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Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.

Summary We propose that the basal ganglia support a basic attentional mechanism operating to bind input to output in the executive forebrain. Such focused attention provides the automatic link between voluntary effort, sensory input, and the calling up and operation of a sequence of motor programmes or thoughts. The physiological basis for this attentional mechanism may lie in the tendency of distributed, but related, cortical activities to synchronise in the _ (30 to 50 Hz) band, as occurs in the visual cortex. 1 Coherent and synchronised elements are more effective when convergence occurs during successive stages of processing, and in this way may come together to give the one gestalt or action. We suggest that the basal ganglia have a major role in facilitating this aspect of neuronal processing in the forebrain, and that loss of this function contributes to parkinsonism and abulia.

The startle response to unexpected auditory and somaesthetic stimulation was studied in 8 patients with hereditary or symptomatic hyperekplexia. It was abnormal in its resistance to habituation and in its exaggerated motor response. Both noise and taps to the face and head elicited a normal early blink response, separate from the subsequent true startle reflex. The earliest reflex EMG activity recorded after the blink was in sternocleidomastoid. EMG activity in masseter, and trunk and limb muscles followed later. This pattern of muscle recruitment suggests a brainstem origin for the abnormal startle responses. In addition, the abnormal startle responses exhibited disproportionately long latencies to the intrinsic hand and foot muscles and relatively slow recruitment of caudal muscles. The pattern of muscle recruitment was similar between patients, irrespective of the absolute latency of the response, and regardless of whether stimulation was auditory or somaesthetic. This suggests that auditory and somaesthetic afferents converge on a common brainstem efferent system, and that this system forms the final common pathway for abnormal startle responses of differing latency. The characteristics of this efferent system differ from those previously described in brainstem reticular reflex myoclonus, but are similar to those described in the normal auditory startle reflex in man. This suggests that the abnormal startle response in hyperekplexia, and the normal startle reflex represent pathological and physiological activity in the same brainstem efferent system.

It has been suggested that the basal ganglia control the release of cortical elements from low-frequency rhythmic idling activity during voluntary movement.(1) This hypothesis was tested by recording the local idling rhythms of the motor cortex, the alpha and beta rhythms, in 12 untreated and treated patients with Parkinson's disease as they moved a wrist. Recordings were made after overnight withdrawal of medication and again 1 hr after levodopa. The treatment-related attenuation of the alpha and beta rhythms picked up over the cortical motor areas contralateral to the active arm correlated with the improvement in size and speed of movement effected by levodopa. The distribution and degree of attenuation depended on the complexity of the task. These results demonstrate for the first time a specific effect of levodopa on the organization of motor cortical activity in the frequency domain, an effect that correlates with improvements in bradykinesia.

Five patients who presented with stimulus-induced jerking as part of an apparent myoclonic or pathological startle syndrome are reported. Neurophysiological observations in these patients suggested the jerks were voluntary in origin. These included (a) variable latencies to the onset of stimulus induced jerks, (b) latencies were greater than that seen in reflex myoclonus of cortical or brainstem origin, and were (c) longer than the fastest voluntary reaction times of normal subjects, (d) variable patterns of muscle recruitment within each jerk and, (e) significant habituation with repeated stimulation. It is argued that these features are consistent with a voluntary origin for the jerks and enable them to be distinguished from the stereotyped electrophysiological characteristics of myoclonus of cortical and brainstem origin. Electrophysiological recordings may help identify patients with this form of psychogenic movement disorder.

SUMMARY The clinical features and family histories of 20 adults with dyskinetic cerebral palsy from 20 families were studied. The majority of the patients showed progressive neurological deterioration in adult life. In only three did the condition stabilise by 10 years of âge and in seven there was deterioration after the âge of 30. Two patients developed a secondary cervical spondylotic myelopathy. Four patients had affected relatives and there were similar proportions of affected parents and siblings. The family data suggest genetic heterogeneity with autosomal recessive and dominant variants. The existence of an X-linked form cannot be excluded, and the demonstration of an increased paternal âge effect among single cases suggests that some of these may arise because of fresh dominant genetic mutation. RESUME IMC dyskinetique: une Aetude clinique et genetique Les caracteristiques cliniques et l'anamnese familiale de 20 IMC adultes dyskinetiques provenant de 20 families ont eteetudees. Une deterioration neurologique progressive durant la vie adulte fut constated chez la majority des patients. La stabilisation apres l'âge de 10 ans ne fut observed que trois fois, la deterioration apres l'âge de 30 ans sept fois. Une myelopathie par spondylose cervicale secondaire apparait chez deux patients. On notait des cas familiaux chez quatre patients, avec une proportion identique chez les parents et dans la fratrie. Les donnees familiales suggerent une heterogeneite genetique avec une variation autosomale recessive et dominante. L'existence d'une forme liee a l'X ne peut etre exclue et la mise en evidence d'un effet d'âge paternel accru parmi les cas isoles suggere un role partiel de mutations genetiques dominantes recentes. ZUSAMMENFASSUNG Dyskinetische Cerebralparese: Eine klinische und genetische Studie Es wurden die klinischen Merkmale und Familienanamnesen von 20 Erwachsenen mit dyskinetischer Cerebralparese aus 20 Familien untersucht. Die Mehrzahl der Patienten zeigte eine progressive neurologische Verschlechterung im Erwachsenenalter. Nur bei drei Patienten stabilisierte sich der Zustand mit 10 Jahren und bei sieben verschlechterte er sich nach dem 30ten Lebensjahr. Zwei Patienten entwickelten eine sekundare cervikale Spondylo-Myelopathie. Vier Patienten hatten ebenfalls betroffene Verwandte und es fanden sich ahnliche Verhaltnisse bei betroffenen Eltern und Geschwistern. Die Familiendaten lassen eine Heterogenic mit autosomal rezessiven oder dominaten Varianten vermuten. Eine X-gebundene Form kann nicht ausgeschlossen werden und der Nachweis, das in einigen Fallen ein erhohtes Alter der Eltern eine Rolle spielt, laBt vermuten, das einige Falle durch neu entstandene dominante genetische Mutationen entstanden sind. RESUMEN Paralisis cerebral disqinetica: estudio clfnico y genetico Se estudiaron los caracteres clinicos y las historias familiares de 20 adultos con paralisis cerebral disquinetica procedentes de 20 familias. La mayoria de los pacientes mostraron una deteriorizacion neurologica progresiva al llegar a adultos. Solamente en tres la situacion se estabilizo a los 10 afios de edad y en siete hubo una deteriorizacion despues de los 30. Dos pacientes desarrollaron secundariamente una mielopatia espondilotica cervical. Cuatro pacientes tenfan familiares afectados y habfa una proporcione similar de padres y hermanos afectados. Los datos familiares sugerian una heterogeneidad genetica, con variantes autosomicas recesivas y dominantes. La existencia de una forma ligada al cromosoma X no puede ser excluida y la demostracion de una edad paterna aumentada en los casos aislados, sugiere que algunos de ellos pueden deberse a una mutacion dominante reciente.

