeutic
exercise setting out to isotonic concentric or eccentric
contracture determines selective recruitment of fast or
slow fibres which prevents selective fibre type atrophies in
paretic muscle. Finally, in an attempt to restore function
and regain motor control, many laboratories are now
focusing a rehabilitation program based on engineering
devices that substitute a motor controlled function (SCI
transcutaneous FES walking). It is easily comprehensible
that these recovery techniques can be utilized only
in well-preserved muscle after SCI. Since it is evident
that muscle atrophy and transformation in their fundamental
properties occur precociously post SCI, rehabilitative
interventions need to be instituted as early as
safetly possible.
Acknowledgements
We gratefully acknowledge for they cooperation: Dr
Sergio Lotta, head of the Rehabilitation Center for paraplegics
G Verdi of Villanova sull’Arda (Pc), Prof Carla
Marchetti and Prof Paola Poggi, professors of the Histology
and Human Anatomy of the University of Pavia,
and Prof Ugo Carraro, head of the CNR Unit for Muscle
Biology and Physiopathology of the Institute of General
Pathology of the University of Padova (Italy).
Address correspondence to:
Prof. R. Scelsi, Istituto di Anatomia e Istologia Patologica,
via Forlanini 14, 27100 Pavia, Italy, phone +39
0382 528476, fax +39 0382 525866, Email apat@unipv.it.
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