Amyotrophic cervical myelopathy in adolescence

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1 565rournl ofneurology, Neurosurgery, nd Psychitry 1995;58:56-64 Deprtment of Physiology, chool of Medicine, Chib University, Chib, Jpn Tom Deprtment of Medicine, Neurology, Ymnshi Medicl College, Ymnshi, Jpn Z hiozw Correspondence to: Dr Tom, Deprtment of Physiology, chool of Medicine, Chib University, 1-8-1, Inohn, Chuo-Ku, Chib, 26, Jpn. Received 8 October 1993 nd in revised form 24 June Accepted 6 July 1994 Amyotrophic cervicl myelopthy in dolescence hinobu Tom, Zenji hiozw Abstrct The clinicl nd rdiologicl fetures in seven ptients who hd symmetric musculr trophy of the hnd nd forerm when young re reported nd new hypothesis for its etiology is proposed. Investigtion of body growth curves ( surrogte for velocity of rm growth) showed close reltion between () the ge when the body height incresed most rpidly nd the onset ge of this disorder, nd (b) the ge when the rpid body growth period ended nd the ge when symptom progression cesed. Cervicl rdiologicl evidence is provided showing symmetric nterior cord trophy, disppernce of slckness of dorsl roots in neck extension, nd nterior nd lterl displcement of the lower cervicl cord ginst the posterior spects of the vertebrl bodies during neck flexion. These results suggest tht disproportionte shortening of the dorsl roots is further ccentuted during the juvenile growth spurt, which determines the onset nd self limited course of the condition, nd tht repeted neck flexion cuses microtrum nd reltive ischemi of nterior horn cells, which finlly results in trophy of the muscles innervted by motoneurons with long xons. Predisposing ntomicl fctors re stright neck due to lck of physiologicl cervicl lordosis nd the presence offoreshortened dorsl roots. (3 Neurol Neurosurg Psychitry 1995;58:56-64) Keywords: myotrophic cervicl myelopthy; dolescence Hirym et l nd Tkgi nd Okbe,' were the first to report, independently in 1959, juvenile cses of unilterl musculr trophy loclised to the hnd nd forerm. Hirym et l initilly clled this disorder juvenile musculr trophy of unilterl upper extremity,3 nd lter designted it juvenile nonprogressive musculr trophy loclised in the hnd nd forerm.4 obue et l! referred to it s distl loclised musculr trophy of upper extremities with juvenile onset, nd therefter rephrsed it s segmentl musculr trophy of distl upper extremity with juvenile onset.6 The disorder is chrcterised by the following conditions: () musculr trophy tht insidiously ppers in youth with much higher incidence in mles thn in femles; (b) distribution of musculr trophy tht is distinctly symmetric nd loclised to the hnd nd forerm; (c) progression of musculr trophy during the erly onset period tht becomes self limiting; nd (d) most cses re spordic nd the ptient's history is generlly non-contributory. Most of the cses were Jpnese7-9 nd only few ptients hve been reported outside Jpn.1'9 Recent dvnces in exmintion techniques hve produced severl chrcteristic findings for this disorder. Hshimoto et!8 pointed out tht soclled stright neck due to lck of norml lordosis of the cervicl spine ws seen in plin rdiogrphs. Mtsumur et!2 confirmed loclised trophy of the lower cervicl cord in CT myelogrphy. Yd et!2" nd Muki et!22 showed with dynmic myelogrphy tht when the neck ws flexed, the durl sc ws shifted nteriorly nd the spinl cord ws compressed nd flttened between the posterior wll of the durl sc nd the cervicl vertebrl body, suggesting tht during neck flexion the durl sc nd cord were overstretched. ince then, this "overstretching" hs been thought to be one of the inductive fctors of this disorder. Although Hirym et!23 reported necropsied cse of this disorder, the true pthogenesis or custive mechnism is not known, nd mny questions concerning the clinicl mnifesttions still remin unsolved. In the present study, our im ws to clrify the custive mechnisms of this disorder by investigting seven ptients in detil. Ptients nd methods Clinicl neurologicl signs nd symptoms, longitudinl growth curves (five ptients only), nd rdiologicl exmintions were nlysed for seven ptients (six mles nd one femle) with symmetric musculr trophy loclised to the hnd nd forerm. We constructed height increse curves to evlute the reltion between the onset of musculr trophy nd rm growth velocity, becuse rm growth is thought to prllel growth in body height. These longitudinl growth curves tken from our five ptients were compred with the Jpnese verge curves obtined from dt published in the 1989 Annul Report of the chool Helth urvey (H) by the Ministry of Eduction ofjpn. Individul clinicl neurologicl symptoms were superimposed on ech curve. Plin rdiogrphy, dynmic myelogrphy,

