Brain : a journal of neurology
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Multicenter Study
Natural history of pulmonary function in collagen VI-related myopathies.
The spectrum of clinical phenotypes associated with a deficiency or dysfunction of collagen VI in the extracellular matrix of muscle are collectively termed 'collagen VI-related myopathies' and include Ullrich congenital muscular dystrophy, Bethlem myopathy and intermediate phenotypes. To further define the clinical course of these variants, we studied the natural history of pulmonary function in correlation to motor abilities in the collagen VI-related myopathies by analysing longitudinal forced vital capacity data in a large international cohort. Retrospective chart reviews of genetically and/or pathologically confirmed collagen VI-related myopathy patients were performed at 10 neuromuscular centres: USA (n = 2), UK (n = 2), Australia (n = 2), Italy (n = 2), France (n = 1) and Belgium (n = 1). ⋯ The relationship between maximal motor ability and forced vital capacity was highly significant (P < 0.0001). This study demonstrates that pulmonary function profiles can be used in combination with motor function profiles to stratify collagen VI-related myopathy patients phenotypically. These findings improve our knowledge of the natural history of the collagen VI-related myopathies, enabling proactive optimization of care and preparing this patient population for clinical trials.
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Writer's cramp is a task-specific focal hand dystonia characterized by involuntary excessive muscle contractions during writing. Although abnormal striatal dopamine receptor binding has been implicated in the pathophysiology of writer's cramp and other primary dystonias, endogenous dopamine release during task performance has not been previously investigated in writer's cramp. Using positron emission tomography imaging with the D2/D3 antagonist 11C-raclopride, we analysed striatal D2/D3 availability at rest and endogenous dopamine release during sequential finger tapping and speech production tasks in 15 patients with writer's cramp and 15 matched healthy control subjects. ⋯ Striatal regions where D2/D3 availability at rest positively correlated with disease duration were lateral and non-overlapping with striatal regions showing reduced D2/D3 receptor availability, except for a cluster in the left nucleus accumbens, which showed a negative correlation with disease duration and overlapped with striatal regions showing reduced D2/D3 availability. Our findings suggest that patients with writer's cramp may have divergent responses in striatal dopamine release during an asymptomatic motor task involving the dystonic hand and an unrelated asymptomatic task, sentence production. Our voxel-based results also suggest that writer's cramp may be associated with reduced striatal dopamine release occuring in the setting of reduced D2/D3 receptor availability and raise the possibility that basal ganglia circuits associated with premotor cortices and those associated with primary motor cortex are differentially affected in primary focal dystonias.
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The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. ⋯ Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.
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Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. ⋯ Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems.
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Marinesco-Sjögren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as the main cause of Marinesco-Sjögren syndrome. Here we describe the results of SIL1 mutation analysis in 62 patients presenting with early-onset ataxia, cataracts and myopathy or combinations of at least two of these. ⋯ As cognitive impairment is not obligatory, patients without intellectual disability but a Marinesco-Sjögren syndrome-compatible phenotype should receive SIL1 mutation analysis. Despite allelic heterogeneity and many families with private mutations, the phenotype related to SIL1 mutations is relatively homogenous. Based on SIL1 expression studies we speculate that this may arise from a uniform effect of different mutations on protein expression.