Symposium of the movement disorder society, June 18–19, 1993

Movement Disorders Vol. 9, No. 2, 1994, pp. 268-284, 0 1994 Movement Disorder Society

Symposium of The Movement Disorder Society, June 18-19, 1993

Motor Cortical Areas Transcranial Stimulation and Motor Control (Poster Session) Myoclonus (Poster Session) New Aspects of Dystonia Dystonia (Poster Session)

78-84 PSS-PlOl

P102-P 106 107-113

P114-Pl43

(In video sessions tapes were presented accompanying posters 115, 117, 119, 122, and 125)

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Internal representations of movement in the cerebral cortex R. Caminifi, Istituto di Fisiologia umana, Universith di Roma "La Sapienza", Rome, Italy.

Essential to arm trajectory formation is the combination of two sources of information, a visually-derived one concerning movement direction and a somatic one concerning the orientation of the arm in space. When movements traveling along parallel pathways are performed within different parts of space, thus changing the the orientation of the arm, in motor (area 4), premotor (area 6 ) and posterior parietal (area 5) cortices, the preferred direction vectors of individual cells rotate in such a way to predict, at the population level, the rotation of the arm necessary to bring the hand from one to another part of the work space. This suggests that coding of reaching in these cortical areas occurs withm a coordinate system centered on the shoulder joint, probably through a rogressive match mechanism between visual and somatic isormation, within a distributed fronto-parietal network.

Combined anatomical and physiological studies offer a biological underpinning to this view. When the early neuronal activity related to the presentation of a visual target is dissonated from later arm movement- and position-related activity, gradients spanning from visual to motor and somatic function can be found across the tangential domain of areas 4, 6, and 5. These cortical gradients seem to be "imposed" by a differential distribution of association parieto-frontal connections among the different fields of this distributed system, where area 5 plays a crucial role by sup lying the frontal motor fields with both the visual an: somatic information necessary for the composition of motor commands for reaching.

19

Studies with uositron emission tomograuhv (PET) on the human motor cortex Riidiger J. Seitz, Department of Neurology, Heinrich-Heine- University Diisseldorf, Germany. Measurements of the regional cerebral blood flow (rCBF) with PET provide a means to visualize human cerebral activity. Accurate anatomical mapping of PET data requires structural information from magnetic resonance imaging (MRI). Integrated PET/MR images contain quantitative and detailed spatial information representative for groups of subjects or individuals. Results of different motor activation studies in hea1th.y subjects and patients with focal brain lesicns will be presented. In healthy volunteers, the rCBF increases in the primary motor cortex were as high in individual finger movements as in sequential finger movements involving all fingers of one hand. In contrast, the areas of task-specific rCBF increases associated with individual finger movements were about half as large as those associated with movements involving all fingers of one hand. They had an individual somatotopy in stereotaxic space. The mean rCBF increases were not related to movement frequency, whereas learning of a complicated finger movement sequence increased the activation area in motor cortex. The rCBF increases in premotor cortex and mesial frontal cortex (supplementary motor area) varied from subject to subject and were related to individual task performance. In neurological patients with residual hand function after severe hemiparesis due to subcortical stroke, finger movements were always associated with rCBF increases in the contralateral motor cortex. Occurrence of rCBF increases outside the primary motor cortex contralateral to the moving fingers varied with the degree of restitution from hemiparesis.

ABSTRACTS FROM THE MOVEMENT DISORDER SOCIETY 269

Mechanisms of Activation of Corticospinal Neurones by Electromagnetic Brain Stimulation S.A. Edgley’ & R.N. Lemon. Department of Anatomy, Cambridge, UK

Recent developments in non-ivasive magnetic stimlilation for activation of the brain have allowed the functions of the motor cortex to be examined in man. One of the problems has been that to interpret the responses evoked by magnrtir stimuli it is important to know how they evoke responses. Our recent work has addressed this question by direct examination of the effects of magnetic stimulation on corticospinal neurones in monkeys, Our results reveal thzt corticospinal neurone: can readily be activated both directly and indirectly (presumably transsynaptically) by magnetic stirnull. Individual neurones are often discharged multip1.y by single stimuli, evoking a complex excitatory potential in motorneurones.

One of the applications of magnetic stimulation has been to look at the development of the corticospinal tract and corticomotoneuronal connections in man. Responses to magnetic stimuli are known to change during development in both monkeys and in man: responses to eLectromagnetic stimuli appear at shorter latencies and with lower thresholds as the individual ages. Current work is correlating responsiveness to magnrtlc stimulatlon with the development of corticomotoneuronal connections and the maturatlon of corticospinal axons

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Transcrarual stupuhon: phvsiolpgy JC Rothwell*, MRC Human Movement and Balance Unit, Institute of Neurology, Queen Square, London WClN 3BG, UK

Transcranial magnetic stimulation is now used routinely to activate the descending motor pathways from the cerebral cortex to the spinal cord. However, if two stimulators are used it is also possible to explore the connections between the motor cortex and other areas of the brain. In these experiments, a conditioning stimulus is given from one stimulator to one area of brain, and its effect on motor cortex excitability is tested at different intervals afterwards by examining the effect on responses to a test stimulus given over the motor cortex. Conditioning stimuli over the cerebellum, contralateral motor cortex, and areas of ipsilateral motor cortex can all produce effects on motor cortical excitability compatible with activity in cerebello-cortical, transcallosal, or conicocortical connections. The effects are predominantly inhibitory and begin at interstimulus intervals of 5 , 7 and lms respectively. Having defined these pathways, it is possible to test how their effectiveness changes in normal subjects when they make different movements, and how their excitability is affected by different disease processes. For example, (i) transcallosal inhibition is greater when subjects perform unimanual as compared with bimanual movements, (ii) cortico-cortical inhibition is reduced during contraction of the target muscle as compared with the resting state, (iii) the depth of inhibition is reduced in many forms of epilepsy, especially those involving the motor areas.

. . .

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Transcranial stimulation: DathoDhvsiology A. Berardelli, Dipartimento di Scienze Neurologiche, Universita’ “La Sapienza”, Roma.

Transcranial stimulation produces a muscle evoked response which is followed by a silent period lasting 2 W 300 ms. The first part of the silent period is due to spinal rnecha- nisms, whde the later part probably results from inhibitory effects at cortical level. In normal subjects the duration of the silent period is modulated by drugs acting on dopaminergic and Gabaergic systems. In Parkinson’s disease the duration of the silent period is shorter than normal subjects. The duration is also shorter when the patients are OFF than when they are ON therapy. A shortening of the silent period is also seen in patients with chronic treatment with dopamine-antagonist neuroleptics. On the other hand, in patients with Huntington’s disease the duration of the silent period is longer than normal subjects. The abnormalities of the silent period in Parkinson’s disease, in patients with dopamine-antagonist neuroleptics and in Huntington’s disease suggest that the duration of the cortical silent period may reflect basal ganglia influ- ence over the motor cortex.

83

CLINICAL ASPECTS OF MYOCLONUS. J.A. Obeso, Neurology, Clinica Universitaria Pamplona, Spain.

Myoclonus may be clinically classified according to its distribution as focal, multiofocal, segmental and generalized and regarding its presentation as spontaneous, act lol l ai-d s.timuius-sai, i iva (r&iexj . Daidii clinical and electrophysiological analysis can separate myoclonus from other movement disorders like tics, chorea and tremor. Myoclonus may coexist with other dyskinesias as for example in “myoclonic dystonia”. The value of looking for the presence of reflex myoclonus in the assessment of parkinsonism and the problem of myoclonus associated with ataxia will be discussed to illustrate to clinical escenarios where appropiate evaluation and understanding of myoclonus are very important.

Movement Disorders, Vol. 9, No. 2, 1994

270 ABSTRACTS FROM THE MOVEMENT DISORDER SOCIETY

pas

Short latency excitation of forearm motoneuronea evoked by transcranial maunetic stimulation F. Baldissera, F . Bracchi & P. Cavallari* Istituto di Fisiologia Umana 11, Univ. di Milano and *Dipartimento di Medicina Sperimentale, Universita dell'Aquila, Italy.

The H-reflex technique has been used to draw the time-course of the corticospinal effects evoked by clockwise magnetic stimuli (MS) in flexor or extensor carpi radialis motoneurones. MS was applied over the scalp in the focus for the lowest threshold response in those muscles. In all subjects (6) the latency of the response to MS at rest was equal or longer than that of the H-reflex in the same muscle. A facilitation was thus expected at conditioning-test intervals positive or equal to zero. Instead, at MS intensities below motor threshold, facilitation of the €I-reflex started when the conditioning stimulus lagged the test stimulus of 4 ms and reached a peak at about -2 ms. The following decay attained a local minimum at about -1 ms. Thereafter, a second facilitatory phase peaked at about +1 m s . The same result was obtained in five subjects on flexor and in one subject on extensor motoneurones. In conclusion, under MS a subliminal excitation precedes of 3-4 ms the motoneuronal discharge, whose timing corresponds the second peak of facilitation. Contrary to current views (cfr. 8. Day et al., Neurosci. Lett. 75:lOl-106, 1987), the earliest synaptic effects produced by magnetic stimuli are as fast as those evoked by transcranial electrical stimulation and considered to be monosynaptic.

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Voluntarv contraction lowers the threshold for activation of cortical neurons bv macrnetic stimulation R. Mazzocchio* and JC Rothwell, MRC Human Movement & Balance Unit. The Institute of ~~

Neurology, Queen Square, London, UK

We investigated whether the threshold intensity of a magnetic cortical stimulus required to produce a descending volley was reduced by the voluntary contraction of the target muscles. Facilitation of the H-reflex of the forearm muscles was used as an index of

neurones. Subthreshold magnetic stimulation was delivered either with a circular coil centred at the vertex or with "8" coil placed above the corresponding motor area. In most subjects, magnetic stimulation produced the earliest facilitatory effect at conditioning- test intervals of -1 to -3 ms (median nerve stimulus before magnetic). At these intervals weak, tonic voluntary contraction of wrist flexors significantly reduced the threshold for obtaining facilitation of the H reflex in all the 7 subjects examined. In 3 subjects stimulation with *laii coil elicited an additional, earlier peak of facilitation at conditioning-test intervals of -3 to -5 ms. With such intervals, voluntary contraction had no effect on the threshold for magnetic facilitation of the H reflex. It is concluded that the reduction in threshold with voluntary contraction reflects increased excitability at cortical level; with a different type and orientation of the coil it is possible to produce probable, cortical D wave activation.

Pa7

____ Motor evoked o ten t i a l t o trans r 1 ma net ic s t imu la t i on dPrin shSo t i atn?i:enetLinq contractions o f the :Doer 'it2 2 s c 1 ~ .

