~~
~~
We examined median somatosensory evoked potentials (SEPs) in 26 patients with sporadic motor neuron disease (MND). SEPs were recorded with multiple scalp derivations, using both the midfront and the earlobe as references for each subject. Central conduction time (CCT) was abnormal in three patients, but only when using the midfront reference. Moreover, an exclusive alteration of the early prerolandic potentials (absent or delayed P20 and/or P22)was noted using the earlobe reference in amyotrophic lateral sclerosis and in progressive bulbar palsy (54% and 50% of patients, respectively) but not in progressive muscular atrophy. These findings correlated with clinical evidence of upper motor neuron signs and with the severity of the disease. In agreement with recent views regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials. Key words: Motor neuron disease amyotrophic lateral sclerosis progressive muscular atrophy cortical somatosensory evoked potentials central conduction time. MUSCLE & NERVE 13:47-55 19%
FAR=FIELDAND CORTICAL SOMATOSENSORY EVOKED POTENTlALS IN MOTOR NEURON DlSEASE GlAMPlETRO ZANETTE, MD, ALBERT0 POLO, MD, MARCELLA GASPERINI, MD, LAURA BERTOLASI, MD, and DOMENICO DE GRANDIS, MD
Motor neuron disease (MND) is widely considered to be a disorder strictly confined to the voluntary motor system with progressive degeneration of the corticospinal tracts and alphamotoneurons. Although some patients with MND experience paresthesias, cramps, and other vague sensations, the observation of sensory deficits is unusual, and objective evaluations of these disturbances have rarely been performed.21932Moreover, investigators disagree about the anatomicopathological involvement of the sensory system in this disease.4325The application of somatosensory evoked potentials (SEPs) in MND has also produced conflicting conclusions: although upper limb SEPs were generally found to be normal in From the Institute of Neurology, University of Verona, Italy Acknowledgment: The authors thank Mr. Anthony Steel for his assistance in preparing the manuscript. This paper was presented in part at the Congress of the International Medical Society of Motor Disturbances, Rome, Italy, June 2-4, 1988. Address reprint requests to Dr. De Grandis at the Institute of Neurology, University of Verona, Italy. Accepted for publication October 21, 1988 CCC 0148-639X/90/01047-09 $04.00 0 1990 John Wiley & Sons, Inc.
SEPs in Motor Neuron Disease
these disorder^,'^'^,^^,^^ some investigators have observed the presence of delayed responses in patients without sensory symptom^.^.^^' 1#13325,30 Recently, however, numerous authors have suggested that some components of SEPs may not originate from activation of generators belonging to the sensory system. In fact, a series of scalp near-field potentials with different polarity and with selective involvement in relation to the site of focal brain lesions have been detected in the parietal and frontal regions. 12.14- 19.31,34,36.3739 Although the nature of the individual waves is not yet fully established, the same investigators suggest the existence of separate generators for frontal and parietal components and, moreover, claim that the early anterior cortical potentials probably represent a sensory input to motor areas. This is an important question which has to be considered especially in a disease where the degeneration of the corticospinal tract may be a prominent feature. For these reasons, the purpose of the present work is not only to verify the presence of alteration of the sensory conduction previously reported but also to detect possible abnormalities of somatosensory cortical potentials in MND. To achieve this aim, we studied SEPs from the me-
MUSCLE & NERVE
January 1990
47
dian nerve in 26 patients with MND using both the parietal-to-frontal montage and multiple scalp derivations, comparing the results with those obtained in 20 healthy subjects. PATIENTS AND METHODS
Twenty-six patients (14 males and 12 females) with MND were investigated. The criteria adopted to formulate the diagnosis and for inclusion in the study were the following: (1) family history negative for MND, (2) clinical evidence of progressive and rapid loss of muscle strength with atrophy and fasciculations dating back at least 6 months, (3) electromyographic picture of denervation in muscles of more than one limb tested and normal sensory nerve conduction, (4) patients older than 25 years (range 30-74, mean age 55 years), (5) normal radiographic investigations of the spine. According to the clinical picture, 3 forms of MND were distinguished: amyotrophic lateral sclerosis (ALS, 14 cases) with both upper and lower motor neuron involvement, progressive muscular atrophy (PMA, 6 cases) without evidence of corticospinal tract dysfunction, and progressive bulbar palsy (PBP, 6 cases). Moreover, owing to the peculiar cliniconeurophysiological correlations reported later, the muscular strength of the hands was also considered at the time of the examination using the Medical Research Council scale (scores from 0 to 5). Although pain due to muscular cramps was a frequent sensory symptom (40%), only one patient experienced paresthesias in a focal area of the left leg that remained stable in the course of the illness. The subjects lay supine on a bed in a quiet room and were requested to remain relaxed with closed eyes. The median nerve was stimulated at the wrist with an intensity capable of eliciting a weak muscular twitch of 2.5-3 times above the sensory threshold whenever the intrinsic muscles of the hand were atrophic. The electrical stimulus had a duration of 0.1 msec and a frequency of 5 Hz. The recordings were carried out with silver-silver chloride electrodes placed at Erb’s point (EP), CVII, and P3/P4 postcentral cortical zones 7 cm lateral to Cz and 3 cm behind the Cz-ear line; these active derivations, contralateral to the stimulated nerve, were referred to the Fz electrode (often the EP lead was referred to a noncephalic (NC) site). SEPs were also obtained with central (C3/C4) and frontal (F3/F4) electrodes according to the 10-20 International System. For all scalp leads, includNeurophysiologic Methods.
48
SEPs in Motor Neuron Disease
ing the postrolandic ones, the ipsilateral earlobe was chosen as the reference instead of Fz in order to record the cortical potentials. The impedance of the electrodes was maintained below 5 kR. T h e signals coming from the leads were processed by a four-channel averager using a bandpass of 5-2000 Hz for scalp EEG activity, while the spine and the EP potentials were amplified by a band-width of 20-2000 Hz. Each trial represented the average of 1000 artifact-free responses and was replicated and superimposed to establish the reliability of the different components. The first 50 msec poststimulus were analyzed measuring the peak latency and peak-to-peak amplitude of the main waves. The interpretation of SEPs was based on the values obtained in 20 healthy subjects, with a mean age similar to that of the patient group. RESULTS
The scalp topography of SEPs recorded in normals corresponded to that reported by other investigators. Briefly, using the earlobe reference, the scalp leads showed a farfield positive P14 component followed by a widely represented N18 wave, whose one set was more appreciable in prerolandic regions (Fig. 1). After this wave, it was possible to detect a number of early and long latency responses with different hemiscalp distribution. In the frontal derivation, the N18 peak was followed by positive-negative components defined as P20 and N30. Wave N30 was not recorded in 4 subjects, and in these cases, it was replaced by a negative peak at about 24 msec. In the contralateral parietal scalp, a N20-P25-N33 complex was observed: of these components, the N33 wave was not obtainable in all cases (it was present in 18 out of 20 normals). The contralatera1 central electrode registered a positive stable response defined as P22, with a peak latency somewhere between the frontal P20 and the parietal P25. The time-locked, opposite-polarity P20 and N20 components, recorded respectively in the frontal and parietal regions, did not have the same peak latency in all normals, but more frequently P20 occurred slightly later than N20 (mean latency difference P20-N20 = 0.4 msec, 0.4 SD). As observed by Desmedt and Bourguet,’“ the use of the frontal reference produces a posterior “N20-P20” complex which represents the subtraction of frontal from parietal traces. The early prerolandic and far-field components are thus cancelled by the activity picked up from the frontal reference electrode. Moreover, it may be noted Normal Subjects.