Rats were treated for 12 months with L-dopa (191.4-210.4 mg/kg/day) plus carbidopa (23.9-26.2 mg/kg/day), or carbidopa (24.4-26.3 mg/kg/day) alone. Four days after drug withdrawal, animals received an acute challenge with either L-dopa (50 mg/kg p.o.) alone or following acute carbidopa (25 mg/kg i.p.) pretreatment, and the uptake and metabolism of L-dopa in muscle was studied. Following the acute bolus challenge, plasma levels of L-dopa peaked between 0.5 and 3 h after L-dopa alone and between 1.5 and 2 h after L-dopa plus carbidopa. Peak levels in muscle were observed between 1.5 and 4 h after L-dopa administration, and this accumulation was enhanced by the acute pretreatment with carbidopa. Chronic administration of L-dopa plus carbidopa or carbidopa alone for 12 months had no effect on the accumulation of L-dopa into muscle following the acute challenge with L-dopa alone or after carbidopa pretreatment. 3-O-Methyldopa, dopamine, DOPAC, and HVA levels were elevated in both plasma and muscle following acute oral challenge with L-dopa or L-dopa plus carbidopa. Levels of these metabolites were unaffected by chronic administration of L-dopa plus carbidopa or carbidopa alone. In conclusion, chronic administration of L-dopa plus carbidopa did not alter the accumulation of L-dopa into muscle following an acute oral challenge with the drug, with or without carbidopa pretreatment.

Forty patients with Parkinson's disease and 24 patients with dystonia took part in a study aiming to assess the value of access to and contact with a nurse practitioner over a 6 month period. Patients in each group were randomly allocated to "intervention" or "control" groups, which were matched on important variables. All patients completed a set of questionnaires relating to psychosocial function at two time points separated by 6 months. In the intervening period, those allocated to the "intervention" group received two home visits and five telephone calls from the nurse practitioner. This contact was not provided to the "control" group. The nurse practitioner had a major impact on the provision of information and the facilitation of referral to other health-care agencies. The results of an independent assessment indicated that the patients in the "intervention" programme had found access to and contact with a nurse practitioner of great value. In contrast, the results of the questionnaire assessment did not reveal any statistically significant change in psychosocial functioning from the first to the second assessment for either the "intervention" or "control" groups. The lack of change in the questionnaire measures is discussed in terms of possible sampling bias and the duration of intervention and follow-up. Recommendations are made for future studies, and for the possible provision of clinical services.

This study has characterized the long-term neurobehavioural changes in a woman who, following the intake of an unidentified substance, sustained subtotal bilateral lesions of the globus pallidus and small lesions at selective sites adjacent to it. Associated with these lesions was a significantly reduced blood flow in multiple frontal cortical regions, most prominently in area 10, the anterior cingulate and the supplementary motor cortex. Her cognitive deficits were generally consistent with those found in patients with frontal lobe dysfunction but some deficits, i.e. in visual memory and learning, were more compatible with temporal lobe dysfunction. Incapacitating personality or obsessive compulsive changes as reported by others with similar lesions were absent and she could live independently. The cognitive changes are consistent with the view that the globus pallidus has important functions in mediating how internal representations of stimulus input are converted into various forms of action, for example, in planning solutions to problems and in working memory.

Changes in depression, disability, body concept, and severity of head deviation were examined in a sample of 67 patients with idiopathic torticollis, who were reassessed 2 years after taking part in an initial study (before the use of botulinum toxin injections). Over the follow-up period, torticollis was unchanged in 41·8%, had improved in 26·9% and deteriorated in 31·3% of cases. The overall levels of depression, disability, and body concept across the two occasions did not change. Changes in the clinical severity of torticollis over the follow-up period had a significant effect on psychological adjustment. Those whose torticollis improved were less depressed and disabled and a had a more positive body concept compared to the patients whose torticollis had worsened. Measures of illness severity had stronger associations with measures of psychological adjustment at follow-up than at the time of initial study. Longer duration of torticollis was associated with larger increases in depression and disability during the 2 years of follow-up. The results suggest that the experience of depression, disability, and negative body concept in a proportion of torticollis sufferers is a reaction to the neurological illness. A minority of the patients who remain chronically depressed are primary candidates for therapeutic intervention aiming at improving their adjustment to the illness.

Eighty-five patients with idiopathic spasmodic torticollis were compared with an equally chronic group of 49 cervical spondylosis sufferers in terms of body concept, depression, and disability. The torticollis patients were significantly more depressed and disabled and had a more negative body concept. Depression had different determinants in the two groups. Extent of disfigurement was a major predictor of depression in torticollis. Neuroticism accounted for the greatest proportion of the variance of depression in cervical spondylosis.