M. Schieppati. G. Abbruzzese', M. Morena and C. Trmpetto - Dept. o f Neurology, University o f Genoa. I t a l y

Changes o f motor p o t e n t i a l s (MEPs) evoked by transcranial magnetic st imulat ion (TMS) o f the motor cortex during flexion-extension movements of the upper l imb were invest igated i n a group o f right-handed normal volunteers. A Novslnetrix Magstin 200 stimulator with a round c o i l (13 a.) centered tangential ly over the vertex (clockwise current f l o w ) was used at an intensity adjusted t o 10% above MEP threshold. Surface 010 recordings were obtained from the biceps brachi i (BB) and brachioradial is (BR) muscles during isanetric, shortening (flexion) and lengthening (extension) contractions, the TMS stimulus occurring a t the same elbow j o i n t angle. Flexion-extension movements were performed with d i f f e r e n t weights and ve loc i t i es . MEP latency, duration and size (normalized t o the rect i f ied Em; signal of the 40 msec. preceding the stimulus) were measured. For corresponding l e v e l s o f preinnervation, MEPs i n the BB and BR muscles were reduced i n s i ze and delayed i n latency dur ing lengthening c o n t r a c t i o n s as compared t o t h e i s o m e t r i c cond i t i on . Changes o f MEPs d u r i n g shortening contract lons were not s i g n i f i c a n t l y d i f f e r e n t from the isometr ic condit ion. These f ind ings i nd i ca te t h a t t he e x c i t a b i l i t y o f t he cortico-motoneuronal system f o r the 6B and BR muscles can be d i f f e r e n t i a l l y modulated dur ing various types of upper limb movements.

rhanges in cxcitaSLlity cf zzrticoiiistJnsGrona1


ABSTRACTS FROM THE MOVEMENT DISORDER SOCIETY 2 71

PSS t i c s-

G.Pavesi*, G.M.Macaluso', G.Luppinot, M.Matel l i t , D.Medici and D . Mancia, I n s t i t u t e s of Neurology, Human Physiology ' , D e n t i s t r y " ; U n i v e r s i t y of Parma, I t a l y . The i n t r o d u c t i o n of c o i l s of new d e s i g n i n t r a n s c r a n i a l magnetic s t i m u l a t i o n (TMS) technique allows one t o o b t a i n an i n c r e a s e of t h e s p a t i a l r e s o l u t i o n i n mapping t h e c o r t i c o s p i n a l pathway. W e examined 7 r ight-handed h e a l t h y vo lun tee r s ( 3 males and 4 f ema les ) w i th t h e head f i x e d by a modif ied c e p h a l o s t a t . TMS w a s performed by a n "eight-shaped' ' c o i l (Dantec Mag. S t i m . ) , l i n k e d t o t h e c e p h a l o s t a t . Tne c o i l was moved i n 1 c m s t e p s s a g i t t a l l y and co rona l ly , s t a r t i n g from t h e v e r t e x . The motor evoked p o t e n t i a l s were recorded by s u r f a c e e l e c t r o d e s from re l axed muscles of t h e c o n t r a l a t e r a l body s i d e ; l a t e n c i e s and ampli tudes were measured and mapped a c c o r d i n g t o t h e p o s i t i o n o f t h e c e n t r e of t h e c o i l . In 5 s u b j e c t s MRI was performed i n o r d e r t o r e l a t e t h e s u l c a l p a t t e r n and t h e magnetic s t i m u l a t i o n map. P r e s e n t d a t a show t h a t t h e c l a s s i c a l complete body r e p r e s e n t a t i o n i s i d e n t i f i a b l e a l s o by means of TMS. The l e g , arm and f a c e f i e l d s a r e we l l s e g r e g a t e d . The arm f i e l d h a s t h e w i d e s t r e p r e s e n t a t i o n . P rox ima l and d i s t a l musc le s r e l a t e d MEPs a r e observed i n l a r g e l y overlapping regions with t h e d i s t a l ones, however, extending more l a t e r a l l y and r o s t r a l l y . The r o s t r o c a u d a l e x t e n t i o n of t h e arm f i e l d appear t o exceed a r e a 4 a s c y t o a r c h i t e c t o n i c a l l y d e f i n e d t h u s s u g g e s t i n g t h e e x i s t e n c e of e x c i t a b l e f i e l d s r o s t r a 1 t o p r e c e n t r a l mo to r c o r t e x . T h i s hypo theses i s s u p p o r t e d a l s o by o b s e r v a t i o n s coming from two p a t i e n t s with r o l a n d i c l e s i o n s .

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The action of transcranial direct currents on the human motor cortex: a study with magnetic brain stimulation A. Priori ( + I , A. Berardelli, S. Rona, N. Accornero, M. Inahilleri and M. Manfredi, DiDartimento di Scienze

The action of transcranial direct currents on the human motor cortex: a study with magnetic brain stimulation A. Priori ( + I , A. Berardelli, S. Rona, N. Accornero, M. Inahilleri and M. Manfredi, DiDartimento di Scienze Neirologiche, Universitd di Roma "La Sapienza", Italy

Direct currents (DCs) applied to the scalp can affect the simple reaction time in humans. Transcranial brain stimulation produces Muscle Evoked Potentials (MEPs) originating in the motor cortices. We tested whether D C s applied over the scalp affect the size of the MEPs. Fifteen voluntary healthy subjects were studied. DCs below perceptive threshold were delivered by a Grass S 4 4 constant current stimulator connected to a pair of electrodes (area: 25 cm2 each), one of which placed over the left motor cortex and the other under the chin. Transcranial magnetic stimuli were delivered by a Novametrix stimulator. MEPs were recorded from relaxed first dorsal interosseus muscle. In five subjects we also recorded the H reflex from the right forearm flexors. In the first experiment we conditioned the MEP alter- nately with anodal and cathodal !on the scalp) DC (300 UA) in the same trial. Anodal DC reduced the size of the MEPs (mean 5 1SE) 8 . 2 3.3% !p<0.03, n=14, paired data) without affecting the size of the H reflex ( ~ 5 ) . Cathodal DC did not affect the size of the MEPs and of the H reflex. Anodal DC lower than 300 uA caused a progressive reduction of MEP inhibition. In a second set of experiments, anodal DC alone (not alternated with cathodal DC) had no significant effect on the MEPs. In conclusion, transcranial anodal DC inhibits the muscle responses evoked by transcranial magnetic stimulation, possibly hyperpolarizing the most super- ficial layer of the motor cortex. Only the anodal- cathodal sequence is effective in changing the excitability of the motor cortex.

p90

Comuarison of exc i t a t o r v and i n h i b i t o r v musc le r e s D o n s e s u s i n u t r a n s c r a n i a l m a u n e t i c s t i m u l a t i o n (TMS) maDuinq S.A.Wilson, G.W.Thickbroom* and F .L .Mas tag l i a . A u s t r a l i a n Neuromuscular Resea rch I n s t i t u t e , Pe r th , A u s t r a l i a .

The topography and s i z e o f t h e c o r t i c a l a r e a s from which a motor evoked p o t e n t i a l (MEP) and s i l e n t p e r i o d (SP) can be evoked i n t h e l e f t a b d u c t o r p o l l i c i s b r e v i s musc le have been compared i n 1 0 normal s u b j e c t s u s i n g a TMS mapping t e c h n i q u e . A 50mm f i g u r e 8 c o i l was uced, s t i w ~ l u s i n t e n s i t y was th re sho ld -ad jus t ed and s t i m u l i were a p p l i e d d u r i n g l o w - l e v e l (10*3%) v o l u n t a r y m u s c l e c o n t r a c t i o n . The ampli tude of t h e averaged MEP and t h e average SP d u r a t i o n were used f o r map c o n s t r u c t i o n . The c e n t r e of t h e MEP maps had a mean l a t i t u d e of 2 8 . 7 ' and a mean l o n g i t u d e of 2 . 1 " . The l o c a t i o n of t h e SP maps corresponded c l o s e l y t o t h a t of t h e MEP maps ( l a t i t u d e 2 7 . 8 " , l ong i tude 2 . 6 " ) . The mean SP map a r e a ( 2 0 .3cm2) w a s found t o be l a r g e r t han t h a t of t h e MEP map (13.0cm2). Thus t h e c o r t i c a l a r e a g i v i n g r ise t o t h e i n h i b i t o r y SP o v e r l a y s and surrounds t h e a r e a f o r t h e e x c i t a t o r y MEP. These f i n d i n g s suggest t h e p o s s i b i l i t y of c o r t i c a l i n h i b i t o r y p rocesses a c t i n g t o l i m i t o r c o n t a i n e x c i t a t o r y c o r t i c o m o t o r o u t p u t . T h i s i n t e r p r e t a t i o n has p a r a l l e l s w i t h t h e phenomenon of s u r r o u n d i n h i b i t i o n i n s e n s o r y c o r t e x , and o f f e r s ev idence t h a t a s i m i l a r phenomenon may a l s o be a c t i v e wi th in t h e human motor c o r t e x .

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Silent Deriod induced bv Maanetic Stimulation: lnvestiaation of muscles innervated bv cranial nerves K.J. Werhahn', J. ClaRen, R. Benecke Department of Neurology, University of Dusseldorf, Germany

W e studied the silent period (SP) induced by magnetic stimulation over the sensorimotor cortex (Magstim 200, figure-of- eight coil, loop diameter 7 cm) in muscles supplied by cranial nerves (M. mentalis, masseter, sternocleidomastoid (SCM) and genioglossus) in normals and patients with localised cortical lesions. Recordings were made using surface or needle electrodes in active muscles. In normals there was a SP in all contralateral as well as ipsilateral muscles. The duration of the SP was independent of the level of preactivation of the target muscles and increased with increasing stimulus intensities. In mentalis, masseter and genioglossus the duration of the SP was in the order of 150 ms and in SCM around 80 ms using a stimulus intensity of 1 .5 times threshold at rest. In patients with lesions of the face-associated cortical areas the SP was shorter on both sides with stimulation over the affected as compared to the unaffected hemisphere even if there was no palsy clinically. In contrast, patients with a lesion in the arm-associated primary motor-cortex or in other motor competent cortical areas showed a longer SP with stimulation of the affected compared to the normal hemisphere. We conclude that the SP in muscles supplied by cranial nerves is mainly generated cortically and is also present in ipsilateral muscles reflecting physiological bilateral innervation.


2 72 ABSTRACTS FROM THE MOVEMENT DISORDER SOCIETY

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lnhibitorv Phenomena in SDinal Motoneurones after Transcranial Magnetic Stimulation (TMS1 J. ClaRen' and R . Benecke, Department of Neurology, Heinrich-Heine-University of Dusseldorf, FRG

After TMS the period of electrical silence following the early excitatory response (SP) increases with increasing stimulus intensities but not preactivation. Little is known about the SP on the single motoneurone level. We investigated the firing probability after TMS (Magstim 200, 12 c m round or 7 c m figure-of-eight coil) in motor units of small hand muscles and distal arm muscles of normal volunteers using concentric needle electrodes (Medelec). Stimuli were applied randomly at slight preactivation of the units. It could be shown that at threshold intensities motor unit discharges can be delayed, consistent with a pure inhibitory effect of TMS. Furthermore the length of zero firing probability (equivalent to SP in surface EMG-recordings) at a given stimulus strength is dependent on the recruitment rank order for voluntary and magne- toelectric activation of the investigated motor unit. In each individual motor unit the suppression of firing probability reaches near-maximal length within a very narrow range of stimulus intensities and can exceed 200 ms while the SP in surface EMG recordings is only in the order of 100 ms. Pre- liminary experiments with topographical mapping showed that excitation and suppression of the single motor units are maximal at stimulation over the same cortical areas. Stimula- tion over the outer zones of these areas, however, lead to a relatively enhanced suppression of motor unit firing. This work was supported by DFG (SFB 194).

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Modulation of the cortical silent Deriod bv GABA and barbiturate druas. M. Inghilleri, A. Berardelli, R. Restante, M.L. Borgia, A. Priori, M. Manfredi, Dipartimento Scienze Neurologiche, Universita' "La Sapienza", Roma.

Transcranial stimulation (TCS) produces a muscle evoked response (MEPs) followed by a silent period of the electromyographic activity (SP). This silence is believed to be due to activation of cortical inhibitory systems (Inghilleri et al. 1993) and could be mediated by GABA (Kmievic et al. 1964). We have now studied the effects of GABA-A (Diazepam) and GABA-B (Baclofen) and the barbiturate (Thiopentone) drugs on the silent period evoked by TCS. The silent period was evoked in the first dorsal interosseous muscle, in ten normal subjects, during a voluntary contraction of about 50% of maximal force. TCS stimuli were given at an intensity twice motor threshold. The SP was also evoked by supramaximal electrical stimulation of the ulnar nerve at the wrist. The injection of Diazepam (0.17 mg/Kg i.v.) significantly reduced the cortical SP (253+97 ms before; 153+71 ms after) but Baclofen (racemicform, 0.6 mg/Kg i.V.) produced no change (195+45 ms before; 200+68 ms after). Neither drug modified ?he motor thresholdor the am li tude of MEPs. The injection of Thiopentone (1.6 m g f ! i.v.) did not modify the duration of the SP (199.2 + 68 ms before; 209+74 ms after) but decreased the amplhde of MEPs (6.4+T.4 mV before; 3.6+1.9 mV after). None of the drugs testcd modified the perip7eral silent period. In conclusion the cortical silent period can be modified by GABA-A but not by GABA-B and by barbiturates. GABA-A modulation probably exerts its action at basal ganglia level by modulating the talamocortical output (Iadarola and Gale 1982).

