Electrical Stimulation of the Human Descending Motor Tracts at Several Levels

Transcription

1 Elecrical Simulaion of he Human Descending Moor racs a Several Levels Yoshlkazu Ugawa, Kieko Genba-Shimizu and Ichiro Kanazawa ABSRAC: he descending moor racs were acivaed using a high volage elecrical simulaion echnique a four levels: he moor corex, brainsem (around he pyramidal decussaion), and he firs and sixh horacic verebral levels (l, 6). Elecromyographic aciviy was recorded from he ibialis anerior or exensor digiorum brevis muscles. Consisen moor acion poenials could be evoked in all normal subjecs. he conducion velociy of he descending racs was esimaed o be 62 o 79 m/s. he sum of synapic delay and uilizaion ime a he mooneurons (spinal delay ime) was esimaed o be 0.5 ± 0.3 ms indicaing a mono- or oligosynapic connecion. In paiens wih diffusely affeced descending racs, he echnique showed slowed conducion along he descending racs and prolonged spinal delay ime which may include he ime required for emporal summaion of exciaory possynapic poenials as well as synapic delay and uilizaion ime. In paiens wih a localized lesion, localized conducion delay was found a he appropriae segmen. RESUME: Simulaion elecrique a plusieurs niveaux des faisceaux moeurs descendans chez Phumain. ous avons acive les faisceaux moeurs descendans, par une echnique de simulaion elecrique a hau volage, a quare niveaux: au niveau du corex moeur e du ronc cerebral (auour de la decussaion pyramidale), e au niveau de la premiere e de la sixieme verebre horacique (Dl, D6). ous avons enregisre l'acivie elecromyographique du jambier anerieur ou du muscle pedieux. Chez ous les sujes normaux, des poeniels moeurs d'acion pouvaien ere evoques de facon consane. La viesse de conducion des faisceaux descendans a ee esimee comme ean de 62 a 79 m/s. La somme du delai synapique e du emps d'uilisaion au niveau des mooneurones (delai spinal) a ee esimee a 0.5 ± 0.3 ms, indiquan qu'il s'agi d'une connexion mono ou oligosynapique. Chez les paiens qui on une pahologie diffuse des faisceaux descendans, cee echnique a monre une conducion ralenie au niveau des faisceaux descendans e un delai spinal prolonge qui peu inclure le emps requis pour la sommaion emporelle des poeniels pos-synapiques exciaeurs ainsi que le delai synapique e le emps d'uilisaion. Chez les paiens qui on des lesions localisees, nous avons observe un delai de conducion localise au niveau du segmen approprie. Can. J. eurol. Sci. 1995; 22: I is now possible o sudy human cenral moor pahways using elecrical and magneic simulaion echniques. 1 Magneic simulaion is virually painless and is now widely used. However, presen magneic simulaors are only capable of exciing he cerebral moor corex in he skull and he spinal nerve roos as hey exi he inerverebral foramen. As ye hey are unable o acivae direcly srucures wihin he spinal cord iself. 12 High-volage percuaneous elecrical simulaion is less comforable for he subjec, bu in conras can be used o excie he moor pahways a almos all levels from he corex o he spinal cord. 35 In he presen paper, we show how his can be used o deec lesions of descending moor racs in he spinal cord. and poserior columnar signs which had begun in childhood. o srucural abnormaliies were presen in he magneic resonance imaging (MRI) scan of her brain and spinal cord. he diagnosis of he paien wih adrenoleukodysrophy (Paien 2) was based on he elevaion of long chain fay acids in he serum. he diagnosis for four paiens (Paiens 3-6) wih a localized srucural lesion compressing he spinal cord was confirmed by MRI and myelography. A 25-yr-old man (Paien 7) had spasic paraparesis and an aonic bladder. His MRI scan revealed one plaque coninuing from he sevenh cervical o he hird oracic verebral level, which disappeared afer predonisolone reamen. In anoher paien wih muliple sclerosis (Paien 8), he MRI scan SUBJECS We sudied 14 paiens (25-60 yrs of age; 10 males and 4 females: cm all) who had abnormaliies of he descending moor racs in he spinal cord. A 32-yr-old woman wih Friedreich's aaxia (Paien 1) showed bilaeral pyramidal From he Deparmen of eurology, Insiue for Brain Research, School of Medicine, Universiy of okyo, okyo. RECEIVED DECEMBER 3, ACCEPED I FIAL FORM JULY 25, Reprin requess o: Dr. Y. Ugawa, Deparmen of eurology, Insiue for Brain Research, School of Medicine, Universiy of okyo, 7-3-1, Hongo, Bunkyo-ku, okyo 113,Japan. 36