The assumption that spasmodic torticollis represents a conversion reaction was examined by evaluating profiles of 61 patients on the hypochondriasis, depression, and hysteria scales of the Minnesota Multiphasic Personality Inventory. Thirty-six per cent of the sample had normal profiles. A conversion "V" profile with scores above 70 was found in a minority (9%) of the patients. The profile of the majority of the group was characterized by the presence of mild depression. It was concluded that a personality profile suggestive of conversion reaction is not typical of patients with spasmodic torticollis.

OBJECTIVES—Although Parkinson's disease is typically characterised by bradykinesia, rigidity, and rest tremor, the possibility that two additional motor deficits are manifest during small hand muscle activity was explored—namely, weakness and abnormal physiological tremor. METHODS—A paradigm previously used in normal subjects reliably records the strength, tremor and surface EMG of index finger abducting contractions against a compliant (elastic) resistance. In addition to the well known physiological tremor at around 10 Hz, there are other co existing peak tremor frequencies at around 20 and 40 Hz; the last of these frequencies corresponds to the range of EMG Piper rhythm. The same technique was used to study parkinsonian patients while on and off dopaminergic medication. RESULTS—The maximum strength of finger abduction produced by first dorsal interosseous contraction was considerably lower when patients were off medication (mean (SD) 6.27 (1.49) N when off v 12.33(3.64) N when on). There was also a marked reduction in the power of Piper frequency finger tremor (p

The diagnosis of essential tremor (ET) and its differentiation from other types of tremor is often difficult. In 1994 Bain et al. defined a classical phenotype by studying 20 patients with pure essential tremor and similarly affected family members in at least three generations. We assessed how many of the patients diagnosed by different neurologists at our institution as having ET conformed to this defined phenotype. We randomly selected 50 patients who were diagnosed with ET by any neurologist at the National Hospital for Neurology and Neurosurgery since the publication of the Bain et al. report, and determined the number of patients who had clinical features compatible with the phenotype that it had defined. Only 25 (50%) of these patients had ET so defined. Ten patients clearly had alternative diagnoses: four had clear additional dystonia, two neuropathic tremor, two had unilateral leg tremor, one drug-induced tremor, and one sudden onset after head trauma. The remaining 15 patients also had atypical features including myoclonus (one), onset in a body part other than the arms (six), sudden onset (two), rest tremor (seven), onset after the age of 65 years (four), a family member with an isolated head tremor (one), or reduced armswing (two). The diagnosis of ET is overused even among experienced neurologists, and other types of tremor should be considered in atypical patients before making this diagnosis.

OBJECTIVES—To interpret clinical features after unilateral lesions of the globus pallidus on the basis of physiology of the basal ganglia. METHODS—Four patients with unilateral lesions in the globus pallidus (GP) were clinically examined and the literature on patients with pallidal lesions was reviewed. RESULTS—Three patients presented with contralateral dystonia largely confined to one arm in one case and one leg in two cases. One patient had predominant contralateral hemiparkinsonism manifested mainly as micrographia and mild dystonia in one arm. The cause of the lesions was unknown in two patients. In the other two symptoms had developed after head trauma and after anoxia. All lesions involved the internal segment of the GP. Two patients, including the patient with hemiparkinsonism, had additional involvement of the external segment of the GP. In the literature reports on 26 patients with bilateral lesions restricted to the GP only two with unilateral lesions were found. The patients with bilateral pallidal lesions manifested with dystonia, parkinsonism, or abulia. One of the patients with unilateral GP lesions had contralateral hemidystonia, the other contralateral arm tremor. CONCLUSION—These cases emphasise the importance of the GP, particularly its internal segment, in the pathophysiology of dystonia.

Conventionally, the standard test for detection of antibodies against botulinum toxin (BT-A) has been the mouse lethality assay (MLA). Because this test has a number of disadvantages, a novel mouse protection assay (MPA) was recently introduced. We sought to compare the results of both tests. Forty-three samples from 38 patients with cervical dystonia and complete or partial subjective BT-A therapy failure underwent simultaneous MPA and MLA testing. Twenty-seven samples showed concordant results in both tests. Eleven of them were MPA- and MLA-positive and 16 MPA- and MLA-negative, resulting in a significant association of the dichotomous test results (Fisher exact test, p

Paroxysmal dystonic choreoathetosis (PDC) is an unusual hyperkinetic movement disorder characterized by attacks of chorea, dystonia, and ballism with onset in childhood. We report a large British family with dominantly inherited PDC linked to chromosome 2q and describe the clinical features in 20 affected family members. Attacks were precipitated by a variety of factors, including caffeine, alcohol, or emotion, and could be relieved by short periods of sleep in most subjects. The clinical features in the family are compared with those of 11 other PDC families in the literature and a core phenotype for PDC suggested. CSF monoamine metabolites measured at baseline and during an attack in one subject were found to increase during the attack. Magnetic resonance spectroscopy of brain and basal ganglia performed both during and between attacks was normal. Positron emission tomography using the D2 receptor ligand, 11C-raclopride, showed no abnormalities.

Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.

Limb apraxia comprises a wide spectrum of higher-order motor disorders that result from acquired brain disease affecting the performance of skilled, learned movements. At present, limb apraxia is primarily classified by the nature of the errors made by the patient and the pathways through which these errors are elicited, based on a two-system model for the organization of action: a conceptual system and a production system. Dysfunction of the former would cause ideational (or conceptual) apraxia, whereas impairment of the latter would induce ideomotor and limb-kinetic apraxia. Currently, it is possible to approach several types of limb apraxia within the framework of our knowledge of the modular organization of the brain. Multiple parallel parietofrontal circuits, devoted to specific sensorimotor transformations, have been described in monkeys: visual and somatosensory transformations for reaching; transformation of information about the location of body parts necessary for the control of movements; somatosensory transformation for posture; visual transformation for grasping; and internal representation of actions. Evidence from anatomical and functional brain imaging studies suggests that the organization of the cortical motor system in humans is based on the same principles. Imitation of postures and movements also seems to be subserved by dedicated neural systems, according to the content of the gesture (meaningful versus meaningless) to be imitated. Damage to these systems would produce different types of ideomotor and limb-kinetic praxic deficits depending on the context in which the movement is performed and the cognitive demands of the action. On the other hand, ideational (or conceptual) apraxia would reflect an inability to select and use objects due to the disruption of normal integration between systems subserving the functional knowledge of actions and those involved in object knowledge.