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m n s c r a nial magnetic st imulat ion 1TMS) in writer's cra mu S.A.Wilson, G.W.Thickbroom, B.A.Laing, R.Stel1 and F.L.Mastaglia*. Australian Neuromuscular Research Institute, Perth, Australia.

We have studied the cortical representation of the right and left abductor pollicis brevis (R,L APB) in two right-handed writer's cramp patients using TMS. Using a 50mm figure 8 coil, 4 threshold adjusted stimuli were delivered to sites over the motor cortex during a low level (10f3%) contraction of the APB. The amplitude of the averaged motor evoked potential (MEP) WF$ used for map construction. For case 1 all map parameters, MEP waveforms and silent period (SP) duration were normal. For case 2 the MEP maps for both hands were more laterally placed than in controls: latitudes of 38.4' & 35.6' for the R & L APB vs. 28.2k2.7" and 28.7f3.5" for 10 controls (p<.05). SP duration near the centre of the motor area was at the lower end of normal range (R APB 97m.5, L APB 116ms). The post-MEP waveforms following stimulation at the periphery of both APB areas showed atypical short EMG bursts every 60-70111s separated by periods of EMG silence. The burst frequency (=16Hz) was not consistent with the frequency of a tremor (6Hz) in the R APB observed during writing. The findings in this case point to a bilateral reorganisation of the corticomotor representation of the hand muscles and to disinhibition of corticomotor output. The normal findings in case 1 indicate that different pathophysiological mechanisms may operate in writer's cramp.

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Late responses evoked by transcran-La_l__-braxn _____ stimulation in patientswith dystona L. Bertolasi (*,l). L. Zanolli (I). R. Eleopra ( 2 ) . G. Tomelleri 11). I). De Grandis ( 2 ) . 11) Clinica Neurologica. Universita' degli Stud1 di Verona: ( 2 ) Divisione Neurologica. Arcispedale S. Anna. Ferrara. Italy.

Transcranial brain stimulation tTCS) evokes normal short latency muscle evoked potentials (MEPs) in patients with dystonia. Longer latency responses at rest have been observed in patients with Wilson's disease. We studied with TCS ten patients with dystonia to see whether they had late MEPs at rest. Six patients had focal dystonia. three had generalized dystonia. and one had hemidystonia. Ten healthy subjects were also studied. MEPs were recorded from proximal and distal limb muscles. In the patients with cranial dystonia and spasmodic torticollis MEPs were also recorded from facial and neck muscles. Normal subjects had late MEPs only during voluntary muscle contraction. Eight of the ten patients had at rest. beside short latency MEPs. late MEPs with a latency longer than 6 0 ms. In patients. voluntary contraction increased the amplitude of late MEPs. The patient with hemidystonia presented late MEPs at rest only in the affected side. We believe that the presence of late MEPs at rest represents an abnormality useful in the physiological evaluation of patients with dystonia.



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Transcranial magnetic st imulation in uatients with stroke: abnormalit ies. clinical cor re la t ions a n d promostic value of mem B. Mercuri, A. Berardelli, M. Inghilleri, G. Cruccu, M. Manfredi, Dipartimento d i Scienze Neurologiche, Universita' "La Sapienza" di Roma.

In a g roup of patients with s t roke we s tudied the Muscle Evoked Potentials (MEPs) 4-28 days after the stroke and o n e month later. We a lso evaluated the correlation between clinical and neurophysiological signs and the value of MEPs as a prognostic index for motor recovery.

Twenty-two patients (mean age 67.7 yrs) with hemiparesis participated in the study. For each patient, a total motor score was calculated taking into account muscle tone and strength, tendon jerks and hand function of the paretic limbs. Magnetic stimuli were delivered with a Novametrix Stimulator (Mag- stim 200; maximal output) and MEPs were recorded from the biceps, thenar and tibialis anterior muscles.

At t he first evaluation MEPs were absent i n 54.5% , delayed in 30.3% and normal in 15.2% of the paretic muscles. One month later, MEPs were absent in 31.8% , delayed in 33 .3% and normal in 34 .9% of the muscles. MEP abnormalit ies in tibialis muscle recovered best. The MEP abnormalities also correlated significantly with the total motor score . Patients with delayed MEPs in the tibialis muscle at the first evaluation had a better lower limb motor improvement after 30 days than the patients with absent MEPs. In the uppe r l imb we found n o prognostic value of biceps and thenar MEPs.

In conclusion, MEPs are a useful method for detecting abnormalities of the corticospinal tract and strongly cor re la te with moto r performance. Thei r prognostic value remains unproved.

F97

evolud DotmtiAlrn A e s e s m notor blocks in Parkinson's diseaae: ma4netiC motor

B.?errarO, K.UbiAli*, H.RASellA*, G.C.GaZZAnigA, H . V i s a r d i * , H.-lingo and A.&moli 2nd -1 Lbpt. " ~ y e i o p a t h O l O s y SeNiw, O n p d A l i R i u i t i , BergaW.1tAly

Tha axpression "motor blocks" (MEs),recently proposed (Giledi et al., 1992) characterize a11 sudden, short

inhibition in executing A mwrmrt or switching frCm one movement p a t t e r n t o another, observed in some

rolr for 111 i m c i m e n t of the s u p p ~ ~ t a z y m t o r area ( E m ) i n t h e genaration of internal ly cued Actions breskdoun, namely in HBs end akinesia i n Parkinson's

W e nnlurrad 10 PD p.tLwtn (4 mlem and 6 fenalsa), meop

age 61f4 years , i l lneSS duration 6f2.2 years And ELY ranging fran 215 to 3/5.Threo patimtn experiencing only ELBa,were ccmpared with 3 patients with akinesia and 4 with tremor.Nona presented the "on-off" phenmnenon or hyprkinesias.The eX.SltlhIAtiOn was performed ongoing sntipsrkinsonian drugs.A Dantsc stimulator was used, m A X h l l m f i e l d strenght of 1.9 T And del iver ing A monophasic current pu1se;delivering of s t imul i waa at learnt with 15 seconds of an interval.Tw0 AglAgC1 8-nun d i h e r cup electr&s rnre placed 4 cm apart over the be l ly of the bi lateral f i r s t dorsal interosseua muscle. 011 A-AW, al l had norm1 central conduction t h , but tho motor evoked p e n t i d s m e larger and the threshold Of SimlllAtiOn W I S 1 0 W . r in pat ients With 1188 And akineaia than those with tremor symptmn (p<O.O5). By-perexcitability of corticamtcmmrron system in MBs and akinesia, but not i n tremcr, i s supporting for t h e hypotbais of SHA impairmsnt.

l a s t i n g epirnodes O f breaks in motion AS W e l l A S

prU& P.tiat.-Al E V i b - pOblt t o a C l X C i A l

diaNne (PD).

P98

EVOKED POTENTIAL STUDIES OF SIMPLE AND CHOICE REACTION TIME PARADIGMS

Dept. of Neurology, University of Munich, Germany BOTZEL, K., MAYER, M.*, PAULUS w .

We recorded evoked scalp potentials of a simple and a choice reaction time paradigm in a group of young and old normal human subjects (average age 25 and 62 yrs) and in patients with Parkinsons disease (62 yn.) under L-Dopa treatment. Also, reaction times were measured. The potentials preceeding the imperative stimulus are discussed in this report. We found a slowly increasing frontal positivity (average 2.5 mcV/s) in young subjects in the simple task and a less steep increase in the complex task (1.5 mcvis). Old subjects showed similar differences between the simple and complex task. Patients showed hardly any slowly increasing frontal positivity before either task. In the patients, on average, the increase of the frontal positivity was slightly more pronounced in the complex task, in opposite to the results of the normal subjects. The results demonstrate that in healthy persons the storing of a preprogrammed motor sequence (simple task) is correlated with a larger frontal positive wave as opposed to the selection of an appropriate motor sequence (complex task). The reversed pattern of electrocortical phenomena in patients and the corresponding reaction times suggest that the patients have difficulties in storing andlor initiating preprogramed motor sequences. (Supported by BMFT 01 KL 9001/1)

P99

VARIATION OF THB CORTICO-SPINAL OUTPUT MODULATES THE MOVEMENT-RELATED POTENTIAL Troni U?; Bianco C.; Coletti Moja M . ; Dotta M. and Forno R 1st Neurological Clinic, University of Turin; via Cherasco. 15 10126 TORINO Italy

In 6 normal subjects the movement-related potential (MRP) prior to self-paced forceful contraction of the 1st inte- msseous muscle ( m a - M R P ) was compared to that prior to the smallest movement of the same muscle (min-MRP). In the latter experiments, monospike EMG activity associated to the discharge of a low threshold motor unit potential was recorded by mean of a coaxial needle electrode inserted in the muscle bell, according to the method described by Kato and Tanji (1972). In all subjects a clear-cut shape change was observed between the cerebral potentials related to the two opposite motor tasks. This difference w a 8 represen ted in the min-MRP by l)a reduction of the amplitude of the NS' component; 2)a nearly complete disappearance of the "premotion positivity" (PMP), which w a s always present in the m a - M R P ; 3)a significantly (60-80 ma) delayed onset of the rising slope of the Motor Potential complex (W). On the contrary, the peak latency of the MP was unchanged. These results demonstrate that modulation of the voluntary cortico-spinal output selectively affects different components of the MRP. In particular, our data indicate that the PMP quantitatively correlates to the cortico-spinal output. On the other hand, the attenuation of the early rising slope of the MP complex, roughly corresponding to the onset of the EMG activity in the m a - M R P , suggests that this specific component may reflect the reafferenta- tion from the contracting muscle.

Movement Disorders, Vol. 9. No. 2, 1W


Ploo

EFFECTS OF AGING ON POSTURAL ADIUSTMENTS ASSOCIATED WITH FAST ELBOW FLEXION MOVEMENTS F. Benvenuti, M. Baccini, E. Girolami, P. Sommazzi, S. Gangemi, A. Baroni. U.O. Geriatria e Riabilitazione, INRCA, Florence, Italy.

The aim of the study was to investigate differences due to age in the maintenance of equilibrium before, during, and after performing fast symmetric elbow flexions (EF). Nine aged (66-79 years) and twelve young (21-32 years) healthy subjects were requested to stand upright holding a horizontal bar with their forearms supinated and eyes open (EO) or closed (EC). After 10-15s of quiet stance they were requested to perform fast EF and, subsequently, to maintain the new position for 13s more. Young subjects performed EF with angular accelerations in the same range as the elderly. Antcrior-posterior displacements of center-of-pressuie (COP) were sampled (100 Hz) using a force platform (Kistler). Elbow, trunk, hip, knee, and ankle angle movements were sampled (50 Hz) with a 3-D video-based motion analysis system (ELITE). Off-line, from the computer recordings, periods of 8 s were selected for each trial (3 s before and 5 s after the onset of En. These periods were further divided in 500 ms intervals in which the total lengths of COP (mm) and joint angular (degrees) movements were calculated. With EO, before the onset of EF, the length of COP, trunk, hip and knee movements was greater in the elderly, while no differences were observed for ankle movements. In the time interval in which EF occurred, the length of movements of COP and joint angles showed a sharp augmentation in both groups. However, the length of movements of trunk, and hip and knee was greater in the elderly. After the end of EF, lengths of movements rapidly decreased. The time required to achieve values similar to those observed before the motor act was longer in the elderly for COP and all postural joints. With EC, the time required for recovering stability was prolonged in the young and decreased in the elderly. Results indicate that elderly subjects adopt a different strategy to maintain standing posture while executing fast EF.