2 LE JOURAL CAADIE DES SCIECES EUROLOGIQUES showed muliple plaques in he cerebral whie maer, brainsem, and spinal cord. Six paiens had idiopahic spasic paraparesis wih a duraion of more han five years. Laboraory ess showed no viamin deficiencies, abnormaliy of long chain fay acids, or posiive ani-hlv-1 anibody iers in any of hem and he MRI showed no srucural abnormaliies. o obain normal values, we sudied eigh healhy voluneers (27-40 yrs of age; 6 males and 2 females; cm all). All he subjecs gave heir informed consen. he procedure was approved by he Ehics Commiee of he Universiy of okyo. MEHODS In all subjecs, surface elecromyographic (EMG) aciviies were recorded from he ibialis anerior (A) and exensor digiorum brevis (EDB) muscles on he righ side. In some subjecs, responses also were recorded on he lef. EMG signals were amplified wih filers se a 80 Hz and 3 khz. he descending moor racs or he moor roos were simulaed a several levels using a high volage elecrical simulaor as described elsewhere. 6 We used special elecrodes for simulaion in mos experimens. hey had a larger conac area (7.1 cm 2 ) han convenional elecrodes (2.0 cm 2 ) in order o reduce pain caused by high curren densiy in he skin. During he examinaion, an elecrocardiogram was aken and blood pressure was moniored o check he effec of simulaion on he hear. o arrhyhmia occurred afer simulaion. Blood pressure and hear rae increased afer simulaion, bu reurned o he original values wihin 20 seconds. o side effecs were noed in any of he individuals. All he paricipans regarded moor roo simulaion o be no more uncomforable han peripheral nerve simulaion, and regarded brainsem simulaion as being he mos uncomforable. All of he normal conrols had experienced brainsem simulaion wih he convenional elecrodes, and repored ha simulaion wih new elecrodes was less uncomforable han simulaion wih he convenional elecrodes. All subjecs oleraed he procedure. For corical simulaion, he anode was placed a he verex and he cahode 5 cm anerior o he anode. For acivaion of he descending racs a he level of pyramidal decussaion 34 he simulaing elecrodes were placed on he incisura masoidea on boh sides. he descending racs were simulaed a wo levels wihin he spinal cord: upper horacic level, wih he cahode on he firs horacic spinous process (Sp[l]), and he anode 5 cm above i, and mid-horacic level, wih he cahode on he sixh horacic spinous process (Sp[6]), and he anode 5 cm above i. he moor roos were acivaed a he level of he conus medullaris 7 wih he cahode placed a he firs lumbar spinous process (Sp[Ll]) and he anode 5 cm above i. hey were acivaed a he poin of exi from he spinal canal using he cahode placed a he fourh lumbar spinous process (Sp[L4]) for he A muscle and a he firs sacral spinous process (Sp[Sl]) for he EDB muscle, wih he anode being placed 5 cm above he cahode. he muscles sudied were acivaed during simulaion of he moor corex or descending racs, bu relaxed during acivaion of he moor roos. oal peripheral conducion ime in each of he normal subjecs and in some paiens was esimaed for each muscle using he convenional F-wave mehod. oal peripheral laency was calculaed from he formula (M+F-l)/2 (M and F: laency of M and F-waves). 