Jaurnal o/" the Neurological Sciences, 1977, 33:387-396
,!~ Elsevier Scientific Publishing Company, Amsterdam
387 Printed in The Netherlands
RESPECTIVE I M P O R T A N C E OF D I F F E R E N T E L E C T R O P H Y S I O L O G I C A L PARAMETERS IN ALCOHOLIC NEUROPATHY
J. C. WILLER and H. DEHEN H6pital Saint-Antoine (JCW), Laboratoire de Neurophysiologie Clinique, 184, rue du Fauboug SaintAntoine, 75012 Paris, and H6pital Beaujon (HD), Clinique Neurologique, 100 Boulevard Gdndra/ Leclerc, F92110, Clichy (France)
(Received 4 March, 1977)
SUMMARY An electrophysiological study of alcoholic and normal subjects is presented. The aim was to evaluate the respective importance of the various parameters. The subjects were divided into 4 groups: (I) normal subjects; (II) chronic alcoholics without clinical evidence of neuropathy; (III) chronic alcoholics with sensory symptoms; (IV) chronic alcoholics with both motor and sensory symptoms. The electrophysiological parameters tested were: conduction velocity (CV) in Ia sensory fibres, motor fibres, and cutaneous sensory fibres of the popliteal nerve, CV in the sural nerve, amplitude of the cutaneous sensory action potentials (SAP) in the sural and popliteal nerves, H reflex and M response of the soleus muscle, and electromyograms from the extensor digitorum brevis muscle. In the 3 groups of alcoholics, the electrophysiological findings were more abnormal than the clinical symptoms could have predicted. The more sensitive parameters were: (1) CV in the la sensory fibres of the popliteal nerve, which is slowed very early (in G r o u p ll) and (2) measurement of the amplitude of sural and popliteal SAP's which are also reduced early (in Group I1). The nature of the mechanisms involved are discussed.
INTRODUCTION Electrophysiological studies in alcoholic neuropathies have shown that only a slight reduction of the motor and sensory conduction occurs in many of them (Jurko, Culrier and Foshee 1964; Walsh and McLeod 1970; Blackstock, Rushworth and Gath 1972). Even in severe neuropathies, significant slowing in conduction velocity is rarely described (Mawdsley and Mayer 1965). In contrast, a reduction in amplitude of Correspondance to be sent to J. C. Wilier.
388 sensory action potentials (SAP) is often observed and has been described as an early sign of alcoholic neuropathy (Gilliatt and Sears 1958; Buchthal and Rosenfalck 1966, 1971 ; Blackstock et al. 1972; Casey and Le Quesne 1972; Burke, Skuse and Lethlean 1974; Willer, Bathien and Dehen 1975; Willer and Dehen 1977). In the same way, Bathien and Guiheneuc (1974) and Guiheneuc and Bathien (1976), using the H reflex from the soleus muscle, observed a reduction of the ratio H max/M max in alcoholic neuropathies. However, recent studies using the H reflex from the extensor digitorum brevis muscle, elicited by stimulating the popliteal nerve, have shown that a significant increase in the latency of the H reflex can occur in latent neuropathy of alcoholic origin (Willer and Dehen 1977). In this work, an electromyographic (EMG) study was undertaken on subjects with alcoholic neuropathy of varying severity and the findings were compared with those in normal subjects, in order to evalute the respective importance of variations in the different parameters currently studied in E M G departments. METHOD The investigations were carried out in 4 groups of subjects: Group 1 - 35 normal adults (20-40 years); Group II - 27 subjects (27-42 years) drinking the equivalent of 300 ml of alcohol per day for at least 3 years, but without any clinical sign of neuropathy; Group III - 24 subjects (31-48 years) who were chronic alcoholics, with sensory symptoms, especially complaints of burning lightning pains and painful paraesthesiae, particularly in the feet and at night; Group IV - 32 subjects (30-55 years) who were chronic alcoholics, with both sensory symptoms (as described above) and motor weakness, involving particularly the distal muscle of the lower limbs, resulting in drop foot in 14 of them. In all patients (Groups II, III, IV), special laboratory investigations showed no evidence of decompensated cirrhosis. During the period of study, the subjects were sitting comfortably in an armchair especially designed so as to obtaingood muscular relaxation. The electrophysiological methods of stimulation and recording were those routinely used : (1) Conduction velocity (CV) in the Ia sensory fibres of the popliteal nerve was studied according to the method previously described (Wilier 1975). It involved evoking 2 monosynaptic responses (H responses) in the extensor digitorum brevis muscle (EDB), elicited by monopolar stimulation of the nerve at 2 points along its pathway (behind the head of the fibula, and 1 cm above and in front of the lateral malleolus). Recordings were made with bipolar surface electrodes, placed on the scratched and degreased skin above the end-plate zone of EDB. The position of the tested limb was identical in all subjects: angulation pelvis-thigh = 120°; thigh-leg ~ 120°; leg-foot = 90° (Fig. 1). Moreover, the subjects were asked to exert a slight voluntary dorsiflexion of the toes, in order to facilitate reflex activity in EDB. The time interval between the two H responses and the distance between the two sites of stimulation were then measured and made possible the calculation of the CV in the Ia sensory fibres. However, it was essential to take two precautions in order to make this method reliable. The first concerns the problem of F waves which are often observed in this
