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Acute peripheral nerve compression in the baboon
403
Journal ~?/the neurological Sciences. 1974, 23 : 403 -420 ' Elsevier Scientific Publishing Company. Amsterdam
Printed in The Netherlands
Acute Peripheral Nerve Compression in the Baboon P. R U D G E , J. O C H O A * AND R. W. G I L L I A T T Institute of Neurology, Queen Square, London (Great Britain) Received 23 April, 1974)
INTRODUCTION
From a previous study of tournxquet paralysis in baboons, it has been suggested that the nerve damage which occurs at the site of compression is a direct mechanical effect of the applied pressure, rather than a result of ischaemia of the compressed nerve (Ochoa, Fowler and Gilliatt 1972). The evidence for this view was based on the anatomical findings during the first few days after compression. A small pneumatic cuff 5 cm in width was used to make the lesions. When this was placed round the knee of a baboon and inflated to a pressure of 1,000 mm Hg for 1 3 hr, the pathological lesions in the medial popliteal nerve were found to be in 2 zones which corresponded to the edges of the cuff, with sparing in the centre. In individual nerve fibres the lesions consisted of displacement of the nodes of Ranvier away from the site of compression towards uncompressed tissue. The Schwann cell junctions, which were not displaced, marked the original sites of the nodes. The terminal loops of the myelin sheath remained attached to the axolemma at the nodes, and there was gross distortion of the paranodal myelin, with stretching on one side of the node and invagination on the other. The end-result of this process was paranodal demyelination. Nerve conduction studies showed that lesions of the type described above would recover after intervals which varied from a few weeks to several months. It was notable that in some fibres a local conduction block could persist for as long as 4-6 months without Wallerian degeneration occurring in their distal parts (Fowler, Danta and Gilliatt 1972). There were certain difficulties in applying these results directly to the problem of human pressure palsies. A pneumatic cuff inflated to 1,000 mm Hg might seem to be very different from the apparently mild forms of pressure on individual peripheral nerves which can sometimes give rise to conduction block (neurapraxia, "Saturday night palsy") in man, particularly in the unconscious patient. This work was supported by the Medical Research Council and the Muscular Dystrophy Group of Great Britain. * Wellcome Senior Research Fellow.
404
P. RUDGE, J. OCHOA, R, W. GILLIATT
We have therefore attempted
t o d e v e l o p in t h e b a b o o n
a method
of a p p l y i n g
pressure to individual peripheral nerves which simulates more closely the mechanisms w h i c h a r e t h o u g h t t o o c c u r in m a n . A b r i e f p r e l i m i n a r y a c c o u n t o f t h i s w o r k h a s b e e n published (Rudge, Gilliatt and Ochoa
1973).
METHODS Experiments were carried out on sexually mature female baboons (Papio papio) weighing I0 16 kg, All procedures were carried out under intravenous pentobarbitone sodium (60-120 tug) after preliminary tranquillisation with intramuscular phencyclidine (2 mg/kg) and promazine (1 mg/kg). Pressure on peripheral nerves was produced at 2 sites (Fig, 1). In one set of experiments the ulnar nerve was compressed just below the ulnar groove at the elbow. In other experiments the anterior tibial nerve was compressed above the ankle. In both cases the nerve was compressed against underlying bone by a loop of nylon cord with a weight attached (Fig: 2). A large loop of cord was placed round the limb so that
S1
~ /
S1
$2
¢
$2
Fig. 1. Sites of nerve compression (arrowed) and of stimulating and recording electrodes, for ulnar nerve (above] and anterior tibial nerve (below).
~anterior t i b i a ~
posterior ~ ~ /
weight
t
~
mediann . ~ J artery ~
.-ulnarnerve \
ulna
weight
Fig. 2. Diagrammatic cross section of lower limb above ankle IA ) and of forearm below elbow (B) to show relation of weighted nylon cord to anterior tibial nerve and ulnar nerve. Note protected position of posterior tibial and median nerve and main artery to limb
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
405
part of it lay on the skin at right angles to the course of the nerve. A transverse bar, 8.5 cm long, was sometimes necessary to reduce the length of cord which was in contact with the skin (Fig. 2B). This was always used in experiments on the ulnar nerve to avoid pressure on the median nerve and its accompanying artery. With this arrangement the cord only compressed the tissues on the ulnar side of the arm. In the case of the anterior tibial nerve the loop of nylon cord did not compress the posterior tibial nerve or artery (Fig. 2A) and a transverse bar similar to that shown in Fig. 2B was only used in a few experiments to which specific reference will be made in a later section. The diameter of the nylon cord was approximately 1.6 mm. The weight attached to the cord varied from 0.5 2.0 kg and the duration of the compression from 1 3 hr in different experiments. Nerve conduction was examined in the motor fibres supplying the abductor digiti minimi muscle in the upper limb and the extensor digitorum brevis muscle in the lower limb. The stimulating cathodes were stainless steel needles placed close to the nerve trunk at the sites shown in Fig. 1. Muscle action potentials were recorded through a subcutaneous needle over the muscle belly, and a remote electrode over the tendon. Potentials were amplified by conventional R - C coupled amplifier and displayed on one beam of a Tektronix 502 oscilloscope, the other beam being used to provide a time-scale. Further details of the technique and of the method of temperature control are given by Fowler et al. (1972). Nerves for histology were fixed by immersion in 4 ' ~ glutaraldehyde in Sorensen's buffer at pH 7.4. After 5 10 rain fixation in situ, the nerves were removed and fixation continued for a further 90 rain. After washing in buffer the nerves were post-fixed in 1 I}~,osmium tetroxide in veronal buffer, dehydrated, and some were impregnated with fluid Epon. From them, single fibres were teased with sharpened forceps, examined under the light microscope and photographed. Selected single fibres were prepared for electron microscopy as described by Ochoa (1972). After dehydration, other samples were embedded in Epon and conventional blocks prepared. From these, 1 iLm sections were cut and stained with 1 o toluidine blue for light microscopy. Additional sections were taken for electron microscopy. ELECTROPHYSIOLOGICAL RESULTS
Maximal motor conduction velocity and muscle action potential amplitude were measured immediately before nerve compression. The sites of stimulating anti recording electrodes were marked by tattooing the skin to ensure that comparable placements could be made in subsequent recordings. Conduction was usually re-examined on the day after compression, although in a few animals this was done on the second or third post-compression day. In some animals serial studies were carried out for periods of up to 16 weeks.. Weight necessary "to produce a lesion To obtain a persistent conduction block in motor fibres at the site of compression, it was usually necessary to use weights of 1.5 or 2.0 kg and to maintain pressure on the nerve for periods of 1-2 hr. From Table 1 it can be seen that in the case of the ulnar nerve a weight of 1.5 kg was insufficient to produce block. When a 2 kg weight was used the results were still variable, 2 of the 5 nerves showing only a conduction delay. This variability may have been due to slight differences in the position of the nylon cord. The ulnar nerve is superficial and can be palpated through the skin immediately distal to the ulnar groove, but beyond this point it is protected by flexor carpi ulnaris. Furthermore, it can no longer be compressed directly against bone as it passes through flexor carpi ulnaris to lie between flexor digitorum profundus and flexor digitorum sublimis (Rudge 1974a). We adjusted the position of the nylon cord to be 1 -3 cm below the medial epicondyle, and it is possible that in some experiments it was too far below the ulnar groove to compress the nerve effectively. Because of this difficulty in obtaining reproducible results, later experiments were concentrated on the anterior tibial nerve. Above the ankle the anterior tibial nerve lies on the anterior surface of the tibia and
406
p. RUDGE. J. OCHOA. R. W. GILLIATT
FABLE I C O N D U C T I O N BLOCK A N D C O N D U C T I O N D E L A Y IN MOTOR FIBRES
18 24
H O U R S AFTER I)IFFEREN I \VEIGItTS AND
PERIODS OF COMPRESSION
Re,suit Nerve
Uln ar
Anterior tibial
Weit.lht ( kg
Time r rain
N o . ot nerl~es
1.5 2.11 2.1/
61"~ 90 60 ~0 120 180
0.5 0.75 1.0 1.5 1.5 1.5
120 90 1211 6/I 911 121) 18(/
block
m unbhwked
tl
~ 2 2
2~ 4 '
11
n n 40 88 100 94 100 100
One additional nerve in this group was examined 48 hr after compression, at which time a 25" block was present.
is covered by the lower part of extensor hallucis and by the tendon of tibialis anterior. In this region it can be easily compressed against the bone. and the exact position of the nylon cord did not seem to be critical provided that it lay 1--2 cm above the ankle joint. From Table 1 it can be seen that weights of 0.5 and 0.75 kg were insufficient to produce block. A partial conduction block was obtained with a weight of 1.0 kg and more complete blocks were obtained by using 1.5 kg.
0
2
4 msec
6
8
Fig. 3. B46. Compression of right anterior tibial nerve with 1 kg for 120 rain. Superimposed traces to sho~ muscle responses to distal and proximal stimulation, before compression (A) and on the fo]lowingday (B}. Stimuli at zero time in each case. In B the response to distal stimulation is unchanged whereas proximal stimulation evokes a small muscle action potential with increased latency. Calibration 5mV_
ACUTE
PERIPHERAL
NERVE
COMPRESSION
IN THE
BABOON
407
Records taken before and after anterior tibial nerve compression are shown in Fig. 3. In this case a weight of 1.0 kg was applied for 2 hr. It can be seen that on the day after compression the muscle action potential evoked by proximal stimulation was reduced in amplitude, and its latency was increased, suggesting a conduction delay in surviving fibres. Comparison of the pre- and post-compression tracings indicates that the amplitude of the negative deflection of the post-compression response was reduced by 40~°J)] and that the conduction delay in surviving fibres amounted to 0.7 msec. In contrast to the partial block shown in Fig. 3, a complete block resulting from compression by 1.5 kg for 90 rain is shown in Fig. 4. It can be seen that there was gradual recovery of motor conduction, a muscle response of normal amplitude being obtained after 70 days. 52
$1
Day 0
/L L
39
70
B57
j
lO mV
.5 msec
_~
ec
Fig. 4. B57. Evoked muscle action potentials from extensor digitorum brevis at different intervals after compressionof the right anterior tibial nerve(1.5kg for 90 rain). Sites of stimulating and recordingelectrodes shown below.
