[Topography of secondary dystonia lesions]. / Topographie des lésions des dystonies secondaires.

Biological causes provoking dystonia can not be systematized, with the exception of the small group of levodopa-responsive dystonia. Therefore the pathophysiology of the dystonic syndrome can be approached by considering the site of the lesions. In 40 cases of uni or bilateral symptomatic dystonias, this site could be identified with CT Scan or MRI. Twenty-one were located in the striatum, six in the pallidum, seven in the thalamus, six in the midbrain. Each group is characterized by etiologic and clinical criteria, sometimes associated with abnormal movements. In the striatal group, the most important, dystonia was often associated by athetosis or choreoathetoid abnormal movements. In some cases, in children, lesions were vascular due to impairment of lenticulo-striatal arteries, often following cranial trauma. The pallidal lesions were usually provoked by metabolic or infectious agents. Most thalamic dystonias were of vascular origin, sometimes accompanied by myoclonia. Midbrain lesions were usually vascular with tremor. Athetosis occurred after striatal rarely after pallidal lesions. It is advisable not to assimilate dystonia and athetosis as both are simultaneously observed if the lesions are located in the striatum, rarely in the the pallidum but not in the midbrain.

Visual cognitive dysfunction in depression: an event-related potential study.

The P3(00) event-related potentials (ERPs) elicited by visual stimuli in two visual tasks were assessed in depressed patients (12 patients with major depression and 11 patients with bipolar disorder) and compared with those of 20 age-matched normal controls. At remission, the ERPs from 18 of the depressed patients were again recorded. The visual oddball (VO) paradigm presented both target and standard visual stimuli and the simple visual (SV) paradigm presented a target but no standard visual stimulus. Subjects performed the VO task significantly less accurately than the SV task, as reflected by the behavioral measures (reaction-time and task accuracy). Depressed patients of the bipolar group showed longer P3 peak latency for the VO task and no change in P3 amplitude. No significant differences were found in any other ERP component between the groups. During remission, slowing RTs and reduced P3 peak latencies were observed for both major depression and bipolar disorder groups. Thus, the P3 ERP may be an index of the contribution of the slowed central processing to psychomotor retardation in clinically homogenous samples of depressive patients performing an appropriately demanding task.

Clinical assessment of olfactory dysfunction in Parkinson's disease.

We used two simple tasks to test the capacities of patients with Parkinson's disease to discriminate and identify olfactory stimuli. The patients presented defective odor identification abilities whereas their capacity to discriminate between odors was apparently unaffected. This raises a question about the nature of olfactory dysfunction in Parkinson's disease. Further clinical data is required for analysis of this dysfunction. We therefore propose simple and rapid tests appropriate for clinical use with Parkinson's disease patients.

[Juvenile GM2 gangliosidosis with progressive spinal muscular atrophy onset]. / Gangliosidose à GM2 juvénile débutant par une amyotrophie spinale progressive.

GM2 gangliosidosis are caused by a beta-hexosaminidase A enzyme deficiency. Mutations in the gene leaving residual enzyme activity give rise to juvenile and adult forms of the disease which have a great clinical heterogeneity. We report three cases which have been considered for some time as Kugelberg-Welander disease. beta-hexosaminidase A was determined with the sulfated synthetic substrate, 4-méthylumbelliferyl-N-acetylglucosamine 6-sulfate (4-MUGS), which allowed the diagnosis. Two of these cases from one family had normal values of hexosaminidase A in serum as found in the B1 variant. Compound mutations were detected. The B1 variants had a classical B1 mutation (G533-->A) and a new mutation located on exon 11. The patient of the second family had the classical mutation of adult GM2 gangliosidosis (Gly269-->Ser) and a new mutation on exon 1, at the initiation codon.

Intracerebral recording of movement related readiness potentials: an exploration in epileptic patients.

Readiness potentials (RPs) preceding voluntary self-paced limb movements were recorded intracerebrally in 13 patients suffering drug resistant, intractable epilepsy. Multilead depth electrodes were positioned using the Talairach's coordinate system; they allowed simultaneous recording from the external and mesial cortices and from the interposed white matter during self-paced unilateral hand or plantar flexions. Our intracerebral explorations have shown RPs in the primary motor cortex (MC) contralateral to the movement and in both supplementary motor areas (SMAs), indicating that at least 3 cortical sites become active before the movement. At variance with the scalp RPs recorded in the same patients, the intracerebral potentials were either negative, or positive, depending on the recording site. No consistent differences in duration and time of onset could be established between the MC and the SMA RPs, at least with the used time resolution. RPs were only occasionally observed in the parietal cortex and hippocampus and none were recorded from the amygdala, the temporal, temporo-occipital, prefrontal, frontal and cingular cortices. The wide topographical distribution of the scalp RPs may not be fully explained by the above intracortical findings, leaving the possibility that other generators exist, whose locations remain to be determined.