PlOl

-movement at the elbow in man U w i n d S.J. Fellows', C.Kaus, H.F.Ross & A.F.Thilmann Neurologische Klinik, Alfried Krupp Krankenhaus, Essen, Germany

The major features of spasticity include hyperreflexia, a velocity-dependent muscle hypertonia and some degree of paresis. In clinical practice, however, the first two of these features are defined with the limb in a passive state. Great differenas, however, exist in the state of the motor system under active and passive conditions. Thus it does not follow that hypertonia and hyperreflexia elicited by a passive displacement will appear in response to a similar movement performed voluntarily. Some studies of reflex behaviour usder xt ivc cczditions have found evidence cf disruption of w l ~ ~ ~ a ~ - movements by stretch activation of an antagonist muscle at the elbow, knee and ankle joints. Other studies, however, have Failed to find evidence of such disruption. One reason for this conflict may have been the range of causes of spasticity of the patient groups in these studies: spasticity is a syndrome and not a disease and will not show the same features in all cases. Accordingly we have studied a homogeneous group of patients, in whom spasticity arose following a unilateral ischaemic lesion in the area of the middle cerebral artery. Patients were tested for isometric strength in the elbow flexors and for their ability to perform discrete elbow flexing movements in a manipulandum against a range of opposing loads. It was found that the degree of paresis was positively correlated with the degree of impairment of the voluntary flexing movements. Movements without opposing load produced exaggerated antagonist (extensor) activity which also increased progressively as the impairment of movement worsened. Elbow flexors, however, are anti-gravity muscles and always operate, under natural conditions, against a load. Under these conditions antagonist activation was completely normal, even in severely hypertonic patients. Thus we conclude that under natural conditions, spastic patients are able to p t e out muscle hypertonia apparent in the passive state and that their impairment is best related to the degree of paresis in the affected muscles.

HYFeflexia ~ ~ r ~ s i s as t h c d o m i n a n t t *n 1- . . .

n f

PlOZ

Electrophvsio~o$zica! asDects of cortical reflex mvoclonus R. Cantello*, M. Gianelli. C. Cward, R.Mutani University Department of Neurology. School of Medmne. Ospedale Maggiore, 28100 Novara (ITALY).

Five consenting patients presented with a reflex myoclonus whose clinical features fit the diagnosis of "cortical reflex myoclonus". With a Dan& Mag2 monophasic magnetic stimulator (max output = 2.3 T ; 9-cm coil centered at the vertex), we measured the minimum motor evoked potential (MEP) latency from the right or left FDI muscle. The size of the MEP was comparable to that of the EMG counterpart of myoclonus. Subjects were instructed to be as relaxed as possible. The background was actually quantified nff-liv to c 'CUT- u?;for-;+-. ir I n&nt '1'~ .?.?fie.? 3 t4e MEP latency me latmq ot UIL N20 ah;' n m e SEP wave m the same subject. Thus, we obtained a TI time, corresponding to that theoretically needed by a nerve pulse to traverse the "transcottical" pahway. Actually, the TI time was longer than the minimum latency of the reflex rnyoclonic FDI jerk in 4 out of 5 five subjects Thus, in the majority of subjects, reflex myoclonus timimg could not be easily explained by the "transcortical hypothesis". By adding to the MEP latency the latency of the first giant SEP component (P25), we obtained a t i e , which was obviously much longer than the reflex myoclonus latency in all subjects. Thus, the reflex myoclonus could not be generated by the giant SEP . Ln collision expenments (ulnar nerve shock preceding the cortical stimulus), uL identified the exact segment of the giant SEP hit by the cortical shock. Indeed, peripheral prestimulation induced a huge facilitation of the FDI MEP, but - in 4 out of 5 subjects - only when the cortex was stimulated after the P25 component had developed therein. Again, the phenomenon was too late to support the "transcohd" hypothesis. Three of the 5 patients often showed double or triple jerks in response to a slngle stimulus to the ulnar nerve. However only the first jerk was unifody preceded by a giant SEP. Therefore, the following jerks were not generated by a giant SEP. Our data suggest that, in at least some subjects with "cortical" reflex myoclonus , the "transcortical" hypothesis may be inadequate.

P103

KaeawhU M. Onofrj, F. Ferracci, L. Curatola, G. Malatesta and T. Fulgente, Department of Neurology, State University of Chieti, Chieti, Italy

We recorded Somatosensory Evoked Potentials (SEPs) to median nerve and tibial nerve stimuli from 19 scalp electrodes in 3 patients affected by cortical reflex myoclonus and in 1 patient suffering from Myoclonus Epilepsy. The cortical reflex myoclonus followed an influenza1 syndrome in 2 patients and was due to methil-bromide intoxication in the third patient. Ten neurologically normal subjects served as controls. In all patients SEPs to median nerve stimuli showed a "giant" component at a latency of 28.4-31.6 msec. (N30), having amplitude values 4 to 7 times higher than those measured in control subjects. The giant component was prominent on bilateral frontal and central derivations. SEPs to tibial nerve stimuli evidenced a high amplitude negative wave (5 to 6 times higher than in controls) peaking at about 47- 49.5 msec. (N48) and prominent o n fronto-central derivations, ipsilaterally to the stimulated limb. Our findings, while showing in cortical myoclonus the presence of a giant component elicited also by stimuli of the lower limbs, seem to suggest that the ipsilateral N48 component is the lower limb equivalent of the anterior N30 obtained with median nerve stimuli.



PlW

Ch&.progressive multifocal myoclonus with intrathecal immunoglobulin synthesis: a study of three cases.

F.Girotti*, F.Carella, V.Ciano, A.Salmaggi, S.Einelli, P. Giovannini, E.Palazzini. Istituto Neurologico Nazionale C Eesta, Milano, Italy.

We describe 3 adult male patients with progressive histories of multifocal action myoclonus and ataxia lasting mg re than 10 years. One patient had generalised epilepsy. A l l had persistent cerebrospinal fluid (CSF) abnormaliti- e s : oligoclonal bands on agarose gel isoelectric focusing and high JgG indes (6.5, 1.8, 2.3 y.y.1 indicating intrathecal immunoglobulin synthesis. Magnetic resonance (MR) revealed progression of the cerebellar atrophy without the white matter signal abnormalities found in inflamma- tory demyelinating diseases. Electrophysiological findings (time-locked EEG everts, somatosensory evoked response) were consistent with cortical reflex action myoclo nus. Other investigations excluded encephalitis, systemic autoimmune, metabolic and lysosomal diseases and mitochg ndrial encephalomyopathy. The clinical and electrophysiological findings in the three patients were similar to those described for cerebellar myoclonic dyssynergia. In- flammatory CSF signs have been sporadically observed in both cerebellar myoclonic dyssynergia and progressive myoclonic epilepsies. The existence of anti-cerebellum an- tibodies in one patient suggests "chronic cerebellitis" similar to that described in paraneoplastic syndromes. (Videotape o f the clinical cases).

P105

Negative myoclonus in Creutzfeldt-Jakobs disease. A. S. Gabellini, P. de Carolis, A. Giovannini, P. De Massis, T. Sacquegna, Bologna, Italia

We describe a case of autopsy proven Creutzfeld-Jakob disease, in which the presenting symptom was a focal myoclonus localized at the left arm. The myoclonus, mild at rest, was increased by motor activity and external stimuli; on posture it became more severe and was aainly negative. Poligraphic recording showed at rest synchronous bursts of EMG activity in forearm flexors and extensor muscles, with a variable duration between 100 and 500 msec often rhythmic at 2.5-3 Hz, while tonic muscular activity was interrupted by lapses of 200-300 msec followed by a brief increase of EMG activity. EEG showed focal slowing of electric activity on the right central area,while jerk-locked averaging disclosed a negative-positive potential of 15 microV starting about 30 msec before the myoclonus in the contralateral arm. This case supports the observation that in C-J disease different types of myoclonus may be present, including negative myoclonus.

P106

Abdominal mvoclonus as onlv sian of root lesion F.Pisano *, G.Miscio, AAomorini * , P.Pinelli '' Fondazione Clinica del Lavoro. IRCCS. Centro Medico di Riabilitazione di Veruno (NO), Servizio di Neurofisiopatofogia; . Osp. SSTrinitB di Varallo Sesia (VC), Divisione di Neurologia; ' *

Ospedale S.Paolo, Milano. Clinica Neurologica 111.

W e report the case of a 77 y.0. woman presenting with abdominal non rhythmic myoclonus for two years. The jerks were occasionally painful, increased in intensity and frequency by emotions, sitting and laying down but diminished on standing and walking. Neurological examination, besides the myoclonic jerks, routine laboratory tests, standard EEG, brain CT, peroneal nerve somatosensory evoked potentials, transcranial and spinal roots magnetic stimulation were normal. Dorsal spine MRI showed T6- T7 and T9-T10 disc protrusions. EMG recordings carried out on the recti abdominis, right T10 paraspinal showed neurogenic signs. Spontaneous muscle jerks were detectable from the right rectus muscle; besides we recorded from the left rectus muscle an EMG activity constantly occuning 40 ms later. The clinical and neurophysiologic features of the muscle jerks of our patient are consistent with a myoclonus of spinal origin: the generator source is most likely at the level of T9-T10 ventral root triggered by the disc wotrusion .

107

Clinical aspects of dvstonia P. Greene. The Neurological Institute, Center for Parkin- son's disease and other movement disorders, New York, U.S.A.

Dystonia may be a symptom of many identified neurological diseases, but is most often idiopathic. The recognition of symptomatic dystonia depends on the presence of atypical clinical fetaures, such as early development of fixed postures and early dysarthria, as well as abnormal laboratory tests and other abnormal neurological findings. A growing number of syndromes of idiopathic dystonia have been recognized: symptoms predominately during sleep (nocturnal dystonia), paroxysmal symptoms Winesi- genic, non-kinesigenic dystonia), dystonia + myoclonus (myoclonic dystonia), dystonia + parkinsonism (Segawa variant, Lubag disease) and the most common CclassicaP) form of dystonia. All forms of idiopathic dystonia may be inherited, and two inheritance patterns have been proven: X-linked recessive in Lubag disease and autosomal dominant with reduced penetrance, as in patients linked to the D m 1 gene on chromosome 9q34. There is evidence that the clinical characteristics of dystonia may differ depend- ing on the underlying gene mutation. Patients with an early age at onset are likely to have inherited dystonia and develop widespread symptoms, although some adolescents develop focal dystonia such as torticollis. Adult onset patients often have focal or segmental symptoms and may or may not appear to be sporadic.

Movemenr Disorders, Vol. 9, No. 2, 1994


108

DYSTONIA: PSYCHOLOGICAL FACTORS A.E. Lang. Movement Disorders Clinic, The Toronto Hospital. Western Division. 399 Bathurst St., MPt 1.306. Toronto, Ontario. Canada

Due to the bizarre nature of dystonic movements and postures, responses to peculiar sensory tricks and the occasional occurrence of spontaneous remissions, idiopathic torsion dystonia has often been misdiagnosed as a primary psychological problem. This has often added unnecessary suffering lo the pronounced physical disability caused by dystonia. Psychological factors have commonly been invoked a s either causative or more common in Datlents with adult-onset focal dystonias. However, recent studies have failed to show significant differences in the psychological profile of these patients compared to controls. On the other hand, severe disability and deforming dystonla may result in considerable psychological morbidity. Drug treatment for dystonla also may cause adverse neuropsychological effects. For example, high doses of anticholinergic drugs may cause slowing of mentation and resultant impaired encoding. Rarely. a dystonic syndrome may be caused by primary psychopathology. Psychogenic dystonia may account for between 2- 5% of dystonic patients seen in movement disorders centres. The role of psychological factors in the etiology of fixed dystonic postures occurring in a small number of individuals following peripheral (often minor) trauma commonly associated with causalgia and reflex sympathetic dystrophy is unknown. The elucidation and management of both primary and secondary psychological factors in patients suffering from dystonic syndromes remains an important challenge to physicians with an interest in movement disorders.