The existence of "benign hereditary chorea" (BHC), a rare disorder of childhood-onset familial chorea without other neurologic features or progression, has increasingly been questioned, because many patients with this disorder were subsequently diagnosed with different conditions. We therefore analyzed all published reports of families with BHC and contacted their authors to obtain follow-up information. In addition, we reviewed all patients in whom at least one of the authors had at some stage considered a possible diagnosis of BHC. Of 42 families reported to have BHC in the literature, we obtained follow-up information on ii families, three of which had been seen by us. An additional seven new, unreported families and four sporadic cases, in which this diagnosis was suspected by at least one of us at one point, were reviewed and videotaped. On reviewing the videotapes of the II families in the Literature, the diagnosis of BHC was changed in nine. In the remaining two families, atypical features suggesting different diagnoses were present in the original reports. In none of our own previously unreported patients (seven familial and four sporadic) was BHC diagnosed unequivocally by all evaluators after review of their video recordings. In three of these families and all four sporadic patients the diagnosis was changed; in one family multifocal myoclonus could, not be differentiated from chorea by any author, and in the remaining three families no consensus between the raters was found. Apart from the II families in whom we obtained follow-up information, analysis of the remaining 31 reports on families with BHC also revealed atypical features in the majority. We conclude that BHC is not a diagnosis, but a syndrome that requires further investigation. Whether there is a distinct entity "BHC" with a single gene abnormality remains to be proven.

Primary orthostatic tremor is characterized by unsteadiness and shakiness of the legs while standing. It is due to a remarkably strong and regular EMG modulation at approximately 16 Hz that is thought to be of CNS origin. Previous studies have shown that the tremor frequency is the same in all involved muscles and that the time relation between bursts of activity in different muscles may be fixed (e.g. always co-contracting or always contracting in an alternating pattern). Here we have used frequency domain analysis of postural muscle EMG signals in five primary orthostatic tremor patients and in two normal controls to explore the nature of such fixed timing patterns. The timing is found not to relate simply to the relative conduction times for passage of rhythmic bursts from a central oscillation to different muscles. Indeed, although the timing pattern (expressed as phase) of the 16-Hz EMG bursts in different postural muscles remains constant while the subject adopts a certain steady posture, it is different for different subjects and also changes when the same subject adopts a different posture. It seems unlikely that such complex task-dependent timing relations of rhythmic postural muscle activity are due to the primary pathology of primary orthostatic tremor. Instead, we suggest that the abnormally strong peripheral manifestation of a 16-Hz CNS oscillation merely unmasks normal central processes so that the timing patterns may provide a clue to the nature of postural motor control.

In a preliminary report we demonstrated an association between the slow acetylator genotype of N-acetyltransferase 2 (NAT2) and familial cases of Parkinson's disease (FPD). Using a considerably more precise NAT2 typing method, which detects all mutant NAT2 alleles with a frequency of >1% in the white population, we have now retyped all the original patients and control subjects to investigate the reliability of our initial findings. The slow acetylator genotype remained considerably more common among FPD (73%) than normal control subjects (NPC, 43%) or the disease (Huntington's disease [HD]) control group (52%) with an odds ratio (OR) of 3.58 (95% confidence interval (CI): 1.96-6.56; p = 0.00003) for FPD versus NPC and an OR of 2.50 (95% CI: 1.37-4.56, p = 0.003) for FPD versus HD. Furthermore, the wild-type allele 4 conferred a protective effect with an OR of 0.39 (95% CI: 0.23-0.64; p = 0.0025) for FPD versus NPC and an OR of 0.50 (95% CI: 0.30-0.85, p = 0.01) for FPD versus HD. The results of this study support an association between the NAT2 slow acetylator genotype and FPD in our population.

Objective - To examine follow up results of unilateral ventral medial pallidotomy in 22 patients with advanced Parkinson's disease more than 1 year after the operation in comparison with their results (previously reported) at 3 months. Methods - Twenty patients who had undergone unilateral pallidotomy were assessed with the core assessment programme for intracerebral transplantation (CAPIT) protocol preoperatively, at 3 months postoperatively, and again after a median postoperative follow up of 14 months. Two further patients had only one evaluation 3 months postoperatively. Results - The reduction of contralateral dyskinesias (median 67%) at 3 months was slightly attenuated after 1 year to 55% (both p < 0.001 compared with baseline). A less pronounced effect on ipsilateral and axial dyskinesias decreased from 39% to 33% (p < 0.005 and p < 0.01), and from 50% to 12.5% (p < 0.001 and p < 0.01), respectively. However, there was no significant change between the 3 month and the follow up assessment. The modest improvement of the contralateral unified Parkinson's disease rating scale (UPDRS) motor score in the 'off' state remained improved compared with preoperative levels, but less significantly (26%, p < 0.001, and 18%, p < 0.01). The activities of daily living (ADL) subscore of the UPDRS in the off state remained improved with median changes of 23% and 22% at follow up (both p < 0.005). There was no significant improvement of 'on' state or ipsilateral off state motor scores. Median modified Hoehn and Yahr scores in off and on state were unchanged, as was the time spent off. Speech in off had significantly deteriorated by 1 year after the operation. Conclusions - The beneficial effects of unilateral pallidotomy persist for at least 12 months and, dyskinesias are most responsive to this procedure.