Abnormal movement related potentials in patients with lesions of basal ganglia and anterior thalamus.

Movement-related cortical potentials (MRCPs) were recorded from scalp electrodes during wrist flexion in 15 dystonic patients with bilateral (nine) or unilateral (six) circumscribed lesions in the striatum (eight), pallidum (six), or anterior thalamus (one). The results were compared with those of 10 age-matched healthy volunteers. The early (BP) and late (NS') MRCP components were assessed in terms of their gradients and distribution on the scalp in Cz, C3', and C4'. The gradients of both BP and NS' components were significantly flatter in the patients with bilateral lesions than in the control subjects. Also, the BP gradient was maximum at Cz, and the NS' component was contralaterally predominant in the control subjects but not in the patients. In patients with unilateral lesions, the gradients were flatter (p < 0.05) during movement of the dystonic wrist than during movement of the normal wrist. This difference was significant for BP and NS', regardless of the location of the electrodes. Also, the normal topographic predominance of BP at Cz and of contralateral NS' disappeared. The BP and NS' components of the MRCPs are thought to reflect preparatory activity in the supplementary motor area and the primary motor cortex before movement. Reduced BP and NS' gradients in patients with both bilateral and unilateral lesions of the basal ganglia, which project towards the supplementary motor area, are consistent with this hypothesis. The bilateral nature of these reductions suggests that both the ipsilateral and the contralateral motor cortex are involved in the genesis of the MRCPs and that the dystonia in these patients is associated with impaired motor preparation.

Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance.

We measured serum antibodies to botulinum toxin (ABT) in 96 patients with focal dystonia who had been treated with type A botulinum toxin. The frequency of detectable ABT was 3% (three patients). Patients with ABT had received more than 50 ng of botulinum toxin, and the shortest time between two injections was significantly less than in patients without ABT. The clinical evolution of the three patients was heterogeneous: one had decreased effectiveness with repeated injections, another had persistent improvement, and the third never responded to toxin injections.

[Positron-emission tomographic study of the dopaminergic system in a case of secondary unilateral tremor after mesencephalic hematoma]. / Etude du système dopaminergique en tomographie par émission de positons dans un cas de tremblement unilatéral secondaire à un hématome mésencéphalique.

A 30 year-old woman developed a postural and rest tremor of the left hand following a right peduncular post-traumatic hematoma. Two years later, positron emission tomography showed a marked decrease in [18F] fluorodopa uptake contrasting with a normal [76Br] bromolisuride uptake in the right striatum. This suggests that: 1) chronic unilateral dopaminergic striatal denervation may occur without persistent D2 dopaminergic receptor upregulation in humans; and 2) symptomatic mesencephalic tremor may be, at least in part, related to dopaminergic striatal denervation.

Chronic administration of L-dopa affects the movement-related cortical potentials of patients with Parkinson's disease.

The chronic effect of L-Dopa administration on the movement-related cortical potentials (MRCPs) was studied in two groups of patients with Parkinson's disease (PD): patients de novo (DN) and patients with on-off fluctuations. The BP and NS' premovement components of MRCPs associated with wrist flexion were assessed by their gradients and by their distribution on the midline (CZ) and the ipsilateral and contralateral hand sensorimotor areas. The treatment efficacy was controlled by a decrease in PD score (Columbia University Rating Scale). The BP component was absent in four out of nine patients DN. After 3 months of treatment, BP and NS' were recorded in six out of seven patients, and the NS' slope was significantly increased in all patients. In the off phase, MRCPs from patients with on-off fluctuations did not present a BP component. In the on phase, the NS' slope was increased and the BP was recorded in two out of nine patients. These patients exhibited an earlier PD stage (Hoehn and Yahr, stage 3). These two patterns of changes in the MRCPs induced by L-Dopa treatment suggest that the BP component was recorded in patients DN when a partial resolution of the nigrostriatal activity could occur. In patients with severe fluctuations, the dopaminergic striatal pathway was more severely affected and the increase of the NS' component demonstrated the activation of extrastriatal dopamine sites within the central nervous system (limbic and cortical structures, in particular).

[Movement-related cortical potentials in aged subjects]. / Les potentiels corticaux liés au mouvement de l'homme âgé.