Duration of compression From the data given in Table 1 the effects of different periods of compression with a standard weight can be analysed. In the case of the ulnar nerve, the results were variable for reasons which have been given above, and no firm conclusions can be drawn. For the anterior tibial nerve, however, Table 1 suggests a relation between the duration of compression and the severity of the resulting block. Of the nerves in which a 1.5 kg weight was used, compression for 2 hr or longer produced a complete conduction block in the m o t o r fibres, whereas the block was incomplete in one of the 4 nerves compressed for 90 rain and in 2 of the 3 nerves compressed for 60 rain. In addition to producing a severe local block, the longer periods of compression with 1.5 kg resulted in Wallerian degeneration affecting a proportion of the m o t o r fibres. This was not a conspicuous feature with the shorter compression times. In
408
P. RUDGE, J. OCHOA, R. W. G1LLIATT
Fig. 4, for example, it can be seen that the amplitude of the muscle response to distal stimulation was only slightly reduced in the post-compression records; indicating that most of the motor fibres were blocked locally and had not undergone Watlerian degeneration. In nerves compressed for 2 hr or longer, however~ the post-compression amplitude (in response to distal stimulation) was more markedly reduced, suggesting that considerable Wallerian degeneration had occurred (Table 2). The extreme example was the nerve B60L, compressed for 3 hr, in which subsequent studies showed that only a few motor units in extensor digitorum brevis could be excited by distal stimulation. Histological examination 6 months later showed that few of the large myetinated fibres had survived distal to the lesion, although numerous small thinly myelinated fibres were present. YABLt- ~ RELATION BETWEEN D U R A T I O N OF COMPRESSION ([ .5
kg), NUMBER OI~ SURVIVING MOTOR FIBRf-,S ,\ND IJ,IiCiIVI RY
TIME OF LOCAL BLOCK IN THE ANTERIOR TIBIAL NERVE
N erre
Duration ~?f c'ompression (rain)
B64R B54L B52L B54R B57R B52R B60R B60L
60 60 60 9(t 90 120 150 180
'~;>Survirin9 .libreg'
85 ~3 93 ,~7 73 69 ~
Time to 50" recocer y ( d~ v.,
- 2 75 32.5 36 38 31 5 45 43.5
Estimated from the amplitude of the post-compression muscle response to distal stimulation between the second and fifth weeks: this value being expressed as a percentage of that obtained before compression. In the case of B64R. follow-up recordings were not made after the second day
In the previous study of Fowler et al. (1972) it was found that the duration of nerve compression affected not only the severity of the initial block and the amount of Wallerian degeneration, but also the recovery time of the local block. To test this in the present study, the duration of compression has been matched with the time to 50 }~ recovery in each case. It should be emphasised that the figures for percentage recovery refer to the recovery of the local block. They are obtained by expressing the amplitude of the response to proximal stimulation as a percentage of the response to distal stimulation in the same experiment. Fibres which had undergone Walterian degeneration would not be expected to contribute to this ratio. Data for 8 anterior tibial nerves are given in Table 2. Using Spearman's ranking test, the relation between the duration of compression and the time to 50 % recovery is significant at the 0.05 level (r =0.778). In Fig. 5 recovery curves for 6 ulnar and 7 anterior tibial nerves are shown by heavy lines, the curves obtained by Fowler et at. 11972) for the medial popliteal nerve after a pneumatic tourniquet being shown by faint lines. When the two sets of data are compared, it is noticeable that the conduction blocks caused by a pneumatic tourniquet sometimes recovered more slowly than any of the blocks produced by nylon cord. This
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
409
100
_~80
60 Z O w
20
20
4~
go
8'o TIME
16o IN
1~o
1;.o
DAYS
Fig. 5. Recovery after conduction block produced in 6 ulnar and 7 anterior tibial nerves shown by heavy lines. Muscle action potentials recorded from abductor digiti minimi in case of ulnar nerve, and from extensor digitorum brevis in case of anterior tibial nerve. Recovery curves of muscle action potentials recorded by Fowler et al. (1972) after compression of 11 medial popliteal nerves by a tourniquet are shown by faint lines. Vertical scale: amplitude of muscle response to proximal stimulation as a percentage of the response to distal stimulation, horizontal scale: time in days after compression.
does not mean that the lesions produced by the nylon cord were necessarily less severe than those produced by the tourniquet. In B60L of the present series, for example, the amount of Wallerian degeneration was greater than that seen in any of the tourniquet experiments. Despite this, the fibres which were blocked locally showed 50° o recovery within 45 days, which may be contrasted with values of 120 and 170 days for the 2 most severely affected nerves in the tourniquet series. Possible reasons for this difference will be discussed in a later section.
Weight applied per unit area of skin In the experiments on the anterior tibial nerve described above, the length of nylon cord in contact with the skin varied from 4.25 cm to 7.5 cm (mean 5.5 cm). Since the width of the cord was 1.6 mm, the mean area of compressed skin was approximately 86 m m 2. If, as a simplification, one assumes that the pressure was uniformly distributed under the cord, then the pressure on the skin in these cases ranged from 1.6-2.1 kg/cm e (mean 1.85 kg/cm2). In order to assess the effect of altering the area of compressed skin, two additional experiments were carried out. (1) In 2 animals the anterior tibial nerve on one side was compressed by the standard loop of nylon cord shown in Fig. 2A. On the other side a transverse bar was inserted (as in Fig. 2B) to reduce the area of skin in contact with the cord from 96-120 mm -~to approximately 50 m m -~. The weight was 0.5 kg and the duration of compression 120 rain for both pairs of anterior tibial nerves. The results are shown in the upper half of Table 3 : from this it can be seen that a pressure of 1.0 kg/cm 2 was sufficient to produce a partial nerve block, whereas a pressure of 0.4-0.5 kg/cm 2 was not. (2) In 2 other animals the anterior tibial nerve on one side was compressed by the standard loop of nylon cord as shown in Fig. 2A. In the other leg the cord was replaced by a band 10 m m wide, the area of compressed skin being increased from 72 88 m m 2 to 450 550 m m 2. In both cases the weight was 1.5 kg and the duration of compression
410
P: RUI)GE, J. OCHOA, R. W. GILLIATT
TABLE 3 R E S U L T S OF V A R Y I N G AREA OF C O M P R E S S I O N W I T H C O N S T A N T W E I G H T A N D C O M P R E S S I O N I 1ME
Motor conduction examined after 24 hr.
Weight
Time
Area o! compressed
Pressure
(k#)
(rain)
.skin ,'mm'~ !
;k~t"cm'~)
Res~dt " block o
delal, in U~iblocked libres .
.
H.
B58R B58L B61R B61L
0,5 0.5 0.5 0.5
120 120 120 120
120 48 96 '~2
0.42 1.04 0.52 096
0 82 0 36
B63R B63L B67R B67L
1.5 1.5 1.5 1.5
90 90 90 90
72 450 88 550
2.04 0.33 1.71 0.27
100 0 94 ~1
, !t
t~
90 min. The results are shown in the lower part of Table 3. From this it can be seen that a pressure of 1.7-2.0 kg/cm 2 produced a severe conduction block whereas a pressure of approximately 0.3 kg cm 2 was ineffective.
ANATOMICAL RESULTS
The typical early lesion In single teased fibres taken from the ulnar or anterior tibial nerve at the site of compression, the characteristic early change appeared to be displacement of the nodes of Ranvier with secondary changes in paranodal myelin. Fig. 6 shows a mild nodal lesion in a single fibre from the ulnar nerve 2 days after compression. In the light micrograph above it can be seen that the normal nodal gap is occluded. The electron micrograph below shows that the node of Ranvier has been displaced from its original position under the Schwann cell junction (j) for about 20 ~m. the new position of the node (n) being identified by the attachment of the myelin sheath to the axolemma and by the altered electron density of the axoplasm at this point. The myelin of the "receiving" paranode on the left has been invaginated by the paranode on the right which lies partly inside it. A tongue of Schwann cell cytoplasm has been drawn in towards the new position of the node from its original site at j, so that it separates the myelin of the ensheathed and ensheathing paranodes. The extent of nodal displacement has varied in different fibres and at different nodes on the same fibre. In contrast to the relatively mild abnormality shown in Fig. 6. the new position of the node in the fibre shown in Fig. 7A is approximately 70 #m from the Schwann cell junction, and partial rupture of the stretched myelin has occurred. Nodal displacements of up to 350 #m have been seen in severely affected fibres. As in Fig. 7A. these have been accompanied by rupture of stretched paranodal myelin. The changes shown in Fig. 7A are very similar to those seen in our previous material after compression by a pneumatic tourniquet. In Fig. 7B. however, the appearances are slightly different, probably due to the early breakdown of infolded myelin. This is
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
n
41 1
j
Fig. 6. B54. Abnormal node of Ranvier from right ulnar nerve 2 days after compression, Light micrograph (above) shows Schwann cell junction (/) and new position of node 01). Bar 20 l~m. Low power electron micrograph (below) shows nodal region of same fibre cut longitudinally . ><,2700.
supported by the fact that in some fibres this appearance has been accompanied by a mild focal cellular reaction. The changes seen in Figs. 7C and D were found in a proportion of the nodes examined during the first few days after compression. In both cases it can be seen that there is localised swelling in the parfinodal region. In Fig. 7C there has been nodal displacement and no gap is visible under the indentation indicating the original site of the node. There is swelling of the "receiving" paranode with thinning of the myelin sheath, and the new position of the node cannot be identified. In Fig. 7D there is a similar change affecting both paranodal regions and it is uncertain whether any paranodal displacement has occurred.
