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Musician's dystonia (MD) is a focal adult-onset dystonia most commonly involving the hand. It has much greater relative prevalence than non-musician's focal hand dystonias, exhibits task specificity at the level of specific musical passages, and is a particularly difficult form of dystonia to treat. For most MD patients, the diagnosis confirms the end of their music performance careers. Research on treatments and pathophysiology is contingent upon measures of motor function abnormalities. In this review, we comprehensively survey the literature to identify the rating scales used in MD and the distribution of their use. We also summarize the extent to which the scales have been evaluated for their clinical utility, including reliability, validity, sensitivity, specificity to MD, and practicality for a clinical setting. Out of 135 publications, almost half (62) included no quantitative measures of motor function. The remaining 73 studies used a variety of choices from among 10 major rating scales. Most used subjective scales involving either patient or clinician ratings. Only 25% (18) of the studies used objective scales. None of the scales has been completely and rigorously evaluated for clinical utility. Whether studies involved treatments or pathophysiologic assays, there was a heterogeneous choice of rating scales used with no clear standard. As a result, the collective interpretive value of those studies is limited because the results are confounded by measurement effects. We suggest that the development and widespread adoption of a new clinically useful rating scale is critical for accelerating basic and clinical research in MD.

The definition of dystonia has been a subject of much debate and controversy for the last century. In this paper, a practical definition of dystonia for the movement disorders expert is presented, based on a new algorithm. (c) 2013 Movement Disorder Society.

Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

In this study, a consanguineous family with progressive myoclonus epilepsy (PME) was clinically examined and molecularly investigated to determine the molecular events causing disease. Since exclusion of known genes indicated that novel genes causing PME still remained unidentified, homozygosity mapping, exome sequencing, as well as validation and disease-segregation analyses were subsequently carried out for both loci and gene identification. To further assure our results, a muscle biopsy and gene expression analyses were additionally performed. As a result, a homozygous, disease-segregating COL6A2 mutation, p.Asp215Asn, absent in a large number of control individuals, including control individuals of Iranian ancestry, was identified in both affected siblings. COL6A2 was shown to be expressed in the human cerebral cortex and muscle biopsy revealed no specific histochemical pathology. We conclude that the COL6A2 p.Asp215Asn mutation is likely to be responsible for PME in this family; however, additional studies are warranted to further establish the pathogenic role of both COL6A2 and the extracellular proteolysis system in the pathogenesis of PME.

OBJECTIVE: To identify brain regions with metabolic changes in DYT11 myoclonus-dystonia (DYT11-MD) relative to control subjects and to compare metabolic abnormalities in DYT11-MD with those found in other forms of hereditary dystonia and in posthypoxic myoclonus. METHODS: [(18)F]-fluorodeoxyglucose PET was performed in 6 subjects with DYT11-MD (age 30.5 +/- 10.1 years) and in 6 nonmanifesting DYT11 mutation carriers (NM-DYT11; age 59.1 +/- 8.9 years) representing the parental generation of the affected individuals. These data were compared to scan data from age-matched healthy control subjects using voxel-based whole brain searches and group differences were considered significant at p < 0.05 (corrected, statistical parametric mapping). As a secondary analysis, overlapping abnormalities were identified by comparisons to hereditary dystonias (DYT1, DYT6, dopa-responsive dystonia) and to posthypoxic myoclonus. RESULTS: We found significant DYT11 genotype-specific metabolic increases in the inferior pons and in the posterior thalamus as well as reductions in the ventromedial prefrontal cortex. Significant phenotype-related increases were present in the parasagittal cerebellum. This latter abnormality was shared with posthypoxic myoclonus, but not with other forms of dystonia. By contrast, all dystonia cohorts exhibited significant metabolic increases in the superior parietal lobule. CONCLUSIONS: The findings are consistent with a subcortical myoclonus generator in DYT11-MD, likely involving the cerebellum. By contrast, subtle increases in the superior parietal cortex relate to the additional presence of dystonic symptoms. Although reduced penetrance in DYT11-MD has been attributed to the maternal imprinting epsilon-sarcoglycan mutations, NM-DYT11 carriers showed significant metabolic abnormalities that are not explained by this genetic model.

Musicians' dystonia is a task-specific and painless loss of motor control in a previously well-executed task. It is increasingly recognized in the medical and musical community. Recent advances in neuroimaging, transcranial magnetic stimulation and novel techniques in electroencephalography have shed light on its underlying pathophysiology. To date, a deranged cortical plasticity leading to abnormal sensorimotor integration, combined with reduced inhibition across several levels of the motor pathway are likely mechanisms.This paper reviews the various phenomenology of musician's dystonia across keyboard, string, brass, flute and drum players. Treatment is often challenging. Medical therapies like botulinum toxin injection and rehabilitation method with sensorimotor training offer symptomatic relief and return to baseline performance to some musicians.

BACKGROUND: Adult-onset focal lower extremity (LE) dystonia is rare, but there have recently been a number of case series that have reported an idiopathic variant triggered during ambulation. METHODS: We describe nine patients with idiopathic, focal task-specific LE dystonia. We conducted a comparative analysis that included our cohort and several recently published case series to further characterize the disorder. RESULTS: A total of 48 patients (37 female, 11 male) were compared. The average age of onset was 48 years; 36 patients had distal extremity involvement (75%), 5 proximal (10%), and 7 both proximal and distal (15%). Among 33 patients in which the dystonic side was known, 20 were affected on the left (61%). Inversion of the foot with flexion of one or more toes was the most prevalent pattern in those with distal extremity involvement. DISCUSSION: This is a novel task-specific dystonia triggered during ambulation that is often misdiagnosed as an orthopedic or psychogenic issue.