[Dystonia, tremor and repetitive instrumental use]. / Dystonies et tremblements d'utilisation instrumentale répétitive.

Three characteristic observations are presented along with three tables presenting 24 patients with the following elements in common: excessively repeated use of an instrument such as a pen, a musical instrument or a tool. The appearance after that use of a central pathological phenomenon that includes a local dystonia of a hand or the mouth, a tremor, or the association of a tremor and a dystonia, all within the muscular domain corresponding to that of the use. The discussion, which is based exclusively on the clinical findings, deals with the following elements: the role of the use of the instrument rather than task itself, the predominant pathogenic factor which is the repetitive action, to which is added a genetic component in one incompletely penetrant case of DYT 1, and a probable genetic susceptibility in the others. The absence of improvement with rest distinguishes this central pathology from rheumatologic or orthopaedic problems involving repetitive activities. The evolution is slowly declining when the responsible action is continued. This occurs in three stages: a specific disorder involving only the use of the particular instrument, a more enlarged involvement affecting other activities and eventually a dystonia associated with a tremor or a postural tremor always located to the initial area. The therapeutic interventions suggested by the pathologic role of the repetitive movement is: (1) to advise a new training for the instrument that excludes the habitual movement; (2) to advise the patient to vary any newly acquired repetitive movements.

Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations.

OBJECTIVE: To clarify the clinical and neurophysiologic spectrum of myoclonus-dystonia patients with mutations of the SGCE gene. METHODS: We prospectively studied 41 consecutive patients from 22 families with documented mutations of the SGCE gene. The patients had a standardized interview, neurologic examination, and detailed neurophysiologic examination, including surface polymyography, long-loop C-reflex studies, and EEG jerk-locked back averaging. RESULTS: We noted a homogeneous electrophysiologic pattern of myoclonus of subcortical origin with short jerks (mean 95 msec, range 25 to 256 msec) at rest, during action, and during posture; there were no features of cortical hyperexcitability (specifically no abnormal C-reflex response and no short-latency premyoclonic potential on back-averaging studies). Myoclonus was either isolated or associated with mild to moderate dystonia, and predominated in the neck/trunk or proximal upper limbs in most cases. We found that 22% of the patients had a spontaneous improvement in their dystonia before reaching adulthood and that hypotonia can occasionally be a presenting symptom of the disorder. CONCLUSION: We describe the myoclonus in patients with mutations in the SGCE gene and characterize the electrophysiologic pattern of this myoclonus. This pattern may help to improve the sensitivity of molecular tests and to define homogeneous populations suitable for inclusion in therapeutic trials.

Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes.

BACKGROUND: Myoclonus dystonia syndrome (MDS) is an autosomal dominant movement disorder caused by mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q21. METHODS: We have screened for SGCE mutations in index cases from 76 French patients with myoclonic syndromes, including myoclonus dystonia (M-D), essential myoclonus (E-M), primary myoclonic dystonia, generalised dystonia, dystonia with tremor, and benign hereditary chorea. All coding exons of the SGCE gene were analysed. The DYT1 mutation was also tested. RESULTS: Sixteen index cases had SGCE mutations while one case with primary myoclonic dystonia carried the DYT1 mutation. Thirteen different mutations were found: three nonsense mutations, three missense mutations, three splice site mutations, three deletions, and one insertion. Eleven of the SGCE index cases had M-D and five E-M. No SGCE mutations were detected in patients with other phenotypes. The total number of mutation carriers in the families was 38, six of whom were asymptomatic. Penetrance was complete in paternal transmissions and null in maternal transmissions. MDS patients with SGCE mutation had a significantly earlier onset than the non-carriers. None of the patients had severe psychiatric disorders. CONCLUSION: This large cohort of index patients shows that SGCE mutations are primarily found in patients with M-D and to a lesser extent E-M, but are present in only 30% of these patients combined (M-D and E-M).

[Gilles de la Tourette syndrome: a self-administered assessment questionnaire]. / Maladie de Gilles de la Tourette. Un auto-questionnaire.