389
~
H1
--3V'----St I
0.2mY 'Sms¢C
St 2
2
EDB
Fig. 1. This figure shows the method used for the calculation of the conduction velocity in the la
sensory fibres of the popliteal nerve, using the H reflex technique. Left: St I and St2 -: monopolar stimulation of the nerve at 2 points along its course. Recordings from the skin over the EDB muscle. Right: 1 HI and M 1 responses elicited from St l ; 2 -- H2 and M2 responses elicited from St2. muscle, especially with distal stimulation, and of which latencies may be nearly in the same range as those of the H responses. Nevertheless, the reflex (H) responses were abolished with maximal and supra-maximal stimulations (M maximal), whereas the F waves persisted. This fundamental characteristic of the H response allowed us to differentiate l:he H reflex from the F waves. Moreover, the latency of the H response did not vary more than -k 1.5 msec (for distal and proximal stimulation), whereas the latency of the F wave varied over a wider range (-k 6-10 msec). The second point concerns potential errors derived from the assumption that both the afferent and efferent pathways are the same for both sites o f stimulation (knee and ankle). For this reason, it was necessary to record identical shapes of the M and H responses evoked by both distal and proximal stimulation. This morphological similarity allowed us to conclude that the same afferent and efferent pathways were activated with the two sites o f stimulation. (2) CV in the fastest conducting m o t o r fibres of the popliteal nerve was measured according to the method described by L a m o n t a g n e and Buchthal (1970): a supramaximal stimulus was applied through surface electrodes positioned at two points along the pathway of the nerve (as in I) above, with the cathode placed distally. The evoked potentials from EDB were also recorded as in (1). (3) The distal CV and the amplitude of the SAP o f the sural nerve were studied
390 according to the method described by Burke et al. (1974). The same technique wa.s used for the study of the terminal branches (purely cutaneous) of the popliteal nerve : the medial and lateral branches of the musculo-cutaneous nerve were stimulated at the level of the 1st, 2nd, and 3rd toes. Orthodromic recordings were performed on the scratched and degreased skin with bipolar electrodes (2 cm apart), placed over the course of the nerve (l cm above the ankle). (4) The H reflex from the soleus muscle, evoked by stimulating the tibial nerve at the popliteal fossa, was also recorded. (5) EMG's were recorded from EDB using a bipolar steel-needle electrode inserted into the muscle. Motor unit potentials were integrated during a maximal voluntary contraction and quantified in arbitrary units (AU). In all cases, electrical stimulation consisted of a single rectangular pulse (0.5-1 msec duration) variable in intensity and delivered at a rate of 0.3 Hz by a constantcurrent stimulator. After amplification, the potentials were channelled into a storage oscilloscope, then into a loudspeaker and into a tape recorder. The room temperature was kept constant at 20 -~ 1 °C. The limb studied was slightly warmed, so as to secure a constant skin temperature of 30 ± 1 °C near to the nerves and near the muscles concerned. The latent period of the potentials (muscles and nerves) was measured to the point of first deflection of the baseline. The amplitude was calculated from peak to peak. The numerical values of the results were analysed statistically: mean, standard deviation, and variance being calculated. The significance of the variations was studied with the Student t-test. RESULTS
(1) Control subjects (Group I) The numerical data are shown in Table 1. They reveal a slight degree of dispersion of the CV in the motor and sensory fibres of the popliteat and sural nerves. In contrast, there is a greater variability in the amplitude of the SAP recorded from these nerves. The study of the H reflex from the soleus muscle showed normal M and H responses with respect to latent period and amplitude. EMG's from the EDB showed normal interference patterns during maximal voluntary contraction. Figure 2 (I) shows an example of the H reflex recorded from EDB and the SAP obtained from the popliteal and sural nerves in normal subjects.