8 he ime required for he nerve impulses o be conduced from he moor corex down o he hree disal acivaion sies in he brainsem and spinal cord was calculaed from he difference in laency beween corical simulaion and he simulaion a he oher sies. In order o esimae conducion velociy of he simulaed descending moor racs, we used average lenghs of brain and spinal cord in posmorem specimens, 910 because here is no reliable way o measure he lenghs in inac subjecs. Conducion ime along he moor roos in he cauda equina also was esimaed from he laency difference beween simulaion over Sp[Ll] and Sp[L4 or SI]. he following five conducion imes were calculaed from he difference in laency beween wo sies: corico-brainsem conducion ime (CX-BS C), brainsem o firs horacic spinous process conducion ime (BS-Sp[l] C), firs o sixh horacic spinous process conducion ime (Sp[l]-Sp[6] C), sixh horacic o firs lumbar spinous process conducion ime (Sp[6]-Sp[Ll] C), and firs lumbar o fourh lumbar (or firs sacral) spinous process conducion ime (Sp[Ll]-Sp[L4 or SI] C). he firs hree indicae conducion imes along he descending racs, and Sp[Ll]-Sp[L4 or SI] C indicaes he conducion ime along he moor roos in he cauda equina. Sp[6]-Sp[Ll] C may include he conducion imes along he descending racs and along he moor roos in he spinal canal, as well as he uilizaion ime and synapic delay a he mooneurons, and he ime required for emporal summaion of EPSPs of he descending moor racs in some paiens. he conducion imes in paiens were considered o be prolonged if hey exceeded he upper limi of he normal range (mean SD). RESULS ormal subjecs Consisen moor responses were obained from all he normal subjecs. he hresholds for muscle acivaion ranged from 200 o 400 V. Represenaive responses o simulaion a six levels in he EDB and A muscles of a single subjec are shown in Figure 1. In he EDB muscle (Figure 1A), he shapes of he EMG responses o brainsem and spinal cord simulaion were simple and biphasic, and very similar o he shapes of he responses elicied by acivaion of he moor roos. In conras, he response o moor corical simulaion was polyphasic and of longer duraion. Very similar resuls were found for he A muscle (Figure IB). he conducion imes (CX-BS C, BS- Sp[l] C, Sp[l]-Sp[6] C, Sp[6]-SpLl] C) were no differen beween he wo muscles. he Sp[Ll]-Sp[Sl] C of he EDB was longer han he Sp[Ll]Sp[L4] C of he A. he average values of all he conducion imes of normal subjecs are given in able 1. he Sp[Ll]-Sp[Sl] C of he EDB was significanly (p < 0.01) longer han he Sp[Ll]-Sp[L4] C of he A. here were no significan differences (p > 0.1) beween he EDB and A muscles for he oher conducion imes. In every normal subjec, we esimaed he conducion velociy of he simulaed descending moor racs and moor roos by linear regression analysis beween he A conducion imes and he lenghs of he descending moor racs (Figure 2). Wih bipolar simulaion he elecrical curren densiy is concenraed beneah he elecrodes. he ouward curren is highes beneah he cahode and acivaion of nerve axons usually occurs a his poin. On he assumpion ha acivaion ook place beneah he cahode during spinal and moor roo simulaion, we esimaed he disance beween he wo acivaion sies from he average lengh of posmorem specimens beneah he cahode. Sp[l] and Sp[6], respecively, are assumed o be he 3 and 8 spinal Volume 22, o. 1 February

3 HE CAADIA JOURAL OF EUROLOGICAL SCIECES Figure 1: Responses recorded from he exensor digiorum brevis (EDB) (A) and ibialis anerior (A) muscles (B) of a normal subjec. he shapes of he moor acion poenials elicied by brainsem (BS) and spinal cord simulaion (Sp[I] and Sp[6]) are very similar o hose of he responses evoked by acivaion of he moor roos. In conras, corical simulaion provoked polyphasic responses of longer duraion. he differences in laency beween wo adjacen simulaion sies are he same for he wo muscles, excep for he conducion ime along he moor roos, which is longer for EDB. CX: corical simulaion BS: Brainsem simulaion (Ugawa el al. [3]) Sp[l]: simulaion a he level of he firs horacic spinous process Sp[6]: simulaion a he level of he sixh horacic spinous process Sp[Ll]: simulaion a he level of he firs lumbar spinous process Sp[L4]: simulaion a he level of he fourh lumbar spinous process Sp[Sl]: simulaion a he level of he firs sacral spinous process. able 1. ormaive daa on conducion imes (ms) Muscle CX-BS BS-Sp(l) Sp(l)-Sp(6) 1.4 ± ±0.2 Sp(6)-Sp(Ll) 3.9 ± ±0.6 Sp(Ll)-Sp(L4orSl) 2.0 ± ±0.4 A 1.6 ± ±0.3 EDB he mean + sandard deviaion is given for he resuls of eigh A: ibialis anerior, EDB: exensor digiorum brevis normal subjecs. (mean + SD) 38