To investigate the possibility that rhythmic activity originating in the central nervous system may modulate human eye movements, anticipatory eye movements were generated by tracking an intermittently obscured sinusoidally moving target. Eight subjects tracked intermittently obscured sinusoids of three different frequencies and of two different amplitudes. Eye movements were recorded by an infra-red reflection technique. The eye velocity records were analysed in the frequency domain by power spectral estimates. During periods where the target was obscured, eye movements consisted of a staggered series of anticipatory saccades with intervening smooth anticipatory eye movements or relatively stationary periods. In sections where the intervening smooth components of anticipatory tracking were of high velocity (above 15 deg/s), a superimposed smooth tremulous oscillation at around 10 Hz was sometimes present. Coherence analysis showed that this 10 Hz range oscillation of smooth anticipatory movement was not derived from head tremor and that the same oscillation was present in both eyes. This oscillation was not generally observed during smooth tracking of pseudorandom waveforms. Investigation of anticipatory eye movements has revealed a 10-Hz range oscillation or "tremor" superimposed upon smooth movements that might in other circumstances be inhibited by direct visual feedback. This smooth eye movement oscillation is thought to originate from the central nervous system and may reflect a widespread frequency modulation of motor commands.

BDNF or vehicle were administered by unilateral supranigral infusion in normal and chronically lesioned MPTP-treated common marmosets (Callithrix jacchus) for four weeks and locomotor activity, disability and response to apomorphine were assessed with nigral TH, GFAP and GAD immunoreactivity and striatal [3H]mazindol autoradiography. Selective contraversive orientation and ipsilateral neglect evolved in MPTP-treated marmosets receiving BDNF with no significant difference in disability or locomotor activity when compared to the vehicle-infused group. Apomor-phine produced an ipsiversive rotational bias in BDNF-treated animals. In normal animals infused with BDNF contralateral neglect, ipsiversive turning, postural instability and ataxia rapidly evolved. In MPTP-treated marmosets BDNF caused increased ipsilateral striatal [3H]mazindol binding with increased somatic size and staining intensity in GAD-immunoreactive cells and a 10–20% loss of nigral TH-immunoreactive cells with increased GFAP staining. In normal common marmosets, both vehicle and BDNF infusion decreased nigral TH-immunoreactivity. Chronic supranigral infusion of BDNF alters motor behaviour and spatial attention in MPTP-treated marmosets which may reflect altered function in residual nigral dopaminergic neurons and brainstem GABAergic neurons and in normal animals produces behavioural and histological signs of nigrostriatal hypofunction.

Three patients are reported on who developed transient generalised weakness after receiving therapeutic doses of botulinum toxin for cervical dystonia (one case) and symptomatic hemidystonia (two cases) respectively. Clinical and electrophysiological findings were in keeping with mild botulism. All patients had received previous botulinum toxin injections without side effects and one patient continued injections without recurrence of generalised weakness. The cause is most likely presynaptic inhibition due to systemic spread of the toxin. Patients with symptomatic dystonia may be more likely to have this side effect and botulinum toxin injections in these patients should be carried out cautiously.

It is generally recognized that focal dystonia of the limbs or cervical region and blepharospasm sometimes follow, and in these cases may be caused or triggered by, peripheral injury. However, the association between peripheral injury and lower cranial dystonia is rare. We report eight cases who developed cranial dystonia within hours to months following a dental procedure. One group of five cases, all women, developed atypical dystonia associated with painful paresthesias at the site of dystonia. Two of these five cases had fixed jaw-deviating dystonia, whereas the remaining three had additional tremor and spread of their dystonia to involve the tongue in all three, and the lips and neck in two cases. These five patients are reminiscent of cases of limb causalgia-dystonia syndrome, which occurs after minor peripheral trauma and can spread. The remaining three cases developed more typical cranial dystonia following the dental procedure. There was no family history of dystonia or prior use of neuroleptics in any of the patients. The close association in time and location of the procedure and onset of symptoms suggests that the onset of the dystonia may have been caused by the dental intervention, but whether there is a causal relationship between the dental intervention and the development of the dyskinesias requires further epidemiologic studies.

It has been suggested that a lesion in the dopaminergic neurons of the substantia nigra pars compacta combined with eye irritation is involved in the pathophysiology of idiopathic blepharospasm. If so, these patients might be prone to develop Parkinson's disease or a parkinsonian syndrome. We therefore conducted a validated questionnaire-based follow-up study to estimate (a) the frequency of local eye disorders at onset and (b) frequency of development of parkinsonian symptoms in blepharospasm patients. Ninety-nine patients previously diagnosed with idiopathic blepharospasm were sent a two-part questionnaire to assess parkinsonian and other symptoms associated with their condition. The average period of follow-up was 12.7 years, ranging from 3 to 26 years, with an average age at onset of 53.5 years. Sixty-two patients reported other ocular symptoms prior to or at the onset of blepharospasm, and therefore ocular disease may act as a trigger to produce blepharospasm in those already predisposed. Only two patients had developed a score on the parkinsonism rating scale indicating possible Parkinson's disease, but clinical examination confirmed this not to be the case. If a lesion in the dopaminergic neurons is involved in blepharospasm, it would appear to be relatively minor (and non-progressive), since patients with idiopathic blepharospasm do not seem prone to develop parkinsonian symptoms.

