Clinically silent dysfunction of dorsal columns and dorsal spinocerebellar tracts in hereditary spastic paraparesis

JOURNAL OF IHE

NEUROLOGICAL SCIENCES EI~SEVIER

Journal ot the Neurological Sclent,es 125 (1994) 206-211

Clinically silent dysfunction of dorsal columns and dorsal spinocerebellar tracts in hereditary spastic paraparesis R.P.M. Bruyn ~'*, J.G. van Dijk b, p. Scheltens c, E.H.J.F. Boezeman '~, B.W. Ongerboer de Visser e a Department of Neurology, Oudenrtln Hospttal Utrecht, can Heucen Goedhartlaan I, 3527 CE Utrecht. The Netlwrland,~ b Department of Neurology and Cltntcal Neurophystology, State Unwerstty Letden, Letden, The Netherland~ Department of Neurology, Free Untl er3tty Hospital, Amsterdam, The Netherlands Department of Neurophystology, St Antontus Ho~pttal. Nwuwegem, The Netherlands Dwtston of Chmcal Neurophystology, Acadermc Medtcal Center, Amsterdam. The Netherland,~

Received 3 January 1994, rewsed 3 May 1994, accepted 10 May 1994

Abstract Hereditary spastic paraparesis (HSP) is a neurodegeneratlve disorder, of whtch progressive spastic paraparesis is the clinical hallmark. Given the neuropathological evidence of degeneration of pyramidal tracts, dorsal columns, and dorsal spmocerebellar tracts, 11 is surprising that sensory symptoms are so lndlstmct compared to motor symptoms. We investigated the involvement of pertpheral conductton and spinal proprioceptive pathways by nerve conduction studies, somatosensory evoked potenttals of the median and tibml nerves, and quantttattve assessment of the vibration perception thresholds of the hands and feet respectively in 32 panents suffering from HSP and healthy control groups We did not find peripheral conducnon abnormalities in HSP patients. Log-transformed vibration perception thresholds of the feet were abnormal in 13/32 HSP patients and in 0/64 controls ( p <0.00001), while tiblal nerve somatosensory evoked potentials were abnormal m 20/32 panents and in 1/17 controls ( p = 0 00001) The values for the upper extremities were within normal limits for nearly all subjects In the HSP group, the neurophysiological disturbances did not correlate slgmflcantly with duration or seventy of the disease, when age was controlled for, except for medmn nerve SSEP latency, which was affected by severity ( p = 0.0072) We conclude that neurophystological methods detected proprloceptlve, subclinical abnormalities in several HSP patients, which may reflect degeneration of the dorsal columns, a n d / o r dorsal spinocerehellar tracts. Since we found no correlation with several &sease variables, the fact that not all HSP paUents displayed these abnormalities may be caused by anatomical varlanons in proprioceptive pathways, rather than by phenotyplcal heterogeneity Key words Hereditary spastic paraparests, Vibration threshold; Somatosensory evoked potentmls; Nerve conducnon

1. Introduction T h e " p u r e " f o r m o f h e r e d i t a r y spastic p a r a p a r e s i s (HSP), o r S t r h m p e l I ' s disease, is a n e u r o d e g e n e r a t i v e d i s o r d e r , o f which p r o g r e s s i v e spastic p a r a p a r e s i s , m o r e p r o n o u n c e d t h a n w e a k n e s s , is the clinical h a l l m a r k . H y p e r r e f l e r a a o f t h e legs, e x t e n s o r p l a n t a r r e s p o n s e s a n d a p o s i t w e family history a r e o t h e r o b l i g a t o r y diagnostic c r i t e r i a (Bruyn a n d S c h e l t e n s 1991). H y p e r reflexla o f t h e arms, slight s e n s o r y d i s t u r b a n c e s o f the feet, a n d u r g e i n c o n t i n e n c e a r e o c c a s i o n a l l y p r e s e n t .

