Peripheral neuropathies and tremor.

We studied 14 patients with tremor and acquired peripheral neuropathies of different origin. Minimal weakness was the only clinical finding common to all patients. Sensory changes, etiology, and course of the neuropathy varied. NO unique pattern of peripheral nerve histopathology could be demonstrated. Slowing of conduction velocity of Ia fibers was found, but the role played by impairment of sensory inputs remains unclear. Tremor associated with peripheral neuropathy seems to be due to enhancement of physiologic tremor by minimal weakness.

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.

Pharmacological modulations on the nociceptive flexion reflex in man.

Pharmacological actions on the nociceptive flexion flexes of the hindlimb were investigated in 14 normal subjects. These reflexes were used as an index of pain and were recorded in the biceps femoris muscle, elicited by electrical stimulation of the ipsilateral sural nerve (RIII,su) and of the skin in the distal receptive field of this nerve (RIII,Cu). The ratio of the threshold of RIII,Cu/RIII,Su was calculated since it gives an indication on the mechanism and the efficacy of the drug. During control periods, the mean values of RIII,Su threshold (10 mA) and of RIII,Cu threshold (5 mA) remained stable, as RIII,Cu/RIII,Su threshold (50%). Cutaneous application of naphthalene provoked a decrease in the RIII,Cu threshold and relative pain threshold, whereas lignocaine increased them. No changes in the RIII,Su, threshold and relative pain were observed. The ratio RIII,Cu/RIII,Su threshold and relative pain were observed. The ratio RIII,Cu/RIII,Su was lowered to 10% with naphthalene and increased to 110% with lignocaine. Intravenous injection of acetylsalicylic acid increased only the RIII,Cu threshold and relative pain threshold. The ratio RIII,Cu/RIII,Su was 90% at the maximal effect of the drug. In contrast, pethidine provoked a decrease in the RIII,Su threshold and an increase in RIII,Cu threshold, parallel with an increase in pain threshold sensation. The ratio was found to be 190% at the maximal effect. Practical implications of these results, concerning a method for testing the efficacy and mechamisms of an analgesic, are then discussed.

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.

Two patterns of results in polyneuropathies investigated with the H reflex. Correlation between proximal and distal conduction velocities.

The Hoffman (H) reflex of the soleus muscle has been used to study peripheral neurological disorders in 79 cases of chronic renal insufficiency prior to the initiation of haemodialysis, and in 94 cases of chronic alcoholism. In both groups, care was taken to ensure that the subjects examined could not be suspected of any other type of neuropathy. The results have been compared with those obtained in 42 normal subjects. The nerve conduction velocity in the reflex pathway was evaluated by an H index formula in which the conduction time (interval between M and H responses) is related to the length of the nervous pathway (a function of the subject's height). This method demonstrated a marked reduction in the conduction velocity of the proximal parts of the peripheral nerves, in both uraemic and alcoholic subjects. The maximal amplitude of the reflex response was evaluated in relation to the maximal amplitude of the direct motor response (H max/M max). It was shown that this ratio diminishes very greatly and very rapidly in the course of alcoholic polyneuritis, while, at comparable conduction velocities, the amplitude of the reflex response is much less changed in chronic renal insufficiency. These results prove that there is a noteworthy difference between uraemic and alcoholic polyneuropathy. Its significance is discussed in the context of currently knwon histopathological and electrophysiological data on the polyneuritides. From a practical point of view, the H reflex appears to be an effective tool for the investigation of peripheral neuropathy in man.

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.

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).

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.

[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.

[Rhythmic quadriceps myoclonia related to sarcomatous involvement of the crural nerve]. / Myoclonies rythmées du quadriceps en relation avec un envahissement sarcomateux du nerf crural.

A case of rhythmic myoclonus of the quadriceps related to involvement of the crural nerve by a schwann-cell sarcoma of the thigh is reported. The rhythm of involuntary contractions varies between 35 and 300 per minute. The myoclonic jerks occur rhythmically in the quadriceps only during full extension of the knee. The jerks are inhibited during lengthening of the quadriceps by active or passive flexion of the knee. Clonazepam is very effective in controlling the myoclonus. It is suggested that the myoclonus is the consequence of a response of alpha-motoneurons of the spinal cord to the excitation of Ia fibers of the crural nerve by the tumor. This activation appears to be enhanced by descending excitation pathway and inhibited by activation of Golgi tendon organs of the quadriceps.

[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.

[Electrophysiological analysis of the blink reflex during hemiplegia due to hemispheric lesions]. / Analyse électrophysiologique du réflexe de clignement (blink reflex) au cours de l'hémiplégie par lésions hémisphériques

Electrical stimulation of the supra-orbital nerve induces at the same threshold an early reflex reaction in the ipsilateral orbicular muscle and a delayed bilateral reflex response. These reflex activities are modified bilaterally by unilateral hemispheric lesions. Reactions on the hemiplegic side are reduced in amplitude, unlike the responses on the "healthy side" which are facilitated. Adaptation of the reflexogenous threshold of the delayed responses to repeated stimulation is also irregular; cumulative depression occurs earlier on the hemiplegic side, the responses on the "healthy side", on the other hand, show less habituation or a total absence of it. These electrophysiological findings agree with experimental results concerning the influence of cortical structures on the activity of the nuclei of the brain stem. They also, by analogy with the results of research carried out on the limbs, support the tactile origin of the two constituents of the blink reflex.

[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.

[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.

[Inhibition in neurophysiology]. / L'inhibition en neurophysiologie.

In Neurophysiology, inhibition is the effect of one neuron upon another tending to prevent it from initiating impulses. At cellular level, there are 3 modes of inhibition: postsynaptic inhibition, presynaptic inhibition and electrical inhibition. The formers are mediated by chemical transmitter. Examples of functional inhibition are presented. They explain its role in the coordination of movement and posture, in the integration of the sensation and in the behaviour.

[Abnormal movements induced by psychotropic drugs]. / Mouvements anormaux induits par les médicaments psychotropes.

The abnormal movements produced by the psychotropic drugs are related to various physiopathological mechanisms: -- dopaminergic receptors blockage provokes neuroleptic parkinsoniam tremor; -- neuroleptic-induced tardive dyskinesia is similar to 1. Dopa abnormal movements; tardive dyskinesia is due to denervation induced hypersensitivity of the dopamine receptor; the 1. Dopa dyskinesia is probably related to altered responsiveness of these receptors due to an increase in dopaminergic receptor sensitivity; -- antidepressant drugs, particularly lithium, provoke tremor, alleviated by beta blockage; it is probably caused by an abnormal sensitivity of the beta noradrenergic receptors.

[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.

[Effect of psychotropic drugs on physiological variations and psychometric scores during attention]. / Effets de drogues psychotropes sur les variations physiologiques et les scores psychométriques au cours de l'attention

A study was undertaken to determine the activation profile and psychometric performances in 10 adult volunteer subjects. The activation profile was evaluated by measuring heart and respiratory rates and also the H reflex (motor response). Psychometric performances during two attention tests were measured by the subjects' scores. The subjects were then submitted to a per os psychotrope drug treatment at a liminar therapeutic dose. Psychometric performances were decreased in subjects given a strong psychoactivator drug (amphetamine, genozolone), while they could be increased to an optimal level with a less active psycho-activation (Pyrisuccidéanol). Under the same conditions, the motor response, tested using the H-reflex, varied in the same way as the psychometric performance curve. However, the cardiac and respiratory rates show changes induced by the administered drugs. These results show some conditions were performance and activation are dissociated under the effect of psycho-active drugs.