Distribution and polarity of lesions Nodal displacement occurred in two zones separated by a region in which the nodes appeared normal. In all cases the direction of displacement was away from the centre of the lesion towards its edge. In the ulnar nerve the affected zones were approximately symmetrical and each measured 5 10 mm: they were separated by a spared region of 1 3 ram. Thus the whole lesion from outer edge to outer edge and including the central spared portion measured 12-22 mm. In mild lesions giving rise to conduction delay only, the affected zones were smaller in relation to the central spared region than they were in more severe lesions associated with conduction block. However, even in the
412
1,. RLJl)GI~. J. f ) C t t O A . R. W . G I t I , I A T I '
[-'ig ?. A b n o r m a l fibres s h o w i n g various t~pes of nodal distortiol~. ~ S c h w a n n cell j u n c t k m : ~ l~e~ posm~-m of node. Bar 2(I/tin. / : B37. Fibre from left ulnar nerve b rain a l t e r release of c o m p r e s s i o n i2 kg for 2 hr). B: B51. Fibre from lefl a n t e r i o r tibial nerve 24 hr after c o m p r e s s i o n 1750 g for 90 minl. ( :rod D" B51 Fibres from right a n t e r i o r tibm nerve 10 rain after release of c o m p r e s s i o n 11 kg 1i)1 all m m l
latter some n o r m a l nodes could be found in the centre of the lesion. In the anterior tibial nerve the affected zones were again symmetrical, each measuring 2~4 m m and being s e p a r a t ~ by a spared zone of 1 -2 m m in the centre. Changes in a single fibre are illustrated in Fig. 8 which shows a minimal lesion caused by compression insufficient to produce a conduction block or conduction delay. Successive nodes are m o u n t e d one below the other and it can be seen that there are 2 normal nodes at the centre of the lesion with 2 affected nodes on either side. In the latter the indentations c o r r e s p o n d i n g to the S c h w a n n cell junctions can still be identified a l t h o u g h there are no nodal g a p s : the new positions of the nodes are m a r k e d by arrows. T h u s Fig. 8 illustrates our general finding that the direction of m o v e m e n t of the nodes of Ranvier is always away from the centre of a lesion towards uncompressed tissue, Localised paranodal swellings of the type shown in k'igs. 7C and 7 D were found in 1
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
413
t'
Fig. 8. B51. Successive nodes from a single fibre in left anterior tibial nerve 24 hr after compression (750 g for 90 min) to show extent of the lesion. The proximal end of the fibre is at the top. Note 2 normal nodes in centre of lesion and nodal displacement on either side (new positions of nodes marked by arrows). Beyond these the nodes are again normal. Bar 20 l~m.
414
P. RUDGE. J. OCHOA. R. W. GII.LIATI
Fig. 9. B46. Successive nodes from a single fibre in the right anterior tibial nerve 8 days after Ci~inpression to show extent of lesion. Early demyelination is present. Note normal: nodes at centre (retouched) and at each edge of lesion. Bar 20 !~m
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
415
ulnar nerve and 3 anterior tibial nerves: in each case the lesion had been a relatively severe one and the changes were only present at its outer edges, so that they were separated by regions in which typical nodal displacements had occurred. The reason for this distribution of the swellings is discussed in a later section.
Demyelination and degeneration The changes which have been described above were best seen during the first 3 days after compression. They were followed by disintegration and subsequent removal of the damaged paranodal myelin, the resulting picture being that of paranodal demyelination. An example is shown in Fig. 9 which was taken 8 days after mild compression which had resulted in the partial conduction block shown in Fig. 3. It can be seen that, by the eighth day, demyelination had occurred at most of the affected nodes. In this case, the total extent of the lesion from edge to edge was 9 mm: there is only one node at the centre of the lesion which can be firmly categorised as normal. When compression had only produced a conduction delay or a mild partial block, Wallerian degeneration was scanty or absent. After compression sufficient to produce a severe or complete block, it was commonly seen. When nerves were examined so long after injury that degenerating fibres had disappeared, the presence of previous degeneration was assumed when large fibres proximal to the lesion, with normal myelin thickness and internodal length, could be seen to give place to thinly-myelinated fibres with short internodes, which continued distally and appeared to be regenerating. These changes were conspicuous in the anterior tibial nerves B52R, B60R and B60k shown in Table 2. In the case of the nerve B60L which was examined 168 days after injury, few large myelinated fibres were seen distal to the site of compression, most of the fibres showing the appearances of regeneration. This'confirmed the electrophysiological evidence of extensive degeneration (see Table 2). Remyelination In nerves examined at intervals of 42-191 days after compression, remyelination was indicated by the presence of short thinly-myelinated intercalated segments similar to those seen in our previous study (Ochoa et al. 1972). The length of the intercalated segments (up to 300 gm) was similar to that of the nodal displacements seen in the early lesions. As might be expected from the distribution of the early lesions, demyelination and remyelination occurred in 2 regions along the nerve fibres separated by a spared centre. The affected regions were wider in the ulnar than the anterior tibial nerve, and this difference applied also to the length of the spared centre which was greater in the ulnar nerve. Increasing thickness of the remyelinating segments was evident with increasing time after injury but there was considerable variation within each nerve, and occasional demyelinated paranodes were seen in nerves in which remyelination was otherwise well advanced. In addition, fibres which had been severely compressed showed irregular swellings of the myelin sheath which were usually localised in the parts of the original internodes adjacent,to the remyelinating segments, but which sometimes affected the original myelin more widely. The loosely-teased bundle of fibres shown in Fig. 10
416
P. R U D G E . J. O C H O A . R. W . G t L L I A T T
illustrates most of the features described above. Five short lengths have been mounted one below the other, the distances along the bundle from which they were taken being shown by the millimetre scale on the left. Normal nodes (arrowed) can bc seen beyond either edge of the lesion and in the centre. The specimen was taken t2 weeks after compression and thinly-myelinated intercalated segments varying in length from 100--280 um can be seen in the affected portions of the bundle. Adjacent to these, the myelin of the original internodes is irregularly swollen.
Fig. 10. B57. P o r t i o n s of loosely teased b u n d l e from right a n t e r i o r tibial nerve 12 weeks alter c o m p r e s sion. N o r m a l n o d e s are arrowed. The regions from which these p h o t o g r a p h s were t a k e n are s h o w n by d i a g r a m of nerve on left Iwith d a m a g e d zones shadedl. Scale on left in m m Bar I00 . m .
As in our previous material obtained after compression by a pneumatic tourniquet, the myelin swellings appeared to be the result of intramyelin or periaxonal oedema. the axons being shrunken and displaced. It seemed likely that the abnormal myelin, which sometimes persisted for several months after compression, was finally removed by phagocytes, as described in our previous paper (Ochoa et al. 1972). Distinct from the fibres showing periaxonal and intramyelin oedema were changes seen in 2 nerves (61R and 67R) during the late recovery period. Although mild in degree, the changes were of the type which had previously been seen in chronic entrapment lesions IOchoa and Marotte 1973) but which had not hitherto been seen in nerves after a single episode of acute compression. In essence, they consisted of a regularly-recurring alteration in the appearance of the internodal myelin, that at one end of the internode appearing thin (nearer to the centre of the lesion) and, at the other end. irregularly thickened. This finding was an unexpected one. and as nothing similar had been seen in the rest of our material, it clearly requires confirmation and further study.