* Corresponding author_ Tel (+31-30) 953 359 0022-510X/94/$07.00 © 1994 Elsewer Science B V_ All rights reserved SSDI 0022-5 10X(94)001 1R.

T h e c o m p l i c a t e d f o r m o f H S P is d i a g n o s e d , when o t h e r n e u r o l o g i c a l signs a r e p r e s e n t , such as ataxm, optic a t r o p h y , e p i l e p s y or e x t r a p y r a m i d a l signs. T h e m o d e of i n h e r i t a n c e o f the " p u r e " l o r m is a u t o s o m a l d o m i n a n t in most cases; a u t o s o m a i recessive t r a n s m i s s i o n is rare. T h e defecUve g e n e has not yet b e e n d i s c o v e r e d (Bruyn et al. 1993; van D e u t e k o m et al. 1994), a l t h o u g h close linkage to a g r o u p o f m a r k e r s on c h r o m o s o m e 14q in o n e family has b e e n f o u n d r e c e n t l y ( H a z a n et al. 1993), and t h e r e Is e w d e n c e for a s e c o n d locus on c h r o m o s o m e 2p ( H a z a n e t al 1994). D e g e n e r a t i o n o f t h e p y r a m i d a l tract, i n c r e a s i n g f r o m cervical to l u m b a r level and, in r e v e r s e d o r d e r , of the g r a c d e fasc~culi a r e c o n s i s t e n t p a t h o l o g i c a l a b n o r m a h -

R I'M

l h m ' n ct al ,' h m r n a l "l the ,M'uroh~;,ual S¢tt'm es 125 (19941 _~0 0 - _" / 1

ties, d e g e n e r a t i o n of the posterior s p m o c e r e b e l l a r tract is p r e s e n t to a lesser extent (Schwarz and Lm 1956, Bruyn and Scheltens 1991). Despite these d e g e n e r a tions of both lateral a n d dorsal columns, tt IS surprising that sensors s}mptoms are so indistinct c o m p a r e d to motor symptoms Neurophys~ological studies ol nerve c o n d u c t i o n a n d somatosensory evoked potentials tSSEPs) have resulted in m c o n s N e n t results, probably due to dflferences m recording techniques, m c n t e r m ol physical, or chnlcal a b n o r m a h t y , and in sevetlt~ and d u r a t i o n of the d~sease ( M a h n 1~76; McLeod et al. 1977, P e d e r s e n and T r o j a b o r g 1981, D~mltrijcvlc et al 1982; U n c i n l et al 1987, Rossini and Cracco 1987: Pelom et al 19ql 1. The p r c s c m report describes the results of a ,~tudy including s o m a t o s e n s o r y evoked potentials, nerve con-

duction e x a m i n a t i o n , and quanUtatwe a s s c s s m c n t Ol the xqbratum p e r c e p t u m threshold (VPT) m a serues of 32 p a t i e n t s wLth pure HSP. in orde~ to d e t e r m i n e the l r e q u e n c y ol a b n o r m a l , subclinical, sensory h n d m g s , and to discuss this m the hght ol k n o w n pathology and neurophyslologlcal studies

2. Patients and m e t h o d s

Pattents and ( onltoLs Thu-ty-two patmnts, 19 males and 13 females, aged 15 75 year', l m e a n 45 6 yrs) with pure HSP trom 9 kinships were e x a m i n e d All patients exhibited a spastic parapal-cs~s, h.~perrcflexm of the legs a n d Bablnski sign. without any other n c t n o l o g l c a l signs or symptoms, m p a r t i c u l a r no sensory d y s l u n c t i o n B e h a n and MaLa's (19741 scolmg scale ~a'~ used to grade seventy ol the paraparesp, 1. mltumal OL no symptoms; 2, spast,c, but u n a | d e d gait, 3. spa,;tic gait, sticks or walking frame required. 4. wheelchair or b e d r i d d e n . For details see Table I T h r e e dfllcrent control groups were tormcd, each ot which was a g e - m a t c h e d to the p a t i e n t group: m e d m n nerve SSFP,, were o b t a i n e d m 79 healthy subjects, t~bml nmwc SSEPs m 17 healthy subjects, and VPTs m hands and lect werc assessed nn 64 healthy subjects