2 Amyotrophic cervicl myelopthy in dolescence 59 Figure 3 Myelogrms nd CT myelogrms of cse No 2 (the ffected side is on the left). (A) Lterl view of myelogrms. In neck flexion, the lower cervicl cord nd the posterior wll of the durl sc re shifted nteriorly, lthough the subdurl spce gets wider posterior to the cord (rrows). The posterior epidurl spce expnds. In neck extension, the cord is moved posteriorly. As result, the nterior subdurl spce gets wider nd is filled more with contrst medium nd the posterior epidurl spce is shrunk. (B) Trnsverse view of CT myelogrms. In neck flexion, the cord is shifted nteriorly, being pulled to the ffected side (rrow hed) nd flttened nteroposteriorly. As the posterior wll of the durl sc shifts nteriorly, the posterior epidurl spce expnds. A spce filled with the contrst medium between the cord nd the posterior dur is seen. In neck extension, cuneiform trophic cord is seen on the left side (rrow hed) nd the nterior subdurl spce is filled more with the contrst medium s the cord is moved posteriorly. by pinioning in n ccident. One yer lter, musculr trophy lso ppered in the right hnd. He underwent cervicl vertebrl fusion t the ge of 17 yers nd 9 months to limit the mobility of his neck. It ws noted tht he hd plyed school volleybll nd bsketbll between the ges of 13 nd 15, during his pek growth period. Figure 2B shows the longitudinl growth curve of femle ptient (ptient No 1). The verge velocity curve for Jpnese femles (H, 1989) peks t 1 1 yers of ge-tht is, two yers erlier thn for mles, nd the nnul verge increse in height t the pek is bout 8 cm, which is 2 cm less thn for mles. The slope of the verge growth velocity curve is lso less steep thn tht of mles. Ptient No 1 strted to grow rpidly t the ge of 11 to 12, lthough her body height ws below verge before the ge of 1 1. At the ge of 13, the ptient ws tller thn verge. Her growth velocity curve peked t the ge of 12 nd the slope ws steeper thn tht of the mle verge. he hd plyed volleybll s school ctivity between the ges of 12 nd 14. The initil symptom ppered s musculr trophy t the ge of 16-tht is, four yers fter the pek of growth velocity. When her growth hd lmost cesed t the ge of 18, the musculr trophy cesed to worsen. Figure 2C, D, nd E show the growth curves of three other mle ptients (Nos 2, 4, nd 7). The pek in their growth velocity curves occurred one to three yers lter thn tht of the norml verge, ltest in ptient No 2. All five curves showed reltion between the rpid growth period nd prolonged sports ctivities. RADIOLOGICAL EXAMINATION Plin rdiogrphy Rdiogrphs of the cervicl spine showed no physiologicl lordosis in ny of the seven ptients, ll of whom hd soclled stright necks. Dynmic myelogrphy with the neck flexed nd extended Lterl view-when the neck ws flexed, the lower prt of the cervicl cord nd the posterior dur mter were moved forwrd nd the posterior epidurl spce ws enlrged (fig 3). There ws some spce filled with contrst medium between the spinl cord nd the posterior dur mter. There ws no evidence tht the cord ws being compressed by the durl sc. Posteronterior view-in norml subjects, when the neck ws extended, there ws slckness of the nerve roots; thus the C8 nerve root runs lmost horizontlly (fig 4C). The ptients showed no slckness of the nerve roots during neck extension. The nerve roots were rther strined nd rn downwrd, especilly on the ffected side. In ddition, the pths of the nerve roots on the ffected side were shorter thn on the unffected side, nd the spinl cord devited towrd the shortened roots (fig 4A, B). When the neck ws flexed forwrd, tension developed nd stretched the lower cervicl nerve roots. Furthermore, the nerve roots on the ffected side were very much under strin becuse of the shortened pths; this resulted in the lower cervicl cord being forcefully pulled to the ffected side (fig 4A). CT myelogrphy When the neck ws extended, the lower prt of the cervicl cord ws shifted slightly, lterlly towrd the ffected side. The nterior subdurl spce ws filled with contrst medium nd cuneiform trophic cord ws seen on the ffected side (fig 3B, fig 5). When the neck ws flexed, the lower prt of the cervicl cord ws shifted nteriorly, nteroposteriorly flttened, nd pulled shrply to the ffected side (fig 3B). The posterior wll of the durl sc ws lso shifted. Therefore, the posterior epidurl spce ws expnded. In ptient No 2, there ws spce filled with contrst medium between the spinl cord nd the posterior dur mter. Therefore, no posterior compression of the spinl cord by the dur ws found (fig 3B). Ptient No 6 hd severe deformtion of the durl sc (fig 6). In the neutrl position, the spinl cord ws flttened nd devited to the left side, especilly t the level of the