INTRODUCTION: An association of patients with Gilles de la Tourette syndrome enabled us to gather a large body of information regarding the disease manifestations, and patient-perceived consequences. METHOD: 350 questionnaires were sent to patients belonging to the AFSGT (French Association of Patients Suffering from Gilles de la Tourette Syndrome). 187 responses were received (53 percent). The patients were divided into four groups: those with motor tics, vocal tics, complex tics and complex tics with coprolalia. This last group corresponds to the DSM IV definition of "Tourette Disorder". The questions were grouped in five sections: simple manifestations, complex manifestations, family study, treatment and psycho-affective perception (social and in the context of schooling). RESULTS: The study of the simple manifestations of the disorder revealed the homogeneity of the four groups with an age of onset at on average 7 years and a male-to-female ratio of 3.5. The first signs of the disorder are motor tics of the face and neck, and the disorder shows a variable and fluctuating course characterized by periods of decreased or absent symptoms. Familial cases (58 percent) are found in all four groups. The complex signs included in part of behaviors corresponding to the definition of tics: sudden, brusque, repetitive, varied, escape despite efforts to repress them and reappearance more intensely after a period of conscious control. The complex signs also consisted of accompanying factors such as agitation, need to organize, classify or count. Treatments have been of limited success and a significant number of patients have abandoned treatment entirely. Our study demonstrates that this condition seriously affects the daily life of patients, including family and social relations, schooling and occupational life. No patients suffering from transient tics responded to our survey, but such tics were reported in family members. CONCLUSION: Overall, the condition is considered to be single family of disorders, despite the broad phenotypic spectrum, from transitory cases by children to very severe forms. Escape despite efforts to repress tics and the rebound after control tics is characteristic of the Georges Gilles de la Tourette syndrome.

Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor.

Leg tremor during standing is a rare feature in idiopathic Parkinson's disease (PD). Tremor during standing usually has a low frequency (range, 4-6 Hz), similar to PD rest tremor frequency, and is improved by levodopa. We describe three cases of fast orthostatic tremor (FoT) of legs and trunk mimicking primary orthostatic tremor (OT) in patients treated with levodopa for PD. Asymmetrical akinetorigid syndrome was accompanied by a rest tremor in two cases. We obtained electrophysiological parameters by electromyographic (EMG) polygraphic recording after 16 hours withdrawal of antiparkinsonian treatment and at the maximal effect of levodopa in order to investigate the effect of dopaminergic stimulation upon such cases of orthostatic tremor in PD. Electrophysiological parameters of orthostatic tremor, especially frequency (range 14-18 Hz), were similar to that seen in POT. Severity of tremor was independent of seriousness and duration of PD. Levodopa had no effect either on the handicap due to OT or on the amplitude and frequency of the EMG OT activity. In contrast, mild improvement of OT was obtained with benzodiazepines in two cases and parkinsonian syndrome was levodopa-sensitive. These findings suggest that FoT in PD would not be directly controlled by the dopaminergic system. However, increased rhythmicities in basal ganglia or in cerebello-thalamic loops at the rapid frequencies range seen in PD could favor the emergence of a primary orthostatic tremor-like tremor in PD patients.

[Secondary dystonias. Clinical analysis and diagnostic approach]. / Dystonies secondaires. Analyse sémiologique et démarche diagnostique.

DEFINITIONS: Dystonia is a muscle contraction disorder marked by sustained involuntary clonic contortions or abnormal posture. Primary dystonias can be divided into familial forms related to genetic anomalies and idiopathic forms. Secondary dystonias are related to an underlying neurological disease. METABOLIC DISEASES: Secondary dystonias related to metabolic diseases generally occur early before puberty although late onset forms have been described. Other signs, in association with the dystonia, include mental retardation, epilepsy, cerebellous or pyramidal signs, oculomotor disorders, or a neuropathy. Occasionally, extraneurological signs suggest the diagnosis. Biological markers are known for most of these dystonias. EVENT-RELATED DISEASES: In some cases, the dystonia is the only sign and develops as a sequela to an earlier neurological event such as neonatal anoxia, trauma, vascular event or adverse effect of neuroleptics. HEMI-DYSTONIAS: Dystonias limited to one side are generally secondary.