Cortical potentials related to freely-executed voluntary wrist flexion (MRPs) were studied in 35 subjects aged 23-80 years. The characteristics of the MPRs in aged subjects were determined in comparison data from 14 young subjects aged 23-40 years. The analysis concerned 3 components of the MRPs: the slow negative shifts (NS1 and NS2) before the movement onset and the motor potential (MP). In the aged subject, the latencies measured at Cz show a significant lengthening of the NS1 and of the duration of NS2 (NS' of Shibasaki et al, 1980). The mean amplitude of the NS1 peak at Cz is decreased, and those of N1 (the negative peak before the movement) and MP are not significantly different from those of the young subjects. The NS2 component in the aged subject (between NS1 and N1) is thus increased. In contrast to the young subjects, who present a predominance of N1 and MP amplitudes of the contralateral motor cortex over the ipsilateral cortex, the aged subjects lose lateralization of these components. Recording of MRPs with subdural electrodes (Neshige et al, 1988) shows taht NS1 results from the activity of the supplementary motor area and from the ipsi-contralateral primary motor cortex. The increase in NS2 might be interpreted as an expression of activity coming from other structures to compensate for the reduction in NS1 in the aged subject and to maintain the level of the motor potential MP.

[Changes in movement-related cortical potentials in Parkinson's patients before and after treatment with levodopa]. / Evolution des potentiels corticaux liés au mouvement chez les patients parkinsoniens, avant et après traitement par la lévodopa.

Cortical potentials associated with voluntary, self-paced wrist flexion (MRPs) were recorded from 3 scalp locations (Cz and psi contralateral hand motor area) in patients with Parkinson's disease (9 de novo patients and 30 L-Dopa treated patients). The analysis concerned 3 components of the MRPs: the 2 slow negative shifts (NS1 and N1) before the movement onset and the motor potential (MP). The NSI amplitude was measured at Cz, the peak negativity N1 and MP from contralateral hand motor area location. The potential distribution was also studied. The amplitude of the MRPs components was the same as in the normals. But in de novo patients, the potential distribution of the NS1 component was different; a Cz preponderance of the NS1 amplitude was not found. In patients treated with L-Dopa, there is a negative correlation between the changes in amplitude and the changes in clinical rating for NS1, N1 and MP components. The decrease in the MRPs components was significant from stage III and IV of the Hoehn and Yahr scales. After L-Dopa therapy, the NS1 component from de novo patients was increased in amplitude. The amplitude of the MRPs components from patients with L-Dopa induced clinical fluctuations was reduced during "off" period in comparison to "on" period. The findings suggest that the NS1 potential and the N1 and MP components share 2 distinct systems for the control of voluntary movement. Their mechanism in Parkinson's disease is discussed.

Therapeutic response to progabide in neuroleptic- and L-dopa-induced dyskinesias.

The results of two trials conducted in human dyskinesia with progabide, a specific gamma-aminobutyric acid (GABA) receptor agonist, are reviewed. In one trial, 13 parkinsonian patients with L-DOPA-induced dyskinesia (LDD) and "on-off" fluctuations were included in a double-blind controlled trial progabide versus placebo. No change was observed during this trial in the severity of dyskinesia on progabide treatment but the drug significantly extended the "on" period as compared with placebo. In the second trial, 20 patients with neuroleptic-induced dyskinesia (TD) entered an open dose ranging trial with progabide. Fourteen of the 16 patients who completed the trial had a good-to-excellent therapeutic response. According to these results, progabide does not seem to have the same therapeutic benefit in LDD as TD. These data suggest that the hypothesis of a dopaminergic supersensitivity as a similar pathogenic substrate for both clinical conditions should be reconsidered. If this hypothesis remains the most consistent to explain the occurrence of LDD, the therapeutic effect of progabide in TD is an argument for an implication of the GABAergic system in the appearance of TD.

Postural adjustments associated with rapid voluntary arm movements in patients with Parkinson's disease.

To determine the extent to which deficits in coordination between posture and movement are influenced by postural disorders, postural adjustments associated with rapid voluntary arm movement were studied in PD patients and controls. EMG activity in postural muscles of the lower limbs and the trunk and local anteroposterior accelerations of the upper part of the leg were recorded in subjects who rapidly raised their arms to a horizontal position in response to a visual signal. The arm movement was characterized electromyographically by EMG activity from the deltoid muscle (anterior portion) and kinetically by acceleration of the arm. Study of characteristics of voluntary movement showed a nonsignificant increase in RT (simple-reaction time task) and an important increase in MT. There were important differences between PD patients and control subjects with regard to postural adjustments. Timing between voluntary movement and postural movement was anticipatory in 5% of PD patients, whereas it was anticipatory in 100% of control subjects. In PD patients, organization of early postural adjustments was not specific to voluntary movement; in control subjects, organization of early postural adjustments was specific to the forthcoming movement. Last, a possible functional relation between the "quality" of postural adjustments and a reduction in motor performance of normal subjects is suggested.