3 58 Tom, hiozw >.'f.:. 1., C 't *- f--itis,+ d FB f itv~~1.. Ft i l j i: tec 18, "I!'I W* * *,I, i g 4 -. t Af(If;,. '.,,. --s B.- * II4 ti... >.. 7.i.-.i i *1 V!:. L Be* w4 Ill >; g is J Neurol Neurosurg Psychitry: first published s /jnnp on 1 Jnury Downloded from A l]fi V'!.tl! V' i51;:.; Figure 2 Individul growth velocity nd longitudinl growth curves in reltion to the ppernce of ech clinicl symptom; thick line with filled circle, growth curve of ech ptient; thin line in A nd B nd the dshed line in C, D, nd E, verge growth curves for Jpnese boys (from H, 1989); broken line in B, verge growth curve for Jpnese girls (from H, 1989); stippled br indictes progression of musculr trophy from onset to rrest; verticl dshed line indictes durtion of strenuous sporting ctivity; = bsketbll nd voleybll; b = volleybll; c = boxing; d = longjump nd sprint; e = sprint. ptient (ptient No 6), who hd remrkbly rpid growth-tht is, more thn 1 cm growth per yer-for two yers between the ges of 12 nd 14. His nnul growth curve (growth velocity curve) t 12 yers of ge strted to increse shrply. Compred with the verge curve for Jpnese mles (from H, 1989), the pek period of the growth A\ t I velocity curve ws wider nd the growth velocity fter the ge of 15 ws lso fster. When the growth velocity peked t the ge of 13, the initil symptom of rditing root pin in the left rm ppered. Musculr trophy in the left hnd ws recognised two yers fter the pek in the velocity curve. At the ge of 15 this ptient's neck ws forcefully flexed on 21 October 218 by guest. Protected by copyright.

4 Amyotrophic cervicl myelopthy in dolescence 57 Clinicl fetures Muscle trophy Tendon reflex Arest of Ptient Age Hnded- Onset Initil Appernce progression ensory Upper Lower No ex (y) ness ge (y) symptom Lterlity Portion ge (y) ge (y) sign extremity extremity 1 F 2 Right 16 Wekness of the Right Hnd nd None Norml Norml right fingers forerm 2 M 21 Left 19 Difficultyinusing Left Hndnd 19 2 Electricsenstioninthe Norml Norml the right hnd forenn forerms when when numbed squtting nd stnding by cold 3 M 3 Left Muscle trophy of Left Hnd nd Numbness nd pin in Norml Norml the right hnd forer-m the neck nd left rm during neck movement 4 M 19 Right 17 Wekness of the Right Hnd nd 18 Lhermitte's sign Diminished lightly right hnd > left forerm exggerted 5 M 68 Right 17 Wekness of the Left Hnd nd None Norml Norml left hnd > right forerm 6 M 17 Right 13 Pin rditing in Left > Hnd nd left 15, Rditing pin in the Diminished Norml the left rm Right forerm right 16 left rm during neck during neck flexion fleidon 7 M 17 Right 13 Wekness of the Right Hnd nd 14 None Diminished Norml right thumb forerm (right) Figure 1 (cse 2). CT myelogrphy, nd MRI were crried out on ll cses. From n ethicl point of view, it is difficult to perform these investigtions in young helthy volunteers s control study; therefore we employed the method of Ishid et l for nlysis of functionl CT myelogrphy.4 The distnce between the posterior mrgin of the 5th vertebrl body nd the centre of the spinl cord ws mesured in the trnsverse sectioned view. The lignment of the cervicl spine ws exmined by mesuring the C4/5 nd C5/6 intervertebrl ngle in the lterl view. The reltion between spinl cord position nd djcent intervertebrl ngles t C5 ws estimted in five ptients nd compred with the dt of Ishid et l from norml Jpnese subjects under 3 yers of ge. Results CLINICAL FEATURE OF PATIENT The tble summrises the clinicl fetures of ech ptient. Two yers before the pper- Musculr trophy loclised to the hnd ndforerm, predominndy on the left nce of musculr trophy ptient No 6 begn to hve rditing pin from the neck to the forerm whenever his neck ws flexed forwrd. Initil symptoms of other ptients were muscle wekness nd cold presis, which were ssocited with musculr trophy. In these ptients, the progress of musculr trophy cesed one or two yers fter its initil recognition. Musculr trophy ws predominntly 'unilterl on the hnd nd ulnr side of forerm, nd the brchiordilis muscle ws not involved (fig 1), except for ptient No 6 whose musculr trophy ws lso present in brchiordilis nd brchilis muscles. Ptient No 5 first complined of symptoms 5 yers previously: his musculr trophy ws loclised to the left hnd nd forerm nd no improvement ws seen. The ptient did not hve ny objective sensory signs, but