Pathology of symptomatic tremors.

Symptomatic tremors are labeled in the literature under different names including rubral tremor, midbrain tremor, thalamic tremor, myorhythmia, Holmes' tremor, cerebellar tremor, and goal-directed tremor. The most common tremor is a delayed-onset postural and action tremor with a low frequency of 3 Hz and a proximal distribution. Resting irregular tremor is sometimes present. Mild cerebellar dysmetria is often detected. The lesions are mainly located in the thalamus, the brain stem, and the cerebellum, with secondary interruption and degeneration of various pathways and olivary hypertrophy. The more consistent lesions are found in the cerebello-thalamo-cortical and dentato-rubro-olivary pathways. The role of superimposed dysfunction of the nigrostriatal system may account for the rest component. The role of the basal ganglia in the emergence and control of tremor is poorly understood.

Quantitative study of Stewart-Holmes test.

Stewart-Homes test (SHT) is an ordinary neurological test performed for the diagnosis for cerebellar disease. We developed a quantitative method based on SHT carried out on the upper limb. Nineteen cerebellar patients and fifteen volunteer healthy subjects were tested. During the test, acceleration of forearm and two associated surface EMGs over biceps and triceps brachialis were recorded and analyzed. (1) Acceleration curve showed an oscillating pattern with flexion and extension over the elbow in both groups, but in cerebellar patient group, the acceleration oscillation wave was more pronounced and latencies of peak acceleration were significantly longer. (2) Correspondingly, the EMGs timing parameters were also different between the two groups: in patient group, ceasing isometric biceps contraction was delayed; rebound EMGs bursts over both biceps and triceps were prolonged. (3) Modelization of the oscillation of acceleration curve with dampened oscillation model showed that in patient group the oscillating amplitude attenuated much more slowly than in control group. A standard curve was established for detecting the acceleration profile abnormalities of SHT in cerebellar patients.

[Dystonia]. / Dystonies.

Dystonia can be considered either as a symptom, or as a disease. An initial classification of dystonia can be made according to the localization and the severity of the spasms or the associated movement disorders such as myoclonus. A second classification differentiates idiopathic dystonia and secondary dystonia. Personnel medical history, familial cases, neurological symptoms such as pyramidal, cerebellar, oculomotor signs are helpful clues in the diagnosis strategy. Drugs, botulinum toxin, physiotherapy are often combined symptomatic treatment regardless of the cause of dystonia.

[Tremors]. / Tremblements.

In this general review of tremors, one must distinguish the parkinsonian rest tremor, which concerns relaxed muscles, from other tremors that accompany muscle activities, such as maintaining a posture or executing a movement. Among various postural and action tremors, essential tremor occupies first place, in terms of its prevalence. The diagnosis of essential tremor is based on precise criteria. Often hereditarily transmitted, essential tremor can sometimes be quite disabling. Essential tremor and parkinsonian tremor are compared on an accompanying table. Other types of tremor are reviewed according to their possible prevalences. i.e. iatrogenic tremor and dystonic tremor. Particular attention is paid to orthostatic tremor, multiple sclerosis tremor and psychogenic tremor.

Fluconazole penetration in cerebral parenchyma in humans at steady state.

We studied fluconazole penetration in the brain in five patients who had a deep cerebral tumor whose removal required the excision of healthy brain tissue. Plasma and brain samples were simultaneously obtained after oral ingestion of 400 mg of fluconazole daily for 4 days (90% of steady state). Fluconazole penetration in healthy cerebral parenchyma was determined. Plasma and brain samples were assayed by high-pressure liquid chromatography. Concentrations in plasma and brain tissue were 13.5 +/- 5.5 micrograms/ml and 17.6 +/- 6.6 micrograms/g, respectively. The average ratio of concentrations in the brain and plasma (four patients) was 1.33 (range, 0.70 to 2.39). Despite the lack of data concerning the penetration of fluconazole in brain abscesses, these results should permit the use of a daily dose of 400 mg of fluconazole in prospective clinical studies that evaluate the effectiveness of this drug in the treatment of brain abscesses due to susceptible species of fungi.