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
417
DISCUSSION
Of the 2 nerves in which we found it possible to produce local lesions, the anterior tibial at the ankle proved to be the more satisfactory. At the elbow the ulnar nerve only remains superficial for a short distance below the groove, after which it is increasingly protected by muscle on both its superficial and deep surfaces as it passes distally. For this reason our standard procedure gave variable results in different animals. In contrast to this, results for the anterior tibial nerve were consistent enough to allow us to compare the effects of varying the weight, the time of compression, and the area of compressed skin. From the experiments on the anterior tibial nerve, it appears that a pressure of 1.6 2.1 kg/cm 2 was sufficient to produce a severe or complete nerve block when applied for 90 rain, whereas a pressure of 1 kg/cm 2 produced a partial nerve block. The histological changes shown in Fig. 8, which were not accompanied by a conduction block, followed a pressure of only 0.75 kg/cm 2. In our previous experiments with a pneumatic tourniquet, 1,000 mm Hg (equivalent to 1.36 kg/cm 2) produced a severe or complete conduction block, and 500 m m Hg (0.68 kg/cm 2) produced mild histological damage without a conduction block. There is thus reasonable agreement between the two sets of experiments in relation to the pressure necessary to produce nerve damage. In man, somewhat higher pressures on the skin may be required as the volume of tissue between the nerve and the skin, and that between the nerve and underlying bone, are greater than in the baboon. However, it is likely that pressures many times greater than those described above are developed in the unconscious patient when the entire weight of a limb is rested on a sharp edge or narrow surface. In the present study, as in the previous one using a pneumatic tourniquet, it was found that a proportion of the compressed fibres underwent Wallerian degeneration. It was not possible to make a quantitative estimate of the amount of Wallerian degeneration from the histological material, but from subjective assessment it appeared that degeneration was scanty or absent in the mild lesions with partial conduction blocks or conduction delays without block : it was more plentiful in association with complete blocks. The nerve conduction studies confirmed that when a standard weight was used, the amount of Wallerian degeneration increased with increasing duration of compression. In the previous study with a tourniquet, it was estimated that not more than 40,~;, of the large motor fibres underwent Wallerian degeneration, even in the most severe lesions after compression for 180 min. This is in contrast to one nerve in the present study, in which a similar period of compression caused degeneration in most of the large motor fibres to the extensor digitorum brevis muscle, with conduction block in the remainder. In the present study, as found previously using a pneumatic tourniquet, the longer compression times were associated with delayed recovery. However, none of the recovery times in the present series was as long as those recorded after severe tourniquet lesions, and the reason for this difference requires discussion. It was suggested previously that the damage in any one fibre could be regarded as a series of separate nodal lesions, each of which recovered at a different rate. It was also suggested that conduction might not be resumed until the last of these had recovered. This point has been
418
P. R U D G E . J. O C H O A . R. W . GILLIATT
emphasised by Rasminsky (1973) in another context: "'Just as a chain is only as strong as its weakest link. a remyelinated fibre is only as functional as its most severely affected internode", Accepting this, the probability of delayed recovery of conduction would be higher with 20 or 30 damaged nodes of Ranvier on a single fibre (as in the tourniquet lesion) than with only 8 or 10 (as in the nylon cord lesion). Regardless of the mechanism, it is important to realise that considerable variation in the recovery time of local conduction blocks can occur in human cases. In a patient with "'Saturday night palsy" described by Trojaborg (1970), repeated conduction studies on the radial nerve showed 50~o recovery of motor conduction after approximately 24 days. In contrast, a patient with a local block due to a tourniquet, recently seen by one of us. did not begin to show recovery of motor conduction through the block until the 90th day; 505/0 recovery was not achieved until the 125th day (Rudge 1974b). While the histological changes seen in the present material were generally similar to those described previously, there were certain interesting differences. As before, the typical lesion involved displacement of the nodes of Ranvier along the fibres, the direction of displacement being away from the centre of the compressed region. The nodes at the centre of the lesion were not displaced. Accompanying the displacement of each node. the typical finding was stretching of the paranodal myelin on one side and invagination of the myelin on the other. There were, however, variations on this pattern in the present material. In some cases the myelin of the "'receiving" paranode was thinned and distended, and no invagination could be seen. Sometimes both paranodal regions were distended ariel the myelin thinned (see Figs. 7 C and Di. These acutely distended paranodes were only seen at the edges of the lesions and this provides a possible clue to their pathogenesis. In order to displace axoplasm along a fibre, there must be a pressure gradient within the axon between its compressed and uncompressed portions. In the compressed zone the myelin sheath is not distended, but beyond its edge there is no external circumferential pressure to prevent this. If axonal distension were to occur, one would therefore expect to see it at the outer edges of the lesion. This prediction is fulfilled in relation to the paranodal swellings described above. The reason why these lesions were more often seen in the anterior tibial than in the ulnar nerve could be that in the former, a larger muscle mass intervened between the skin and the nerve and tended to distribute the external pressure more widely. From the results obtained previously using a pneumatic tourniquet, it was concluded that the nerve damage was a mechanical effect of the applied pressure, and that ischaemia played, at the most, a minor part. This conclusion is reinforced by the results of the present experiments, in which ischaemia of the whole limb has been avoided. Two points in particular are against any primary role of ischaemia. In the first place the histological lesions clearly involve mechanical displacement of neural structures: furthermore they extend beyond that part of the nerve which is directly compressed. In contrast, the nodes of Ranvier at the centre of the lesion and directly under the nylon cord remain normal. Is it necessary to invoke ischaemia in order to explain why compression for 3 hr produced a more severe lesion than compression for 1 hr? A simpler explanation might be that the work done on the nerve by the external compressive force increases with time. and that the presence or absence of ischaemia
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
419
is irrelevant. Further experiments are required to clarify this question. An interesting point arises in relation to the pathological changes shown in Fig. 8. This lesion was not accompanied by either delay or blocking of motor conduction. It is thus analogous to the lesion which occurs in man when compression or trauma is too mild to produce a clinical deficit but is sufficient to leave histological evidence of nerve damage. A succession of such lesions during daily life might result in the irregularity of internodal length found in the biopsied human nerves of elderly subjects by Thomas and Lascelles (1966), and by Fullerton (1969). When only the endresult of such a process is seen, it is impossible to decide how much is due to ischaemia associated with ageing, and how much is due to previous compression. A comparative study of superficial nerves which are vulnerable to compression, and of deep nerves from the same subject, might help to answer this question. Is there, in fact, any evidence that nodal displacement does occur after acute compression in man? At present this question cannot be satisfactorily answered owing to the difficulty of obtaining acutely compressed nerves for pathological study. However, a case which goes some way towards providing an answer has recently been recorded by Neary, Ochoa and Gilliatt (1974). In a series of 24 human median and ulnar nerves, examined as early as possible after death, the common abnormalities were those characteristic of chronic entrapment (Ochoa and Marotte 1973) rather than of acute compression, but one median nerve at the wrist did show nodal displacement suggestive of an acute lesion. Immediately before death, the patient had been in a state of decorticate rigidity with extreme flexion of the wrists, and it seemed likely that this had resulted in acute nerve compression under the distal edge of the carpal ligament. Post-mortem studies of other patients who might have sustained pressure lesions immediately before death (e.9. patients in drug-induced coma) would contribute further to this subject. ACKNOWLEDGEMENTS We wish to thank Mr. H. Long and Mr. K. Yogendran for technical assistance.
SUMMARY AND CONCLUSIONS
As a model of acute pressure neuropathy ("Saturday night palsy") in man, a weighted nylon cord lying across the limb has been used to produce local compression of the ulnar and anterior tibial nerves in anaesthetised baboons. Motor nerve conduction studies were carried out 18-24 hr after compression; in some animals they were repeated at intervals for periods of up to 16 weeks. In the ulnar nerve the results were variable, but in the anterior tibial nerve, compression by a 1.5 kg weight for 90 rain regularly produced a severe or complete conduction block. In such cases the pressure on the skin over the nerve ranged from 1.6-2.1 kg/cm 2. A pressure of approximately 1.0 kg/cm 2 caused a partial conduction block with a conduction delay in the unblocked fibres. A pressure of 0.75 kg/cm 2 or less caused no conduction defect. When the periods of compression were extended from 90 min to 120, 150 or 180
420
1,. R U D G F . J. OCHOA. R. W , GIL1JA'FT
min. the conduction blocks were accompanied by increasing amounts of WMlerian degeneration. The local blocks produced by the longer periods of compression were also slower to recover. The histological features o1 the lesions were basically similar to those described previously after nerve compression by a pneumatic lourniquet. In the large myelinated fibres there was displacement of the nodes of Ranvier along the fibres awa~ fiom the site of pressure. This movement occurred in 2 zones near the edges of the lesion, the nodes at the centre of the lesion being spared. Accompanying the nodal displacement there was stretching of the paranodal myelin on one side of the node and invaginat ion on the other. At the extreme edges of the lesion there was sometimes distension of the paranodal regmns with thinning of the myelin. These changes were followed by demyelination and finally by remyehnation. In the recovery phase irregular myelin swellings were seen which were similar m appearance to those seen previousb m recovering nerves after a pneumatic tourmquet These results, together with those described previously, indicate that in "'Saturda). night palsy" and similar pressure lesions of peripheral nerves, the conduction block is due to a direct mechanical effect of the applied pressure on myelinated fibres, and that ischaemia, due to compression of the mtra-neura[ blood vessels, plays little ~l" any part.
REFERENCES FOWLER. T. J.. G. DANTA AND R W. GILLIAI-r (1972) R e c o v e r y of nerve conduction alter ~t p n c u m a u c tourniquet: ObserVations on the hind-limb of the baboon. J. Neurol. Neurosuru. Psvchiat.. 35 : 638-647 FULLERTON, P. M. (19691 Electrophysiological and histological observations on peripheral nerves in acrylamide poisoning in man. J Neurol. Neurosuro. Psychial.. 32: 186-192. NEARY. D.. J.OcHOA AND R. W. GILLIAI~f [ 1975 ) Sub-clinical entrapment neuropathy in man. ,1 ~wuml. Sci., 24: In press. OCHOA. J. (1972) Ultrathin longitudinal sections of single m3elinated fibres Ior elecmm microscopy, J. neurol. Sei.. 1 7 : 1 0 3 106. OCHOA. J AND L. MAROTTE {1973) The nature of the nerve lesion caused by chronic e n u a p m e m m the guinea-pig, J. neurol, Sci.. 1 9 : 4 9 1 4 9 5 OCHOA, J., T. J. FOWLER AND R. W. Gn,L1A'rT (t 972) Anatomical changes in peripheral ncrves c,x)mpressed by a pneumatic tourniquet. J. Anat. (l,ond . 113: 3. 433-455. RAMINSKY. M. (19731 The effects of temperature on conduction m demyelinated smglc fibres. Arch Neural. ( C h i c . . 2 8 : 2 8 7 292. RUDGE. P. 11974a) M.D. Thesis. University of London. In preparauon. RUOGE, P. 1974bl Tourniquet paralysis with prolonged conduction block : an electrophysiological stud3, J. Bone Jt Surg., In press. RUDGE. P.. R. W GILLIAT'I AND J. OCHOA 11973) Acute peripheral nerve compression m ~lae baboon Electroenceph. clin. Neurophysiol., 34: 806. THOMAS. P. K. Ar4D R. G. LASCI~Lt,ES (1966) Changes due to age in internodal length in the sural nerve m man. J Neurol. Neurosur.q, Psvchiat.. 2 9 : 4 0 - 4 4 . TROJABORG. W. (t970) R a t e of recovery in motor and sensory fibres of the radial nerve: clinical and electrophysiologieal aspects..L Neurol. Neurosura. P,~vchiat.. 33: 625-638.