subjectively experienced bnorml senstions in his shoulder nd rm, nd rditing pin to his forerm when his neck ws flexed. The deep tendon reflexes were within the norml rnge but occsionlly were slightly reduced in the upper extremities nd slightly exggerted in the lower extremities. Ptient No 6 hd experienced severe pinioning of his rms nd hed t the ge of 15, when he herd his neck "crck". He ws not ble to move for two hours, nd he hd severe dysesthesi nd pin in both rms. It took whole dy for both rms to regin norml function. The remining six ptients presented here hd no history of trum. It ws noted tht six of these seven ptients hd prticipted in strenuous sporting ctivities t school in their teens-tht is, during their rpid growth period-nd they therefter developed musculr trophy within one to three yers despite discontinuing their sports (fig 2). RELATION BETWEEN ARM GROWTH AND ONET OF MUCULAR ATROPHY Rpid growth in height usully ccompnies rpid rm nd leg growth. Theoreticlly rm spn is nerly equl to body height. Figure 2A shows the longitudinl growth curve of mle

5 6 Figure 4 Posteronterior view myelogrms. (A) Cse No 2 (ffected side is on the left). In neck extension, the 6th, 7th, nd 8th nerve roots on the left (three white rrow heds) re very strined, nd the cord hs trction t these points. The 7th nd 8th nerves (white rrow) on the right re lso slightly strined. In neckflexion, the nerve roots on the left re extremely strined nd the cord is moved more lteruly to the left. (B) Cse No 1 (the ffected side is on the right). In neck extension, slckness of the nerve roots on the left is lmost norml (the rrow on the left indictes the 8th nerve). On the other hnd, the slckness is lost on the nerve roots on the right side, nd the cord is pulled towrds the right (three white rrow heds). (C) Norml subject ged 3. The nerve roots hve norml slckness in neck extension nd run lmost horizontlly, especilly the 8th root (rrow). flexed A extended Figure 5 CT myelogrms of cse No I (the ffected side is on the right). In neck extension, the lower cervicl cord is shifted lterlly to the right. Cuneiformed trophic cord is seen on the ffected side (rrow heds). The nterior subdurl spce is filled more with the contrst medium s the cord is moved posteriorly. In neck flexion, the cord is shifted nteriorly, shrply pulled w the ffected side (rrow heds), ndflttened nteroposteriorly. As the posterior wll of the durl sc shifts nteriorly, the posterior epidurl spce expnds. extended B Tom, hiozw extended C5-7 vertebrl bodies (rrow hed fig 6) nd there ws spce filled with contrst medium nterior to the cord. When the neck ws flexed, the cord ws shifted nteriorly, the right side of the spinl cord ws rotted in the right nterior direction round the left entry zone of the C5-6 dorsl roots, nd the durl sc ws constricted long the posterior midline portion. No subdurl spce ws seen on the right side nterior to the cord, especilly t the C5-7 vertebrl bodies, nd the right posterior subdurl spce ws filled with contrst medium. Therefore, it ws confirmed tht there ws no compression of the spinl cord by the posterior dur mter. Figure 7 explins how the cord ws rotted nd the durl sc deformed. Figure 8 shows the reltion between spinl cord position nd djcent intervertebrl ngles t C5 in five ptients. The slopes of the regression lines for those ptients under 3 yers old were steeper thn those for norml controls obtined from the study of Ishid et l.24 These results indicte tht the degree of nterior shift of the spinl cord in neck flexion ws more prominent in the ptients thn in norml young subjects. MRI Asymmetric cord trophy with dominnce on the sme side s the musculr trophy ws found t the C5-C7 level by MRI. When MRI ws tken with the neck ventroflexed, n nterior shift of the cord nd durl sc ws seen nd flttened cord contcted the ventrl border of the vertebrl body. In ddition, gdolinium-gtpa enhnced MRI in TI imges often showed highly enhnced venous plexus in the posterior epidurl spce from the lower cervicl to the thortic vertebrl body during neck flexion. C

