59 research outputs found

    Genomewide association study in cervical dystonia demonstrates possible association with sodium leak channel.

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    Dystonia is a common movement disorder. A number of monogenic causes have been identified. However, the majority of dystonia cases are not explained by single gene defects. Cervical dystonia is one of the commonest forms without genetic causes identified. This pilot study aimed to identify large effect-size risk loci in cervical dystonia. A genomewide association study (GWAS) was performed. British resident cervical dystonia patients of European descent were genotyped using the Illumina-610-Quad. Comparison was made with controls of European descent from the Wellcome Trust Case Control Consortium using logistic regression algorithm from PLINK. SNPs not genotyped by the array were imputed with 1000 Genomes Project data using the MaCH algorithm and minimac. Postimputation analysis was done with the mach2dat algorithm using a logistic regression model. After quality control measures, 212 cases were compared with 5173 controls. No single SNP passed the genomewide significant level of 5 × 10(-8) in the analysis of genotyped SNP in PLINK. Postimputation, there were 5 clusters of SNPs that had P value <5 × 10(-6) , and the best cluster of SNPs was found near exon 1 of NALCN, (sodium leak channel) with P = 9.76 × 10(-7) . Several potential regions were found in the GWAS and imputation analysis. The lowest P value was found in NALCN. Dysfunction of this ion channel is a plausible cause for dystonia. Further replication in another cohort is needed to confirm this finding. We make this data publicly available to encourage further analyses of this disorder. © 2013 International Parkinson and Movement Disorder Society

    Long-term efficacy of botulinum toxin A for treatment of blepharospasm,hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes

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    PURPOSE: To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. CONCLUSIONS: This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation

    A prevalence study of primary distonia in eight European countries

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    There have been few epidemiological studies of dystonia. Most previous studies have provided estimates based on few cases. A European prevalence study was undertaken to provide more precise rates of dystonia by pooling data from eight European countries. Diagnosed cases were ascertained by adult neurologists with specialist movement disorder land botulinum toxin) clinics. The crude annual period prevalence rate (1996-1997) for primary dystonia was 152 per million (95 % confidence interval 142-162), with focal dystonia having the highest rate of 117 per million (108-126). Prevalence rates for cervical dystonia, blepharospasm and writer's cramp were as follows: 57 (95 % confidence interval 51-63), 36 (31-41), and 14 (11-17). The age-adjusted relative rates were significantly higher in women than in men for segmental and focal dystonias with the exception of writer's cramp. Comparing rates between centres demonstrated significant variations for cervical dystonia, blepharospasm and writer's cramp, probably due to methodological differences. Our results provide the first data on the prevalence of primary dystonia and its subtypes across several European countries. Due to under-ascertainment of cases, our rates should be seen as conservative and an under-estimate of the true prevalence of dystonia

    Mengenal Aphrodisiaka

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    A prevalence study of primary dystonia in eight European countries

    No full text
    There have been few epidemiological studies of dystonia. Most previous studies have provided estimates based on few cases. A European prevalence study was undertaken to provide more precise rates of dystonia by pooling data from eight European countries. Diagnosed cases were ascertained by adult neurologists with specialist movement disorder (and botulinum toxin) clinics. The crude annual period prevalence rate (1996-1997) for primary dystonia was 152 per million (95% confidence interval 142-162), with focal dystonia having the highest rate of 117 per million (108-126). Prevalence rates for cervical dystonia, blepharospasm and writer's cramp were as follows: 57 (95% confidence interval 51-63), 36 (31-41), and 14 (11-17). The age-adjusted relative rates were significantly higher in women than in men for segmental and focal dystonias with the exception of writer's cramp. Comparing rates between centres demonstrated significant variations for cervical dystonia, blepharospasm and writer's cramp, probably due to methodological differences. Our results provide the first data on the prevalence of primary dystonia and its subtypes across several European countries. Due to under-ascertainment of cases, our rates should be seen as conservative and an under-estimate of the true prevalence of dystonia
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