[Propriospinal myoclonus in a HIV seropositive patient]. / Myoclonies propriospinales chez un patient séropositif pour le virus de l'immunodéficience humaine.

We report axial myoclonic jerks causing flexion of the trunk, neck, left shoulder, hips and knees in a 28-years-old HIV positive patient. The clinical and electromyographic features of the jerks were consistent with a spinal origin and corresponded to the new concept of propriospinal myoclonus. No structural lesion was identified in this patient. Neurological examination was otherwise normal. HIV specific antibodies were detected in CSF, suggesting central nervous system infection. Spinal myoclonus should be considered an unusual and early manifestation of central nervous system HIV infection.

Familial essential tremor and idiopathic torsion dystonia are different genetic entities.

Familial essential tremor (ET) is an autosomal dominant disorder presenting as an isolated postural tremor. Its frequent association with dystonia suggests that the two disorders might be pathogenically related. We report the exclusion of the DYT1 locus on chromosome 9q32-34, responsible for idiopathic torsion dystonia (ITD), in two large ET families. We conclude that ET and ITD are distinct genetic disorders.

[Hemifacial spasm treated with botulinum toxin]. / Traitement du spasme hémifacial par la toxine botulique.

Botulinum toxin produces a transient presynaptic focal block at the neuromuscular junction. Thus it induces muscle weakness which has a significant beneficial effect on hemifacial spasm. Fifty-four patients were treated and received at least 2 and at the most 22 consecutive injections over a 5-year period. Injections were repeated every 9 weeks on average. The interval between injections corresponded to the time elapsed between the last injection and the re-emergence of spasms. Nineteen patients abandoned the treatment for various reasons. The most frequent side-effect was a ptosis which was observed in 1 out of 6 injections. Ptosis is due to diffusion of the botulinum toxin over a territory larger than expected. The results obtained in 42 patients were analyzed: there was no effect in 7 patients (17%); 11 patients improved by less than 50%; 13 by 50 to 70% and 11 more than 75%.

[Prolactin microadenoma in men. Study of 14 cases]. / Le microadénome à prolactine chez l'homme. Etude de 14 cas.

Macroprolactinomas have been well documented in men over the past several years. By contrast, to the best of our knowledge, there have been no reports of microprolactinomas in men. We describe here 14 cases of microprolactinomas occurring in male patients (14 to 53 years old) and discovered on the basis of endocrine symptoms. Nine patients complained of impotence and/or decreased libido, 8 had gynecomastia with or without galactorrhea, 1 had undergone incomplete puberty. All patients had hyperprolactinemia (225 +/- 65 micrograms/l, mean +/- SEM, N less than 13 micrograms/l); plasma testosterone levels were low in 9 (162 +/- 33 ng/dl, mean +/- SEM; N = 308 - 876 ng/dl), while plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and their responses to LH-releasing hormone (LHRH) were normal in all cases. Among the 14 patients, 12 had no hypopituitarism and 2 had only partial corticotrope insufficiency; none had visual disturbances and only one complained of headaches. The sella turcica was normal in size and shape in 2 cases but a double floor and/or a thinner part of the floor was observed in 12. CT scan of MRI demonstrated in all cases an intrasellar microadenoma with a mean size of 7 mm (range, 3 to 10 mm) and no preferential localization. One patient was treated with bromocriptine, while the others underwent surgery via the transsphenoidal route. Immunocytochemistry demonstrated immunoreactive-prolactin (IR-PRL) cells in all the adenomas. Surgery resulted in normalization of plasma PRL in 11 of the 13 patients and in lowering PRL levels in the others 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Tremor and idiopathic dystonia.