Nettrol)hystoh~gtcal ~studtes Motor n e i v e c o n d u c t i o n vclocitms ol the right med n m aim ttbm[ nerves were c o n v e n t u m a l l y d e t e r m n l e d with a M e d e l e c MS 8 machine, using surface electrodes o'vcr 1he a b d u c t o r pollicls brevts and a b d u c t o r hallucls muscles rcspcctwcl.'~, T h e shortest latency of bye F-responses was noted_ Sensory nerve c o n d u c t i o n velocity ol the ilgtlt m e d i a n nerve was d e t e r m i n e d using ling electrodes on the m t d d l c - h n g e r H o f m a n n (H)-reflcxes wcrc r c c o l d c d over the right soleus muscle. T e m p e r a ture ol the skin was b c t w c c n 30 and 32°C

2(17

Table I Pat+cnt d a t a P,ttlent

No',,

A g e (_,ds)

('lnnLcal g r a d e

l)u],ttuon

I 2 3

t M M

15 lt~ 2(I

It II I1

c,

4

M

2t~

1

2~ q

s ~, 7 s '~

7

M M v M I-

2¢~ 29 29 33 ~4

1[) II

M M

3t~ 3S

I 11

12

F

:,s

2S

13

F

3t)

11 I

~4 I~

~ M

411 41

Ill

24

In 17

NI M

42 42

I 1\

IS Itj In 21

M g M

42 4 ~, 45 46

Ill II ix,. II1

1

11 11 I1 II

[ M

52

111

24 2s 26 27 28 29 ~1 31 ~2

M F F M M F M F M

"~u ¢~8 {~,", ~)9 7[~ 71 72 74 7~

II1 I1 III 11l IX, I11 1\ 111 I~

F

56

22

2ql

I1

22

2~

(vrs)

V) 32 ~2 3h

11

17 2S S ~) 4ql 71

~2 2D

SSEPs were recorded following s t m m l a t u m ol the right m e d i a n and Ubml nerves Two a~crages ol 5(10 arUlact-free sweeps each were o b t a i n e d with a Nlhon K o h d e n N e u r o p a c k 8 T h c m c d m n nerve was s u m u lated at the wrist a n d recordings were made from Erb's point, 7th cervical v e r t e b r a and C3/P3, while a reference electrode was placed at Fz ( 1 0 - 2 0 m t c r n a t m n a l system) We have not a t t e m p t e d to rccord using an a n t c r i o r cervical reference ( M a u g t n ~ r e anti Rcstuccm 1991) m view of 1he hkclihood ol i n d u c e d muscle artilacts m our p a t i e n t group_ T h e latcncies ol thc NO, N I 4 a n d N20 peaks were m e a s u r e d , and the N14-2(1 l n t c r p c a k latency was calculated_ T h e Iibtal nerve was s h m u l a t c d at the m e d m l malleolus, recordings wine made from CPz (2 cm b e h i n d Cz) and referred to FPz. A t t e m p t s were m a d c to ~ccord l u m b a r N21 peaks so as to m e a s u r e central c o n d u c t i o n , but these could not be l e c o r d e d rchably m the patient group due to spastlclty-relatcd muscle artthtcts, these pcaks will not be discussed l u r t h c l Latency and a m p h rude ol the P37 peak were m e a s m e d SSEPs were c o n s i d e r e d a b n o r m a l when they could not be elicited, w h e n latencms were p r o l o n g e d (N20 a n d / o r N I 4 - 2 0