MUSCLE & NERVE
January 1990
Right stim. EP-NC
T.S.
A
p
EP
p
43 yre
- -
N13
C7-Fz
N33
N20
C minus E
Fz reference
N20-P20
+ l 5 msec
I
I
FIGURE 1. Median nerve SEPs in a normal subject. Note that the anterior P20 (E) is virtually the mirror image of the parietal N20 wave (C). The parietal versus frontal montage shows a negativity resulting from the algebraic summation of early posterior and prerolandic potentials (C minus E, F). This peak, labelled “N20-P20,”has the same latency as the N20 wave.
that the mean latencies of the N20 peak obtained using both the earlobe and the midfront as references had very similar values (19.3 and 19.1 msec, respectively). Based on normality data, SEP abnormalities were defined as follows: 1. Absence of one of the stable components always obtainable in healthy subjects: N13, P14, N20, P20, P22, and P25. Amplitude difference between the hemiscalp responses was not considered owing to the high variability of this parameter. 2. A prolongation of the interpeak latencies EPN13, EP-P14, N13-N20, P14-N20, P14-P20, P14-P22, and P20-N20. 3. A significant difference in central conduction time (CCT) between the two stimulation sides.
SEPs in Motor Neuron Disease
Regarding points 2 and 3, the values were considered abnormal when they exceeded the mean plus 3 SD. Moreover, the values of the intervals EP-N13, EP-P14, N13-N20 (Fz Ref.) and N13N20 (Au Ref.) in normals were compared with those obtained in MND patients using the Student’s t-test (Table 1). The cervical SEPs from the median nerve were normal in all cases examined, and the mean latencies of the EP-N13 and EP-P14 intervals showed no significant differences compared with controls. Using the midfront reference, the N 13-N20 central conduction was clearly abnormal in 3 ALS patients (12%) on one stimulation side and was significantly increased compared with the normal group. This result was not confirmed on measuring the N13-N20 interval ob-
MND Patients.
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49
Table 1. SEP interwave latencies in 20 healthy subjects and in 26 MND patients [mean (SD) tn milliseconds] lnterpeak
Controls
MND patients
EP-N13 EP-PI4 N13-NZ0 (Fz Ref) N13-N20 (Au Ref )
3 7(0 34) 4 8(0 47) 5 5(0 44) 5 6(0 47)
3 6(0 35) 4 9(0 42) 6 l(0 49)* 5 5(0 53)
*P < 0.001.
tained with the earlobe reference: no patients showed abnormal values, and there was no statistical difference versus controls. These discordant data are illustrated in Fig. 2, which shows the traces recorded in one of the three patients with a prolonged N 13-N20 interpeak. Using the earlobe
as reference, the N20 component was earlier than that obtained with the parietal-to-frontal montage, and, in this case, the N13-N20 central conduction was normal. The subtraction of anterior (F3) from posterior (P3) scalp traces yielded an N20 latency and morphology similar to those recorded using the cephalic reference. This algebraic operation, forming a P3-F3 artificial montage, confirmed an increase in the N20 peak. These results, which were also observed in the other t w o patients with abnormal N13-N20 intervals, were never seen in normals, where the N20 wave latency was not significantly modified by the type of reference utilized. It should be stressed that these three patients showed distinctly abnormal anterior cortical potentials mainly formed by a delayed P20 wave ipsilateral to the abnormal N20 obtained with the
Right etim.
A.D.
a" 5 2 y r s
EP
+Pa0
f 24 a sJ
NZO -P 2 0 5 msec
FZ reference I
..
FIGURE 2. Significant prolongation of the N13-N20 interpeak obtained using the midfront reference (F, C minus E) not confirmed by the earlobe reference (C). The frontal electrode records an increased P20 (E), whereas the central one registers a positivity appearing as an anterior spread of the P25 (D) (case 1).
50
SEPs in Motor Neuron Disease
MUSCLE & NERVE
January 1990
volvement had a prevalence of normal P20 and P22 potentials. All cases with only lower motor neuron signs (PMA) and with marked reduction of strength showed well-defined normal peak latency of the central and frontal components bilaterally (Fig. 4). Thus, the pathological modifications of the P20 and P22 waves appeared to correlate closely with the clinically detectable involvement of the corticospinal tract and might have an asymmetrical scalp distribution in relation to the extent of the functional impairment of the upper limbs. A doubt persists regarding the numerous cases with abnormal early anterior potentials showing regular CCT. In these subjects, the posterior “N20-P20” complex was never significantly altered. This fact was explained by means of the summation of traces, proving that 1. Absence of the anterior components did not modify the latency of the parietal potentials. 2. The anterior responses, when present, had such a minimal increased latency (no more than 0.9 msec beyond the normal upper limits considering the P20-N20 interpeak) and/ or such a low amplitude as not to affect the posterior components. Another interesting observation was that, whenever the frontal P20 wave was missing, the later anterior N30 was also often strongly altered or absent (Fig. 3). Nevertheless, this finding was not quantified since a simultaneous bilateral stimula-
Table 2. Early anterior SEPs in MND patients MND
Total patients’ sides
Percent abnormal P20 and/or P22
ALS PBP PMA
27 12 12
54% 50% 0 Yo
midfront reference. On the same hemiscalp, the P22 wave was absent in two cases and delayed in one. Thus, in three of our patients the use of the cephalic reference produced a posterior “P20N20” complex pathologically modified by abnormal anterior components. The early central and frontal potentials, together or singly, were delayed or strongly altered so as to be undetectable also in subjects with normal CCT (Fig. 3). These abnormalities had a high incidence, but only the patients with ALS and PBP were affected (54 and 50%, respectively; Table 2). Moreover, the abnormal SEPs were correlated with clinical evidence of corticospinal tract involvement and with the degree of functional impairment of the hands (Table 3). It was observed that abnormal P20 and/or P22 were a very frequent finding in ALS and PBP patients with upper motor neuron signs (90% and 83%, respectively) when stimulating the sides with high muscular weakness (0-3). On the other hand, the patients belonging to the same group but with slight unilateral o r bilateral functional in-
B.L.