4 LE JOURAL CAADIE DES SCIECES EUROLOGIQUES cord levels." he laencies from he corex were calculaed by subracing he laency of he response elicied by simulaion over he poin of ineres from he corical laency. he laency from he corex o he L4 spinal cord level was obained by subracing (M+F-l)/2 from he corical laency. he graph was drawn as he laency from he moor corex, shown on he abscissa, and he lengh from he L4-L5 foramen on he ordinae (Figure 2). From he slope of he regression line (r = ), we esimaed he conducion velociy of he descending moor racs o be 62 o 79 m/s (mean ± SD: m/s). ha of he moor roos was 31 o 50 m/s (mean + SD: m/s). he ime difference beween wo regression lines a he spinal segmen (L4) was calculaed in all normal subjecs. I ranged in differen subjecs beween 0.2 and 0.9 ms (mean + SD: ). his value approximaes ime difference beween arrival of he firs descending volley and acivaion of he spinal mooneurons. In his paper we define his value as "spinal delay ime", which mus include ime required for emporal summaion of descending volleys, synapic delay, and uilizaion ime. In normal subjecs' acive muscles, however, i does no include he ime for emporal summaion because he firs descending volley elicis EMG responses. he presen resuls hus suggesed ha he sum of synapic delay and uilizaion ime a spinal mooneurons was ms in normals. Similar resuls were obained for he EDB muscle. Paiens Responses recorded from he righ EDB muscle of a 35-yearold woman wih Friedreich aaxia (Paien 1) are shown in Figure 3. he EMG aciviies elicied by moor roo simulaion had normal shapes, and he Sp[Ll]-Sp[Sl] C was wihin he normal range. he responses evoked by brainsem or spinal cord simulaion, however, were small and polyphasic, as compared o he simple, biphasic responses of he normal subjecs. he laency differences beween he responses o simulaion a wo sies in he descending racs were longer han he normal values, indicaive of slow conducion in he cenral moor racs. he relaionship beween he conducion imes of he EDB muscle in his paien and he lengh of he descending racs is shown in Figure 4. Linear regression analysis showed ha conducion ime along he cenral moor pahways was highly correlaed wih he lengh of he descending racs (r = 0.98), indicaing ha conducion in hese racs is similarly affeced a all levels. he esimaed conducion velociy of he descending racs was abnormally slow (28 m/s). Conducion in he moor roos (conducion velociy: 38 m/s) was wihin he normal range. he spinal delay ime a he SI mooneurons was esimaed o be 3.7 ms. Responses from he EDB muscle of a paien wih ossificaion of he yellow ligamen (OYL) a he fourh horacic (4) verebral level (Paien 4) are shown in Figure 5. o brainsem simulaion was done on his paien because he lesion was suspeced o be below he l verebral level and he CX-Sp[l] C was wihin he normal range. Only he Sp[l]-Sp[6] C was abnormally prolonged (6.5 ms). his suggess ha conducion in he descending moor racs was delayed somewhere beween he l and 6 verebral levels. We presume ha compression of he spinal cord by OYL a he 4 verebral level was he cause of he localized conducion delay in his paien. Resuls for he 14 paiens are given in able 2. All he conducion imes along he descending racs were prolonged in he Figure 2: Relaionship beween he conducion imes o he A muscles and he lenghs of he descending racs. Resuls of all normal subjecs are superimposed. Cenral moor conducion is shown in he upper figure, and peripheral moor conducion in he lower. Doed line indicaes he esimaed LA spinal cord level in boh figures. he difference beween corical laency and he laency of he response recorded a each simulaion sie is ploed agains he lenghs of he descending racs esimaed from posmorem specimens. 