109

GENETIC ASPECTS OF DYSTONIA A.E. Hardinq, Institute of Neurology, London, UX

Idiopathic tortion dystonia (ITD) is most commonly caused by an autosomal dominant gene or genes with reduced penetrance. The ITD locus has been mapped to chromosome 9q34 in one non-Jewish and several Jewish kindreds in the USA. The gene for dopa responsive dystonia does not map to this locus. We have performed linkage studies in one large Australian family and 27 European small families with I T D , 4 of which were Ashkenazi Jewish, using the highly poiymorphic loci ASS and ABL which map to 9q34. In the Australian family and 3 European families a disease locus on 9q34 could be excluded. Analysis of all the European data showed significant heterogeneity, and indicated that about 55% of families have ITD caused by a gene on 9q34. The allelic association observed between ASS/ABL and ITD in Ashkenazi families in the USA was also present in British Jewish cases, both familial and sporadic. These results suggest genetic heterogeneity for ITD in Europe; the families in which linkage to 9q34 could be excluded were indistinguishable from the others.

110

Abnormalities of the electron t ramof t chain in dvstonia R. Benecke* Department of Neurology, University of Dusseldorf, Germany

It has been suggested that dystonia is caused by an autoso- ma1 gene with reduced penentrance and a consequent biochemical abnormality affecting cell activity within the basal ganglia. No consistent biochemical disturbance however has been identified so far. In the present study, activities of the mitochondria1 electron transfer complexes (ETC) were measured in platelets and lymphocytes of 61 patients with idiopathic focal, segmental, or generaked dystonia. Enzyme assays of these patients were compared to measurements in 44 control subjects. A significant decrease of complex 1 activity was observed in patients, whereas the activities of other ETCs were normal. The severity of complex I defect was more pronounced in patients with segmental or generaked forms than in those with focal dystonia. There was no age dependency of complex I activity in patients or controls. It is not known why different basal ganglia diseases, e. g. Parkinson's disease, should be induced by the same enzyme defect. It is possible that defects in different components of complex I can have graded effects on nerve cells, from cell death to abnormal electrophysiological behaviour.

111

New Aspects of Dvstonia -- Pathophysiolog Mark Hallett', Human Motor Control Section, NINDS, Bethesda, MD, USA

Kinematic and EMG analysis of voluntary movement in dystonia shows prolonged movement duration and co- contraction of antagonist muscles. Considerable work has shown that a number of spinal and brainstem reflexes, usually studied at rest, show deficient inhibition. Exampfes include reciprocal inhibition in the upper extremity and the blink reflex recovery curve. Valls et al. have now demonstrated that the abnormality of reciprocal inhibition is also present during voluntary movement. Such abnormalities are likely to result from deranged descending commands from the brain. The frontal N30 component of the median nerve somatosensory evoked potential is increased in amplitude in some patients suggesting abnormal sensory processing. Studies of movement related cortical potentials by Deuschl et al. show a slight deficiency of the NS' component. Tor0 et al. have evaluated these EEG signals with techniques of event related desynchonization and found a selective deficiency of the normal loss of power in the 20 to 30 Hz band in the central regions. These studies indicate abnormalities of cortical function, but there is not yet a clear unifying interpretation.

Movement Disorders, Vol. 9 , No . 2, 1994


112

PET studies on Familial Idiooathic Dvstonia

DJ Brooks and ED Playford MRC Cyclotron Unit, Hammersmith Hospital, London, UK

There have been several studies on resting regional cerebral glucose metabolism or blood flow (rCBF) in dystonia. These have produced conflicting results: nomal, raised, and reduced striatai function contralateral to affected limbs have all been reported. A problem with these studies is that heterogeneous cohorts of dystonic patients have been enrolled. We have examined rCBF in six patients with familial idiopathic torsion dystonia (FITD). Patients were studied at rest, and when performing paced joystick movements in freely chosen directions. Compared to age-matched controls the FITD group showed no differences in resting rCBF. On performing movements the FITD patients experienced involuntary co- contraction of agonists and antagonist muscles and had raised levels of smatal, premotor, and dorsolateral prefrontal KBF. This suggests that dystonia is associated with inappropriate overactivity of basal ganglia-frontal connections. We also studied striatai J8F-dopa uptake in FITD. This was normal in eight but mildly reduced in three cases. It is unlikely, therefore, that dysfunction of dopaminergic terminals is the primary determinant of familial dystonia, but may occassionally be found as an epiphenomenon.

113

Treatment of Dvstonia: Drugs and Botulinum Toxin J. Jankovic, Department of Neurology, Baylor College of Medicine, Houston, Texas.

The selection of the most appropriate therapy for dystonia is primarly guided by etiology, age, and the anatomic distribution. Most dystonias are idiopathic, but some are secondary to identifiable and potentially curable causes such as Wilson's disease. Because of the possibility of dopa-responsive-dystonia, all patients with childhood onset dystonia should be treated initially with levodopa. Generalized dystonia is usually treated with anticholinergic drugs; these may need to be combined with benzo- diazepines, baclofen, tetrabenazine, and rarely neuroleptics. The introduction of botulinum toxin (BTX) in the treatment of focal dystonia represents one of the most imporrant advances in neurologic therapeutics. Recent evidence suggests that by acting as an endopeptidase at the synaptic vesicle membrane, BTX disrupts the release of acetylcholine from the presynaptic nerve terminal at the neuromuscular junction. Local chemodenervation following BIX injections usually markedly ameliorates focal dystonia and other disorders associated with excessive or abnormal muscle contractions. The efficacy and safety of BTX has been well demonstrated and the role of BTX in therapy of neurologic and non-neurologic disorders is rapidly expanding. Because of the potential for development of immunoresistance to BTX type A, new serotypes of BTX (B and F) are currently being investigated in clinical trials.

P114

Uvstonia as the maior manifestation of Leiqh's svndrome K. Ehatia*, G. Lera and C.D. Marsden, Department of Cllnical Neurology, Institute of Neurology, Queen Square, London

We report eight patients with a progressive illness dominated by generalised dystonia who had clinical and imaging features suggestive of Leigh's syndrome (LS). Early development was usually normal, the onset of the dystonia ocurring at a mean age of 3 years (range 2 months to 7 years). A l l had abnormalities in the basal ganglia on brain imaging; symmetrical bilateral lucencies or calcification were seen in the basal ganglia on CT scan i n five cases, and high signal lesions were evident in these regions on T2 weighted MRI sequences in seven cases. Raised blood lactate levels were found in four of the eight patients. Muscle biopsies done in seven patients were normal and the common mutations associated with mitochondria1 encephalomyopathies were not found. LS presenting as a pure dystonic syndrome should be considered in the differential diagnosis of symptomatic dystonia presenting in

childhood.

P115

Focal dvsto nia and athet osis seconday to ce r v i d demvelhating lesioq A UncinP. A.-M Muzlo, A, Lugaresi. D. Gambi. Institute of Cllnical Neurolom and Behavioral Sciences,

I h e few cases of h a n d dystonia, in which a localized lesion could be found, showed involvement of the posterolateral thalamic nuclei, parietal cortex a n d I e n t S o m nuclei. We report a patient with definite multiple sclerosis who acutely developed right hand dystonia and athetosis with cutaneous sensory loss and astereognosls. Elementary strenght of right hand and forearm muscles was normal. MRI T2-weighted images showed many hyperintense lesions In centri sernfovali but not in basal ganglia and thalami. Cervical MRI disclosed a lesion in the right posterolateral cervical spine at C5-C6 level. SEPs from right median neme stimulation showed a delayed cervlcal N13 with absent frontal a n d parietal components. S tudy of long latency response from right median nerve stimulation showed a n o d latency V l b u t absent V2. MEP latency recorded from right abductor policls brevls after left transcranial cortical stimulation was normal with a C M A P / MEP amplitude ratio 2 1% smaller than the contralateral. Clinical and electrophysiological abnormalities reverted to normal in six months. We think that, in this case, dystonia and athetosis could be ascribed to the cervical lesion involving descending pathways regulating reciprocal inhibition of motoneurons and to the block of large diameter afferents.

Movement Disorders. Vot. 9. No. 2, 1994


P116

Cervical dvstonia: familv historv and tremor D.D. Duane., M. Clark, L. Gottlob, L.L. LaPointe & J. Case,

Arizona Dystonia InstitutelArizona State University, Scottsdale, AZ, USA

This study investigates tremor and dystonia characteristics and family history of movement disorder (Mov Dis) - familial tremor (FT), Parkinson's disease, dystonia, scoliosis in 231 cervical dystonia (CD) patients, 127 of whom have non- Parkinsonian tremor (CDil) and 34 patients with only idiopathic tremor (ET). Evaluation included accelerometer and high resolution audio recordings. Female Gender: CD n o T 71 %, CD/T 79%, ET 53%. Mean Age Onset: CD no T 44.5 yr, CD/T 46 yr, ET 54 yr. Family History: Mov Dis - CD no T 47%. C D i l 55%. ET

53%. FT - CD no T 19%. CDlT 32% (P = < .01), ET 53%.

Isolated Cervical Dystonia: CD no T 81 %, C D i l 65% ( P = <.l)

Tremor Distribution: C D i l - 81 head, 27 headlhands, 12 hands, 5 headlvoice, 2 headlhandslvoice. ET - 2 head, 5 headlhands, 19 hands, 1 handlvoice, 4 headthandstvoice, 2 handslvoice, I voice.

FT is common in ET and more common when CD is associated with tremor. Presence of tremor in CD increases the probability of extranuchal dystonia. In CD, tremor has a cephalad bias.

P117

Spasmodic dystonic laterocollis in familial cerebellar ataxia

F. Carella, C. Ciano*, P. Giovannini, F. Girotti, T. Caraceni - Prima Divisione di Neurologia and "Servizio di Neurofisiologia - Istituto Nazionale Neurologico C. Besta Milano

-

Various dystonic manifestations can be recognised in cerr bellar ataxias and rarely torticollis is the presenting feature of a degenerative ataxic disorder. Spasmodic torticollis however is an infrequent manifestation of fami- iial cerebellar ataxias and little is known of the patho- genesis the dystonic symptoms in the setting of a primiti ve cerebellar disorder. It is reported the case of a 37 years old patient affected by a familial cerebellar at2 xia in whom marked spasmodic laterocollis and axial spasm were part of the clinical picture. The recovery cur ve of the R 2 component of the blink reflex was altered like that of a control group of idiopathic dystonic patients. Treatment with clonazepam improved spasmodic late rocollis. This case suggests that dystonic symptoms in in familial ataxias may share common pathogenetic symptoms with idiopathic dystonia

Pll8

Torticollis as the Dresenting sien in benien intracranial hvuertension S. Bohlega*, A. Idris, and S. Omer, King Faid Specialist HosDital and Research Centre, Riyadh and King Fahad Hospital, Medina, Saudi Arabia

A 32-year-old woman experienced intermittent forced turning of the head to the left with elevation of left shoulder. Two weeks later she developed persistent bilateral headache with abdominal pain and vomiting. Severe visual deterioration uccurrcd four weeks after the onset of headache. The abdominal pain and headache subsided but torticollis remained unchanged. Eight years before she had similar torticollis which recovered in six months.

There was severe bilateral papilloedema and torticollis, the rest of the neurological examination was unremarkable. Lumbar puncture revealed an opening pressure of 460 mmlH20. Cerebrospinal fluid was normal. Immunologic, metabolic and hematological work-up, cervical spine x-ray, cranial-cervical MRI and cerebral angiogram were all normal. Biopsy proved tuberculous peritonitis was discovered during lumbo-peritoneal shunt insertion. Vision improved but torticollis required botulinurn toxin injection.

To our knowledge this is the first report of torticollis appearing in association with benign intracranial hypertension.

P119

CLINICAL AND NEUROPHYSIOLOGICAL STUDY OF THREE PATIENTS WITH DOPA RESPONZIVE DYSTONIA.

~~ ~

P. Lamberti, L. Margari*, M. de Mari, G . Iliceto, L. Serlenga and E. Ferrari. Institute of Neurology, University of Bari, Italy.