6 Amyotrophic cervicl myelopthy in dolescence 61 Figure 6 CT myelogrms of cse No 6. In neck flexion, the cord is shifted nteriorly nd the right side of the spinl cord is rotted in the right nterior direction. There is no subdurl spce nterior to the cord becuse it touches the posterior border of the vertebrl body t the level of C 5-7. The right posterior subdurl spce is filled with the contrst medium. The durl sc is constricted long the midline of the posterior wll. In the neutrl position, the cord is situted posteriorly nd devites to the left (rrow heds) nd spce filled more with contrst medium is seen nterior to the cord. Discussion In dynmic myelogrphy of ptients with myotrophic cervicl myelopthy, nterior shifting of the posterior dur mter, together with flttening of the lower cervicl cord between the posterior wll of the durl sc nd the vertebrl body, were found when the neck ws flexed.2' 22 Thus some investigtors hve referred to this condition s flexion myelopthy,25 overstretch mechnism,2' or tight durl cnl in flexion25 nd considered it to be prt of the pthogenesis of flexion myelopthy. Both the spinl cord nd durl sc re overstretched in verticl direction when the neck is flexed, nd then the spinl cord is pushed ginst the posterior vertebrl body. The cuse of this disorder is thus explined by the imblnce between development of the cervicl cord nd the spine. This, in turn, cuses strin on the durl sc during neck flexion, which results in the spinl cord being pushed nteriorly. In most ptients with this disorder, however, there ws n ctul spce between the nteriorly displced cord nd the posterior dur mter, nd compression of the cord from the posterior dur ws rrely seen. Figure 9 schemtises the dynmic chnges in the cervicl cord nd durl sc on flexion nd extension of the neck. During neck extension in norml subjects, the spinl cord ws shifted cudlly, nd the dorsl roots nd the blood vessels were slck (fig 9A). When the neck ws flexed forwrd in norml subjects, the dorsl roots were extended in n nterorostrl direction with n nterorostrl shift of the cervicl cord (fig 9A).6 In fct, the cervicl spinl cord shifted nteriorly in flexion nd posteriorly in extension of the neck, nd ws flttened t the midcervicl level in flexion in norml young subjects.24 In the present study, however, we found tht the ptients' dorsl roots did not show slckness when the neck ws extended (fig 9B). When the ptient's neck ws flexed, the dorsl roots were insufficiently extended due to lck of slckness in extension. This resulted in the dorsl roots becoming short in reltion to the spinl cord elongtion during neck flexion (fig 9B). The spinl cord connects with the durl sc by mens of the denticulte ligments nd the septum subrchnoidle posterius, nd flots in the CF. In these ptients, the reltively short dorsl roots pull the spinl cord nteriorly beyond the norml degree of shift when the spinl cord is stretched during neck flexion, even over smll rnge. Becuse the spinl cord is tightly connected to the durl sc on the posterior side by the septum subrchnoidle posterius, this shift of the spinl cord lso mkes the posterior wll of the durl sc move forwrd. Becuse these ptients hve symmetric shortening on the right nd left dorsl roots, the cord is then pulled to the side where the shortening is most severe (fig 9B). Finlly, lrge nd extremely symmetric difference of forwrd nd upwrd force would generte pronounced symmetric forwrd shift nd upwrd stretch of the cord, which could result in serious sitution s seen in ptient No 6-tht is, rottion of the cord nd deformtion of the durl sc (figs 6 nd 7). Dilttion of the venous plexus ppers in these ptients during neck flexion, becuse the pressure inside the posterior epidurl spce decreses when the posterior wll of the durl sc moves forwrd (fig 9B). We think tht the dorsl roots become short becuse the growth of the cervicl roots does not keep up with the rte of skeletl rm growth during the rpid growth period in some young people. Reid27 confirmed, in cdvers, tht lterl movements my be seen in the cervicl roots on bduction of the rm t the shoulder or on pulling the rm downwrd. Therefore, this reltive shortness of the C5-Thl dorsl roots during the rpid growth period pulls the lower cervicl cord nteriorly when the neck is flexed. As result, the spinl cord is compressed by the vertebrl body, nd chronic degenertive chnges cn occur in the nterior horns. This disorder occurs minly in young mles who re growing rpidly. In such people, not only body height, but lso rm nd leg lengths increse considerbly. In ddition, it hs been