[Bilateral thalamic infarcts with abnormal movements and permanent amnesia]. / Infarctus thalamique bilatéral avec mouvements anormaux et amnésie durable.

A 45 year-old woman with mitral valve disease developed bilateral thalamic infarcts presenting as vigilance disorders, with mutism and downwards gaze paralysis during several days, followed by involuntary rhythmic movements over 13 days. These movements affected the four limbs with a rhythm variable with time as alternate or synchronized agonist-antagonist periods. Subsequent examinations demonstrated global, lasting amnesia and a subclinical disorder of vertical ocular movements. Repeat CT scan confirmed the presence of bilateral anterior thalamic infarcts affecting polar and/or paramedian territories. Emphasis is placed on the similarity of the abnormal movements in this case with L-dopa induced involuntary movements.

EMG patterns in abnormal involuntary movements induced by neuroleptics.

Electromyographic (EMG) activity of abnormal involuntary movements and their modifications after Piribedil, a dopaminergic agonist, were analysed in patients presenting with tremor or tardive dyskinesia induced by treatment with neuroleptics. Quantitative analysis of EMG bursts and of their phase relationships with bursts of antagonist muscles revealed differences between tremor and tardive dyskinesia; three separate EMG types of the latter were found. In tremor, EMG activity was coordinated between agonists and antagonists. Length and frequency of bursts are characteristic. In tardive dyskinesia, phase histograms of antagonist muscle bursts showed an absence of reciprocal organisation of EMG activity. This activity was made up of either rhythmical bursts (type I and II according to the frequency) or irregular discharges (type III). Piribedil decreased tremor but facilitated EMG activity in tardive dyskinesia. These results give an objective measurement or classification of tremor and tardive dyskinesia induced by neuroleptics.

Conduction of the sciatic nerve in its proximal and distal segment in patients with ALS (amyotrophic lateral sclerosis).

Conduction in the proximal segment of the sciatic nerve was assessed by recording the latencies of M and H responses from soleus muscle, in the distal segment by comparing the latencies of M waves from the abductor hallucis muscle, obtained by stimulating the tibial nerve in the popliteal fossa and at the ankle. Data from 30 patients with amyotrophic lateral sclerosis (ALS) were compared with an age-matched group of healthy subjects. We observed an increase in the difference between the latencies of M and H responses from soleus, and a lengthening of the distal latency of the M wave from abductor hallucis. The motor conduction velocity of the tibial nerve was preserved. The functional significance of the data are discussed. It is suggested that they indicate a slowing of conduction in the proximal segment of the sciatic nerve and that they can be correlated with pathological findings in proximal nerves in ALS and in the experimental anterior horn cell disorder.

[Activation motor response in depressive states. Changes in the Hoffmann reflex during psychomotor testing]. / Réponse motrice de l'activation dans les états dépressifs. Variation du réflexe de Hoffmann au cours d'épreuves psychomotrices.

Psychophysiological response of activation was explored both in control and depressed patients before and after antidepressant treatment. Hoffmann reflex (H reflex) and heat rate were recorded. Two psychomotor tests were studied in order to modify the level of vigilance. Control subjects had two different psychophysiological responses: slight increase of cardiac rhythm together with facilitation of H reflex or marked increase of cardiac rhythm associated with inhibition of H reflex. Depressed patients always showed an increase in H reflex during each task. H reflex was reduced only when patient recovered after a period of treatment. In both populations, heart rate for a given test was modified in the same way. Results are discussed in the light of the existence of two different activating systems. In depressed patients the lack of inhibition of H reflex could be explained by the decrease of initial arousal.

The abdominal cutaneous reflex circuit in the rat: a spinobulbo-spinal reflex in phenobarbital-anesthetized animals.

A description is given of an abdominal reflex (ACR) in the rat evoked by cutaneous stimulation. Latency of the ACR in response to stimulation of the contralateral hindlimb was 28.5 +/- 3.2 msec. Data from the analysis of discharges in dorsal and ventral roots and from bulbar reticular neurons triggered by ACR stimuli reveal that a spino-bulbo-spinal loop seems to be implicated. This is also supported by the chronic effects of pontile and spinal transections. ACR-concomitant discharges were also recorded in other axial (digastric m. and internal intercostal m.) and proximal limb muscles. The possible spino-bulbo-spinal mechanism of this cutaneous reflex is discussed.