Journal ~?/the neurological Sciences. 1974, 23 : 403 -420 ' Elsevier Scientific Publishing Company. Amsterdam
Printed in The Netherlands
Acute Peripheral Nerve Compression in the Baboon P. R U D G E , J. O C H O A * AND R. W. G I L L I A T T Institute of Neurology, Queen Square, London (Great Britain) Received 23 April, 1974)
INTRODUCTION
From a previous study of tournxquet paralysis in baboons, it has been suggested that the nerve damage which occurs at the site of compression is a direct mechanical effect of the applied pressure, rather than a result of ischaemia of the compressed nerve (Ochoa, Fowler and Gilliatt 1972). The evidence for this view was based on the anatomical findings during the first few days after compression. A small pneumatic cuff 5 cm in width was used to make the lesions. When this was placed round the knee of a baboon and inflated to a pressure of 1,000 mm Hg for 1 3 hr, the pathological lesions in the medial popliteal nerve were found to be in 2 zones which corresponded to the edges of the cuff, with sparing in the centre. In individual nerve fibres the lesions consisted of displacement of the nodes of Ranvier away from the site of compression towards uncompressed tissue. The Schwann cell junctions, which were not displaced, marked the original sites of the nodes. The terminal loops of the myelin sheath remained attached to the axolemma at the nodes, and there was gross distortion of the paranodal myelin, with stretching on one side of the node and invagination on the other. The end-result of this process was paranodal demyelination. Nerve conduction studies showed that lesions of the type described above would recover after intervals which varied from a few weeks to several months. It was notable that in some fibres a local conduction block could persist for as long as 4-6 months without Wallerian degeneration occurring in their distal parts (Fowler, Danta and Gilliatt 1972). There were certain difficulties in applying these results directly to the problem of human pressure palsies. A pneumatic cuff inflated to 1,000 mm Hg might seem to be very different from the apparently mild forms of pressure on individual peripheral nerves which can sometimes give rise to conduction block (neurapraxia, "Saturday night palsy") in man, particularly in the unconscious patient. This work was supported by the Medical Research Council and the Muscular Dystrophy Group of Great Britain. * Wellcome Senior Research Fellow.
404
P. RUDGE, J. OCHOA, R, W. GILLIATT
We have therefore attempted
t o d e v e l o p in t h e b a b o o n
a method
of a p p l y i n g
pressure to individual peripheral nerves which simulates more closely the mechanisms w h i c h a r e t h o u g h t t o o c c u r in m a n . A b r i e f p r e l i m i n a r y a c c o u n t o f t h i s w o r k h a s b e e n published (Rudge, Gilliatt and Ochoa
1973).
METHODS Experiments were carried out on sexually mature female baboons (Papio papio) weighing I0 16 kg, All procedures were carried out under intravenous pentobarbitone sodium (60-120 tug) after preliminary tranquillisation with intramuscular phencyclidine (2 mg/kg) and promazine (1 mg/kg). Pressure on peripheral nerves was produced at 2 sites (Fig, 1). In one set of experiments the ulnar nerve was compressed just below the ulnar groove at the elbow. In other experiments the anterior tibial nerve was compressed above the ankle. In both cases the nerve was compressed against underlying bone by a loop of nylon cord with a weight attached (Fig: 2). A large loop of cord was placed round the limb so that
S1
~ /
S1
$2
¢
$2
Fig. 1. Sites of nerve compression (arrowed) and of stimulating and recording electrodes, for ulnar nerve (above] and anterior tibial nerve (below).
~anterior t i b i a ~
posterior ~ ~ /
weight
t
~
mediann . ~ J artery ~
.-ulnarnerve \
ulna
weight
Fig. 2. Diagrammatic cross section of lower limb above ankle IA ) and of forearm below elbow (B) to show relation of weighted nylon cord to anterior tibial nerve and ulnar nerve. Note protected position of posterior tibial and median nerve and main artery to limb
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
405
part of it lay on the skin at right angles to the course of the nerve. A transverse bar, 8.5 cm long, was sometimes necessary to reduce the length of cord which was in contact with the skin (Fig. 2B). This was always used in experiments on the ulnar nerve to avoid pressure on the median nerve and its accompanying artery. With this arrangement the cord only compressed the tissues on the ulnar side of the arm. In the case of the anterior tibial nerve the loop of nylon cord did not compress the posterior tibial nerve or artery (Fig. 2A) and a transverse bar similar to that shown in Fig. 2B was only used in a few experiments to which specific reference will be made in a later section. The diameter of the nylon cord was approximately 1.6 mm. The weight attached to the cord varied from 0.5 2.0 kg and the duration of the compression from 1 3 hr in different experiments. Nerve conduction was examined in the motor fibres supplying the abductor digiti minimi muscle in the upper limb and the extensor digitorum brevis muscle in the lower limb. The stimulating cathodes were stainless steel needles placed close to the nerve trunk at the sites shown in Fig. 1. Muscle action potentials were recorded through a subcutaneous needle over the muscle belly, and a remote electrode over the tendon. Potentials were amplified by conventional R - C coupled amplifier and displayed on one beam of a Tektronix 502 oscilloscope, the other beam being used to provide a time-scale. Further details of the technique and of the method of temperature control are given by Fowler et al. (1972). Nerves for histology were fixed by immersion in 4 ' ~ glutaraldehyde in Sorensen's buffer at pH 7.4. After 5 10 rain fixation in situ, the nerves were removed and fixation continued for a further 90 rain. After washing in buffer the nerves were post-fixed in 1 I}~,osmium tetroxide in veronal buffer, dehydrated, and some were impregnated with fluid Epon. From them, single fibres were teased with sharpened forceps, examined under the light microscope and photographed. Selected single fibres were prepared for electron microscopy as described by Ochoa (1972). After dehydration, other samples were embedded in Epon and conventional blocks prepared. From these, 1 iLm sections were cut and stained with 1 o toluidine blue for light microscopy. Additional sections were taken for electron microscopy. ELECTROPHYSIOLOGICAL RESULTS
Maximal motor conduction velocity and muscle action potential amplitude were measured immediately before nerve compression. The sites of stimulating anti recording electrodes were marked by tattooing the skin to ensure that comparable placements could be made in subsequent recordings. Conduction was usually re-examined on the day after compression, although in a few animals this was done on the second or third post-compression day. In some animals serial studies were carried out for periods of up to 16 weeks.. Weight necessary "to produce a lesion To obtain a persistent conduction block in motor fibres at the site of compression, it was usually necessary to use weights of 1.5 or 2.0 kg and to maintain pressure on the nerve for periods of 1-2 hr. From Table 1 it can be seen that in the case of the ulnar nerve a weight of 1.5 kg was insufficient to produce block. When a 2 kg weight was used the results were still variable, 2 of the 5 nerves showing only a conduction delay. This variability may have been due to slight differences in the position of the nylon cord. The ulnar nerve is superficial and can be palpated through the skin immediately distal to the ulnar groove, but beyond this point it is protected by flexor carpi ulnaris. Furthermore, it can no longer be compressed directly against bone as it passes through flexor carpi ulnaris to lie between flexor digitorum profundus and flexor digitorum sublimis (Rudge 1974a). We adjusted the position of the nylon cord to be 1 -3 cm below the medial epicondyle, and it is possible that in some experiments it was too far below the ulnar groove to compress the nerve effectively. Because of this difficulty in obtaining reproducible results, later experiments were concentrated on the anterior tibial nerve. Above the ankle the anterior tibial nerve lies on the anterior surface of the tibia and
406
p. RUDGE. J. OCHOA. R. W. GILLIATT
FABLE I C O N D U C T I O N BLOCK A N D C O N D U C T I O N D E L A Y IN MOTOR FIBRES
18 24
H O U R S AFTER I)IFFEREN I \VEIGItTS AND
PERIODS OF COMPRESSION
Re,suit Nerve
Uln ar
Anterior tibial
Weit.lht ( kg
Time r rain
N o . ot nerl~es
1.5 2.11 2.1/
61"~ 90 60 ~0 120 180
0.5 0.75 1.0 1.5 1.5 1.5
120 90 1211 6/I 911 121) 18(/
block
m unbhwked
tl
~ 2 2
2~ 4 '
11
n n 40 88 100 94 100 100
One additional nerve in this group was examined 48 hr after compression, at which time a 25" block was present.
is covered by the lower part of extensor hallucis and by the tendon of tibialis anterior. In this region it can be easily compressed against the bone. and the exact position of the nylon cord did not seem to be critical provided that it lay 1--2 cm above the ankle joint. From Table 1 it can be seen that weights of 0.5 and 0.75 kg were insufficient to produce block. A partial conduction block was obtained with a weight of 1.0 kg and more complete blocks were obtained by using 1.5 kg.
0
2
4 msec
6
8
Fig. 3. B46. Compression of right anterior tibial nerve with 1 kg for 120 rain. Superimposed traces to sho~ muscle responses to distal and proximal stimulation, before compression (A) and on the fo]lowingday (B}. Stimuli at zero time in each case. In B the response to distal stimulation is unchanged whereas proximal stimulation evokes a small muscle action potential with increased latency. Calibration 5mV_
ACUTE
PERIPHERAL
NERVE
COMPRESSION
IN THE
BABOON
407
Records taken before and after anterior tibial nerve compression are shown in Fig. 3. In this case a weight of 1.0 kg was applied for 2 hr. It can be seen that on the day after compression the muscle action potential evoked by proximal stimulation was reduced in amplitude, and its latency was increased, suggesting a conduction delay in surviving fibres. Comparison of the pre- and post-compression tracings indicates that the amplitude of the negative deflection of the post-compression response was reduced by 40~°J)] and that the conduction delay in surviving fibres amounted to 0.7 msec. In contrast to the partial block shown in Fig. 3, a complete block resulting from compression by 1.5 kg for 90 rain is shown in Fig. 4. It can be seen that there was gradual recovery of motor conduction, a muscle response of normal amplitude being obtained after 70 days. 52
$1
Day 0
/L L
39
70
B57
j
lO mV
.5 msec
_~
ec
Fig. 4. B57. Evoked muscle action potentials from extensor digitorum brevis at different intervals after compressionof the right anterior tibial nerve(1.5kg for 90 rain). Sites of stimulating and recordingelectrodes shown below.