7 62 rf\it I ii Figure 7 chemtic digrm ofdynmic chnge of the cord nd the durl sc during neck flexion in cse No 6. When the neck is flexedforwrdfrom the neutrl position, upwrd extension force () ndforwrd trction force (b) re generted over the right nd left dorsl root entry zone of the cervicl cord ccording to their root extensibilities. In ptient No 6, the extensibility of the roots is symmetric-tht is, left roots re not ble to extend ny more becuse they re too short (indicted by open rrows). During neck flexion, the left dorsl roots t the Cth nd 6th vertebrl bodies do not move. The right side of the cord is ble to extend upwrd nd t the sme time to rotte in the right nterior direction (indicted by rrows) round the immovble left nerve root entry zone (open rrow). The durl sc is, consequendy, constricted long the posterior midline becuse the spinl cord is tighdy connected with the durl sc on the posterior side by the septum subrchnoidle posterius (s). reported tht in this growing period, the rtio of sitting height to height is the smllest. From this point of view, the present results re not consistent with the hypothesis of the overstretching of the spinl cord due to imblnced development between the cord nd spine during the growing period.2' The comprtive nlysis between the growth curve nd ge of onset showed tht this disorder occurs t n ge when the length of the rms, s well s body height, develop most rpidly. Musculr trophy generlly ppered two to four yers fter the onset of the initil symptoms, nd stopped progressing when rpid growth ws over. The dt from H showed tht young Jpnese men grow most rpidly t ge 13, nd rpid growth continues until yers of ge. This period is considered to be the ltent period of recognisble musculr trophy. We found 49 ppers written in Jpn on this disorder. Among them, the ge t onset ws recorded for 16 mle ptients, 8% of whom hd initil symptoms before they were 19 yers old. As in most cses the initil symptom is musculr trophy of the hnd, clinicl fetures of the disorder re estblished when musculr trophy is noticed. The growth pek of women is two yers erlier thn in men. The lrgest increse in nnul body height is bout 8 cm, 2 cm less for women thn for men, nd the slope of the growth velocity curve of women is not s steep Tom, hiozw s for men. Therefore, women re rrely fflicted with this type of musculr trophy. The growth rte of the left nd right rm re not usully uniform. This my explin why musculr trophy cn pper on either side, nd why the mjor symptoms pper on only one side. According to one report,4 more ptients hve musculr trophy in the right rm thn in the left, which might be relted to fster growth of the right rm. No reltions hve been found to the ptients' hndedness, however.819 There re severl reports on fmilies with histories of this disorder,7 923 not surprising s growth ptterns re lrgely dependent on hereditry fctors. Becuse of its benign course, studies on the pthology of this disorder hve rrely been performed. Hirym et t3 first reported pthologicl findings on ptient with this disese who died of lung cncer. Lesions existed only in the nterior horns of the bilterl lower cervicl cord, nd showed shrinkge nd necrosis, vrious degrees of degenertion of nerve cells, nd mild gliosis. They suggested tht the lesions were produced by consequent circultory insufficiency of the cervicl cord. Pushing the E E C._ v2 Flexion Norml control (y =.7x ) Ptient No 1 (y = -1lx + 3.6) Ptient no 2 (y(o.1 = 3x + 4.4) A Ptient No 3 Ptient no 6 (y =.21x ) Ptient No Extension Figure 8 Reltion between djcent intervertebrl ngles nd loction of the spinl cord t the level of C5 in ptients under 3 yers old. X = um of ngles t C415 nd C516; Y = vlues ofdistnce to the vertebrl body t C5. The slopes of the regression lines in the three ptients re lrger thn those of norml controls from the dt ofishid et l. 24 The lower cervicl cords in the ptients re situted more nterior thn in norml controls, especilly during neck flexion.

8 Amyotrophic cervicl myelopthy in dolescence 63 Figure 9 chemtic drwings of the mechnism ofdynmic chnge of the cervicl cord nd durl sc relted to dorsl roots during neck extension nd flexion. Verticl broken line shows the midline of the body. The longer horizontl broken line shows the centre of the cord during neck extension. The shorter horizontl broken line indictes the cord shifted nteriorly during flexion. (A) Norml subject; during neck extension the dorsl roots, cord, nd dur in the cervicl cnl re slck. On neck flexion, the roots, cord, nd dur re drwn out; elongtion of the dorsl roots nd cord is permitted by the slck present in neck extension (1 = dorsl root; 2 = spinl cord; 3 = durl sc; 4 = septum subrchnoidle; 5 = epidurl spce). (B) Ptient ffected on the right side (rrows); during neck extension, slckness of the dorsl roots disppers on the ffected side (right) in which the rm grows fster thn on the other side. On neckflexion, the right dorsl roots cnnot extend, nd this cuses the spinl cord to be drwn nteriorly to the right. A B Left Extension Extension Right nterior spect of the spinl cord to the vertebrl body might result in chronic