Paroxysmal kinesigenic choreoathetosis (PKC) is a neurological condition which results in abnormal involuntary movements that are precipitated by sudden movement. Because of its rarity, large case series of PKC have not been published. We studied 26 patients with PKC, which represents the largest series thus reported. We reviewed our cases with respect to attack characteristics, aetiology, family history, and treatment response. Our population consisted of 23 men and 3 women. Seven patients had a family history of paroxysmal dyskinesia. None of our patients had clear evidence of symptomatic PKC. Two-thirds of our patients had attacks lasting between 30-60 s, and over one-half experienced one to ten attacks per day. Attack distribution varied widely, and most experienced pure dystonia rather than choreodystonic movements. Most patients responded very well to anticonvulsant therapy. We also report the PET results from two of our patients and Bereitschaftspotential abnormalities recorded from two others.

OBJECTIVE—To investigate whether the stiff limb syndrome may be separated from the stiff man syndrome and progressive encephalomyelitis with rigidity on simple clinical grounds, and whether such a distinction has implications for aetiology, treatment, and prognosis. METHODS— Twenty three patients referred over a 10 year period with rigidity and spasms in association with continuous motor unit activity, but without evidence of neuromyotonia, extrapyramidal or pyramidal dysfunction or focal lesions of the spinal cord were reviewed. The patients were divided into those with an acute or subacute illness, leading to death within 1 year, and those with a chronic course. The latter were divided into those in whom rigidity and spasms dominated in the axial muscles, or in one or more distal limbs, at the time of their first assessment. RESULTS—This simple division identified three distinct groups of patients. (1) Progressive encephalomyelitis with rigidity: two patients had a rapidly progressive condition characterised by widespread rigidity which resulted in death within 6 and 16 weeks. One patient had negative anti-GAD and anti-neuronal antibodies, but had markedly abnormal CSF and widespread denervation. The principal pathological findings in this case were a subacute encephalomyelitis which primarily affected the grey matter. In the remaining patient anti-GAD antibodies were not tested, and postmortem was refused. (2) Stiff man syndrome: eight patients had rigidity and painful spasms of the lumbar paraspinal, abdominal, and occasionally proximal leg muscles associated with a lumbar hyperlordosis. There was no involvement of the upper limbs, distal lower limbs, sphincters or cranial nerves. Seven had anti-GAD antibodies and most had additional evidence of autoimmune disease. Neurophysiologically there was continuous motor unit activity with abnormal exteroceptive reflexes, but a normal interference pattern during spasms. The patients all responded to baclofen/diazepam and remained ambulant. (3) Stiff limb syndrome: thirteen patients had rigidity, painful spasm, and abnormal postures of the distal limb, usually the leg. About half went on to develop sphincter or brainstem involvement. Generalised myoclonic jerks were not a feature. Only two had truncal rigidity, and another two had anti-GAD antibodies. Most had no evidence of autoimmune disease. Neurophysiologically they had continuous motor unit activity in the affected limb, abnormal exteroceptive reflexes, and abnormally segmented EMG activity during spasms. The disease ran a protracted course, and most patients had only a partial response to baclofen or diazepam. About half became wheelchair bound. CONCLUSIONS—The stiff limb syndrome seems distinct from the stiff man syndrome or progressive encephalomyelitis with rigidity, and is an important cause of rigidity and spasm in the setting of continuous motor unit activity.

We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa-responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH-1 deficiency. A large number of new heterozygote mutations (seven point mutations, two splice site mutations, and one deletion) as well as a new homozygote mutation in the child with atypical phenylketonuria were detected. In addition, two previously described mutations were found in two other cases. We further extended our investigation of GCH-1 to the 5' and 3' regulatory regions and report the first detection of point mutations in the 5' untranslated region. Demethylation of CpG islands does not appear to be an important causative factor for the GCH-1 mutations in DRD. In addition, we have extended the clinical phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing and remitting course, and DRD with onset in the first week of life. None of our DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.

There has been significant progress in our knowledge of the cause, the pathogenesis, and the nature of the mechanism of cell death in Parkinson's disease (PD). Mutations in single genes have now been shown to be able to cause PD but likely only account for a small number of cases. Alternatively, there is evidence that environmental factors play a large role in the majority of cases of sporadic PD. Most likely, genetic factors predispose patients to develop PD if combined with other gene mutations or environmental toxins. Interest has thus focused on factors that contribute to the pathogenesis of neurodegeneration and the mechanism of cell death in an attempt to design a neuroprotective therapy. Oxidant stress, mitochondrial dysfunction, excitotoxicity with excess nitric oxide formation, and glia and inflammatory processes are all thought to contribute to the cell death process and agents that interfere with these events may be neuroprotective. It is now generally held that the final culmination of these events is the induction of apoptosis in nigral dopaminergic neurons and this too offers opportunities for providing neuroprotection. A rational argument can be made for investigating a large number of different approaches or combination of approaches in the hope of developing a meaningful neuroprotective therapy, using clinically relevant indices and neuroimaging markers of nigral dopaminergic neurons. It is evident that conventional approaches to trials that utilize large numbers of patients in search of small incremental effects are costly and time consuming. As such, it will be virtually impossible to test all of the potentially valuable neuroprotective agents that are now at hand, let alone those that will likely soon emerge. We suggest that it may be more profitable to test a large number of agents in a small number of selected patients in search of a more robust neuroprotective effect. In this way, we will reduce the risk of missing a powerful neuroprotective treatment with a treatment that might not otherwise have been studied because of a lack of time, money, or patients.

Co-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable than normal, and there is particular difficulty switching between component movements of a complex task. Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition). These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory. Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements. Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia. Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability. Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia. All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata). This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.