Duration of compression From the data given in Table 1 the effects of different periods of compression with a standard weight can be analysed. In the case of the ulnar nerve, the results were variable for reasons which have been given above, and no firm conclusions can be drawn. For the anterior tibial nerve, however, Table 1 suggests a relation between the duration of compression and the severity of the resulting block. Of the nerves in which a 1.5 kg weight was used, compression for 2 hr or longer produced a complete conduction block in the m o t o r fibres, whereas the block was incomplete in one of the 4 nerves compressed for 90 rain and in 2 of the 3 nerves compressed for 60 rain. In addition to producing a severe local block, the longer periods of compression with 1.5 kg resulted in Wallerian degeneration affecting a proportion of the m o t o r fibres. This was not a conspicuous feature with the shorter compression times. In
408
P. RUDGE, J. OCHOA, R. W. G1LLIATT
Fig. 4, for example, it can be seen that the amplitude of the muscle response to distal stimulation was only slightly reduced in the post-compression records; indicating that most of the motor fibres were blocked locally and had not undergone Watlerian degeneration. In nerves compressed for 2 hr or longer, however~ the post-compression amplitude (in response to distal stimulation) was more markedly reduced, suggesting that considerable Wallerian degeneration had occurred (Table 2). The extreme example was the nerve B60L, compressed for 3 hr, in which subsequent studies showed that only a few motor units in extensor digitorum brevis could be excited by distal stimulation. Histological examination 6 months later showed that few of the large myetinated fibres had survived distal to the lesion, although numerous small thinly myelinated fibres were present. YABLt- ~ RELATION BETWEEN D U R A T I O N OF COMPRESSION ([ .5
kg), NUMBER OI~ SURVIVING MOTOR FIBRf-,S ,\ND IJ,IiCiIVI RY
TIME OF LOCAL BLOCK IN THE ANTERIOR TIBIAL NERVE
N erre
Duration ~?f c'ompression (rain)
B64R B54L B52L B54R B57R B52R B60R B60L
60 60 60 9(t 90 120 150 180
'~;>Survirin9 .libreg'
85 ~3 93 ,~7 73 69 ~
Time to 50" recocer y ( d~ v.,
- 2 75 32.5 36 38 31 5 45 43.5
Estimated from the amplitude of the post-compression muscle response to distal stimulation between the second and fifth weeks: this value being expressed as a percentage of that obtained before compression. In the case of B64R. follow-up recordings were not made after the second day
In the previous study of Fowler et al. (1972) it was found that the duration of nerve compression affected not only the severity of the initial block and the amount of Wallerian degeneration, but also the recovery time of the local block. To test this in the present study, the duration of compression has been matched with the time to 50 }~ recovery in each case. It should be emphasised that the figures for percentage recovery refer to the recovery of the local block. They are obtained by expressing the amplitude of the response to proximal stimulation as a percentage of the response to distal stimulation in the same experiment. Fibres which had undergone Walterian degeneration would not be expected to contribute to this ratio. Data for 8 anterior tibial nerves are given in Table 2. Using Spearman's ranking test, the relation between the duration of compression and the time to 50 % recovery is significant at the 0.05 level (r =0.778). In Fig. 5 recovery curves for 6 ulnar and 7 anterior tibial nerves are shown by heavy lines, the curves obtained by Fowler et at. 11972) for the medial popliteal nerve after a pneumatic tourniquet being shown by faint lines. When the two sets of data are compared, it is noticeable that the conduction blocks caused by a pneumatic tourniquet sometimes recovered more slowly than any of the blocks produced by nylon cord. This
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
409
100
_~80
60 Z O w
20
20
4~
go
8'o TIME
16o IN
1~o
1;.o
DAYS
Fig. 5. Recovery after conduction block produced in 6 ulnar and 7 anterior tibial nerves shown by heavy lines. Muscle action potentials recorded from abductor digiti minimi in case of ulnar nerve, and from extensor digitorum brevis in case of anterior tibial nerve. Recovery curves of muscle action potentials recorded by Fowler et al. (1972) after compression of 11 medial popliteal nerves by a tourniquet are shown by faint lines. Vertical scale: amplitude of muscle response to proximal stimulation as a percentage of the response to distal stimulation, horizontal scale: time in days after compression.
does not mean that the lesions produced by the nylon cord were necessarily less severe than those produced by the tourniquet. In B60L of the present series, for example, the amount of Wallerian degeneration was greater than that seen in any of the tourniquet experiments. Despite this, the fibres which were blocked locally showed 50° o recovery within 45 days, which may be contrasted with values of 120 and 170 days for the 2 most severely affected nerves in the tourniquet series. Possible reasons for this difference will be discussed in a later section.
Weight applied per unit area of skin In the experiments on the anterior tibial nerve described above, the length of nylon cord in contact with the skin varied from 4.25 cm to 7.5 cm (mean 5.5 cm). Since the width of the cord was 1.6 mm, the mean area of compressed skin was approximately 86 m m 2. If, as a simplification, one assumes that the pressure was uniformly distributed under the cord, then the pressure on the skin in these cases ranged from 1.6-2.1 kg/cm e (mean 1.85 kg/cm2). In order to assess the effect of altering the area of compressed skin, two additional experiments were carried out. (1) In 2 animals the anterior tibial nerve on one side was compressed by the standard loop of nylon cord shown in Fig. 2A. On the other side a transverse bar was inserted (as in Fig. 2B) to reduce the area of skin in contact with the cord from 96-120 mm -~to approximately 50 m m -~. The weight was 0.5 kg and the duration of compression 120 rain for both pairs of anterior tibial nerves. The results are shown in the upper half of Table 3 : from this it can be seen that a pressure of 1.0 kg/cm 2 was sufficient to produce a partial nerve block, whereas a pressure of 0.4-0.5 kg/cm 2 was not. (2) In 2 other animals the anterior tibial nerve on one side was compressed by the standard loop of nylon cord as shown in Fig. 2A. In the other leg the cord was replaced by a band 10 m m wide, the area of compressed skin being increased from 72 88 m m 2 to 450 550 m m 2. In both cases the weight was 1.5 kg and the duration of compression
410
P: RUI)GE, J. OCHOA, R. W. GILLIATT
TABLE 3 R E S U L T S OF V A R Y I N G AREA OF C O M P R E S S I O N W I T H C O N S T A N T W E I G H T A N D C O M P R E S S I O N I 1ME
Motor conduction examined after 24 hr.
Weight
Time
Area o! compressed
Pressure
(k#)
(rain)
.skin ,'mm'~ !
;k~t"cm'~)
Res~dt " block o
delal, in U~iblocked libres .
.
H.
B58R B58L B61R B61L
0,5 0.5 0.5 0.5
120 120 120 120
120 48 96 '~2
0.42 1.04 0.52 096
0 82 0 36
B63R B63L B67R B67L
1.5 1.5 1.5 1.5
90 90 90 90
72 450 88 550
2.04 0.33 1.71 0.27
100 0 94 ~1
, !t
t~
90 min. The results are shown in the lower part of Table 3. From this it can be seen that a pressure of 1.7-2.0 kg/cm 2 produced a severe conduction block whereas a pressure of approximately 0.3 kg cm 2 was ineffective.
ANATOMICAL RESULTS
The typical early lesion In single teased fibres taken from the ulnar or anterior tibial nerve at the site of compression, the characteristic early change appeared to be displacement of the nodes of Ranvier with secondary changes in paranodal myelin. Fig. 6 shows a mild nodal lesion in a single fibre from the ulnar nerve 2 days after compression. In the light micrograph above it can be seen that the normal nodal gap is occluded. The electron micrograph below shows that the node of Ranvier has been displaced from its original position under the Schwann cell junction (j) for about 20 ~m. the new position of the node (n) being identified by the attachment of the myelin sheath to the axolemma and by the altered electron density of the axoplasm at this point. The myelin of the "receiving" paranode on the left has been invaginated by the paranode on the right which lies partly inside it. A tongue of Schwann cell cytoplasm has been drawn in towards the new position of the node from its original site at j, so that it separates the myelin of the ensheathed and ensheathing paranodes. The extent of nodal displacement has varied in different fibres and at different nodes on the same fibre. In contrast to the relatively mild abnormality shown in Fig. 6. the new position of the node in the fibre shown in Fig. 7A is approximately 70 #m from the Schwann cell junction, and partial rupture of the stretched myelin has occurred. Nodal displacements of up to 350 #m have been seen in severely affected fibres. As in Fig. 7A. these have been accompanied by rupture of stretched paranodal myelin. The changes shown in Fig. 7A are very similar to those seen in our previous material after compression by a pneumatic tourniquet. In Fig. 7B. however, the appearances are slightly different, probably due to the early breakdown of infolded myelin. This is
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
n
41 1
j
Fig. 6. B54. Abnormal node of Ranvier from right ulnar nerve 2 days after compression, Light micrograph (above) shows Schwann cell junction (/) and new position of node 01). Bar 20 l~m. Low power electron micrograph (below) shows nodal region of same fibre cut longitudinally . ><,2700.
supported by the fact that in some fibres this appearance has been accompanied by a mild focal cellular reaction. The changes seen in Figs. 7C and D were found in a proportion of the nodes examined during the first few days after compression. In both cases it can be seen that there is localised swelling in the parfinodal region. In Fig. 7C there has been nodal displacement and no gap is visible under the indentation indicating the original site of the node. There is swelling of the "receiving" paranode with thinning of the myelin sheath, and the new position of the node cannot be identified. In Fig. 7D there is a similar change affecting both paranodal regions and it is uncertain whether any paranodal displacement has occurred.