compressive mild circultory chnges to the nterior horn tissues, which re the most vulnerble to ischemi. In generl, chronic functionl dmge to neurons for two or more yers will cuse dysfunction of muscles, especilly when they re innervted by long xons; these xons hve the gretest demnd for resupply, nd their distl regions re the most remote res of soml irrigtion.28 This is presumbly the reson why musculr trophy is loclised in the hnd nd the ulnr side of the forerm, s soclled oblique myotrophy.29 Electromyogrphic findings showed typicl neurogenic chnges not only in the trophied muscles, but lso in the non-trophic homonymous muscles. uch bnorml chnges were not found in the brchiordil, extensor clpi rdilis longus, prontor teres, nd pectorlis mjor muscles, despite their C5-7 segmentl Left Flexion Flexion Right innervtions.'3' This could be explined by the fct tht the motor points of these muscles re locted in more proximl portion of the upper extremity. Ptients occsionlly reported subjective sensory symptoms. Our ptient No 6 hd rdiculr pin s n initil symptom when the neck ws flexed forwrd. This pin preceded recognised musculr trophy by bout two yers. There re some reports of rdiculr pin during neck flexion, nd of Lhermitte's sign.32 We think tht the rdiculr stimulting sign is due to trction of lower cervicl rootlets or roots when the neck is flexed. In this sitution sensory disturbnces hve not yet been studied in detil, becuse the severity of orgnic chnges of the dorsl rootlets is usully mild nd objective signs re few. In ptient No 6, myelogrphy nd CT myelogrphy were performed four nd hlf yers fter the initil symptoms, nd depicted the spinl cord showing extreme rottion in

9 64 Tom, hiozw right nterior direction round the shortened left nd fixed C5-6 dorsl root entry zone, nd the nterior right hlf of the cord touched the vertebrl body (fig 6). These findings lso indicted the presence of musculr trophy in the right hnd, which ppered lter thn the left hnd trophy. In this ptient in the erliest stges, dmge to the left nterior horns developed from the severe shift of the cord to the left. As growth continued, the left dorsl roots could not extend when the neck ws flexed, nd the cord begn to rotte to the right round these left unextensible roots (fig 6). There is possibility tht the forceful pinioning, which occurred, when the ptient ws 15 yers old, triggered rottion of the cord nd then deformtion of the durl sc. The degree of shift nd rottion of the cord could depend on the blnce between the rm growth process nd the reltive shortening of the roots. The cuse of this disorder depends on how the skeleton of the body grows during the dolescent period. We think tht the incidence will be higher in persons whose growth is initilly slow but which suddenly increses lter s in our ptient No 1. Persons with stright necks, who do not hve physiologicl cervicl lordosis, re more prone becuse their roots might be lredy stretched. The occurrence of this disorder might be prevented by voiding physicl exercises tht cuse frequent nd violent flexion of the neck. trenuous exercise in sports ws often noted in ptient cse histories From our studies, we propose tht prticiption in sports during the rpid growth period is one of severl high risk fctors for this disese. The risk of ppernce of this disorder will decrese fter skeletl growth slows down nd dorsl root slckness develops sufficiently. In ptient No 5, musculr trophy hs not improved for 5 yers, but the ptient is cpble of performing simple isotonic finger movements. In principle, dmged neurons cn be repired if degenertive chnges of the distl prts of xons re reversible. Therefore, for both high risk persons nd people who hve hd symmetric musculr trophy of the hnd nd forerm, forwrd flexion of the neck should be voided until skeletl growth hs been completed. We thnk Drs Y Yoshiym, K Ktym, nd M Mochizuki for performing the neurordiologicl exmintion for ptient No 6. We re grteful to Drs Y Ishid nd K Ohmori for giving vluble dvice on norml controls. We grtefully thnk Professor Akir Tkhshi for vluble comments on the mnuscript. 1 Hirym K, Toyokur K, Tsubki T. tudies on motor neuron disese (4). Considertion of twelve specil cses of juvenile onset musculr trophy with motor disturbnces s min symptoms. Psychitri et Neurologi Jponic 1959;61:1861. (In Jpnese.) 2 Tkgi, Okbe Y. Juvenile distl musculr trophy of unilterl upper extremity. Psychitri et Neurologi Jponic 1959;61: (In Jpnese.) 3 Hirym K, Toyokur Y, Tsubki T. Juvenile musculr trophy of unilterl upper extremity; new clinicl entity. Psychitri et Neurologi Jponic 1959;61: (In Jpnese.) 