(2) Alcoholic patients without clinical evidence of neuropathy (Group II) In this group, types of abnormality were observed (Table 1): the first was a very significant reduction (30 %) in the CV of the Ia fibres of the popliteal nerve, compared with control values. The second modification was a significant reduction in the amplitude of the cutaneous SAP's of the popliteal and sural nerves. It is of interest to note that this reduction was more marked with the popliteal (45 %) than with the sural nerve (25 %). The other parameters were within normal limits. The motor CV (distal latent period included) and the cutaneous CV were not significantly different from
391 TABLE I NUMERICAL VALUES OF THE MEAN (M) AND STANDARD DEVIATION (SD) OF THE PARAMETERS STUDIED IN EACH GROUP
Popliteal nerve la sensory fibres CV (m/sec) Motor fibres distal latency (m/sec) CV (m/sec) Cutaneous sensory fibres CV (m/sec) amplitude (/tV) EMG's (AU) a
Group 1 (n = 32)
Group Ii (n :- 27)
Group III (n ~ 24)
Group IV (n = 32)
M
M
M
M
SD
SD
SD
69
2
48
4***
4 45
0.5 3
4 44
0.6 NS 5 4 NS 40
I* 2*
6 38
1** 1"*
51 25 248
4 NS 45 10"** 18 12 NS 204
3* 12'** 7*
38 10 150
2*** 6*** 10'**
6 30 50
0.6 NS 6 0.8 NS 31 2 NS 21
7 36 l0
1* 2** ***
50 37
4 NS 40 9** 25
52 45 251
Tibial nerve latency M (m/sec) latency H (m/sec) Hmax/M max ratio(~o)
6 30 52
Sural nerve CV (m/sec) amplitude (/tV)
51 44
4 9 10 0.5 1 3 3 10
ABS.
SD
ABS.
0.8 NS I NS 4*** 3** 10"**
34 18
4*** 9***
~LIntegrated activity of the EDB muscle during a maximal voluntary contraction (EMG) is expressed in arbitrary units (AU). * P ~< 0.02; ** P ~< 0.01; ***P~< 0.001. NS ~ not significant.
those measured in G r o u p 1. Similarly, the study of the H reflex from the soleus muscle revealed n o r m a l M a n d H responses (latency a n d amplitude), a n d were n o t significantly different from the identical responses of G r o u p 1. E M G ' s from EDB showed n o r m a l recruitment d u r i n g a progressive contraction, and a n o r m a l interference pattern was o b t a i n e d d u r i n g maximal contraction. There was no significant difference in A U between G r o u p i a n d G r o u p II. Figure 2 (11) shows an example of the main parameters studied in this group. (3) Alcoholic patients with sensory symptoms (Group HI) In this group, almost all of the parameters were a b n o r m a l , except for the latency of the M a n d H responses of the soleus muscle (Table 1). However, the major differences concerned the amplitude of the SAP more t h a n the CV, a n d the absence of an H response in EDB (Fig. 2 (Ill)). A very significant reduction in the amplitude of the popliteal nerve SAP (60 ~ ) and of the sural nerve SAP (45 ~ ) were observed. The H reflex EDB was never observed, even d u r i n g a sustained voluntary contraction, whereas n u m e r o u s F waves were then recorded. The ratio H max/M max of the soleus muscle was very significantly lowered. In contrast with these marked abnormalities, CV was only slightly slowed, particularly m o t o r CV. However, the sensory CV was
392
I
II
Trr
w
A-H1
b
I Fig. 2. This figure shows variations in the most sensitive parameters tested in the 4 groups of subjects (I, II, III, IV). a: H responses (at arrows) from EDB observed in I and II. None is shown in 111 and IV because these responses were lost in these cases. Calibration: horizontal 30msec; vertical 100 #V. b: sensory action potentials from the distal cutaneous branches of the popliteal nerve, c: sensory action potentials from sural nerve. Each trace is a superimposition of at least 10 responses (40 in bI). Calibration: horizontal 5 rnsec; vertical 30 #V. significantly slowed by 19~o in the sural nerve, and by 147o in the popliteal nerve, while the motor CV was only slowed by 11 9/0 in this latter nerve. By contrast, normal lateneies were noted for the M and H responses of the soleus muscle, EMGs from the EDB showed some slight abnormalities during a weak contraction: there was an increase in the amplitude of the motor unit potentials (2-3 mV) and some excess of polyphasic potentials. However, during a maximal contraction, a full interference pattern was easily obtained, but a significant reduction in A U was noted after integration (see Table 1 and Fig. 3).