Susceptibility to develop Parkinson's disease has been linked to abnormalities of P450 enzyme function. Multiple P450 enzymes are expressed in brain but the relationship of these to Parkinson's disease is unknown. We have investigated the expression of P450 enzymes in the rat substantia nigra and their co-localization in tyrosine hydroxylase-positive neurons and astrocytes. Immunohistochemistry was performed using anti-peptide antisera against the following P450 enzymes: CYP1A1, CYP1A2, CYP2B1/2, CYP2C12, CYP2C13/2C6, CYP2D1, CYP2D4, CYP2E1, CYP3A1, CYP3A2 and NADPH-P450 oxidoreductase. Immunoreactivity in nigral cells was found only for CYP2E1 and CYP2C13/2C6. CYP2E1 immunoreactivity was localized to many midbrain nuclei including the substantia nigra pars compacta but not the substantia nigra pars reticulata while immunoreactivity to CYP2C13/2C6 was found in the substantia nigra pars compacta, substantia nigra pars reticulata and many other midbrain nuclei. Sections of rat midbrain double labelled for either CYP2E1 or CYP2C13/2C6 and tyrosine hydroxylase or glial fibrillary acidic protein were examined for co-localization by confocal laser scanning microscopy. CYP2E1 and CYP2C13/2C6 immunoreactivity was found in tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta but not in glial cells. CYP2C13/2C6, but not CYP2E1, was also found in non-glial, non-tyrosine hydroxylase-expressing cells in the substantia nigra pars reticulata. Isoniazid induction increased CYP2E1 fluorescence signal intensity from nigral dopaminergic neurons. At least two P450 enzymes are found in nigral dopamine containing cells and one, namely CYP2E1, is selectively localized to this cell population. CYP2E1 is a potent generator of free radicals which may contribute to nigral pathology in Parkinson's disease. The expression of CYP2E1 in dopaminergic neurons in substantia nigra raises the possibility of a causal association with Parkinson's disease.

The purpose of this study was to relate abnormalities of motor conduction time to the presence of spinal cord MRI lesions in progressive multiple sclerosis and to investigate the relationship between changes in motor conduction over time and clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the brain and spinal cord, and clinical evaluations were carried out in 20 patients with primary and secondary progressive multiple sclerosis. CMCT was carried out at the beginning and end of the study whilst the clinical and MRI examinations occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior correlated with disability measured on the Expanded Disability Status Scale. Latencies to upper limb muscles correlated with cervical MRI lesion load and the presence of atrophy of the cervical cord. Over the 12-month study period, 15 of 19 patients deteriorated clinically. However, an increase in motor response latencies occurred only in the four patients who had developed new cord lesions. The results suggest that prolonged CMCT is related to spinal cord lesion load and that, over time, changes in the CMCT occur only when spinal cord lesion load increases. Clinical change in progressive multiple sclerosis may therefore occur without either the development of new lesions on MRI scans or an increase in motor conduction time. This suggests that clinical deterioration in these patients may occur by a mechanism other than increasing demyelination. This may be progressive axonal degeneration.

The cause of neuronal loss in patients with idiopathic Parkinson's disease is unknown. Oxidative stress and complex I deficiency have both been identified in the substantia nigra in Parkinson's disease but their place in the sequence of events resulting in dopaminergic cell death is uncertain. We have analysed respiratory chain activity, iron and reduced glutathione concentrations in Parkinson's disease substantia innominata and in the cingulate cortex of patients with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies to investigate their association with neuronal death and Lewy body formation. No abnormalities of mitochondrial function, iron or reduced glutathione levels were identified in Parkinson's disease substantia innominata or cingulate cortex. Mitochondrial function also appeared to be unchanged in cingulate cortex from patients with Alzheimer's disease and from patients with dementia with Lewy bodies, however, iron concentrations were mildly increased in both, and reduced glutathione decreased only in Alzheimer's disease. These results confirm the anatomic specificity of the complex I deficiency and decreased levels of reduced glutathione within the Parkinson's disease brain and suggest that these parameters are not associated with cholinergic cell loss in Parkinson's disease nor with Lewy body formation in this or other diseases. We propose that our data support a 'two-hit' hypothesis for the cause of neuronal death in Parkinson's disease.

Most positron emission tomography (PET) studies of regional cerebral function in idiopathic torsion dystonia (ITD) have failed to show abnormalities, but there have been few studies of the changes in regional cerebral blood flow (rCBF) that occur during movement in dystonia. Using PET, we have studied six patients with familial generalized ITD both at rest and while moving a joystick with the right hand. The patterns of CBF change obtained were compared with those in six age-matched control subjects. In the dystonia group, free selection of movement was associated with relative increases in rCBF above that observed in control subjects in the left premotor area, the supplementary motor area (SMA), the anterior cingulate cortex, and the left dorsolateral prefrontal area. Subcortical increases were observed within the cerebellum and the putamen. There was a relative decrease in flow through the contralateral primary sensorimotor cortex. These findings contrast with those reported in patients with Parkinson's disease undertaking the same task in which the activity in the SMA and putamen was decreased. We suggest that arm dystonia in ITD is associated with overactivity of the premotor areas, including the SMA, and that this results from release of the thalamus from the normal inhibitory influence of the globus pallidus internal segment. Other abnormalities of basal ganglia control of brain stem centers may be involved in axial dystonia.

Objective: To investigate psychiatric and neurological morbidity, diagnostic stability, and indicators of prognosis in patients previously identified as having medically unexplained motor symptoms. Design: Follow up study. Setting: National Hospital for Neurology and Neurosurgery, London—a secondary and tertiary referral hospital for neurological disorders. Subjects: 73 patients with medically unexplained motor symptoms admitted consecutively in 1989-91. 35 (48%) patients had absence of motor function (for example, hemiplegia) and 38 (52%) had abnormal motor activity (for example, tremor, dystonia, or ataxia). Main outcome measures: Neurological clinical diagnosis at face to face reassessment by a neurologist and a psychiatric diagnosis after a standardised assessment interview—the schedule for affective disorders and schizophrenia—conducted by a psychiatrist. Results: Good follow up data were available for 64 subjects (88%). Only three subjects had new organic neurological disorders at follow up that fully or partly explained their previous symptoms. 44/59 (75%) subjects had had psychiatric disorders; in 33 (75%) patients, the psychiatric diagnosis coincided with their unexplained motor symptoms. 31/59 (45%) patients had a personality disorder. Three subjects had developed new psychiatric illnesses at follow up, but in only one did the diagnosis account for the previous motor symptoms. Resolution of physical symptoms was associated with short length of symptoms, comorbid psychiatric disorder, and a change in marital status during follow up. Conclusions: Unlike Slater9s study of 1965, a low incidence of physical or psychiatric diagnoses which explained these patients9 symptoms or disability was found. However, a high level of psychiatric comorbidity existed. Key messages Motor symptoms that remain unexplained medically despite thorough investigation are a common clinical problem, but the emergence of a subsequent organic explanation for these symptoms is rare The prevalence of coexistent affective and anxiety disorders is high and many patients also have a personality disorder Patients with a shorter duration of symptoms and coexistent anxiety or depression are likely to do better at follow up Reinvestigation of these patients is both expensive and potentially dangerous and should be avoided where no clear clinical indication exists