Dopa responsive dystonia with marked diurnal fluctuations ( D R D ) is characterized by: a) onset in childhood or adolescence of lower limb dystonia with gait disturbances; b ) coexistence o r subsequent development of parkinsonian signs; c) a dramatic response to low doses of L-Dopa. We studied two familial cases and one sporadic case of DRD. In all patients the clinical picture was markedly improved by treatment with low doses of L-Dopa. Patients were also investigated with median nerve Somatosensory Evoked Potentials (SEPs). Latencies of early evoked potentials and CCT were normal as well N20/25 aplitude. In all patients the frontal N30 component was significatively reduced in amplitude. These results are similar to those reported in patients with idiopathic Parkinson's disease (PD). In parkinsonian patients the reduction in N30 amplitude has been referred to a decreased output of basal ganglia to Supplementary Motor Area (SMA), that could disrupt SMA function with a decrement of its modulation on primary motor cortex. Our results suggest a common pathophysiological mechanism for PD and DRD.

Movement Disorders, VoI. 9, No. 2, 1994


P1M

Dopa-responsive r e v e r s i b l e dys ton ia : 8 case r e p o r t

M . D i Capua and E. B e r t l n i , Sec t ion of Nrurophysiology, Bambino GesG Ch i ld rens Hosp i t a l , Rome, I t a l y

Dopa-responsive dys ton ia ( D R D ) is a v a r i a n t o f i d i o p a t h i c torsion dystonia . DRD has onse t i n childhood usua l ly with g a i t d i s o r d e r s . Improvement wi th therapy of levodopa is impressive and cons t an t du r ing t r ea tmen t , a l s o a t low doses. We r e p o r t t he case of a boy who p resen ted l e f t foo t dystonia a t the age of 6 y-ars and 2 months. Dystonia reached t h e maxirnum esp res s ion wi th in 2 months. The pa ren t s were not r e l a t e d and the p a t i e n t has a o l d e r b ro the r i n good h e a l t h . This boy presented lef t equinovarus only du r ing t h e g a l t . The p a r e n t s r e f e r r e d a d l u r n a l f l u c t u a t i o n of g a i t d i s tu rbances , with improvement during t h e evening hours . Neurological examination showed no muscle tone abnormali- t i e s . Carbidopa/levodopa (Sinemet) 6.25 /52 .5 mg was adminis tered i n i t i a l l y once d a i l y , i nc reas ing g radua l ly u n t i l a dosage of 12.5/125 m g 2 t i m e s d a i l y was reached. With t h i s therapy t h e p a t i e n t r e tu rned t o normal cond i t ion i n 2 months with no s i d e e f f e c t s . Two months l a t e r t he p a r e n t s decided t o withdraw the rapy , g r a d u a l l y , over 3 months. A follow-up after 6 months without therapy showed no dys ton ic postur ing. Videotape follow-up r eco rd ings of t h e p a t i e n t w i l l be shown.

PlZl

Dopa-responsive Dystonia and Parkinson's disease (diagnosis ,prognosis, treatment &!.FUarkova,M.D. , Department of Neurogen?tics, Institute of Neurology, Moscow, Kussia bpa-responsive Cys'conia (DhD) is one of the forms of Torsion Dystonia ( T D ) ,characterized by pathological posture and some parkinsonian features (muscle rigidity and tremor). Diffe- rential diagnosis of DHD and Parkinson's disease (PD) is not easy,but important f o r prognosis,genetiC counseling, treatment. The purpo- se of our work was to estimate the differential criteria between DHD and PD. We carried out long-term observation of 78 DKD and 72 PD patients from 5 to 82 years old. 5 families included 12-15 patients each from 4-5 generati- ons,lO families had more than 2 patients each, 20 cases were sporadic. The commoa clinical features for D& and PD were rigidity and tremor in hands and head. In DkD we revealed dys- balance of neurotransmitters similar to that in PD,as well as positive effect of levodopa therapy. The differential signs between D M and PD were the following: DHD patients had dystonic postures (more often in legs) which were the first symptom always found inspite adding of parkinsonian signs ; the earlier onset and milder pro ression of DaD; higher positive ("drarnatic"7 effect of little doses of levodopa with no side-effect in DifU. The genetic analysis indicated on the heterogeneity o f yD - predominantly autosomal dominent (with restricted penetrance) and X-linked inheritance. The true mode of transmission of DfiD and PD can be determined only by molecular genetic methods with mapping Of the mutant genes.

Pl2Z

DYSTONIA. SPASTIC PARAPARESIS AND AMYOTROPHY: A CASE REPORT.

E. Fincati, L . Bertolasi, G . Tomelleri Clinica Neurolosica, Universita' degli Studi di Verona. Italia.

We describe a case of a 23 yrs old man complalnlng progressive lnvoluntary head movements and neck pain since 5 yrs and recently, weakness of the upper rlght and lower limbs. 2 uncles were affected by progressive generalized motor impairment. The neurolouical examination showed : paraparethic gait, generalized weakness, brisk tendon jerks. bilateral Babinski sign. bilateral ankle clonus. dystonic postures of the head. of the right hand and feet. Laboratory findings (routine blood t e s t s and blood f i Im. copper. ceruloplasmin. hexosaminidases) were norma 1 . Neuroradiological investigatlons were normal. The EMG showed: SFOntaneoUS activitv and motor unit potentlals with increased amplitude and duration in proximal muscles of upper limbs; motor and sensory CondUction velocities were normal. Motor responses evoked by transcranial stlmulation were either delayied or absent. BAERs showed an abnormal V wave bilaterally. SEPs and VEPs were normal. This association of dystonia. spastic paraparesis and spinal muscular atrophy will be discussed.

P123

FAMILIAL INVESTIGATION ADULT-ONSET CRANIAL DYSTONIA G. Defazio *, P. Livrea, V. Lepore. P. Lamberti and E. Ferrari. Institute of Neurology, University of Bari, I- 70124 Bari . Italy.

The cause of idiopathic cranial dystonia is unknown but familial occurrence in previous reported large series was an argument in favour of heredity. Neverthe- less. familial concentration might merely reflect the presence of environmental fac tors o r t h e relat ive prevalence of the disease.

A family study in 29 patients with idiopathic adult onset bsepnarospasm in.16) L.rlu L r k . - a cer<iLd uy.pcu..-c

(n.13) w a s undertaken by examining 189 first-degree relatives. Six relatives with dystonia were identified in s ix families. A further three affected relatives, now deceased, were from two other families. A l l the secondary cases w e r e parents or siblings and there w a s a tendency for affected relatives to have the same type of dystonia of index patients.

Theoretically, different s t ra tegies (A. a study of twins; B. the comparison of the prevalence rates among patients' relatives and the general population. or C. an appropriate control group) can be employed t o evaluate the role of genetic factors i n a given disorder. W e assessed the significance of secondary cases by comparing the incidence of affected siblings between pro- bands and their spouses. Dystonia w a s found in 5 out of 120 proband siblings whereas none of 142 spouse siblings w a s affected (p < 0.05). Thus. a significant genetic contribution t o cranial dystonia appeared to be likely in the present series. Segregation analysis suggested an autosomal dominant transmission and reduced penetrance or, alternatively, polygenic inheritance.

I .

Movement Disorders, Vol. 9. No. 2. fPP4


P124

Basal h m e r m e t a b h u n

G . Gal a rd i , F. G rassi , D . Pe ra n i , S .Am a d i 0 , LAaderna, G.Comi, N.Cana1, F.Faz1o. Scientific Institute H S Raffaele, University of Milan,

. . odic t o r t i e

INB-CNR.

The pathophysiology of spasmodic torticollis, a focal dystonia involving neck muscles, is still unclear. According to a recently proposed model, dystonia would be the consequence of a putaminal hyperactivity, ieaaing 10 m e breakdown of the pallidal inhibitory control on thalamus and thalamo-cortical projections with the excitation of premotor cortex. Positron Emission tomography (PET) studies showed either an increase as well as a decrease of regional cerebral metabolic rate of glucose (rCMRglu) in basal ganglia. In the present study, [18F]FDG and PET was used to measure rCMRglu in 7 patients with spasmodic torticollis. All cases, with a short disease duration, were untreated, except one patient with 15 years duration, treated with anticholinergics. rCMRglu exceeded mean normal values by more than 2 SD in the putamen (4 patients, bilaterally), caudate (5 patients, in one unilateral) and thalamus (4 patients, in one unilateral). The patient treated, with a long history, had hypometabolism in caudate and putamen. These preliminary data show enhanced metabolism in basal ganglia and thalamus as a functional correlate of focal dystonia.

P125

Hemidvstonia associated with controlateral corticid

!%%$A. Hammoutil, P. Maquet2, E. Hirschl and C. Marescauxlg WHU Strasbourg (France), 2CHU Sart Tilman, Liege (Belgique)

A 60-year-old man presented a brief episode of weakness of the right foot associated with paresthesia. Initial neuroradiological examinations (CT scan, MRI) were normal. A right hemidystonia progressively developped over the next three years. At 63 years, the dystonic posture and movements of the right face, arm and leg do not allow certain gestures. Walking was no more possible. MRI showed two small pontine lesions. 18 FDG PET revealed a very marked left fronto-temporo-parietal hypermetabolism and a bilateral lenticular hypometabolism. Pharmacological treatment (trihexyphenidyl, L-dopa, baclofen, piracetam) and chronic stereotactic stimulation of the left thalamus were ineffective.

This case suggests that pontine lesions (without associated basal ganglia damage) can induce hemidystonia. The significance of the controlateral cortical hypermetabolism will be discussed and cofionted to the results obtained with PET in other cases of hemidystonia.

olism and oonh 'ne lesiong

P126

A case of apomomhine and L-dopa responsive kinesieenic foot dvstonia S. Dethy*, S. Goldman and D. Zegers de Beyl, Department of Neurology and PET/Biomedical Cyclotron Unit, Hapita1 Erasme, Brussels, Belgium.

We report a case of exercise-induced foot dystonia in a SO-year- old man. For one year, the patient complained of painful left foot eversion after walking for about 100 meters. At the beginning, the neurological examination was normal and a psychogenic disturbance was suspected. One year later, rigidity of the left arm was noted with reduced arm swing when he walked. He dragged his left leg and left foot eversion occurred after about 150 meters walking. A l*F-FDG PET scan showed hypermetabolism of the right smatum suggestive of Parkinson disease (D. Eidelberg et al., Mov Dis, 5: 203-213, 1990). On a walking distance of 160 meters, the patient presented 3 times consecutively a painful left foot eversion. Two milligrams of subcutaneous apomorphine reverted the patient to a dystonic-free state after IS minutes. Then, the patient was aeated with L-dopa (3 x 200 mg with 3 x 50 mg benserazid daily) during two months and was tested again in the same conditions. No dystonic position appeared. However, the rigidity and reduced arm swing were not improved by apomorphine or L-dopa. The marked difference between responses of dystonia and extrapyramidal features to dopaminergic stimulation is surprising and suggests differences in pathogenic mechanisms.

F a m i l i a l s p a s m o d i c d y s p h o n i a w i t h l o w A r y l s u l p h a t a s e A ( A S A ) l e v e l M . M o n t a n a r i ' , M . I p p o l i t i , M . M o c h i , S . S a n g i o r g i a n d P . M a r t i n e l l i , I n s t i t u t e o f N e u r o l o g y , U n i v e r s i t y o f B o l o g n a , B o l o g n a , I t a l y

A p a r t i a l l y r e d u c e d ASA a c t i v i t y h a s b e e n d e s c r i b e d a s s o c i a t e d t o g e n e r a l i z e d d y s t o n i a o r t o o t h e r m o v e m e n t d i s o r d e r s l i k e c h o r e o a t h e t o s i s S o m e o f t h e s e o b s e r v a t i o n s a r e f a m i l i a l . We d e s c r i b e t w o s i b l i n g s w i t h v o i c e s p a s m o d i c d y s p h o n i a a n d p o s t u r a l t r e m o r a s s o c i a t e d t o l o w ASA l e v e l ( r 5 6 U / m g / h ) . O t h e r f a m i l y m e m b e r s s h o w e d a s i m i l a r s y m p t o m a t o l o g y o v e r t h r e e g e n e r a t i o n s . S u c h a s s o c i a t i o n b e t w e e n f o c a l d y s t o n i a o f a d u l t o n s e t a n d l o w ASA l e v e l h a s n e v e r b e e n p r e v i o u s l y d e s c r i b e d . O u r o b s e r v a t i o n s s u p p o r t t h e h y p o t h e s i s o f g e n e t i c p r e d i s p o s i t i o n b o t h f o r f o c a l d y s t o n i a a n d f o r m e t a b o l i c l y s o s o m i a l i m p a i r m e n t .



