Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis.

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature.

[Topography of secondary dystonia lesions].

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.

Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism.

Mutation detection in the tyrosine hydroxylase gene (TH) was performed in patients from two families. DNA sequencing revealed the presence of four novel missense mutations (exon 9 and 14 in family A, exon 8 and 9 in family B); the mutations were confirmed with restriction enzyme analysis, and did not occur in control alleles. Three mutations are in the catalytic domain of the enzyme and one may disturb tetramerization.

[Action of piribedil in Parkinson disease. Multicenter study].

Objectives: Several controlled trials have shown that Trivastal (piribedil), a direct dopamine agonist, is active in the treatment of Parkinson's disease. The aim of the present clinical trial was to assess the efficacy of Trivastal 50 mg LP administered as monotherapy in patients naive to treatment with L-dopa.

Patients And Methods: This 3-month multicenter study was conducted in 113 patients (66 men and 47 women), aged 63.

[Recessive dopa-responsive form of dystonia due to a mutation of the tyrosine hydroxylase gene].

The cause of Dystonia Musculorum Deformans (DMD) is most frequently unknown, therefore the treatment can only be symptomatic and often disappointing. In 1971 we reported the first two cases of recessive dopa-responsive dystonia, simulating a severe form of idiopathic DMD, however remarkably well reacting to levodopa treatment. We found that the first above mentioned two cases are related to mutations in the tyrosine hydroxylase gene itself in the chromosome 11p.

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.

Juvenile-onset spinal muscular atrophy caused by compound heterozygosity for mutations in the HEXA gene.

Progressive proximal muscle weakness is present both in spinal muscular atrophy (SMA) type III (Kugelberg-Welander disease) and in GM2 gangliosidosis, diseases that segregate in an autosomal recessive fashion. The SMN gene for SMA and the HEXA gene for GM2 gangliosidosis were investigated in a woman with progressive proximal muscle weakness, long believed to be SMA type III (Kugelberg-Welander type). She and her family underwent biochemical studies for GM2 gangliosidosis.

[Juvenile GM2 gangliosidosis with progressive spinal muscular atrophy onset].

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.

A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype.

We describe two adult siblings who had had mild GM2 gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM2 gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide.

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'.

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.

Linkage analysis in British and French families with idiopathic torsion dystonia.

Idiopathic torsion dystonia is most commonly caused by an autosomal dominant gene or genes with reduced penetrance. An idiopathic torsion dystonia locus has been mapped to chromosome 9q34 in one large non-Jewish and several Jewish kindreds in the USA. Linkage analysis was performed in 27 (26 British, one French) small families with idiopathic torsion dystonia, three of which were Ashkenazi Jewish, using the highly polymorphic loci argininosuccinate synthetase (ASS) and Abelson oncogene (ABL) which map to 9q34.

[Positron-emission tomographic study of the dopaminergic system in a case of secondary unilateral tremor after mesencephalic hematoma].

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).

Postural disturbances due to homonymous hemianopic visual ataxia.

Patients with visual defects often complain of disturbances of equilibrium. In order to measure the influence of visual stimulation on posture, a study was made comparing the posture of hemianopic patients with that of healthy volunteers before and after occlusion of half of the monocular visual field. Hemianopia increases lateral oscillations in patients in the standing position and the projection of the body's centre of gravity shifts towards the hemianopia: in the volunteers, the same shift is noted after masking half the visual field.

Activity and acceptability of piribedil in Parkinson's disease: a multicentre study.

Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.

[Dopa-sensitive dystonia].

Dopa-sensitive dystonia has been recognised for twenty years. It may occur in the first years of life. It first affects the lower limbs, then generalized becomes, as in torsion dystonia.

The shadow of movement.

Movement is preceded, accompanied and followed by reactions which give to the primary action its correct execution and ensure that the body's axis, together with the limbs, maintains the right balance. If these reactions are interfered with, incoordination of movement, lack of balance, hypertonia or dystonia may all appear. In the case of dystonia, postural mechanisms tend to become dominant and take over from the kinetic component of movement.

TGF-beta-like activity produced during regression of exacerbations in multiple sclerosis.

Samples representative of different stages of disease from a longitudinal study of multiple sclerosis patients were tested in the anchorage-independent growth assay for TGF-beta and an increased activity was detected in the supernatants from 2-day blood cell cultures from patients with active disease compared to patients without active disease and healthy donors. Within the group of patients with active disease, the TGF-beta like activity was significantly increased in the subgroup of patients tested during the period of regression of the symptoms where it appeared in 86.9% of the samples.

[Movement-related cortical potentials in aged subjects].

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).