R i g h t stim.
Left stim.
2L/--=
d 33yrs
EP
EP-NC
N20 Earlobe reference
@ ..
I
L-
.
J
pi4
-If +
I”..
FIGURE 3. An asymmetric involvement of the prerolandic waves can be seen: on left stimulation only the P20 is observed, whereas on right stimulation no anterior peaks are detected (case 10).
SEPs in Motor Neuron Disease
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51
Table 3. Clinical features and SEP findings in 26 MND patients. SEP findings
SEP findings MND
Patient and sex
ALS
1M 2M 3M
4F 5F 6M
PBP
PMA
7M 8F 9F 10 M 11 M 12 M 13 M 14 F 15 F 16 F 17 M 18 F 19 M 20 M 21 F 22 M 23 F 24 F 25 F 26 M
UMN signs
+ + + + + + + + + + + + + + + + + +
-
Hand strength 0-3
P20
P22
1* 1 1 1
D D A D
A
2
Dt
A
1
A D A
A
I
D A
1 1 2 2 2
1 1 1 2
A
D
1 1
2
1 1 1 2 1
A
A
D
A D At A
P22
D
Dt A
D A A At
D D/A
A
1 1 1
A
A
1 2
A
2 2 2
-
2
-
2
-
2 ~~
Note UMN = upper motor neuron, A and D = absent and delayed response, ticity, Babinski sign, absence of abdominal reflexes * A score of 1 couid not be obtained ?Bilaterally abnormal
tion of the median n e r ~ e , ~ ' , permitting ~' evaluation of the long latency SEPs, was not performed. DISCUSSION
The determination of SEPs is commonly regarded as a valid electrophysiological test for detecting even a subclinical involvement of the sensory pathways. Recently, some investigators have observed the presence of delayed evoked responses in tients without sensory disturbances. 2,5,11,13,3t& Considering the current views regarding the sources of these potentials, nearly all authors have postulated the presence of subclinical involvement of the central sensory system in MND, probably localized within the dorsal columns and the lemniscal pathways. In supporting this opinion, electrophysiological data have been correlated with occasional pathological evidence of minor neuronal degeneration found outside the motor system, particularly in the central sensory tracts and n~clei.~~"." An alternative explanation has been formulated on the basis of the well-known feed-
SEPs in Motor Neuron Disease
P20
2
~~~~~
52
Hand strength 4-5
+
~
~
= presence of two or more of the following signs hypereflexia spas-
back-type modulation exerted by the motor pathways on the afferent stimuli, especially at dorsal horn l e ~ e I . ~ It ' *has ~ ~ been suggested that a lack of such action, caused by lesions confined to the pyramidal tract, might produce delayed evoked somatosensory responses.' l~~~ As regards the estimation of CCT from the median nerve, a percentage of abnormalities ranging from 12 to 23% has emerged on pooling together the findings of all authors. Our data also showed an increase in CCT in a similar number of cases (12%) using the upper limb SEPs. Nevertheless, we think that these changes found in MND patients may be related to the peculiar nature and alterations of the cortical responses. In fact, we observed that the use of parietal-to-frontal montage gave rise to a contralateral delayed N20 peak due to the algebraic summation of preserved postrolandic response and abnormal frontal potentials in 3 out of 26 patients. It is likely, therefore, that the prolonged CCT from the median nerve occasionally noted in MND does not represent an
MUSCLE & NERVE
January 1990
Right stim.
V.A.
9 44yrs
EP EP-NC
N20
@ .
Earlobe
P22
\
reference
FIGURE 4. Patient with PMA showing normal subcortical and cortical SEPs (case 23).
involvement of central afferent pathways but depends more probably on the type of methodological determination of SEPs.15 Moreover, delayed or absent P20 and P22 components were noted not only in patients with abnormal CCT but also in numerous other cases. Considering that in normals the early cortical responses are stable and constantly reproducible, their alteration is a reliable pathological indicator. Such abnormalities were found only in patients with ALS and PBP and appeared to correlate closely with the presence of pyramidal signs and with the severity of the functional muscular impairment of the hands. Interestingly, similar results were reported by Bosch et al.5 in 30 patients with MND using a central scalp derivation. They observed a higher percentage of abnormal median nerve SEPs in patients with ALS and PBP than in patients with PMA, mainly consisting of delayed or absent N32 andlor N60 late components. We also noted marked abnormalities of the frontal N30 component, but only in association with an absent or strongly altered P20 peak. Therefore, it is possible that the alterations of the long-latency SEPs described may be explained in terms of an involvement of the earlier cortical anterior peaks.
SEPs in Motor Neuron Disease
Recently, numerous clinical, topographic, and experimental studies have been performed to detect and localize the generators of the early cortical components obtained by upper limb nerve stimulation, particularly the anterior ones. On the basis of the results obtained, almost all investigators have suggested that the P22 potential probably represents the depolarization of the primary motor area evoked by afferent inputs via direct thalaniocortical projections, whereas discordant opinions persist regarding the source of P20. Some investigators suggest that the time-locked P20 and N 2 0 Components more probably represent a tangential equivalent dipole qenerated in the postrolandic parietal cortex. 1.691d322,2b Others claim that P20 is not the mirror image of the N20 wave but probably represents the activity of distinct cortical populations of neurons located in the frontal areas,9s19228,34q367,79 possibly in the premotor cortex.36 T h e postulate whereby not only the primary sensory area but also the prerolandic cortex are probably activated by afferent inputs agrees with our neurophysiological observations in relation to the pathological studies carried out in Charcot's disease. A massive loss and degeneration of neurons in the motor cortex is
MUSCLE & NERVE
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53
constantly described, and, in most instances, lesions in the frontal gyri have been In view of the fact that the alteration of the anterior responses appears to be directly correlated not only with the presence of pyramidal tract involvement but also with the severity of the disease, it is likely that an intense neuronal loss in the motor areas provides evidence of an appreciable modification of the prerolandic cortical ~
responses. Furthermore, in healthy subjects the P20 wave occurred slightly later than the N20, and some patients showed an involvement of individual anterior peaks combined with normal N20 components. This evidence is at variance with the “equivalent dipole” theory but supports the idea that specific and partially independent cortical generators may give rise to early scalp responses.