Distribution and polarity of lesions Nodal displacement occurred in two zones separated by a region in which the nodes appeared normal. In all cases the direction of displacement was away from the centre of the lesion towards its edge. In the ulnar nerve the affected zones were approximately symmetrical and each measured 5 10 mm: they were separated by a spared region of 1 3 ram. Thus the whole lesion from outer edge to outer edge and including the central spared portion measured 12-22 mm. In mild lesions giving rise to conduction delay only, the affected zones were smaller in relation to the central spared region than they were in more severe lesions associated with conduction block. However, even in the
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[-'ig ?. A b n o r m a l fibres s h o w i n g various t~pes of nodal distortiol~. ~ S c h w a n n cell j u n c t k m : ~ l~e~ posm~-m of node. Bar 2(I/tin. / : B37. Fibre from left ulnar nerve b rain a l t e r release of c o m p r e s s i o n i2 kg for 2 hr). B: B51. Fibre from lefl a n t e r i o r tibial nerve 24 hr after c o m p r e s s i o n 1750 g for 90 minl. ( :rod D" B51 Fibres from right a n t e r i o r tibm nerve 10 rain after release of c o m p r e s s i o n 11 kg 1i)1 all m m l
latter some n o r m a l nodes could be found in the centre of the lesion. In the anterior tibial nerve the affected zones were again symmetrical, each measuring 2~4 m m and being s e p a r a t ~ by a spared zone of 1 -2 m m in the centre. Changes in a single fibre are illustrated in Fig. 8 which shows a minimal lesion caused by compression insufficient to produce a conduction block or conduction delay. Successive nodes are m o u n t e d one below the other and it can be seen that there are 2 normal nodes at the centre of the lesion with 2 affected nodes on either side. In the latter the indentations c o r r e s p o n d i n g to the S c h w a n n cell junctions can still be identified a l t h o u g h there are no nodal g a p s : the new positions of the nodes are m a r k e d by arrows. T h u s Fig. 8 illustrates our general finding that the direction of m o v e m e n t of the nodes of Ranvier is always away from the centre of a lesion towards uncompressed tissue, Localised paranodal swellings of the type shown in k'igs. 7C and 7 D were found in 1
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
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t'
Fig. 8. B51. Successive nodes from a single fibre in left anterior tibial nerve 24 hr after compression (750 g for 90 min) to show extent of the lesion. The proximal end of the fibre is at the top. Note 2 normal nodes in centre of lesion and nodal displacement on either side (new positions of nodes marked by arrows). Beyond these the nodes are again normal. Bar 20 l~m.
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P. RUDGE. J. OCHOA. R. W. GII.LIATI
Fig. 9. B46. Successive nodes from a single fibre in the right anterior tibial nerve 8 days after Ci~inpression to show extent of lesion. Early demyelination is present. Note normal: nodes at centre (retouched) and at each edge of lesion. Bar 20 !~m
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
415
ulnar nerve and 3 anterior tibial nerves: in each case the lesion had been a relatively severe one and the changes were only present at its outer edges, so that they were separated by regions in which typical nodal displacements had occurred. The reason for this distribution of the swellings is discussed in a later section.
Demyelination and degeneration The changes which have been described above were best seen during the first 3 days after compression. They were followed by disintegration and subsequent removal of the damaged paranodal myelin, the resulting picture being that of paranodal demyelination. An example is shown in Fig. 9 which was taken 8 days after mild compression which had resulted in the partial conduction block shown in Fig. 3. It can be seen that, by the eighth day, demyelination had occurred at most of the affected nodes. In this case, the total extent of the lesion from edge to edge was 9 mm: there is only one node at the centre of the lesion which can be firmly categorised as normal. When compression had only produced a conduction delay or a mild partial block, Wallerian degeneration was scanty or absent. After compression sufficient to produce a severe or complete block, it was commonly seen. When nerves were examined so long after injury that degenerating fibres had disappeared, the presence of previous degeneration was assumed when large fibres proximal to the lesion, with normal myelin thickness and internodal length, could be seen to give place to thinly-myelinated fibres with short internodes, which continued distally and appeared to be regenerating. These changes were conspicuous in the anterior tibial nerves B52R, B60R and B60k shown in Table 2. In the case of the nerve B60L which was examined 168 days after injury, few large myelinated fibres were seen distal to the site of compression, most of the fibres showing the appearances of regeneration. This'confirmed the electrophysiological evidence of extensive degeneration (see Table 2). Remyelination In nerves examined at intervals of 42-191 days after compression, remyelination was indicated by the presence of short thinly-myelinated intercalated segments similar to those seen in our previous study (Ochoa et al. 1972). The length of the intercalated segments (up to 300 gm) was similar to that of the nodal displacements seen in the early lesions. As might be expected from the distribution of the early lesions, demyelination and remyelination occurred in 2 regions along the nerve fibres separated by a spared centre. The affected regions were wider in the ulnar than the anterior tibial nerve, and this difference applied also to the length of the spared centre which was greater in the ulnar nerve. Increasing thickness of the remyelinating segments was evident with increasing time after injury but there was considerable variation within each nerve, and occasional demyelinated paranodes were seen in nerves in which remyelination was otherwise well advanced. In addition, fibres which had been severely compressed showed irregular swellings of the myelin sheath which were usually localised in the parts of the original internodes adjacent,to the remyelinating segments, but which sometimes affected the original myelin more widely. The loosely-teased bundle of fibres shown in Fig. 10
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illustrates most of the features described above. Five short lengths have been mounted one below the other, the distances along the bundle from which they were taken being shown by the millimetre scale on the left. Normal nodes (arrowed) can bc seen beyond either edge of the lesion and in the centre. The specimen was taken t2 weeks after compression and thinly-myelinated intercalated segments varying in length from 100--280 um can be seen in the affected portions of the bundle. Adjacent to these, the myelin of the original internodes is irregularly swollen.
Fig. 10. B57. P o r t i o n s of loosely teased b u n d l e from right a n t e r i o r tibial nerve 12 weeks alter c o m p r e s sion. N o r m a l n o d e s are arrowed. The regions from which these p h o t o g r a p h s were t a k e n are s h o w n by d i a g r a m of nerve on left Iwith d a m a g e d zones shadedl. Scale on left in m m Bar I00 . m .
As in our previous material obtained after compression by a pneumatic tourniquet, the myelin swellings appeared to be the result of intramyelin or periaxonal oedema. the axons being shrunken and displaced. It seemed likely that the abnormal myelin, which sometimes persisted for several months after compression, was finally removed by phagocytes, as described in our previous paper (Ochoa et al. 1972). Distinct from the fibres showing periaxonal and intramyelin oedema were changes seen in 2 nerves (61R and 67R) during the late recovery period. Although mild in degree, the changes were of the type which had previously been seen in chronic entrapment lesions IOchoa and Marotte 1973) but which had not hitherto been seen in nerves after a single episode of acute compression. In essence, they consisted of a regularly-recurring alteration in the appearance of the internodal myelin, that at one end of the internode appearing thin (nearer to the centre of the lesion) and, at the other end. irregularly thickened. This finding was an unexpected one. and as nothing similar had been seen in the rest of our material, it clearly requires confirmation and further study.
