Clinical characterization of dystonia in adult patients with Huntington's disease.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant, neurodegenerative movement disorder, typically characterized by chorea. Dystonia is also recognized as part of the HD motor phenotype, although little work detailing its prevalence, distribution, severity and impact on functional capacity has been published to date. METHODS: Patients (>18 years of age) were recruited from the Cardiff (UK) HD clinic, each undergoing a standardized videotaped clinical examination and series of functional assessment questionnaires (Unified Huntington's Disease Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale and modified version of the Toronto Western Spasmodic Torticollis Rating Scale). The presence and severity of dystonia were scored by four independent neurologists using the Burke-Fahn-Marsden Dystonia Rating Scale and Unified Huntington's Disease Rating Scale. Statistical analysis included Fisher's exact test, Wilcoxon test, anova and calculation of correlation coefficients where appropriate. RESULTS: Forty-eight patients [91% (48/53)] demonstrated evidence of dystonia, with the highest prevalence in the left upper limb (n = 44, 83%), right upper limb most severely affected and eyes least affected. Statistically significant positive correlations (P < 0.05) were observed between dystonia severity and increasing HD disease stage and motor disease duration. Deterioration in functional capacity also correlated with increasing dystonia severity. No significant relationship was observed with age at motor symptom onset or CAG repeat length. CONCLUSIONS: We report a high prevalence of dystonia in adult patients with HD, with worsening dystonia severity with increasing HD disease stage and motor disease duration. The recognition and management of dystonic symptoms in routine clinical practice will aid overall symptomatic treatment and functional improvement.

A review of psychiatric co-morbidity described in genetic and immune mediated movement disorders.

Psychiatric symptoms are an increasingly recognised feature of movement disorders. Recent identification of causative genes and autoantibodies has allowed detailed analysis of aetiologically homogenous subgroups, thereby enabling determination of the spectrum of psychiatric symptoms in these disorders. This review evaluates the incidence and type of psychiatric symptoms encountered in patients with movement disorders. A broad spectrum of psychiatric symptoms was identified across all subtypes of movement disorder, with depression, generalised anxiety disorder and obsessive-compulsive disorder being most common. Psychosis, schizophrenia and attention deficit hyperactivity disorder were also identified, with the psychiatric symptoms often predating onset of the motor disorder. The high incidence of psychiatric symptoms across such a wide range of movement disorders suggests a degree of common or overlapping pathogenic mechanisms. Our review demonstrates the need for increased clinical awareness of such co-morbidities, which should facilitate early neuropsychiatric intervention and allied specialist treatment for patients.

Non-motor symptoms in genetically defined dystonia: Homogenous groups require systematic assessment.

INTRODUCTION: Dystonia is a movement disorder involving sustained or intermittent muscle contractions resulting in abnormal movements and postures. Identification of disease causing genes has allowed examination of genetically homogenous groups. Unlike the motor symptoms, non-motor characteristics are less clearly defined, despite their impact on a patient's quality of life. This review aims to examine the evidence for non-motor symptoms, addressing cohort size and methods of assessment in each study. METHODS: A systematic and standardised search strategy was used to identify the published literature relating to psychiatric symptoms, cognition, sleep disorders, sensory abnormalities and pain in each of the genetically determined dystonias. Studies were divided according to cohort size, method of assessment and whether comparison was made to an appropriate control group. RESULTS: Ninety-five articles were identified including reported clinical histories (n = 42), case reports and smaller case series (n = 12), larger case series (n = 23) and case-control cohorts (n = 18). Psychiatric symptoms were the most frequently investigated with anxiety, depression and Obsessive-Compulsive disorder being most common. Cognitive impairment involved either global deficits or isolated difficulties in specific domains. Disturbances to sleep were most common in the dopa-responsive dystonias. Sensory testing in DYT1 cases identified an intermediate subclinical phenotype. CONCLUSION: Non-motor symptoms form an integral component of the dystonia phenotype. However, future studies should involve a complete assessment of all symptom subtypes in order to understand the frequency and gene-specificity of these symptoms. This will enable early symptom identification, appropriate clinical management, and provide additional outcome measures in future clinical trials.

SGCZ mutations are unlikely to be associated with myoclonus dystonia.

BACKGROUND: Myoclonus dystonia syndrome (MDS) is a hyperkinetic movement disorder caused, in a proportion of cases, by mutations of the maternally imprinted epsilon-sarcoglycan gene (SGCE). SGCE mutation rates vary between cohorts, suggesting genetic heterogeneity. E- and ζ-sarcoglycan are both expressed in brain tissue. In this study we tested whether zeta-sarcoglycan gene (SGCZ) mutations also contribute to this disorder. METHODS: Patients with clinically suspected MDS and no SGCE mutation were recruited and classified, according to previously published criteria, as to their likelihood of the movement disorder. All SGCZ exons and intron/exon boundaries were screened by direct sequencing. RESULTS: Fifty-four SGCE mutation-negative patients were recruited from the UK and the Netherlands. Subdivided according to the likelihood of the movement disorder resulted in 17 'definite', 16 'probable' and 21 'possible' cases. No pathogenic SGCZ mutations were identified. CONCLUSIONS: SGCZ mutations are unlikely to contribute to the genetic heterogeneity in MDS.