~~~~
REFERENCES 1. Allison T, Goff WR, Williamson PD, Van Gilder JC: On the neural origin of early components of the somatosensory evoked potentials, in Desmedt JE (ed): Clinical Uses of Cerebral, Brainstem and Spinal Smatosensory Evoked Potentials. Basel, S. Karger, 1980, vol 7: Progress in Clinical Neurophysiology, pp 51-68. 2. Anziska BJ, Cracco RQ: Short-latency somatosensory evoked potentials to median nerve stimulation in patients with diffuse neurological disease. Neurology. 1983;33:989993. 3. Averback P, Crocker P: Regular involvement of Clarke’s nucleus in sporadic amyotrophic lateral sclerosis. Arch Neurol. 1982; 39:155-156. 4. Bonduelle N: Amyotrophic lateral sclerosis, in Vinken P, Bruyn GW (eds): Handbook of Clinical Neurology, Amsterdam, Elsevier-North Holland, 1975, vol 22, pp 281-338. 5. Bosch EP, Yamada T, Kimura J: Somatosensory evoked potentials in motor neuron disease. Muscle Nerve. 1985; 8:556-562. 6. Broughton RJ: Discussion, in Donchin E, Linsley DB (eds): Averaged Evoked Potentials. Washington, DC, NASA, 1969, SP-191: U.S. Government Printing Office, pp 79-84. 7. Cascino GD, Ring SR, King PJL, Brown RH, Chiappa KH: Evoked potentials in motor system diseases. Neurology. 1988;38:231-238. 8. Castaigne P, Cambier J , Escourolle L, Brunet P: Sclerose laterale amyotrophique et lesions degeneratives des cordons posterieurs.] Neurol Sci. 1971;13:125- 135. 9. Cheron G, Borenstain S: Specific gating of the early somatosensory evoked potentials during active movement. Electroenceph Clin Neurophysiol. 1987;67:537- 548. 10. Chiappa K: Evoked Potentials in Clinical Medicine. New York, Raven Press, 1982, p 296. 11. Cosi V, Poloni M, Mazzini L, Callieco R: Somatosensory evoked potentials in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 1984;47:857- 86 1. 12. Cracco RQ: Traveling waves of the human scalp-recorded somatosensory evoked response: effects of differences in recording technique and sleep on somatosensory and somatomotor responses. Electroenceph Clin Neurophysiol. 1972;33:557-566. 13. Dasheiff RM, Drake ME, Brendle A, Erwin CW: Abnormal somatosensory evoked potentials in amyotrophic lateral sclerosis. Electroenceph Clin Neurophysiol. 1985;60:306-311. 14. Deiber MP, Giard MH, Manguiere F: Separate generators with distinct orientations for N20 and P22 somatosensory evoked potentials to finger stimulation. Electroenceph Clin Neurophysiol. 1986;65:321-334. 15. Desmedt JE, Bourguet M: Color imaging of parietal and frontal somatosensory potential fields evoked by stimulation of median or posterior tibia1 nerve in man. Electroenceph Clin Neurophysiol. 1985;62: 1- 17. 16. Desmedt JE, Cheron G: Somatosensory evoked potentials to finger stimulation in healthy octogenarians and in young adults: wave forms, scalp topography and transit
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times of parietal and frontal components. Electroenceph Clin Neurophysiol. 1980:50:404- 425. 17. Desmedt JE, Cheron G: Non-cephalic reference recording of early somatosensory potentials to finger stimulation in adult or aging man: differentiations of widespread N18 and contralateral N20 from the prerolandic P22 and N30 components. Electroenceph Clin Neurophysiol. 1981;52:553570. 18. Desmedt JE, Nguyen TH, Bourguet M: Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses. Electroenceph Clin Neurophysiol. 1987;68:1- 19. 19. De Weerd AW, Looijenga A, Veldhuizen RJ, Van Hufflen AC: Somatosensory evoked potentials in minor cerebral ischaemia: diagnostic significance and changes in serial records. Electroencephal Clin Neurophysiol. 1985;62:45- 55. 20. Dustman RE, Snyder EW, Callner DA, Beck EC: Evoked responses as a measure of cerebral dysfunction, in Begleiter H (eds): Evoked Brain Potentials and Behavior. New York, Plenum Press, 1979, pp 321-363. 21. Dyck PJ, Stevens JC, Mulder DW: Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis: morphometry of deep and superficial peroneal nerves. Neurology. 1975;25:781-785. 22. Goff GD, Matsamiya T, Allison T, Goff WR: The scalp topography of human somatosensory and auditory evoked potentials. Electroenceph Clin Neurophysiol. 1977;42:57- 76. 23. Hagbarth KE, Kerr DIB: Central influences on spinal afferent conductions. J Neurophysiol. 1954; 17:295-307. 24. Hughes JT: Pathology of amyotrophic lateral sclerosis, in Rowland LP (eds): Human Motor Neuron Diseuses. New York, Raven Press, 1982, pp 61-71. 25. Iwata M, Hirano A: Current problems in the pathology of amyotrophic lateral sclerosis, in Zimmerman HM (ed): Progress in Neuropathology. New York, Raven Press, 1979, VOI 4, pp 277-298. 26. Lueders H, Lesser R, Hahn J, Dinner DS, Klem G: Cortical somatosensory evoked potentials in response to hand stimulation. J Neurosurg 1983; 58:885- 894. 27. Luthy F, Martin F: Observation de cas de sclerose laterale amyotrophique avec consideration particuliere sur la participation sensitive. Schweiz Med Swchr. 1947;25:694-697. 28. Maccabee PJ, Pinkhasow El, Cracco RQ: Short-latency somatosensory evoked potentials to median nerve stimulation: effect of low frequency filter. Electroenceph Clin Neurophysiol. 1983; 55:34-44. 29. MacNealy MA, Rentz LE: Somatosensory evoked potentials in patients with amyotrophic lateral sclerosis. Am Osteopath Ass. 1981;81:93- 101. 30. Mathenson JK, Harrington HJ, Hallett M: Abnormalities of multimodality evoked potentials in amyotrophic lateral sclerosis. Arch Neurol. 1986;43:338-340. 31. Mauguiere F, Desmedt JE, Courjon J: Asterognosis and dissociated loss of frontal or parietal components of somatosensory evoked potentials in hemispheric lesions: de-
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tailed correlations with clinical signs and CT scanning. Brain. 1983;10627 1 - 3 11. 32. Mulder DW, Bushek W, Spring E, Karnes J, Dyck PJ: Motor neuron disease (ALS): evaluation of detection theshold Neurology (Cleveland). of cutaneous sensation. 1983;33:1625- 1627. 33. Oh SJ, Sunwoo IN, Kim HS, Faught E: Cervical and cortical somatosensory evoked potentials differentiate cervical spondylotic myelopathy from amyotrophic lateral sclerosis (abstract). Neurology. 1985;35(Suppl 1): 13. 34. Papakostopoulos D, Crow HJ: Direct recording of the somatosensory evoked potentials from the cerebral cortex of man and the differences between precentral and postcentral potentials, in Desmedt JE (ed): Clinical Uses of Cerebral, Brainstem avid Spinal Somatosensory Evoked Potentials. Basel, S Karger, 1980, vol 7: Progress in Clinical Neurophysiology, pp 15-26. 35. Radtke RA, Erwin A, Erwin CW: Abnormal sensory evoked potentials in amyotrophic lateral sclerosis. NeurolO S ~ . 1986;36:796-801. 36. Rossini PM, Gigli GL, Marciani MG, Zarola F, Caramia M:
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37.