~[~,~,

R P ~l BHtlpz c/a/

I,mtml/ ~/ the Vcupolog, al Actentes 12~ t1Q94~ 20~ _'//

fl)r the m e d i a n nerve, a n d P37 lor the ttblal nerve), or when a m p l i t u d e s were decreased (vide lnfra). V P T was m e a s u r e d using a V t b r a m e t e r type IIl (Somedic AB, Stockholm, S w e d e n ) In o r d e r to avoid differences m application pressure of the vtbratory rod, a special device was used to allow for c o n s t a n t pressure ( B e r t e l s m a n n 1987) T h e a m p l i t u d e of vibration, measured in m i c r o m e t e r , increased from zero to the value at which the p a t i e n t perceived the vibratton_ Thts was r e p e a t e d three ttmes, and V P T was d e f i n e d as the a r i t h m e t i c m e a n of the three m e a s u r e m e n t s . VPTs were m e a s u r e d at the right second m e t a c a r p a l ( V P T h) a n d first m e t a t a r s a l ( V P T I) V P T a b n o r m a l i t y was defined as either a n t m m e a s u r a b l e response or an increased threshold (vide mfra). Skin t e m p e r a t u r e was between 30-32°C Statistical analysis D a t a were i n s p e c t e d for n o r m a l i t y of d i s t r i b u t i o n a n d l o g - n o r m a l i s e d w h e n necessary. Differences were c o m p a r e d with analysis of variance ( A N O V A ) or twosided t-tests, with allowances for u n e q u a l variances. W h e r e necessary, effects of q u a n t i t a t i v e variables were taken into a c c o u n t with an analysis of covarlance ( A N C O V A ) As it was hypothesised that SSEPs a n d VPTs would be a b n o r m a l in the p a t t e n t group, onesided tests were applied for these data O t h e r variables (age, length) were c o m p a r e d with two-sided tests. Linear regression t e c h n i q u e s were used to analyse relationships A n a l y s e s were p e r f o r m e d with the NCSS p a c k a g e (NCSS, Kaysville, U t a h ) SSEP and V P T data were individually labeled as n o r m a l or a b n o r m a l . T o do so, a b n o r m a l i t y criteria were d e f i n e d as an a b s e n t response, or as all values above the m e a n plus two s t a n d a r d deviations (SD) of control data for SSEP latencles ( N 1 4 - 2 0 a n d N20 latencies for the m e d i a n n e r v e SSEP, and P37 latency for the tIblal nerve) a n d l o g - n o r m a l l s e d VPT, or as a d e c r e a s e d a m p l i t u d e . SSEP a m p l i t u d e s often have a n o n - n o r m a l distribution, a n d in this case the m e a n m i n u s 2 SD was lower than zero. Thus, any value below the 97.5 p e r c e n t i l e value, as identified in the control group, was tdentlfied as a b n o r m a l Note that c o m b i n i n g a b n o r m a l i t y criteria increases the false positive rate (van Dijk 1992; van Dijk et al 1992), b u t the p r o c e d u r e was a i m e d at a c o m p a r i s o n of p r o p o r t i o n s of n o r m a l a n d a b n o r m a l results between the groups, a n d not at d e f i n i n g a diagnostic a b n o r m a l i t y threshold. P r o p o r t i o n s were c o m p a r e d with F i s h e r ' s exact test. A significance level of p < 0.05 was chosen

3. Results C o m p a r i s o n s between patients a n d controls M o t o r n e r v e c o n d u c t i o n velocity a n d c o m p o u n d muscle action p o t e n t i a l ( C M A P ) a m p l i t u d e , o b t a i n e d