PI28

Psychopathologic disturbances in a group of 42 subjects With essential Slepharospasn. Maurri S., 3arontini P., I11 Neurologic Clinic, Florence I

Among 296 patients with focal rlystonia cured by botulinum toxin at our center for movement disorders 110 were affect ed by blepharospasrn. We ruled out 12 cases with symptomatic blepharospasm (blepharitis,entropion etc.). In 42 cases classifiable as essential blepharospasm we investigated for eventual psychopathologic disturbances. We took as controls a group of sex and age matched subjects with various neurologic disorders. 5 Out of 42 essential ble- y;~dusyawi pai i cr i ia siivwaii iiia raquisi Leu for clinicaliy established "psychogenic" blepharospasm. 7 patients had some characteristics of psychogenicity. No patient satis- fied the requisites for documented psychogenic blepharospasm. The prevalence of psychic disorders in blepharospasm patients was not significantly superior than in controls. The diagnosis of hysterism (301.50 according to DSM-111-R) was well represented in women with essential blepharospasm although it was not significantly more frequent than in controls. 10% of blepharospasii, patients showed a high degree of psychogenicity. They had a bad response to botulinum toxin treatment.

P129

SUCCESSFULL 'PREATMENT OF SI'ASMODTC 'PORTTCOLLIS BY MICROVASCULAR DECOMPRESSION ( M I D )

GRECO R . : BRUNI P . . BRUNORI A . , DELITALA A.

D i v i s i o n of Neurosurgery, S . C a m i l l o Hosp., ROME.

Although t h e concep t of c r a n i a l n e r v e s vascu- lar compression (VC) has r e c e n t e l y gained in- c r e a s i n g acceptance t o e x p l a i n h e m i f a c i a l spasm and t r i g e m i n a l o r g l o s s o p h a r i n g e a l n e u r a l g i a . spasmodic t o r t i c o l l i s ( S T ) is g e n e r a l l y considered an e x t r a p i r a m i d a l or psychogenic d i s o r d e r .

Several s u r g i c a l p rocedures have been proposed i n o r d e r t o i n t e r r u p t the invo lved motor pathways: s tereotact ic thalamotomies, cervical neu- rectomies and r h i z o t o m i e s v a r i o u s l y combined w i t h myotomies. However, the c l i n i c a l outcomes of s u r g i c a l l y treated p a t i e n t s are n o t u n i v o c a l , ref lect ing the poor comprehension of the patho- g e n e s i s of S T . Anyway, s o m e r e c e n t , encourag ing , s u r g i c a l r e s u l t s can be e x p l a i n e d o n l y on the base of a n e u r o p e r i p h e r a l mechanism, j u s t i f i n g the i n c l u s i o n of at least some cases of ST i n the group o f VC syndromes.

W e p r e s e n t a p a t i e n t w h o s e ST. due t o "neuro- v a s c u l a r c o n f l i c t " between vertebral artery and a c c e s s o r y n e r v e , w a s cu red by W D .

P130

A case of spasmodic rorticollis: pharmacoloeical- rehabilitative and psichotherapeutical app-. F Di Stefano*. S. Capizzi. A. Pirri. G Ouattrocchi. R. Raimondo, Centro di 'Riabilitazionc per disabili USL 45, Barcellona P.G. (Messina), Italia.

The authors first summarize the pathogenetical hypothesis and the evaluation techniques of spasmodic rorticollis and then describc the clinical and therapeutical features of a single case. The approach was initially pharmacological (general and local mesotherapy) and subsequently psichotherapeutical, by mean of the "imaginative distension" technique. After six months of treatment we have observed a complete regression of the torticollis, with a good improvement of the quality of life of the patient. The authors suggest that the psichodiagnostic and psichoterapeutical approach is useful in spasmodic torticollis. In this case the psycho- therapy and particularly the "imaginative distension" technique gave good results.

P131

Excessive blinkinr: focal tic or focal dystonia? A . Albanese*, A.R. Bentivoglio, E. Cassetta, D. Carretta, C. Colosi- mo, P. TonaIi, Istituto di Neurologia, Universiti Cattolica, Roma, Italy.

I n a series of 94 consecutive outpatients, referred to us with a diagnosis of blepharospasm, we selected six cases (4 men and 2 women) who presented excessive eye blinking, but did not meet diagnostic criteria for blepharospasni. The patients neither had gems afVfljiouisfc5, nor they attempted to voluntarily open their eyes. None of these patieiits had signs of cranial or cervical dystonia in extraocular regions. One patient presented simple motor tics of the eyehrows and of nne shoulder. Involuntary eye closure was not worsened by reading or watching television; i t was reported to worsen when the patients were exposed to a bright light, although this did not force any of the patients to start using sunglasses. In addition, no conjunctival distress occurred in these patients. Tics were looked for in every body district, by performing repeated videotape recordings. No patient presented eye- winking tics or other motor tics; no vocal tics were noticed neither reported, although family histories were often remarkable for motor and vocal tics. All patients underwent a psychiatric interview; family history was collected by any available relative of theirs. The occurrence of obsessive-compulsive personality disorder was defined according to the DSM-IIIR criteria. Local injections of botulinum toxin were performed in all patients. Our data showed that excessive blinking occurred in families in which either tics or the obsessive-compulsive phenotype occurred. All patients benefitted from treatment with botulinum toxin. Excessive blinking appears to be a focal form of tic disorder. However, since focal dystonia is often associated with an obsessive-compulsive personality disorder, the dystonic nature of excessive blinking cannot be ruled out.

Movement Disorders, Vol. 9 , No. 2, 1994

ABSTRACTS FROM THE MOVEMENT DISORDER SOCIETY

P132

Brainstem interneuronal excitability in blepharospasm and torticollis. A study of the blink reflex and of the exteroceptive suEression of the contracting sternocleidoma - stoid muscle

F. Carella, C. Ciano*, V. Scaioli, Prima Divisione di Neu rologia and *Servizio di Neurofisiologia. Istituto Nazio- nale Neurologic0 C. Besta Milano

The blink reflex and the exteroceptive suppression of EMG activity in the contracting sternocleidomastoid muscle produced by electrical stimulation of the supraorbital nerve were studied in normal subjects and inpatientswith blepharospasm o r torticollis. The latency of the R 1 andR2 components of the blink reflex was normal while the duration but not the amplitude of the R2 componentshowedsome minor difference between groups. However, recovery of the R2 component of the hlink reflex was enhanced in patients with either blepharospasm o r torticollis. The latency and duration of the exteroceptive suppression in the contracting sternocleidomastoid were normal in the patientswhile the depth of the suppression was reduced in both groups of patients. These result are indicative of interneuronal abnormalities in patients with blepharospasm and tortical lis which are not restricted to the systems controlling the muscle involved in the dystonia.

P133

Trinemino-cervical reflexes i n c e r v i c a l dystonia z. LisJ i , Department o f Neurology, Postgraduate Medical. I n s t i t u t e , NsP RuZinov Brat i s l a v a , S1 ovakia Reflex responses i n s ? l e n i u s c a p i t i s and s terno- cleidomastoidsus muscles a f t e r s l i g h t t a p on t h e face region ,/ upper and lower l i p , t h e chreks of both s i d e s / i n a group o f 22 heal thy s u b j e c t s and 26 p a t i e n t s wi th c e r v i c a l dystonia / t o r t i - collis l a t e r o c o l l f s a r , d . r c t r o c o l l i s / ware s t u - died. ?he ENPJ a c t i v i t y picked out f r o m splenius c a p i t i s muscle by t h e needle and f r o 3 s t e r n o c l e i - domsstoideus by t h e sur face ezectrodes was by means of I X G epuipment r q i s t e r e d . A t t h e moment of t h e t a p on t h e f a c e t r i g g e r e d EMG a c t i v i t y with time base o f 230 m s was r e c t i f i c r l and ave- rqged. Maximally o f 50 t r i a l s wer* averneed. ?he l a t e n c i e s , amplitudes end areas n f inEivi3rxal s n o r t and long-latency r p f k responses w r e measured an8 the f i n e i n g s i n heal thv S'ib*pcts end p a t i e n t s were cozpared an2 s t a t i s t i r d v evelua- tee . Ic a g r o u ~ of p s t i e n t s t h e var iocs sSr?ormi?l p t t e r n s o f r e f l e x responces were f w n d such a s side a s y m e t r y , d i s i d i b i t i c n o f short- ia tcccy ar.d zubpressfon o r p o l o n e e d e:iration o f Zong- ia tency re f lex respsnses . T'.e c h a r a c t e r i s t i c +awes of these r e f l e x e s lr. pa',icints with c m - v l c a l clystonia Can be .;sea a3 9 key t 6 un?ePtaR- d ing pathophysiol*)gy and f o r prec ise th?rapy Of t h i s dicorder.

P134

ibular j&pxd mstural re- &XI vaw modulation of vest Btients with tortlcollls BL Day*, MA Pastor & CD Marsden MRC Human Movement & Balance Unit, Institute of Neurology, Queen Square, London WClN 3BG

Abnormalities of reflex eye movements to different types of vestibular stimuli have been reporkd for patients with torticollis. It has been proposed that these reflect an abnormality of central interactions between vestibular input and other inputs which signal head and eye positions. To pursue this idea we looked for a dismptinn of vestibular-neck interactions used for the control of upright posture in a group of 10 patients with idiopathic torticollis. Patients were selected for tonicollis which was largely rotatory either to the right (n=5; mean +SD yaw angle=29 f 19deg) or left (n=5; yaw angle=33 f 16deg) and compared with a group of normal subjects (n=Zl). A small, direct current (0.5mA) was passed for 2s between two electrodes t i e d over the mastoid processes of the subject who stood with feet together, eyes closed and head voluntarily rotated through one of five yaw angles determined by a target light. The demanded head yaw angle and polarity of stimulation were randomised across 100 trials for each subject. In normal subjects, the stimulus produced a response characterised by an increase in the speed of body sway in a direction approximately towards the anodal ear. The magnitude and direction of the patients' responses were not statistically different from those of normaI subjects. Furthermore, within the patient group, there was not a sigmficant relationship between the natural, unrestrained head yaw angle of torticollis and angular deviations of the induced response from the idealised direction of the anodal ear. We conclude that vestibular-neck interactions used for the control of upright stance is normal in patients with torticollis.

P135

Botulinum toxin injections for the treatment o f

craniocervical dystonia

Dr .N.htekin, Dr .M.F .&tekin,SSK Ankara Hospital

Department o f Neurology

. .

-

We followed 65 patients of whom 21 with spasmodic torticollis, 25 with hemifacial spasm and 9 with blepharospasm for at least 1 year up to 3 years, during

which t ime they received 436 injections in 246 visits.

The patients were followed with clinical assesment and

videotape recordings.Sixty E o f spasmodic torticollis

patients improved substantially according to the 0-4

scale after one or more visits.The improvement rate was

65 X in the hemifacial spasm group, and 67 % in the

blepharospasm group.Most patients noted improvement

within the first week after injection and the duration

of maximum benefit was 11 months in the spasmodic torticollis group.0nly 3 patients with spasmodic

torticollis(%9.9) and 3 patients with blepharospasm(%l2)

had complications as mild disphonis and transcient pitosis.We conclude that botulinum toxin is an effective

treatment for most patients with craniocervical dystonia.



P136

Botulinup-Atoxin injection-in patients with blepharo-- spasm, torticollis and hemifacial spasm L. Capus*, M. Mucchiut, M. Zaramella, G. Cazzato, Clinica Neurologica dell'Universit5 di Trieste, Ospedale di Cattinara, Strada di Fiume n"447, Trieste, Ital ia.