4 Hirym K. Juvenile non-progressive musculr trophy loclized in the hnd nd forerm: observtions in 38 cses. Clinicl Neurology (Tokyo) 1972;12: (In Jpnese.) 5 obue I, ito M, lid M, Ando K. Distl loclized musculr trophy of upper extremities with juvenile onset: A new musculr trophy nd its clinicl fetures. Igku No Ayumi (Tokyo) 1972;82: (In Jpnese.) 6 ito M. egmentl musculr trophy of distl upper extremity with juvenile onset. Jourml of the Ngoy Medicl Assocition (Ngoy) 1977;99: (In Jpnese.) 7 Hirym K, Tsubki T, Toyokur Y, Okink. Juvenile musculr trophy of unilterl upper extremity. Neurology 1963;13: Hshimoto, Asd M, Oht M, Kuroiw Y. Clinicl observtions of juvenile nonprogressive musculr trophy loclized in hnd nd forerm. Y Neurol 1976;211: obue I, ito N, lid M, Ando K. Juvenile type of distl nd segmentl musculr trophy of upper extremities. Ann Neurol 1978;3: Pilgrd. Unilterl juvenile musculr trophy of upper limbs. Act Orthop cnd 1968;39: Compernolle T. A cse of juvenile musculr trophy confined to one upper limb. EurNeurol 1973;1: ingh N, chdev KK, usheel AK. Juvenile musculr trophy loclized to rms. Arch Neurol 198;37: Gourie-Devi M, uresh TG, hnkr K. Monomelic myotrophy. Arch Neurol 1984;41: Tn CT. Juvenile musculr trophy of distl upper extremities. Y Neurol Neurosurg Psychitry 1985;48: Leys D, Petit H. Amyotrophie juvenile distle chronique unilterle loclisee un membre superieur (type Hirym): un cs europeen. Rev Neurol (Pris) 1987; 143: Chine P, Bouche P, Leger JM, Dormont D, Cthl HP. Atrophy musculire progressive loclisee l min: forrme monomelique de mldie du motoneurone? Rev Neurol (Pris) 1988;144: Biondi A, Dormont D, Weitzner I Jr, Bouche P, Chine P, Bories J. MR imging of the cervicl cord in juvenile myotrophy of distl upper extremity. Am Y Neurordiol 1989;1: Gio JM, Lechevlier B, Hommel M, Vider F, Chpon F, Perret J. Amyotrophie spinle chronique des membres superieurs de l'dulte jeune (syndrome de O'ullivn et McLeod): etude en IRM de l moelle cervicle. Rev Neurol (Pris) 1989;145: Peiris JB, enevirtne KN, Wickremsinghe HR, Guntilke B, Gmge R. Non fmilil juvenile distl spinl musculr trophy of upper extremity. Y Neurol Neurosurg Psychitry 1989;52: Mtsumur K, Inoue K, Ygishit A. Metrizmide CT myelogrphy of Hirym's disese. A loclized trophy of the lower cervicl spinl cord. Clinicl Neurology (Tokyo) 1984;24: (In Jpnese.) 21 Yd K, Tchibn, Mii K, Okd K. pinl cord lesion due to reltive imblnce of cervicl spine nd cervicl cord. In: 1983 nnul report ofprevention nd tretment for the congenitl nomlies of the spine nd spinl cord. Tokyo: The Ministry of Helth nd Welfre of Jpn, 1984; (In Jpnese.) 22 Muki E, obue I, Muto T, Tkhshi A, Goto. Abnorml rdiologicl findings on juvenile-type distl nd segmentl musculr trophy of upper extremities. Clinicl Neurolog.y (Tokyo) 1985;25:62-6 (In Jpnese.) 23 Hirym K, Tomong M, Kitno K, Ymd T, Kojim, Ari K. Focl cervicl poliopthy cusing juvenile musculr trophy of distl upper extremity: pthologicl study. Y Neurol Neurosurg Psychitry 1987;5: Ishid Y, uzuki K, Ohmori K. Dynmics of the spinl cord: n nlysis of functionl myelogrphy by CT scn. Neurordiology 1988;3: Iwski Y, Tshiro K, Kikuchi, Kitgw M, Isu T, Abe H. Cervicl flexion myelopthy: "tight durl cnl mechnism". JNeurosurg 1987;66: Breig A. Adverse mechnicl tension in the centrl nervous system. An nlysis of cuse nd effect. Relief by functionl neurosurgery. tockholm: Almqvist nd Wiksell Interntionl, 1978: Reid JD. Effects of flexion-extension movements of the hed nd spine upon the spinl cord nd nerve roots. 7 Neurol Neurosurg Psychitry 196;23: pencer P, chumburg HH. Experimentl models of primry xonl disese induced by toxic chemicls. In: Dick PJ, Thoms PK, Lmbert EH, Bunge R, eds. Peripherl neuropthy. Vol 1. Phildelphi: W B unders, 1984: Hirym K. Non-progressive juvenile spinl musculr trophy of the distl upper limb (Hirym's disese). In: Vinken PJ, Bruyn GW, Klwns HL, eds. Diseses of the motor system. Hndbook of clinicl neurology. Vol 15. Amsterdm: Elsevier, 1991: Hirose K, Bb M. Quntittive electromyogrphy of the musculr trophy of Hirym-obue type ( provisionl nme)-it chrcteristics nd reltionship to pthology. Jpnese Jouml of Electroencephlogrphy nd Electromyogrphy (Tokyo) 1978;6: (In Jpnese.) 31 Ngok M, Hirym K, Chid T, Yokochi M, Nrbyshi H. Electromyogrphic nlysis on juvenile musculr trophy of unilterl upper extremity. Brin nd Nerve (Tokyo) 198;32: Tsukgoshi H, Mnnen T, Toyokur Y. ome considertions in juvenile musculr trophy of the unilterl upper extremity (Hirym). Clinicl Neurology (Tokyo) 1971; 11:771. (In Jpnese.)