The effects of vision on spatial and temporal characteristics of free unrestrained reaching movements of the arm were examined in 17 patients with ataxic syndromes due to degenerative disease of the cerebellum and its connections. Subjects were required to reach out and touch a visually presented target either in the dark or with the target and their finger visible. Overall, patients had prolonged reaction times and their movements were performed slower than normal. The spatial paths described by their fingertips were more circuitous, being of greater length than normal, a characteristic that was uninfluenced by visual conditions. Ataxic movements were less accurate than normal in two ways. First, there was greater spatial variability between repeat paths to the same target. The increased variability was present very early in the movement trajectory and at that stage was not influenced by visual feedback. Secondly, there were large constant errors at the end of movement, but only when moving in darkness. Patients with Friedreich's ataxia as well as those with intrinsic cerebellar degeneration showed the above abnormalities, although there were some quantitative differences between the two groups. We suggest these spatial errors arise because the cerebellum contributes either directly or indirectly to preparatory motor processes which, based on limb proprioceptive and retinal information, compute the pattern of muscle activity required to launch the limb accurately towards a target. Patients were largely successful at using visual guidance to make midflight adjustments to their movements in order to improve accuracy. This manifested as a reduction in spatial variability between repeat paths as the target was approached and a reduction in constant error. However, the visual correction mechanism did not appear normal. Under visual guidance, the end-phase of movement was often prolonged and characterized by excessive deviations or direction changes in the path. These deviations may be the expression of a visual guidance system producing corrections which themselves contain error requiring further correction. Thus, this process may be abnormal for the same reason that the initial pattern of muscle activity is misjudged.

This multicentre randomised double-blind 3- to 5-year trial was designed to assess whether initial therapy with cabergoline alone or in combination with levodopa prevents or delays the occurrence of long term motor complications in patients with early Parkinson's disease. Patients eligible for study inclusion (n = 412) had early idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 3) and had received no previous treatment with levodopa, selegiline or dopamine agonists. Patients were randomised to receive either cabergoline (0.25 to 4 mg once daily) or levodopa (100 to 600 mg/day) titrated over a maximum period of 24 weeks. Once the optimum or maximum tolerated dose was achieved, it was maintained up to the end-point (development of motor complications confirmed at 2 consecutive 3-month visits) or up to a minimum of 3 years' treatment. Open labelled levodopa was added in both treatment arms when the improvement in motor disability [Unified Parkinson's Disease Rating Scale (UPDRS) factor III] decreased below 30% vs baseline. Both treatments improved motor disability, decreasing UPDRS factor III scores and factor II scores for activities of daily living. The development of motor complications (end-point) was significantly less frequent in patients treated with cabergoline than in levodopa recipients (22% vs 34%; p < 0.02). The relative risk of developing motor complications during treatment with cabergoline was more than 50% lower than with levodopa. Serious adverse events, either drug related or not, were slightly more frequent in cabergoline-treated patients (31%) than in those treated with levodopa (25%). The withdrawal rate in the cabergoline vs levodopa group was 16 vs 13%. In conclusion, the study shows that, in patients with early Parkinson's disease, cabergoline is effective either as monotherapy or combined with levodopa. Moreover, starting treatment with cabergoline significantly delays the development of motor complications.

The clinical features and natural history of 18 patients with adult onset axial predominant severe truncal primary dystonia are presented. The mean age of onset was 41 (42 for men, 39 for women) and there was a higher proportion of men (10:8). Analysis of their clinical features and follow up over three to five years or more showed that these patients generally conform to the characteristics of other types of adult onset primary dystonias. They tended to remain focal although there could be an initial contiguous spread, sometimes beginning in the craniocervical region and spreading axially or, rarely, vice versa. If spread occurred, involvement of the head, neck, and arms was mild in comparison with the severe dystonia of the trunk. However, in none of the patients with craniocervical or truncal onset did the dystonia spread to involve the legs. More than a third (seven of 18) of the patients had a prior history of injury at the site subsequently affected by dystonia. Treatment response to various drugs overall was poor but a third of the patients improved on treatment either with triple therapy (a combination of tetrabenazine, pimozide, and an anticholinergic drug) or high dose anticholinergic drugs alone. Severe depression occurred in 33% of patients, mainly due to the negative personal image arising from their disfiguring dystonia. None of the patients had a family history of dystonia and at the moment it is unclear whether these patients with sporadic axial dystonia are non-genetic phenocopies or are a manifestation of one or more of the genes that cause generalised dystonia or torticollis.

We report eight new sporadic cases of paroxysmal dystonia induced by prolonged or sustained exercise and review an additional seven previously reported cases. The attacks in our patients lasted from a few minutes to up to 2 h, and patient age at onset ranged from 2 to 30 years. Four of the eight patients had hemidystonic attacks, both legs were involved in two other cases, and the remaining two patients had involvement of the right foot only. We propose that such cases should be classified as paroxysmal exercise-induced dystonia.