910 he values on he abscissa a LA (principal spinal cord level innervaing A) were obained by subracing (M+F-l)/2 from he corical laency. he mean laency is highly correlaed wih he lenghs of he descending racs (r = ). From he slope of he regression lines, conducion velociy was esimaed o be 62 o 79 (68 ± 5) m/s for cenral moor conducion, and 31 o 50 (40 ± 7) m/s for peripheral moor conducion (moor roos). he ime differences beween he wo lines a he LA spinal cord level (spinal delay ime) were 0.2 o 0.9 ms (0.5 ± 0.3). Abbreviaions are he same as in Figure I. wo paiens wih diffusely affeced descending racs (Paiens 1, 2). Of he five paiens wih one localized lesion (Paiens 3-7), cenral moor conducion was delayed a a level consisen wih a lesion in four of hem (Paiens 3, 4, 5 and 7). In Paien Volume 22, o. 1 February

5 HE CAADIA JOURAL OF EUROLOGICAL SCIECES CX -v^v^vi BS ~s^-~i 47.3 Mil Sp(0 -v^j J 40.V Sp(s) isr-^xxm Sp(L,) 1HM f^^f^^ Figure 4: Regression lines for he EDB muscle responses of he paien in Figure 3 (Paien I). he graph is drawn in he same way as Figure 2. Cenral and peripheral moor conducion are ploed in he same figure. Circles represen conducion in he descending moor racs and dos represen ha in he moor roos. Laency is highly correlaed wih he lengh of he descending moor racs. he respecive esimaed conducion velociies for cenral and peripheral moor conducion are 28 m/s and 38 m/s. Abbreviaions are he same as in Figure I. SI: he firs sacral spinal cord level. Sp(S,) cenral moor conducion was diffusely affeced in four; alhough i was normal in he oher wo, he hreshold for acivaing he descending racs (700 o 800 V) was abnormally high. DISCUSSIO 20 ms Figure 3: Responses recorded from he EDB muscle of a paien wih Friedreich aaxia (Paien I). Moor acion poenials produced by acivaion of he descending racs are small, of long duraion, and polyphasic. All he conducion imes along he descending racs are prolonged alhough Sp[LI]-Sp[SI] C is wihin he normal range. Abbreviaions are he same as in Figure 1. 7, he MRI showed ha here was a plaque in he region of he coricospinal rac, which coninued from he C7 o 3 verebral level. he paien wih spinal arachnoid cys a he 3 verebral level (Paien 6), had delayed Sp[6]-Sp[Ll] C in addiion o prolonged Sp[l]-Sp[6] C. Prolongaion of he Sp[6]- Sp[Ll] C in his paien may be due o axonal degeneraion of he descending rac below he level of compression. One paien wih muliple sclerosis (Paien 8) showed no response on boh sides when he descending rac was acivaed. Of he six paiens wih idiopahic spasic paraparesis (Paiens 9-14), We used high volage elecrical simulaion o acivae direcly long racs wihin he spinal cord and produce exciaion of lumbar mooneurones a shor laency. Many possible racs may be acivaed by his echnique including coricospinal, reiculospinal, vesibulospinal, propriospinal sysems. Indeed, here may even be anidromic aciviy in dorsal column fibers which could acivae mooneurones via local reflex pahways in he lumbar spinal segmens. I is no clear which, if any, of hese sysems is he mos imporan in producing he resuls observed here. However, since neiher A nor EDB muscles have prominen monosynapic reflexes afer peripheral nerve simulaion, we hink ha he conribuion from anidromic dorsal column aciviy is likely o be small. We shall herefore refer o he responses as being due o exciaion of descending moor pahways. A he presen ime, hese srucures can no be acivaed by he more widely used magneic simulaors. 1-2 Wih his mehod we esimaed he conducion velociy of he descending moor racs o be 68 ± 5 m/s. his velociy is only approximae because i is based on average lenghs of he pahways in posmorem specimens and on he assumpion ha acivaion occurs beneah he simulaing cahode. In addiion, he value refers only o he fases conducing fibers wihin hose 40

