Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome.

We report on the effects of bilateral neurostimulation of the ventral intermediate thalamic nucleus (VIM) in a patient with medically intractable and progressing inherited myoclonus dystonia syndrome (IMDS). Postoperatively, the patient improved by approximately 80% on the modified version of a myoclonus score without any significant change in the dystonic symptoms. This suggests that neurostimulation of the VIM may be an effective treatment for myoclonus in pharmacologically intractable IMDS.

Inherited Myoclonus-dystonia syndrome: narrowing the 7q21-q31 locus in German families.

Genetic studies were performed in four German families with autosomal dominant myodonus-dystonia syndrome. Mutations in the D2 dopamine receptor gene, which have been implicated in this disorder, were excluded in all four families by linkage analysis and direct sequencing. All four families supported linkage to the second reported locus on chromosome 7q21 with a combined maximum multipoint lod score of 5.99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480.

Charcot-Marie-Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible "hotspot" on Thr124Met.

Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, P0), cause hereditary disorders of Schwann cell myelin such as Charcot-Marie-Tooth neuropathy type 1B (CMT1B), Dejerine-Sottas syndrome (DSS), and congenital hypomyelinating neuropathy (CHN). More recently, P0 mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the P0 gene. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor. Our data suggest that P0 mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution. The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the P0 gene as well.

Phenotypic expression of the DYT1 mutation: a family with writer's cramp of juvenile onset.

Recently, the mutation causing early-onset generalized torsion dystonia has been identified as a GAG deletion in the gene for an adenosine triphosphate-binding protein named torsinA. We describe a German family with 5 clinically affected individuals carrying this mutation. In at least 4 of the 5 patients, the disease presented as a dystonic writer's cramp during late childhood or adolescence, which affected sequentially both sides but did not progress to a generalized form of dystonia. We conclude that familial writer's cramp may be a manifestation of the DYT1 mutation.

Botulinum toxin in writer's cramp: objective response evaluation in 31 patients.

OBJECTIVES: To quantify the treatment effect of local botulinum toxin injections in writer's cramp a newly developed rating scale of writing performance and a computer assisted analysis of writing speed were used in 31 patients undergoing botulinum toxin therapy. METHODS: Baseline data of the writer's cramp rating scale (WCRS, see appendix) and computer based writing speed analysis were compared with those obtained at the time of subjective best response as recorded during follow up visits. RESULTS: The mean dose injected per session was 133.2 units Dysport divided between two forearm muscles. Of all 124 injection sessions during mean follow up of one year 76% produced a good improvement. The most common side effect was weakness (72% of the follow up visits). The WCRS scores as assessed by a blinded videotape review by four independent raters showed good reliability between raters and a significant improvement after treatment (P < 0.001). The speed of pen movements showed a significant (P < 0.05) increase after treatment at subjective best effect recordings and a significant correlation with WCRS subscores, documenting the validity of the scale. CONCLUSION: The present study is the first to show significant effects of botulinum toxin treatment in patients with writer's cramp on the basis of a quantifiable scale for writing performance which correlates significantly with writing speed measurements. The WCRS as employed in this study might therefore prove a useful rating instrument in other studies assessing severity and treatment response in patients with writer's cramp.

Hemimasticatory spasm in hemifacial atrophy: diagnostic and therapeutic aspects in two patients.

We report two cases of hemimasticatory spasm in association with progressive hemifacial atrophy. On the basis of neurophysiological and magnetic resonance imaging assessments, a peripheral irritation of the trigeminal nerve--probably due to entrapment of the motor branches in the infratemporal fossa--is suggested as the cause of the involuntary movement. Local injections of botulinum toxin type A into the masticatory muscles proved to be a successful treatment in both patients.