The clinical and electromyographic characteristics of tremor were studied in 45 patients presenting with various forms of idiopathic dystonia. Dystonic tremor was shown to be postural, localized, and irregular in amplitude and periodicity, absent during muscle relaxation, exacerbated by smooth muscle contraction, and associated frequently with myoclonus. Although it resembles essential tremor, dystonic tremor seems to be a distinct entity: it is more irregular with a broader range of frequencies; it is asymmetric and remains localized; myoclonus is sometimes associated. This type of tremor is most often seen in the presence of dystonia, but may be observed without evident dystonic symptoms.

[Treatment of spasmodic torticollis by local injections of botulinum toxin]. / Traitement du torticolis spasmodique par injections locales de toxine botulinique.

Injections of botulinum toxin into the main cervical muscles responsible for abnormal posture and movements in spasmodic torticollis reduced pain and attenuated dystonia for a period of 2 months on average. After several sessions 9 out of 36 patients (25 p. 100) felt they had improved by at least 50 percent, 16 (44 p.100) by 50 to 75 percent, and 6 (17 p. 100) by more than 75 percent. There were six failures.

Resistance to bromocriptine in prolactinomas.

Bromocriptine therapy normalizes PRL secretion in most, but not all, patients with prolactinomas. This study was undertaken to determine the mechanism(s) responsible for bromocriptine resistance in patients with a PRL-secreting macroadenomas (n = 5) or microadenomas (n = 3). Their mean basal plasma PRL value was 807 +/- 220 (+/- SE) micrograms/L before treatment, and their nadir mean value was 354 +/- 129 micrograms/L during chronic therapy with 15-30 mg bromocriptine daily; four of the eight patients had an increase in tumor size during therapy. In cultures of prolactinoma cells from patients normally responsive to bromocriptine therapy (n = 10), considered as controls, 10(-9) mol/L bromocriptine inhibited PRL release by 71 +/- 6% (+/- SE), and the half-inhibitory dose was 7 x 10(-11) mol/L. In contrast, in cultures of prolactinoma cells from five patients resistant to bromocriptine, PRL release was inhibited by only 3-42% at 10(-9) mol/L bromocriptine. This partial inhibition was reversed by a 100-fold excess of haloperidol. In contrast, the effects of other inhibitors of PRL release (10(-8) mol/L T3 and 10(-8) mol/L somatostatin) or of a stimulator (10(-8) mol/L angiotensin-II) on cells from resistant and normally responsive patients were similar. In cell membranes from five bromocriptine-responsive adenomas the density of dopaminergic binding sites, labeled by [3H] spiroperidol was 243 +/- 65 (+/- SE) fmol/mg protein. In adenomas from the eight patients resistant to bromocriptine therapy the density of [3H]spiroperidol-binding sites lower (145 +/- 31 fmol/mg protein). In adenomas from five resistant patients whose tumor had grown during therapy the density of binding sites was 25 +/- 3 fmol/mg protein, 10% of that in normally responsive patients. The effects of dopamine on adenylate cyclase activity also were different in the three groups of adenomas. Dopamine inhibited adenylate cyclase activity by 28.8 +/- 5.6% in five bromocriptine-responsive tumors and by 16.5 +/- 4.3% in adenomas from eight resistant patients. In contrast, in the five patients whose tumors grew during therapy dopamine paradoxically stimulated adenylate cyclase activity (+26.4 +/- 9.8%). There was a very good correlation between the density of dopaminergic binding sites and maximal inhibition of adenylate cyclase activity in bromocriptine-responsive prolactinoma patients (r = 0.90) and resistant patients who had no tumor growth during therapy (r = 0.94).(ABSTRACT TRUNCATED AT 400 WORDS)

[Stereotaxic treatment in Parkinson's disease]. / Le traitement stéréotaxique de la maladie de Parkinson.

For the stereotactic treatment of Parkinson's disease, the target is usually located in the thalamus; this point is related to nearby structures (third ventricle). Then the position is controlled by electrophysiological recordings. The lesion of the target results in permanent suppression of the contralateral tremor and/or rigidity but it changes neither the course of the disease nor the akinesia. Owing to the risk of dysarthria with bilateral procedures, the main indication for surgery is parkinsonism with unilateral tremor or rigidity. Particularly interesting for the future are the possibilities of stimulation through implanted chronic electrodes.