38.
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Noninvasive evaluation of input-output characteristics of sensorimotor cerebral areas in healthy human. Electroenceph Clin Neurophysiol. 1987;68:88- 100. Shmp JC, Tamas LB, Stolov WC, Wyler AR: Somatosensory evoked potentials after removal of somatosensory cortex in man. Electroenceph Clin Neurophysiol. 1986;65:111117. Wood CC, Spencer DD, Allison T, McCarthy G, Williamson PD, Goff WR: Localization of human sensorimotor cortex during surgery by cortical surface recording of somatosensory evoked potentials. J Neurosurg. 1988;68:99111. Yamada T, Kayamori T, Kimura J, Beck DO: Topography of somatosensory evoked potentials after stimulation of the median nerve. Electroenceph Clin Neurophysiol. 1984;59:2443. Yamada T , Kimura J, Wilkinson T , Kayamori R: Shortand long-latency median somatosensory evoked potentials. Findings in patients with localized neurological lesions. Arch Neurol 1983;40:215- 220.
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55
~~
We examined median somatosensory evoked potentials (SEPs) in 26 patients with sporadic motor neuron disease (MND). SEPs were recorded with multiple scalp derivations, using both the midfront and the earlobe as references for each subject. Central conduction time (CCT) was abnormal in three patients, but only when using the midfront reference. Moreover, an exclusive alteration of the early prerolandic potentials (absent or delayed P20 and/or P22)was noted using the earlobe reference in amyotrophic lateral sclerosis and in progressive bulbar palsy (54% and 50% of patients, respectively) but not in progressive muscular atrophy. These findings correlated with clinical evidence of upper motor neuron signs and with the severity of the disease. In agreement with recent views regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials. Key words: Motor neuron disease amyotrophic lateral sclerosis progressive muscular atrophy cortical somatosensory evoked potentials central conduction time. MUSCLE & NERVE 13:47-55 19%
FAR=FIELDAND CORTICAL SOMATOSENSORY EVOKED POTENTlALS IN MOTOR NEURON DlSEASE GlAMPlETRO ZANETTE, MD, ALBERT0 POLO, MD, MARCELLA GASPERINI, MD, LAURA BERTOLASI, MD, and DOMENICO DE GRANDIS, MD
Motor neuron disease (MND) is widely considered to be a disorder strictly confined to the voluntary motor system with progressive degeneration of the corticospinal tracts and alphamotoneurons. Although some patients with MND experience paresthesias, cramps, and other vague sensations, the observation of sensory deficits is unusual, and objective evaluations of these disturbances have rarely been performed.21932Moreover, investigators disagree about the anatomicopathological involvement of the sensory system in this disease.4325The application of somatosensory evoked potentials (SEPs) in MND has also produced conflicting conclusions: although upper limb SEPs were generally found to be normal in From the Institute of Neurology, University of Verona, Italy Acknowledgment: The authors thank Mr. Anthony Steel for his assistance in preparing the manuscript. This paper was presented in part at the Congress of the International Medical Society of Motor Disturbances, Rome, Italy, June 2-4, 1988. Address reprint requests to Dr. De Grandis at the Institute of Neurology, University of Verona, Italy. Accepted for publication October 21, 1988 CCC 0148-639X/90/01047-09 $04.00 0 1990 John Wiley & Sons, Inc.
SEPs in Motor Neuron Disease
these disorder^,'^'^,^^,^^ some investigators have observed the presence of delayed responses in patients without sensory symptom^.^.^^' 1#13325,30 Recently, however, numerous authors have suggested that some components of SEPs may not originate from activation of generators belonging to the sensory system. In fact, a series of scalp near-field potentials with different polarity and with selective involvement in relation to the site of focal brain lesions have been detected in the parietal and frontal regions. 12.14- 19.31,34,36.3739 Although the nature of the individual waves is not yet fully established, the same investigators suggest the existence of separate generators for frontal and parietal components and, moreover, claim that the early anterior cortical potentials probably represent a sensory input to motor areas. This is an important question which has to be considered especially in a disease where the degeneration of the corticospinal tract may be a prominent feature. For these reasons, the purpose of the present work is not only to verify the presence of alteration of the sensory conduction previously reported but also to detect possible abnormalities of somatosensory cortical potentials in MND. To achieve this aim, we studied SEPs from the me-
MUSCLE & NERVE
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47
dian nerve in 26 patients with MND using both the parietal-to-frontal montage and multiple scalp derivations, comparing the results with those obtained in 20 healthy subjects. PATIENTS AND METHODS
Twenty-six patients (14 males and 12 females) with MND were investigated. The criteria adopted to formulate the diagnosis and for inclusion in the study were the following: (1) family history negative for MND, (2) clinical evidence of progressive and rapid loss of muscle strength with atrophy and fasciculations dating back at least 6 months, (3) electromyographic picture of denervation in muscles of more than one limb tested and normal sensory nerve conduction, (4) patients older than 25 years (range 30-74, mean age 55 years), (5) normal radiographic investigations of the spine. According to the clinical picture, 3 forms of MND were distinguished: amyotrophic lateral sclerosis (ALS, 14 cases) with both upper and lower motor neuron involvement, progressive muscular atrophy (PMA, 6 cases) without evidence of corticospinal tract dysfunction, and progressive bulbar palsy (PBP, 6 cases). Moreover, owing to the peculiar cliniconeurophysiological correlations reported later, the muscular strength of the hands was also considered at the time of the examination using the Medical Research Council scale (scores from 0 to 5). Although pain due to muscular cramps was a frequent sensory symptom (40%), only one patient experienced paresthesias in a focal area of the left leg that remained stable in the course of the illness. The subjects lay supine on a bed in a quiet room and were requested to remain relaxed with closed eyes. The median nerve was stimulated at the wrist with an intensity capable of eliciting a weak muscular twitch of 2.5-3 times above the sensory threshold whenever the intrinsic muscles of the hand were atrophic. The electrical stimulus had a duration of 0.1 msec and a frequency of 5 Hz. The recordings were carried out with silver-silver chloride electrodes placed at Erb’s point (EP), CVII, and P3/P4 postcentral cortical zones 7 cm lateral to Cz and 3 cm behind the Cz-ear line; these active derivations, contralateral to the stimulated nerve, were referred to the Fz electrode (often the EP lead was referred to a noncephalic (NC) site). SEPs were also obtained with central (C3/C4) and frontal (F3/F4) electrodes according to the 10-20 International System. For all scalp leads, includNeurophysiologic Methods.