by s t i m u l a t i o n of the right m e d i a n and ttblal nerve were within n o r m a l hmlts in all patients The same obtains for the sensory nerve c o n d u c t t o n veloctty and a m p h t u d e ot the right m e d i a n nerve potential [:-response latencies and soleus H-reflex [atencles were normal in all patients. V P T t could be m e a s u r e d in 23 p a t i e n t s and the m a x i m u m level of s t i m u l a t o r o u t p u t could not be felt m 9 patients. V P T could be m e a s u r e d m both the h a n d s and feet of all control subjects_ The c o m p a r i s o n ol m e a n s of variables b e t w e e n the groups revealed that VPTs were higher in the p a t i e n t than in the control group As the d i s t r i b u t i o n of V P T was m a r k e d l y skewed m h a n d s a n d feet of both controls a n d p a t i e n t s a l o g - t r a n s f o r m a t i o n was a p p l i e d ( " l o g - V P T " ) L o g - V P T was significantly higher in p a t i e n t s than in controls, especially in the feet ( p ~ 0 004) To c o u n t e r any rem a i n i n g effects of age, age was i n c l u d e d as a covarlate in an A N C O V A : log-VPT~ r e m a i n e d highly significantly different b e t w e e n the groups ( p < 0 0001), but Iog-VPT h lost tts significance ( p = 0 056)_ A ttb~al nerve SSEP could not be elicited in 7 patients, and was p r e s e n t in 25 p a t i e n t s O f these, [ had a p r o l o n g e d latency only, 9 had a decreased a m p h rude and n o r m a l latency, and 3 had an increased latency a n d decreased a m p l i t u d e . CortLcal t~blal and m e d i a n nerve SSEPs could be ehclted in all control subjects, the m e d i a n nerve N9 and N I 4 peaks could not be reliably r e c o r d e d m 3 patients. Both latency and a m p l i t u d e of the tiblal nerve SSEP were stgntficantly

Table 2 Description of groups HSP hereditary spastic paraparesls, vpt vlbrahon perception threshold control group, n = 64, meal rnedxan nerve SSEP control group, n = 79, hb. tvbnal nerve SSEP control group, n = 17. Latencles of SSEPs are given m ms, and amphtudes m /~V ± 1 SD is given m parentheses p values refer to t-test or to Flsher's exact test (only lor sex rahos) HSP

controls

Men women

19

Age (yrs)

45_6(176)

VPT Iog-VPTh tog-VPTt Median nerve SSEP N91atency Nl41atency N20 latency N14-20 mterlatency amphtude Tiblal nerve SSEP P37 latency amphtude

13

-079(082) 1 16 (1 60)

p-value

35 29 39 40 5 12 41 2(156) 409(1I/5) 395 (7 5)

0 42 vpt 0_23 med 0 04 tlb (122 vpt I117 reed I) l0 hb

--1 [7 (074) 0 13 (1 2l)

0011 l) 004

10.55(099) 1448(099) 20 42 (l 60) 5 74 (1 24) 308(1 83)

1 0 6 1 ((184) 1421 (102) 20_19 (1 20) 5 99 (0 62) 218 (123)

063 0 ll (~24 I).84 09q

42 22 (5 12) l 59 (1 09)

40 05 (2 64) 3 03 ([ 78)

0 040 (1_003

2{19

R 11)M lip Itl n e t al ,'Jour Hal 01 the N c u l l , l o e u al '~c n ' m ~'~ 125 (IOn4) _On _ l 1

