Evaluation of a programming algorithm for deep brain stimulation in dystonia used in a double-blind, sham-controlled multicenter study.

BACKGROUND: Programming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia. METHODS: A standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming. RESULTS: The mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia (n = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years (n = 63) and 53 ± 31% at 5 years (n = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia (n = 9) correlated significantly with improvement after 3 years, but not 5 years. CONCLUSIONS: Monopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT00142259.

Pallidal deep brain stimulation improves quality of life in segmental and generalized dystonia: results from a prospective, randomized sham-controlled trial.

As part of the first randomized, sham-stimulation controlled trial on deep brain stimulation (DBS) in primary segmental or generalized dystonia, health-related quality of life (HRQoL) was assessed by SF-36. After the 3-month sham-controlled phase, significant HRQoL improvement occurred only in the active-stimulation group. The open-label extension phase resulted in a significant improvement in all SF-36 domains following 6 months of neurostimulation. These results demonstrate a favorable impact of DBS on HRQoL in primary dystonia.

Pallidal deep-brain stimulation in primary generalized or segmental dystonia.

BACKGROUND: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial. METHODS: Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment. RESULTS: Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria. CONCLUSIONS: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].).

Mutation at the SCA17 locus is not a common cause of primary dystonia.

Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.

Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias.

Primary dystonias represent a clinically and genetically heterogeneous group of movement disorders. Mutations in the epsilon-sarcoglycan (SGCE) gene have been found recently to cause myoclonus-dystonia (MD). Considerable clinical variation of SGCE mutation carriers leads to the hypothesis that mutations in the SGCE gene might also be relevant for other subtypes of dystonias. To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia. Patients with mutations in the DYT1 gene were excluded. We could not detect a mutation in the SGCE gene in any of the 298 patients. Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia.

Fracture of the odontoid process complicating tardive dystonia.

We report on a 57-year-old woman with frequent and powerful retrocollis. The involuntary movements combined with rheumatoid arthritis and osteoporosis led to a fracture of the axial odontoid process. Neurologists with a focus on movement disorders should screen for diseases putting the patient at risk for spinal lesions and consider early treatment.

Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia.

BACKGROUND: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. A 3-base pair (GAG) deletion in the DYT1 gene is held responsible for most cases of early-onset primary generalized dystonia in the Ashkenazi Jewish population as well as in non-Jewish patients. OBJECTIVES: To investigate the prevalence of the GAG deletion in the DYT1 gene and the phenotypic variability in the general population by testing patients with different subtypes of dystonia from 4 different movement disorder outpatient clinics in Germany. METHODS: Two hundred fifty-six patients were tested for the GAG deletion mutation in the DYT1 gene by means of published primers and polymerase chain reaction amplification to determine GAG deletion status. RESULTS: Six of the 256 patients did carry the GAG-deletion in the DYT1 gene. However, only 2 of the 6 mutation carriers presented with what is thought to represent classic features of early-onset primary generalized dystonia. The DYT1 mutation was also detected in 2 patients with multifocal dystonia, 1 of them presenting with involvement of cranial and cervical muscles, and in 2 patients with writer's cramp of both hands with only slight progression. Our findings demonstrate that the mutation may be associated with not only generalized but also segmental and multifocal forms of dystonia. CONCLUSIONS: Our data underline the wide range of phenotypic variability of the DYT1 mutation. A priori prediction of the mutation carrier status in dystonic patients and genetic counseling of affected families with respect to the clinical manifestation may prove difficult.