48
SEPs in Motor Neuron Disease
ing the postrolandic ones, the ipsilateral earlobe was chosen as the reference instead of Fz in order to record the cortical potentials. The impedance of the electrodes was maintained below 5 kR. T h e signals coming from the leads were processed by a four-channel averager using a bandpass of 5-2000 Hz for scalp EEG activity, while the spine and the EP potentials were amplified by a band-width of 20-2000 Hz. Each trial represented the average of 1000 artifact-free responses and was replicated and superimposed to establish the reliability of the different components. The first 50 msec poststimulus were analyzed measuring the peak latency and peak-to-peak amplitude of the main waves. The interpretation of SEPs was based on the values obtained in 20 healthy subjects, with a mean age similar to that of the patient group. RESULTS
The scalp topography of SEPs recorded in normals corresponded to that reported by other investigators. Briefly, using the earlobe reference, the scalp leads showed a farfield positive P14 component followed by a widely represented N18 wave, whose one set was more appreciable in prerolandic regions (Fig. 1). After this wave, it was possible to detect a number of early and long latency responses with different hemiscalp distribution. In the frontal derivation, the N18 peak was followed by positive-negative components defined as P20 and N30. Wave N30 was not recorded in 4 subjects, and in these cases, it was replaced by a negative peak at about 24 msec. In the contralateral parietal scalp, a N20-P25-N33 complex was observed: of these components, the N33 wave was not obtainable in all cases (it was present in 18 out of 20 normals). The contralatera1 central electrode registered a positive stable response defined as P22, with a peak latency somewhere between the frontal P20 and the parietal P25. The time-locked, opposite-polarity P20 and N20 components, recorded respectively in the frontal and parietal regions, did not have the same peak latency in all normals, but more frequently P20 occurred slightly later than N20 (mean latency difference P20-N20 = 0.4 msec, 0.4 SD). As observed by Desmedt and Bourguet,’“ the use of the frontal reference produces a posterior “N20-P20” complex which represents the subtraction of frontal from parietal traces. The early prerolandic and far-field components are thus cancelled by the activity picked up from the frontal reference electrode. Moreover, it may be noted Normal Subjects.
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January 1990
Right stim. EP-NC
T.S.
A
p
EP
p
43 yre
- -
N13
C7-Fz
N33
N20
C minus E
Fz reference
N20-P20
+ l 5 msec
I
I
FIGURE 1. Median nerve SEPs in a normal subject. Note that the anterior P20 (E) is virtually the mirror image of the parietal N20 wave (C). The parietal versus frontal montage shows a negativity resulting from the algebraic summation of early posterior and prerolandic potentials (C minus E, F). This peak, labelled “N20-P20,”has the same latency as the N20 wave.
that the mean latencies of the N20 peak obtained using both the earlobe and the midfront as references had very similar values (19.3 and 19.1 msec, respectively). Based on normality data, SEP abnormalities were defined as follows: 1. Absence of one of the stable components always obtainable in healthy subjects: N13, P14, N20, P20, P22, and P25. Amplitude difference between the hemiscalp responses was not considered owing to the high variability of this parameter. 2. A prolongation of the interpeak latencies EPN13, EP-P14, N13-N20, P14-N20, P14-P20, P14-P22, and P20-N20. 3. A significant difference in central conduction time (CCT) between the two stimulation sides.
SEPs in Motor Neuron Disease
Regarding points 2 and 3, the values were considered abnormal when they exceeded the mean plus 3 SD. Moreover, the values of the intervals EP-N13, EP-P14, N13-N20 (Fz Ref.) and N13N20 (Au Ref.) in normals were compared with those obtained in MND patients using the Student’s t-test (Table 1). The cervical SEPs from the median nerve were normal in all cases examined, and the mean latencies of the EP-N13 and EP-P14 intervals showed no significant differences compared with controls. Using the midfront reference, the N 13-N20 central conduction was clearly abnormal in 3 ALS patients (12%) on one stimulation side and was significantly increased compared with the normal group. This result was not confirmed on measuring the N13-N20 interval ob-
MND Patients.
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49
Table 1. SEP interwave latencies in 20 healthy subjects and in 26 MND patients [mean (SD) tn milliseconds] lnterpeak
Controls
MND patients
EP-N13 EP-PI4 N13-NZ0 (Fz Ref) N13-N20 (Au Ref )
3 7(0 34) 4 8(0 47) 5 5(0 44) 5 6(0 47)
3 6(0 35) 4 9(0 42) 6 l(0 49)* 5 5(0 53)
*P < 0.001.
tained with the earlobe reference: no patients showed abnormal values, and there was no statistical difference versus controls. These discordant data are illustrated in Fig. 2, which shows the traces recorded in one of the three patients with a prolonged N 13-N20 interpeak. Using the earlobe
as reference, the N20 component was earlier than that obtained with the parietal-to-frontal montage, and, in this case, the N13-N20 central conduction was normal. The subtraction of anterior (F3) from posterior (P3) scalp traces yielded an N20 latency and morphology similar to those recorded using the cephalic reference. This algebraic operation, forming a P3-F3 artificial montage, confirmed an increase in the N20 peak. These results, which were also observed in the other t w o patients with abnormal N13-N20 intervals, were never seen in normals, where the N20 wave latency was not significantly modified by the type of reference utilized. It should be stressed that these three patients showed distinctly abnormal anterior cortical potentials mainly formed by a delayed P20 wave ipsilateral to the abnormal N20 obtained with the
Right etim.
A.D.
a" 5 2 y r s
EP
+Pa0
f 24 a sJ
NZO -P 2 0 5 msec
FZ reference I
..