(4) Alcoholic patients with both motor and sensory symptoms (Group IV) In this last group, all the parameters were significantly abnormal, CV included. However, as in Group III, the most important alterations concerned the amplitude of the SAP and the absence of the H reflex in EDB. The SAP were reduced in amplitude by 78 9/0 in the popliteal nerve and by 51 9/0 in the sural nerve (Fig: 2 (IV)). The ratio H max/M max from the soleus muscle was lowered to 10%, i.e. a reduction of 80% or more, compared to normal values (52 %). In the case of CV, the sensory CV was more slowed than motor: by 35 7Ofor the sural nerve and 28 % for the popliteal nerve.
393
me group I ~groop'lT
~
~
group TIT group I V
a
b
c
d
e
f
g
h
1
j
Fig. 3. Histogram of the mean and standard deviation of the parameters studied in each group (see numerical data and significance in Table 1). a: CV (m/sec) in the la fibres of the popliteal nerve (PN); b: CV (m/sec) in the largest diameter cutaneous fibres of PN ; c: amplitude (/iV) of the evoked potential of PN ; d: CV (m/sec) in the largest diameter fibres of sural nerve; e: amplitude (/tV) of the sural sensory evoked potential ;f: CV (m/sec) in the fastest motor fibres of PN ; g: latency (m/sec) of the motor response (M) recorded in the soleus muscle; h: latency (m/sec) of the H response recorded in the soleus muscle; i: H max/M max ratio of g and h; j: integrated EMG's (AU see text) from EDB recorded during a maximal voluntary contraction.
In the s a m e way, the latency o f the H response from the soleus muscle was increased by 1 9 ~ . In contrast, the m o t o r CV o f the popliteal nerve was only slowed by 16~,, a n d the latency o f the M response o f the soleus muscle was increased by 1 5 ~ . E M G ' s from EDB showed classical changes o f p a r t i a l denervation during slight a n d m a x i m a l c o n t r a c t i o n . In the case o f slight c o n t r a c t i o n , the m o t o r units were o f large a m p l i t u d e (3-3.5 mV) increased d u r a t i o n (10-18 msec) a n d were c o m p o s e d o f n u m e r o u s polyphasic potentials. D u r i n g m a x i m a l c o n t r a c t i o n , which was often weak, the recruitment o f the same m o t o r units increased, a n d these units discharged with a high frequency (50-80 Hz). The total n u m b e r o f m o t o r units was substantially reduced. These results are presented in Fig. 3 and in Table 1. DISCUSSION This study reviews the electrophysiological features o f alcoholic n e u r o p a t h y o f varying clinical severity. Its aim was essentially to assess the relative i m p o r t a n c e o f the electrical p a r a m e t e r s as an index o f clinical severity. (A) The results show that the electrophysiological disturbances occur early, before the a p p e a r a n c e o f detectable clinical a b n o r m a l i t i e s , especially the CV in the largest d i a m e t e r sensory fibres (sensory Ia fibres), and the a m p l i t u d e o f the SAP. T h u s : - In alcoholic subjects without any clinical sign o f n e u r o p a t h y , a reduction in the a m p l i t u d e o f the c u t a n e o u s S A P o f the sural a n d popliteal nerves can be observed, as well as significant slowing in the CV in the l a sensory fibres o f the latter nerve. In patients with sensory s y m p t o m s , the electrophysiological findings described
394 above are more pronounced and the abnormalities also involve the la fibres of the tibial nerve (H max/M max ratio decreased). Moreover, the cutaneous CV (sural and popliteal nerves) are slightly slowed, and the la sensory fibres of the popliteal nerve are no longer excitable. - In the worst affected group of patients, with both sensory and motor manifestations, all the electrophysiological parameters are abnormal: these include the amplitude of the SAP and the CV in the motor and sensory fibres of the popliteal, sural and tibial nerves. However, in these results, it is of interest to note that the major disturbances concern the amplitude of the cutaneous SAP and the CV in the la sensory fibres of the