6 LE JOURAL CAADIE DES SCIECES EUROLOGIQUES able 2. Conducion imes for he various diseases. Paien Diagnosis (level) Friedreich's aaxia Adrenoleukodysrophy Cervical varix (CI-C2) OYL (4) Arachnoid cys (4) Arachnoid cys (3) Muliple sclerosis (C7-3) Muliple sclerosis Spasic paraparesis Spasic paraparesis Spasic paraparesis Spasic paraparesis Spasic paraparesis Spasic paraparesis CX BS R BS Sp(l) R OYL: Ossificaion of he yellow ligamen, : normal, R: no response, : prolonged Sp(l)-Sp(6) R Sp(6) Sp(Ll) R Sp(Ll) Sp pahways and may no be a represenaive figure for he majoriy of racs involved. everheless, we could show significan slowing of conducion in he descending moor racs of paiens wih diffuse involvemen (Paiens 1, his slow conducion in paiens can be accouned for by he following wo possibiliies: (i) he maximum conducion velociy of he descending moor racs hrough which he responses normally are produced is decreased, or (ii) in paiens he simulus acivaes differen, slower conducing racs han in conrols. Simulaion of paiens wih a localized lesion showed localized conducion delay a comparable segmens, or delay a all levels caudal o he damage. Conducion delay caudal o he lesion may be caused by Wallerian degeneraion of he descending rac which is secondary o he primary involvemen. he CX Sp(,) Sp(e) Sp(U) Sp(S0-1 ^ EDB L wl^^^^ =^ ^1] 22.W 10ms/div 1 mv/div Figure 5: Moor evoked poenials from he EDB of a paien wih localized spinal cord compression caused by an ossified yellow ligamen a he fourh horacic verebral level (Paien 4). Responses were elicied by simulaion a all he sies. Only he Sp[l]- Sp[6] C is prolonged. Abbreviaions are he same as in Figure 1. echnique repored here provides a means of esimaing he spinal level of a lesion. We have calculaed he spinal delay ime from he ime difference beween wo regression lines a he spinal segmen. his value includes synapic delay and uilizaion ime in acive muscles of normal subjecs. Average spinal delay ime in normal subjecs was ms (mean + SD). Assuming ha uilizaion ime is some 0.2 ms, synapic delay is esimaed o be a mos 0.9 ms (p < 0.05). his suggess ha he descending moor racs simulaed wih his mehod have a mono- or oligosynapic connecion o mooneurons. Spinal delay ime was abnormally prolonged in some paiens. his prolongaion may resul from eiher: (i) emporal summaion of pahologically small and dispersed exciaory pos synapic poenials (EPSPs) or (ii) involvemen of polysynapic pahways no normally used in conrol subjecs. MRI scans are now a powerful ool for deecing inrinsic spinal cord lesions in clinical pracice. Our sudy showed ha our echnique revealed lesions in he spinal cord which could no be deeced by MRI scan (Paiens 1, 2, 11-14). Showing such abnormaliies in he spinal cord is one of he values of his echnique. his mehod will no be widely used because of pain induced by elecrical simulaion. However, i could be useful in a limied number of cases when funcional localizaion of a spinal cord lesion is criical for reamen or when he MRI scan shows no lesion in he spinal descending moor racs even hough clinical signs srongly sugges a spinal cord lesion. Large simulaing elecrodes mus be used in such cases because, as we have noed, hey reduce he induced pain. ACKOWLEDGEMES he auhors are very graeful o Dr. J.C. Rohwell (MRC human movemen & balance uni, Queen Square, London) for his kind revision of his aricle and for his helpful advice. REFERECES 1. Murray ME he clinical usefulness of magneic corical simulaion. Elecroencephalogr Clin europhysiol 1992; 85: Volume 22, o. I February

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