FIGURE 2. Significant prolongation of the N13-N20 interpeak obtained using the midfront reference (F, C minus E) not confirmed by the earlobe reference (C). The frontal electrode records an increased P20 (E), whereas the central one registers a positivity appearing as an anterior spread of the P25 (D) (case 1).
50
SEPs in Motor Neuron Disease
MUSCLE & NERVE
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volvement had a prevalence of normal P20 and P22 potentials. All cases with only lower motor neuron signs (PMA) and with marked reduction of strength showed well-defined normal peak latency of the central and frontal components bilaterally (Fig. 4). Thus, the pathological modifications of the P20 and P22 waves appeared to correlate closely with the clinically detectable involvement of the corticospinal tract and might have an asymmetrical scalp distribution in relation to the extent of the functional impairment of the upper limbs. A doubt persists regarding the numerous cases with abnormal early anterior potentials showing regular CCT. In these subjects, the posterior “N20-P20” complex was never significantly altered. This fact was explained by means of the summation of traces, proving that 1. Absence of the anterior components did not modify the latency of the parietal potentials. 2. The anterior responses, when present, had such a minimal increased latency (no more than 0.9 msec beyond the normal upper limits considering the P20-N20 interpeak) and/ or such a low amplitude as not to affect the posterior components. Another interesting observation was that, whenever the frontal P20 wave was missing, the later anterior N30 was also often strongly altered or absent (Fig. 3). Nevertheless, this finding was not quantified since a simultaneous bilateral stimula-
Table 2. Early anterior SEPs in MND patients MND
Total patients’ sides
Percent abnormal P20 and/or P22
ALS PBP PMA
27 12 12
54% 50% 0 Yo
midfront reference. On the same hemiscalp, the P22 wave was absent in two cases and delayed in one. Thus, in three of our patients the use of the cephalic reference produced a posterior “P20N20” complex pathologically modified by abnormal anterior components. The early central and frontal potentials, together or singly, were delayed or strongly altered so as to be undetectable also in subjects with normal CCT (Fig. 3). These abnormalities had a high incidence, but only the patients with ALS and PBP were affected (54 and 50%, respectively; Table 2). Moreover, the abnormal SEPs were correlated with clinical evidence of corticospinal tract involvement and with the degree of functional impairment of the hands (Table 3). It was observed that abnormal P20 and/or P22 were a very frequent finding in ALS and PBP patients with upper motor neuron signs (90% and 83%, respectively) when stimulating the sides with high muscular weakness (0-3). On the other hand, the patients belonging to the same group but with slight unilateral o r bilateral functional in-
B.L.
R i g h t stim.
Left stim.
2L/--=
d 33yrs
EP
EP-NC
N20 Earlobe reference
@ ..
I
L-
.
J
pi4
-If +
I”..
FIGURE 3. An asymmetric involvement of the prerolandic waves can be seen: on left stimulation only the P20 is observed, whereas on right stimulation no anterior peaks are detected (case 10).
SEPs in Motor Neuron Disease
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51
Table 3. Clinical features and SEP findings in 26 MND patients. SEP findings
SEP findings MND
Patient and sex
ALS
1M 2M 3M
4F 5F 6M
PBP
PMA
7M 8F 9F 10 M 11 M 12 M 13 M 14 F 15 F 16 F 17 M 18 F 19 M 20 M 21 F 22 M 23 F 24 F 25 F 26 M
UMN signs
+ + + + + + + + + + + + + + + + + +
-
Hand strength 0-3
P20
P22
1* 1 1 1
D D A D
A
2
Dt
A
1
A D A
A
I
D A
1 1 2 2 2
1 1 1 2
A
D
1 1
2
1 1 1 2 1
A
A
D
A D At A
P22
D
Dt A
D A A At
D D/A
A
1 1 1
A
A
1 2
A
2 2 2
-
2
-
2
-
2 ~~
Note UMN = upper motor neuron, A and D = absent and delayed response, ticity, Babinski sign, absence of abdominal reflexes * A score of 1 couid not be obtained ?Bilaterally abnormal
tion of the median n e r ~ e , ~ ' , permitting ~' evaluation of the long latency SEPs, was not performed. DISCUSSION
The determination of SEPs is commonly regarded as a valid electrophysiological test for detecting even a subclinical involvement of the sensory pathways. Recently, some investigators have observed the presence of delayed evoked responses in tients without sensory disturbances. 2,5,11,13,3t& Considering the current views regarding the sources of these potentials, nearly all authors have postulated the presence of subclinical involvement of the central sensory system in MND, probably localized within the dorsal columns and the lemniscal pathways. In supporting this opinion, electrophysiological data have been correlated with occasional pathological evidence of minor neuronal degeneration found outside the motor system, particularly in the central sensory tracts and n~clei.~~"." An alternative explanation has been formulated on the basis of the well-known feed-
SEPs in Motor Neuron Disease
P20
2
~~~~~
52
Hand strength 4-5
+
~
~
= presence of two or more of the following signs hypereflexia spas-
back-type modulation exerted by the motor pathways on the afferent stimuli, especially at dorsal horn l e ~ e I . ~ It ' *has ~ ~ been suggested that a lack of such action, caused by lesions confined to the pyramidal tract, might produce delayed evoked somatosensory responses.' l~~~ As regards the estimation of CCT from the median nerve, a percentage of abnormalities ranging from 12 to 23% has emerged on pooling together the findings of all authors. Our data also showed an increase in CCT in a similar number of cases (12%) using the upper limb SEPs. Nevertheless, we think that these changes found in MND patients may be related to the peculiar nature and alterations of the cortical responses. In fact, we observed that the use of parietal-to-frontal montage gave rise to a contralateral delayed N20 peak due to the algebraic summation of preserved postrolandic response and abnormal frontal potentials in 3 out of 26 patients. It is likely, therefore, that the prolonged CCT from the median nerve occasionally noted in MND does not represent an
MUSCLE & NERVE
January 1990
Right stim.
V.A.
9 44yrs
EP EP-NC
N20
@ .
Earlobe
P22
\
reference
FIGURE 4. Patient with PMA showing normal subcortical and cortical SEPs (case 23).
involvement of central afferent pathways but depends more probably on the type of methodological determination of SEPs.15 Moreover, delayed or absent P20 and P22 components were noted not only in patients with abnormal CCT but also in numerous other cases. Considering that in normals the early cortical responses are stable and constantly reproducible, their alteration is a reliable pathological indicator. Such abnormalities were found only in patients with ALS and PBP and appeared to correlate closely with the presence of pyramidal signs and with the severity of the functional muscular impairment of the hands. Interestingly, similar results were reported by Bosch et al.5 in 30 patients with MND using a central scalp derivation. They observed a higher percentage of abnormal median nerve SEPs in patients with ALS and PBP than in patients with PMA, mainly consisting of delayed or absent N32 andlor N60 late components. We also noted marked abnormalities of the frontal N30 component, but only in association with an absent or strongly altered P20 peak. Therefore, it is possible that the alterations of the long-latency SEPs described may be explained in terms of an involvement of the earlier cortical anterior peaks.