popliteal nerve. These results, showing a selective involvement of muscles of the antero-lateral compartment of the leg and of the popliteal nerve in alcoholic neuropathy, confirm those of previous studies (Jurko et al. 1964; Bergamini, Gandiglio, Fra, Bergamasco, Bram and Mombelli 1965; Mawdsley and Mayer 1965; Blackstock et al. 1972; Walsh and McLeod 1970; Wilier and Dehen 1977). (B) However, the major interest of our study is related to the electrophysiological disturbances observed in latent neuropathy, i.e. a decrease in the amplitude of the sural and popliteal SAP's and slowing in the CV in the la sensory fibres of the popliteal nerve. - Many authors have shown that a reduction in amplitude of the nerve action potentials associated with normal motor and sensory CV is an early sign of axonal degeneration (Gilliatt and Sears 1958; Gilliatt 1966; Buchthal and Rosenfalck 1971). In experimental acrylamide neuropathy (Fullerton 1969; Hopkins and Gilliatt 1971) as well as in vincristine neuropathy (McLeod and Penny 1969), axonal degeneration was demonstrated to be the principal pathological mechanism. In these neuropathies, the amplitude of the motor and sensory nerve action potentials was reduced, while the respective CV's were within normal limits. Histological studies of nerve biopsies in such cases have shown a marked reduction in the number of nerve fibres, associated with redundant projections of membranes into the axoplasm with paranodal collections of vesicles and mitochondria (Collins, Webster and Victor 1964), or accumulation of abnormal mitochondria and other abnormal cells (Dyck, Johnson, Lambert and O'Brien 1971). On the other hand, the slowing of the CV in the Ia sensory fibres of the poptiteal nerve, tested with the H reflex method and recorded from EDB, is also observed to occur very early in alcoholic neuropathy, and seems to be a sensitive test. At this stage of latent neuropathy, the H reflex from the soleus muscle still remains normal. This change can be explained by the presence of segmental demyelination occurring concurrently with the axonal degeneration in the largest diameter fibres. This hypothesis is supported by the observations of some authors suggesting that, on the one hand, the sensory fibres are damaged earlier than the motor neurone in various polyneuropathies (Bannister and Sears 1962; Lamontagne and Buchthal 1971); on the other hand, it has also been shown that the largest fibres are first affected in experimental neuropathies (Hopkins and Gilliatt 1971). The interrelationship between axonal degeneration and segmental demyelination needs further discussion. According to Dyck -
395 (1973), irregularities of the myelin sheath a n d lack of myelin along the axis cylinder may be a sign of axonal degeneration. Other authors have noted marked irregularities of myelin in thiamine-deficient and chronically starved rats, which they a t t r i b u t e d to a n a b n o r m a l i t y of axons, a n d possibly to a decrease in the volume of the axon (Collins et al. 1964). I n the same way, in uraemic neuropathy, Dyck et al. (1971) came to similar conclusions: the irregularities of the myelin sheath a n d segmental demyelination are secondary to axonal degeneration. However, the degeneration was more severe distally, whereas the d e m y e l i n a t i o n was not r a n d o m l y distributed a n d occurred only in certain fibres. It is possible to consider that similar processes may occur early in alcoholic neuropathy. Moreover, segmental demyelination can result from a decrease in volume of the axis cylinder a n d even if this axon does not degenerate, but demyelination between a series of intercalated internodes provides some evidence of previous axonal damage (Dyck 1973). These findings are in agreement with the suggestions of D e n n y - B r o w n (1958), to the effect that segmental d e m y e l i n a t i o n can appear early in the largest diameter fibres in patients with alcoholic neuropathy, and can be reversible.
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