T a b l e :~ Proportions

ol n o r n t a l ,rod a b n o r m a l

le,,ults

S e e lcxt l o r d c h n l t l o n s

1tSP

loi eat_h test

p v,tlucs r¢lc~ to Fisht.i s c\at_t lest

Controls

normal log VPFI~ I o g - V P ft medkm SSEI' hl~l,tl N S F P

ol , i b n o r m a h l ' ,

abnormal

y

normal

abnormal

I1

¢¢

I1

r (

II

¢¢

28 19 311 12

87 q g~l 4 03 8 t7 S

4 13 2 211

12 5 4(I 6 . ~, (~2 5

62 64 75 lh

0~ II)0 04 94

longer respectwely lower m the p a t m n t group, but n o n e ot the m e d i a n nerve SSEP latencies (Ng, N14, N I 4 - 2 ( I , N20) differed b e t w e e n the groups T a b l e 2 s u m m a r i z e s results in patients and controls Age did not dffter significantly b e t w e e n the patients and thc rcspectivc control groups, b u t body height did differ b e t w e e n p a t m n t s and the tlblal nerve control group T h e r e l o r e , length was i n c l u d e d as a c o v a n a t e in an A N C O V A , for the tlbml nerve SSEP_ the differonce, however, r e m a i n e d s~gnlficant b e t w e e n the two groups. Results ol classifying tests as n o r m a l or a b n o r m a l with the criteria d c h n e d above are stated m T a b l e 3 VPT, and the tlblal nerve SSEP were highly significantly more often a b n o r m a l m the p a t i e n t than m the control group In t.ontrast, the p r o p o r t i o n s of n o r m a l and a b n o r m a l results d~d not differ for the m e d m n nerve SSEP and VP'fl,

E~le~ I,~ o / d l ~ e a w duration and ~et'erttv R e l a t u m s h i p s b e t w e e n SSEP- and V P T - v a n a b l c s and d~scase-rclatcd laetors such as s e v e n t y and duration could bc m t l u c n c e d by c o n l o u n d m g effects of age. illustrated by the f o l l o w i n g in the p a t i e n t group, logVPTj was significantly Influenced by s e v e n t y (correlation coel!hcmnt t () 43, p = (I 039) However, log-VPT~ was also mlquenced by age (r = (158, p = 0004), and seventy was also i n f l u e n c e d by age ( r = 0 6 1 , p= 0 0002) In a d d m o n , d u r a t u m was s~gmficantly related to age (p=t~(1(1(14, r = 0 5 9 ) , and to s e v e n t y ( p < 0 0001, r = 0 78) This hnkage o[ older age with greater severity and h m g c r d u r a t u m m e a n s that, for instance, an effect ol d u r a t i o n on V P T or the SSEP could m fact r e p r e s e n t an effect ot age or severity' To c o u n t e , the influence of each of the disease variables, a forward slepwlse regressmn analysis was p e r l o f m e d with Iog-VPT or S S E P - l a t e n c y or -amphrude as the d e p e n d e n t variable (3'), and dul-atlon. severity aml age as the i n d e p e n d e n t variables (x). For Iog-VPT h and Iog-VPT~ and n b m l SSEP latency, only age e m e r g e d as a slgmficant effect ( p < 0 0 0 0 1 , p = (I 004, p = I1044 respecnvely). M e d m n nerve SSEP latency w,as s~gnlficant[y i n f l u e n c e d by severity ( p =

t, {I tj I

II

((

2 0 4 I

3 I {1 {I 5 I S t)

{1 0t)q 0 I}O(t(ll 11 77{I I) (lll(ll

00(172), and not by age or d u r a t i o n SSEP a m p l i t u d e s showed no sigmficant elfccts of any Ot these threc variables