SEPs in Motor Neuron Disease
Recently, numerous clinical, topographic, and experimental studies have been performed to detect and localize the generators of the early cortical components obtained by upper limb nerve stimulation, particularly the anterior ones. On the basis of the results obtained, almost all investigators have suggested that the P22 potential probably represents the depolarization of the primary motor area evoked by afferent inputs via direct thalaniocortical projections, whereas discordant opinions persist regarding the source of P20. Some investigators suggest that the time-locked P20 and N 2 0 Components more probably represent a tangential equivalent dipole qenerated in the postrolandic parietal cortex. 1.691d322,2b Others claim that P20 is not the mirror image of the N20 wave but probably represents the activity of distinct cortical populations of neurons located in the frontal areas,9s19228,34q367,79 possibly in the premotor cortex.36 T h e postulate whereby not only the primary sensory area but also the prerolandic cortex are probably activated by afferent inputs agrees with our neurophysiological observations in relation to the pathological studies carried out in Charcot's disease. A massive loss and degeneration of neurons in the motor cortex is
MUSCLE & NERVE
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53
constantly described, and, in most instances, lesions in the frontal gyri have been In view of the fact that the alteration of the anterior responses appears to be directly correlated not only with the presence of pyramidal tract involvement but also with the severity of the disease, it is likely that an intense neuronal loss in the motor areas provides evidence of an appreciable modification of the prerolandic cortical ~
responses. Furthermore, in healthy subjects the P20 wave occurred slightly later than the N20, and some patients showed an involvement of individual anterior peaks combined with normal N20 components. This evidence is at variance with the “equivalent dipole” theory but supports the idea that specific and partially independent cortical generators may give rise to early scalp responses.
~~~~
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times of parietal and frontal components. Electroenceph Clin Neurophysiol. 1980:50:404- 425. 17. Desmedt JE, Cheron G: Non-cephalic reference recording of early somatosensory potentials to finger stimulation in adult or aging man: differentiations of widespread N18 and contralateral N20 from the prerolandic P22 and N30 components. Electroenceph Clin Neurophysiol. 1981;52:553570. 18. Desmedt JE, Nguyen TH, Bourguet M: Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses. Electroenceph Clin Neurophysiol. 1987;68:1- 19. 19. De Weerd AW, Looijenga A, Veldhuizen RJ, Van Hufflen AC: Somatosensory evoked potentials in minor cerebral ischaemia: diagnostic significance and changes in serial records. Electroencephal Clin Neurophysiol. 1985;62:45- 55. 20. Dustman RE, Snyder EW, Callner DA, Beck EC: Evoked responses as a measure of cerebral dysfunction, in Begleiter H (eds): Evoked Brain Potentials and Behavior. New York, Plenum Press, 1979, pp 321-363. 21. Dyck PJ, Stevens JC, Mulder DW: Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis: morphometry of deep and superficial peroneal nerves. Neurology. 1975;25:781-785. 22. Goff GD, Matsamiya T, Allison T, Goff WR: The scalp topography of human somatosensory and auditory evoked potentials. Electroenceph Clin Neurophysiol. 1977;42:57- 76. 23. Hagbarth KE, Kerr DIB: Central influences on spinal afferent conductions. J Neurophysiol. 1954; 17:295-307. 24. Hughes JT: Pathology of amyotrophic lateral sclerosis, in Rowland LP (eds): Human Motor Neuron Diseuses. New York, Raven Press, 1982, pp 61-71. 25. Iwata M, Hirano A: Current problems in the pathology of amyotrophic lateral sclerosis, in Zimmerman HM (ed): Progress in Neuropathology. New York, Raven Press, 1979, VOI 4, pp 277-298. 26. Lueders H, Lesser R, Hahn J, Dinner DS, Klem G: Cortical somatosensory evoked potentials in response to hand stimulation. J Neurosurg 1983; 58:885- 894. 27. Luthy F, Martin F: Observation de cas de sclerose laterale amyotrophique avec consideration particuliere sur la participation sensitive. Schweiz Med Swchr. 1947;25:694-697. 28. Maccabee PJ, Pinkhasow El, Cracco RQ: Short-latency somatosensory evoked potentials to median nerve stimulation: effect of low frequency filter. Electroenceph Clin Neurophysiol. 1983; 55:34-44. 29. MacNealy MA, Rentz LE: Somatosensory evoked potentials in patients with amyotrophic lateral sclerosis. Am Osteopath Ass. 1981;81:93- 101. 30. Mathenson JK, Harrington HJ, Hallett M: Abnormalities of multimodality evoked potentials in amyotrophic lateral sclerosis. Arch Neurol. 1986;43:338-340. 31. Mauguiere F, Desmedt JE, Courjon J: Asterognosis and dissociated loss of frontal or parietal components of somatosensory evoked potentials in hemispheric lesions: de-
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tailed correlations with clinical signs and CT scanning. Brain. 1983;10627 1 - 3 11. 32. Mulder DW, Bushek W, Spring E, Karnes J, Dyck PJ: Motor neuron disease (ALS): evaluation of detection theshold Neurology (Cleveland). of cutaneous sensation. 1983;33:1625- 1627. 33. Oh SJ, Sunwoo IN, Kim HS, Faught E: Cervical and cortical somatosensory evoked potentials differentiate cervical spondylotic myelopathy from amyotrophic lateral sclerosis (abstract). Neurology. 1985;35(Suppl 1): 13. 34. Papakostopoulos D, Crow HJ: Direct recording of the somatosensory evoked potentials from the cerebral cortex of man and the differences between precentral and postcentral potentials, in Desmedt JE (ed): Clinical Uses of Cerebral, Brainstem avid Spinal Somatosensory Evoked Potentials. Basel, S Karger, 1980, vol 7: Progress in Clinical Neurophysiology, pp 15-26. 35. Radtke RA, Erwin A, Erwin CW: Abnormal sensory evoked potentials in amyotrophic lateral sclerosis. NeurolO S ~ . 1986;36:796-801. 36. Rossini PM, Gigli GL, Marciani MG, Zarola F, Caramia M:
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