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DISCUSSION
Of the 2 nerves in which we found it possible to produce local lesions, the anterior tibial at the ankle proved to be the more satisfactory. At the elbow the ulnar nerve only remains superficial for a short distance below the groove, after which it is increasingly protected by muscle on both its superficial and deep surfaces as it passes distally. For this reason our standard procedure gave variable results in different animals. In contrast to this, results for the anterior tibial nerve were consistent enough to allow us to compare the effects of varying the weight, the time of compression, and the area of compressed skin. From the experiments on the anterior tibial nerve, it appears that a pressure of 1.6 2.1 kg/cm 2 was sufficient to produce a severe or complete nerve block when applied for 90 rain, whereas a pressure of 1 kg/cm 2 produced a partial nerve block. The histological changes shown in Fig. 8, which were not accompanied by a conduction block, followed a pressure of only 0.75 kg/cm 2. In our previous experiments with a pneumatic tourniquet, 1,000 mm Hg (equivalent to 1.36 kg/cm 2) produced a severe or complete conduction block, and 500 m m Hg (0.68 kg/cm 2) produced mild histological damage without a conduction block. There is thus reasonable agreement between the two sets of experiments in relation to the pressure necessary to produce nerve damage. In man, somewhat higher pressures on the skin may be required as the volume of tissue between the nerve and the skin, and that between the nerve and underlying bone, are greater than in the baboon. However, it is likely that pressures many times greater than those described above are developed in the unconscious patient when the entire weight of a limb is rested on a sharp edge or narrow surface. In the present study, as in the previous one using a pneumatic tourniquet, it was found that a proportion of the compressed fibres underwent Wallerian degeneration. It was not possible to make a quantitative estimate of the amount of Wallerian degeneration from the histological material, but from subjective assessment it appeared that degeneration was scanty or absent in the mild lesions with partial conduction blocks or conduction delays without block : it was more plentiful in association with complete blocks. The nerve conduction studies confirmed that when a standard weight was used, the amount of Wallerian degeneration increased with increasing duration of compression. In the previous study with a tourniquet, it was estimated that not more than 40,~;, of the large motor fibres underwent Wallerian degeneration, even in the most severe lesions after compression for 180 min. This is in contrast to one nerve in the present study, in which a similar period of compression caused degeneration in most of the large motor fibres to the extensor digitorum brevis muscle, with conduction block in the remainder. In the present study, as found previously using a pneumatic tourniquet, the longer compression times were associated with delayed recovery. However, none of the recovery times in the present series was as long as those recorded after severe tourniquet lesions, and the reason for this difference requires discussion. It was suggested previously that the damage in any one fibre could be regarded as a series of separate nodal lesions, each of which recovered at a different rate. It was also suggested that conduction might not be resumed until the last of these had recovered. This point has been
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emphasised by Rasminsky (1973) in another context: "'Just as a chain is only as strong as its weakest link. a remyelinated fibre is only as functional as its most severely affected internode", Accepting this, the probability of delayed recovery of conduction would be higher with 20 or 30 damaged nodes of Ranvier on a single fibre (as in the tourniquet lesion) than with only 8 or 10 (as in the nylon cord lesion). Regardless of the mechanism, it is important to realise that considerable variation in the recovery time of local conduction blocks can occur in human cases. In a patient with "'Saturday night palsy" described by Trojaborg (1970), repeated conduction studies on the radial nerve showed 50~o recovery of motor conduction after approximately 24 days. In contrast, a patient with a local block due to a tourniquet, recently seen by one of us. did not begin to show recovery of motor conduction through the block until the 90th day; 505/0 recovery was not achieved until the 125th day (Rudge 1974b). While the histological changes seen in the present material were generally similar to those described previously, there were certain interesting differences. As before, the typical lesion involved displacement of the nodes of Ranvier along the fibres, the direction of displacement being away from the centre of the compressed region. The nodes at the centre of the lesion were not displaced. Accompanying the displacement of each node. the typical finding was stretching of the paranodal myelin on one side and invagination of the myelin on the other. There were, however, variations on this pattern in the present material. In some cases the myelin of the "'receiving" paranode was thinned and distended, and no invagination could be seen. Sometimes both paranodal regions were distended ariel the myelin thinned (see Figs. 7 C and Di. These acutely distended paranodes were only seen at the edges of the lesions and this provides a possible clue to their pathogenesis. In order to displace axoplasm along a fibre, there must be a pressure gradient within the axon between its compressed and uncompressed portions. In the compressed zone the myelin sheath is not distended, but beyond its edge there is no external circumferential pressure to prevent this. If axonal distension were to occur, one would therefore expect to see it at the outer edges of the lesion. This prediction is fulfilled in relation to the paranodal swellings described above. The reason why these lesions were more often seen in the anterior tibial than in the ulnar nerve could be that in the former, a larger muscle mass intervened between the skin and the nerve and tended to distribute the external pressure more widely. From the results obtained previously using a pneumatic tourniquet, it was concluded that the nerve damage was a mechanical effect of the applied pressure, and that ischaemia played, at the most, a minor part. This conclusion is reinforced by the results of the present experiments, in which ischaemia of the whole limb has been avoided. Two points in particular are against any primary role of ischaemia. In the first place the histological lesions clearly involve mechanical displacement of neural structures: furthermore they extend beyond that part of the nerve which is directly compressed. In contrast, the nodes of Ranvier at the centre of the lesion and directly under the nylon cord remain normal. Is it necessary to invoke ischaemia in order to explain why compression for 3 hr produced a more severe lesion than compression for 1 hr? A simpler explanation might be that the work done on the nerve by the external compressive force increases with time. and that the presence or absence of ischaemia
ACUTE PERIPHERAL NERVE COMPRESSION IN THE BABOON
419
is irrelevant. Further experiments are required to clarify this question. An interesting point arises in relation to the pathological changes shown in Fig. 8. This lesion was not accompanied by either delay or blocking of motor conduction. It is thus analogous to the lesion which occurs in man when compression or trauma is too mild to produce a clinical deficit but is sufficient to leave histological evidence of nerve damage. A succession of such lesions during daily life might result in the irregularity of internodal length found in the biopsied human nerves of elderly subjects by Thomas and Lascelles (1966), and by Fullerton (1969). When only the endresult of such a process is seen, it is impossible to decide how much is due to ischaemia associated with ageing, and how much is due to previous compression. A comparative study of superficial nerves which are vulnerable to compression, and of deep nerves from the same subject, might help to answer this question. Is there, in fact, any evidence that nodal displacement does occur after acute compression in man? At present this question cannot be satisfactorily answered owing to the difficulty of obtaining acutely compressed nerves for pathological study. However, a case which goes some way towards providing an answer has recently been recorded by Neary, Ochoa and Gilliatt (1974). In a series of 24 human median and ulnar nerves, examined as early as possible after death, the common abnormalities were those characteristic of chronic entrapment (Ochoa and Marotte 1973) rather than of acute compression, but one median nerve at the wrist did show nodal displacement suggestive of an acute lesion. Immediately before death, the patient had been in a state of decorticate rigidity with extreme flexion of the wrists, and it seemed likely that this had resulted in acute nerve compression under the distal edge of the carpal ligament. Post-mortem studies of other patients who might have sustained pressure lesions immediately before death (e.9. patients in drug-induced coma) would contribute further to this subject. ACKNOWLEDGEMENTS We wish to thank Mr. H. Long and Mr. K. Yogendran for technical assistance.
SUMMARY AND CONCLUSIONS
As a model of acute pressure neuropathy ("Saturday night palsy") in man, a weighted nylon cord lying across the limb has been used to produce local compression of the ulnar and anterior tibial nerves in anaesthetised baboons. Motor nerve conduction studies were carried out 18-24 hr after compression; in some animals they were repeated at intervals for periods of up to 16 weeks. In the ulnar nerve the results were variable, but in the anterior tibial nerve, compression by a 1.5 kg weight for 90 rain regularly produced a severe or complete conduction block. In such cases the pressure on the skin over the nerve ranged from 1.6-2.1 kg/cm 2. A pressure of approximately 1.0 kg/cm 2 caused a partial conduction block with a conduction delay in the unblocked fibres. A pressure of 0.75 kg/cm 2 or less caused no conduction defect. When the periods of compression were extended from 90 min to 120, 150 or 180
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min. the conduction blocks were accompanied by increasing amounts of WMlerian degeneration. The local blocks produced by the longer periods of compression were also slower to recover. The histological features o1 the lesions were basically similar to those described previously after nerve compression by a pneumatic lourniquet. In the large myelinated fibres there was displacement of the nodes of Ranvier along the fibres awa~ fiom the site of pressure. This movement occurred in 2 zones near the edges of the lesion, the nodes at the centre of the lesion being spared. Accompanying the nodal displacement there was stretching of the paranodal myelin on one side of the node and invaginat ion on the other. At the extreme edges of the lesion there was sometimes distension of the paranodal regmns with thinning of the myelin. These changes were followed by demyelination and finally by remyehnation. In the recovery phase irregular myelin swellings were seen which were similar m appearance to those seen previousb m recovering nerves after a pneumatic tourmquet These results, together with those described previously, indicate that in "'Saturda). night palsy" and similar pressure lesions of peripheral nerves, the conduction block is due to a direct mechanical effect of the applied pressure on myelinated fibres, and that ischaemia, due to compression of the mtra-neura[ blood vessels, plays little ~l" any part.
REFERENCES FOWLER. T. J.. G. DANTA AND R W. GILLIAI-r (1972) R e c o v e r y of nerve conduction alter ~t p n c u m a u c tourniquet: ObserVations on the hind-limb of the baboon. J. Neurol. Neurosuru. Psvchiat.. 35 : 638-647 FULLERTON, P. M. (19691 Electrophysiological and histological observations on peripheral nerves in acrylamide poisoning in man. J Neurol. Neurosuro. Psychial.. 32: 186-192. NEARY. D.. J.OcHOA AND R. W. GILLIAI~f [ 1975 ) Sub-clinical entrapment neuropathy in man. ,1 ~wuml. Sci., 24: In press. OCHOA. J. (1972) Ultrathin longitudinal sections of single m3elinated fibres Ior elecmm microscopy, J. neurol. Sei.. 1 7 : 1 0 3 106. OCHOA. J AND L. MAROTTE {1973) The nature of the nerve lesion caused by chronic e n u a p m e m m the guinea-pig, J. neurol, Sci.. 1 9 : 4 9 1 4 9 5 OCHOA, J., T. J. FOWLER AND R. W. Gn,L1A'rT (t 972) Anatomical changes in peripheral ncrves c,x)mpressed by a pneumatic tourniquet. J. Anat. (l,ond . 113: 3. 433-455. RAMINSKY. M. (19731 The effects of temperature on conduction m demyelinated smglc fibres. Arch Neural. ( C h i c . . 2 8 : 2 8 7 292. RUDGE. P. 11974a) M.D. Thesis. University of London. In preparauon. RUOGE, P. 1974bl Tourniquet paralysis with prolonged conduction block : an electrophysiological stud3, J. Bone Jt Surg., In press. RUDGE. P.. R. W GILLIAT'I AND J. OCHOA 11973) Acute peripheral nerve compression m ~lae baboon Electroenceph. clin. Neurophysiol., 34: 806. THOMAS. P. K. Ar4D R. G. LASCI~Lt,ES (1966) Changes due to age in internodal length in the sural nerve m man. J Neurol. Neurosur.q, Psvchiat.. 2 9 : 4 0 - 4 4 . TROJABORG. W. (t970) R a t e of recovery in motor and sensory fibres of the radial nerve: clinical and electrophysiologieal aspects..L Neurol. Neurosura. P,~vchiat.. 33: 625-638.