4. Discussion

Abnormality rates From n o r m a l teatures ol e l e c t r o n e u r o g r a p h l c lindrags, late responses and SSEPs at E l b ' s point, it can bc c o n c l u d e d that there was no consistent e w d e n c e in lavour ot a p e r i p h e r a l c o n d u c t u m abnornaahty m HSP patients As the comparative analysis did not take mat acc o u n t the n u m b e r ol patients m w'honl a VPT~ could not be m e a s u r e d or m whom a tlbml ner~'c SSEP was absent, the results were d~chotomized as elthcr normal or a b n o r m a l based on increased Iog-VPT or not measurable ~esponses, or on increased [atencles, r e d u c e d a m p l i t u d e s or absent t e s p o n s c s tol lhc SSEPs ( ' o m p a n n g these resulting p r o p o r t i o n s ol n o r m a l and abnormal results m the p a t m n t and control groups revealed that Iog-VPTj Lind the tlbldl ner,,e SSEP were highly slgnlhcantly more o l t c n a b n o r m a l in the patienl group In contrast, n e i t h e r Iog-VPT~, nor the m e d i a n n e p < SSEP showed evidence ol disturbed l u n c l l o n T h e r e were thus p r o p n o c c p t w e a b n o r m a h t i c s m the lower limbs, but m m c in the u p p e r Schady and Sheard (Schadv and Sheard 19t)0) e x a m i n e d 23 p a t m n t s with HSP, 8, ol them showing othm neurological Mgns tin well, so It may bc clear that not all 23 p a n c n t s had a p i n e spastic parapares~s in their series, vd31-atum thresholds m the loot were elevated m 13 out ot 211 patients, including 5 p a t m n t s with a p o l y n c u r o p a t h y , and elevated m the h a n d in only I patient. Tfl~ud ncrx, e SSEPs were r e c o r d e d in 10 p a t i e n t s v, lthout polyncuropathy, and, when recordablc. P4() latenc~ was norreal The m e a n a m p h t u d c ol the P40 potentml, however, was signlhcantly reduced, m a g r e e m e n t with otu results, rellcctmg axonal d e g c n c r a n o n As peripheral n c ~ ' e c o n d u c t i o n was normal, the source ot a b n o r m a l SSEP and V P T h n d m g s must hc m the d y s l u n c t t o n ol ascending pathways ol the spinal

21(~

Rt'M

BJ¢¢xpr(Ta/

/~mtnalotlh,' \ctuolog, u,d S(t('m('~ 125(l~)~)4J2mJ

cord, Given the degeneration o1 the dorsal columns 171 patients with HSP and the fact that SSEPs are med)atcd predominantly (but not exclusively) via the dorsal colunms (Greenberg et al 1987). our fmding that 20 out o! 32 tibtal nerve SSEPs were abnormal m the patient group ~s not surprising. Since disease-related factors duration and seventy had little effect on VPT-or SSEP-vartables, provided that confoundmg etfects were taken into account, the normal tlbial nerve SSEPs m 12 and normal Iog-VPT) m 19 patients suggest anatomical variability in sensory pathways

Anatomical ~mphcattons There are several possible explanations for the striking discrepancy between the paucity of sensory disturbances, and the pathological substrate. First, a considerable degeneration of the dorsal columns must have taken place before this becomes apparent through neurologic examination. Second, ascending fibers outside the posterior funiculus are capable of transmitting propnoception as well, medmted by SSEPs or VPTs, resuiting m normal findings Third, a combination of both may account for the normal results. Finally, genetic heterogeneity may also play a role m explaming why some may show more sensory dysfunction than others It has been cla~med that the traditional role ot the dorsal columns, supposedly transmittmg propnoception, light touch and vibration to the dorsal column nuclei, whose axons project to the contralateral ventral posterolateral nucleus of the thalamus and then to the sensortmotor cortex is no longer tenable (Davidoff 19891. Furthermore, vibration sensation has been found not to travel by dorsal columns (Netsky 1953; Cook and Browder 1965; Wall and Noordenbos 1977; Ross et al. 19791; instead, the dorsal spinocerebellar tracts were said to be mvolved (Schwartzman and Bogdonoff 1968; Ross et al. 1979). In our patient group 40.6% ( 1 3 / 3 2 ) had a disturbed Iog-VPT t, which is tn keepmg with pathological data, according to which degeneration of the dorsal spmocerebellar tracts occurs m approximately 50% of the patients (Bruyn and Scheltens 1991) Our fmdmgs could thus be taken to support the hypothesis that these tracts are responsible for vibration sensation Dorsal columns and dorsal spinocerebellar tracts relay information about somatic stimuh, but the complexity of these pathways is much greater than we, chmclans, are aware of and the view on the trad]tional accepted functions of these tracts may need a change Regardless of the precise proprtoceptlve pathways mvolved, the present study does show that there are proprtoceptive abnormalihes in HSP patients, albett subclinical and not m all, located in the spmal cord, and confmed to the lower limbs.

"~

Acknowledgement We wtsh to thank I)l assistance

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Bout I()] It),, c o m p u t c ~

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