We present the first experiences of Neurological Clinic of Trieste in the treatment of focal dystonias with botulinum A toxin. Since July 1992 16 patients, 10 women and 6 men, w i t h blepharos?,esm (7 pszients) hemifacial spa"" (4 patients) and torticollis ( 5 patients) were treated with botulinum A toxin (Oculinum-Allergan). The mean dose of neurotoxin for blepharospasm was 40 U. for hemifacial spasm was 25 U, and for torticollis was 150 U. Blepharospasm and hemifacial spasm were evaluated with the Fahn-Mardsen Rating Scale and torticollis by the Tsui Scale, before each injection, later on every 3 days in the first 2 weeks and then every 2 weeks. 14 patients improved after the treatment. The onset of benefit varied from 3 to 12 days after the injection and the duration of the clinical effect from 6 to 22 weeks. 2 patients, one with blepharospasm and another one with hemifacial spasm, had poor improvement, and decided to discontinue the treatment. We didn't observe any side effect.

PI37

Modulation of t h e EMG a c t i v i t v o f w r i s t f l exo r and extensor muscles bv u e r i u h e r a l nerve e l e c t r i c a l s t i m u l i i n u a t i e n t s w i t h w r i t e r ' s cramv. 30sep Valls-Sole', M . 3 . M a r t i , E. 5 . Tolosa and Mark H a l l e t t , U n i t a t d'EMt, Hosp i ta l C l i n i c , Barcelona, Espana, and N I N D S , N I H , Bethesda, Morylond, U . S . A .

Processing of segmental a f fe ren t i n p u t s du r ing performance of a task may be abnormal i n p a t i e n t s w i t h dystonia. We hove s tud ied t h e modulat ion o f t h e EMG a c t i v i t y o f t he w r i s t f l exo r and extensor muscles by r a d i a l and median nerve e l e c t r i c a l s t i m u l i , a t an i n t e n s i t y j u s t subthreshold f o r a motor response, du r ing sustained vo lun ta ry w r i s t f l e x i o n and w r i s t extens ion of 19% Qf t he w b l e c t ' s masimal force. In con t ro l subjects , a c h a r a c t e r i s t i c sequence of e x c i t a t o r y (E) and i n h i b i t o r y (1) phases o f modulat ion was de f i ned f o r t h e two muscles s tud ied. according t o t h e task performed and nerve s t imulated. For comparison w i t h the p a t i e n t s , t he sequence o f E and I phases was analyzed by t a k i n g i n t o account 1. muscle func t i on Cagonrst o r antagonist), 2 . r e l a t i o n s h i p between nerve s t imu la ted and muscle s tud ied (homonymous o r rec ip roca l ) . and 3 . temporal r e l a t i o n s h i p o f t he phases i n the two muscles ( i . e . , combined rec ip roca l o r opposi te e f fec ts ) . Po t ien ts w i t h w r i t e r ' s cramp e x h i b i t e d t h e fo l l ow ing abnormol f i nd ings : 1. E and I phases were sma l le r i n t h e ogonis t muscle, w h i l e E phases were genera l l y l a r g e r i n the antagonis t muscle, 2 . I phases were smal ler i n t h e w r i s t f l e x o r s w i t h s t i m u l i t o homonymous and rec ip roca l nerves, and 3 . combined rec ip roca l and opposi te e f f e c t s were reduced du r ing w r i s t f l e x i o n . These r e s u l t s suggest t h a t p a t i e n t s w i t h w r i t e r ' s cramp may have abnormal cen t ra l nervous system con t ro l o f t he i npu ts generated by ex te rna l s t i m u l i du r ing vo lun ta ry con t rac t i on . Such a de fec t i ve sensory-motor i n t e g r a t i o n may p a r t l y u n d e r l i e t h e pathophysiology of t h e motor dys func t i on i n these p a t i e n t s . Reciprocal i n h i b i t i o n of w r i s t f l e x o r s , which has been repor ted abnormal a t r e s t , was found t o be a l s o abnormal d u r i n g vo lun ta ry con t rac t i on .

P138

Efficacy of electromyographic recordings in botulinum toxin treatment of spasmodic torticollis. C. Marin, M.J. Marti, M. Alday, I. Charques, E. Tolosa. Servei de Neurologia, Hospital Clinic i Provincial, Barcelona, Spain

The use of electromyographic (EMG) recordings to identify the dystonic muscles suitable for botulinum toxin (Botox) injections in spasmodic torticollis (ST) has been a debated subject in the last years. Several authors use EMG to recognize the muscles in which to inject botox, while others inject the muscles according to clinical examination of the abnormal posture of the head.

In order to investigate the usefulness of EMG before botox treatment in ST, we have compared the improvement obtained in 20 patients treated according to muscular activity detected by EMG (group A) with the improvement obtained in 10 patients injected according to clinical examination (group B). Subsequently, a second treatment was performed and patients were randomly distributed again in group A (23 patients) or group B (7 patients) of treatment independently of the type of the first treatment received.

EMG was performed with skin electrodes recording bilaterally sternocleidomastoid, splenius and trapezius muscles. Clinical evaluation was performed following Tsui scale. Significant improvement was considered when more than a 25% decrease in Tsui scale was achieved.

After the first treatment, patients in group A showed greater improvement (58 f 4%) than patients in group B (42 i8%). After the second treatment, patients injected under clinical criteria obtained less improvement than when the same patients were injected under EMG criteria in the first treatment ( ~ 0 . 0 5 ) . In the same group of patients A or B, the percentage of patients which improved increased when they were treated under EMG criteria.

The results of this study indicate that the use of EMG to identify muscles involved in ST and to guide botox injections, enhances the degree of improvement and increases the percentage of patients which respond to botox.

P139

Electromyographic single motor unit potentials after repeated botulinum toxin treatments in cervical dvstonia T. Odergren, A. Tollback, J. Borg, Department of Neurolo- gy, Karolinska and Soder Hospital, Stockholm, Sweden.

The restitution of muscular function after botulinum toxin injection is usually attributed to neuroterminal sprouting, based on morphological studies mainly of M Orbicularis oculi. The aim of this study was to characterise the motor units in M Sternocleidomastoideus (STM) with emg methods before treatment, and after one year of repeated injections at the time of clinical need for reinjection. 10 patients were examined with concentric needle emg with computerassisted analysis of 20 separate motor unit action potentials (MUP) per examination. MUP amplitude and area were reduced @<0.05), and there was no poly- phasia or satellite potentials after treatment. 6 patients were examined with Macroemg electrodes, collecting a total of 110 MacroMUP in both treated and untreated STM at clinical need for reinjection. A reduction was found in both amplitude and area @<0.05) on the treated side, while the fiber density failed to increase significantly. These results indicate that the pattern of terminal innervation is mainly restored after botulinum toxin injections. Clinical relapse should be due to recovery of the original nerve terminals, or to nerve sprouts closely imitating the blocked terminal nerve twigs.

Movement Disorders. Vol. 9, No. 2, 1994


P140

The action of Botulinum toxin in blepharospasm: Single fiber EMG and blink reflex study. P . Girlanda'. A. Quartarone, S . Sinicropi, C. Nicolosi, C. Messina, Clinica Neurologica 2 - University of Messina. Italy

We have studied six patients affected with BF. BOTOX w a s injected around only one eye while the other received the same amount of saline solution. Single fiber EMG (SFEMG) and blink reflex were performed before and 1, 2, 4. 8, weeks after treatment. Clinical and electrophysiological evaluations were done blindly.

spasm relief was more evident on the side injected with BOTOX. SFEMG revealed statistically significant changes on both sides even if the orbicularis oculi muscle treated with BOTOX showed more neuromuscular blocking and a more marked increase of jitter value. Blink reflex excitability study failed to reveal changes after treatment.

The results confirm that BOTOX does not modify the enhanced excitability of brainstem interneurons occurring in BF and exerts its effects exclusively on the neuromuscular junctions. This effect is present bilaterally also for unilateral injection probably because of toxin spreading.

A beneficial effect was observed bilaterally, but the

P141

BOTULINUM TOXINi.LS. THERE A SPECIFIC EFFECT O N DYSTONIC MU5CLE ACTIVITY?

. ~~ ~

D. Dressler

Dyskinesia Clinic, Psychiatry Department Georg-August-University, Gijttingen. Germany

Botulinum Toxin (BT) is generally accepted as first choice therapy for reduction of dystonic muscle activity (DMA) in various dystonic syndromes. It remains unclear, however, whether BT acts specifically on DMA or whether its action is caused by a general weakening of the target muscle. To answer this question the BT induced reduction of voluntary muscle activity (VMA) and DMA was measured in 9 sternocleidomastoid muscles of 8 patients with spasmodic tortimllis by standardized surface emg recording. When the BT induced reduction of VMA and DMA given in percent of the pre injection values were compared in each patient the mean difference was 0.37% only with a standard deviation of 5.2% and a maximal value of 10.7%. This indicates that ther-e is no specific action of BT on DMA and that a dystonia relevant site of action other than the neuromuscular function is unlikely.

P142

MdCHtlIfISIti OF ACTION OF T m BUTULINUV~ 'POXIDTS D. De GrandisO, R. Xleopra, V. Tugnoli U i v i s i a n of Neurology, F e r r a r a , I t a l y

a f t e r a review o f t h e L i t e r a t u r e about t h e bio_ chemical a c t i o n of t h e d i f f e r e n t botulinuni tax_ ins into t e r m i n a l endings of t h e c h o l i n e r g i c f i b e r s , we d e s c r i b e t h e r o l e o f v a r i o u s and d i f f e r e n t chemicel f a c t o r s : type and nunbers o f r e c e p t o r s , t y n e s o f z inc b inding enzyme, c a l c L urn concentrwtion and s o on. In p a r t i c u l a r o.b& U t t h e r e g u l e t i o n of t h e drug endocytosis t h r Q ugh t h e wall c e l l . Puthermore t h e ! iuthors ref_ f e r r e d about t h e preva len t way of t h e 'ootulinu_ n t o x i n c i i f fus ion , i n o r d e r t o j u s t i f y t h e pre_ sence of l o c a l and d i s - t a t e l f e c t s . F i n a l l y we r e a o r t e d t h e d i f f e r e n t individuc.1 c l i n i c a l response t o t h e botu l inun t o x i n i n j e c t i o n s , evz lu- t ing B8 s u b j e c t s a f f e c t e d by n'ocg 1 d g s t o n i a w i t h e l e c t r o p h y s i o l o g i c a l t e s t s , i n o r d e r t o ane lyze t h e ver i?* t ion o f t h e i1euroi:n- s c u l a r bloc^ i n time. Therefore t h e .Lu-thors s t r e s s t h e p o s s i b i l i t y t o ae te rmina te t h e i n d i v i d u a l c l i n i c a l sens ib& l i t y t o t h e drug u s i n g t h e neurophys io logicn l technique.

P143

2-4 Diaminovvridine (DAPI for side-effects of therapeutic botulinum toxin (BtAI. AP Moore*, Dept of Neurology, Walton Hospital, Liverpool, UK.

This was a pilot study to assess the value of DAP in treating the side-effects of BtA. DAP enhances acetylcholine release from motor nerve terminals and can increase neuromuscular transmission in BtA poisoning in vitro.

DAP was given open-labs1 in doses increasing to 100mgfday after 5 days, and each patient's most effective dose was determined. Patients then entered a double-blind crossover trial comparing this dose with placebo, spend- ing 2 days in each phase. Overnight washout was allowed. Objective self-rating scales were devised for each BtA side effect.

In the open study, 4 1 6 reported some benefit, useful in 3 . In the blinded study only 2 1 6 were (marginally) better on active DAP than placebo. Side effects were paresthes- iae in 3 , abdominal pain in 2 , weakness in 2 .

The study was confounded by the partial recovery of 416 patients from BtA side-effects during the blinded phase. Further studies using earlier randomisation are needed. Side effects will limit effective blinding.


Documents

Symposium of the movement disorder society, June 18–19, 1993