Journal of the neurological sciences
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Fatigue is highly prevalent in multiple sclerosis (MS). It appears to be multifactorial, with "primary" or disease-related factors involved, as well as "secondary" factors, including comorbidities. Sleep disturbances are frequent in MS as well, and often result from disease-related factors. ⋯ Data from neuroimaging studies and studies of molecular consequences of sleep disorders in the general population, with particular attention to sleep-disordered breathing (SDB), are briefly reviewed. Potential biologic interactions with MS are discussed in this context. We conclude that further studies of sleep disorders in MS are needed, to objectively establish their significance in this disease, and also to document any impact of treatment of sleep disorders on biologic and clinical outcomes such as fatigue.
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Childhood spinal muscular atrophy (SMA) is an autosomal recessive disorder characterised by loss of the alpha motor neurones of the spinal cord. SMA is cause by mutations in the survival motor neuron (SMN) gene. There are two copies of the SMN gene: SMN1 and SMN2. ⋯ Therefore, SMA is triggered by a fall in the levels of expressed full-length protein, and the levels expressed by the retained SMN2 gene control the severity. As a result, RNA manipulation to suppress the alternative splicing event and thus increase SMN exon 7 inclusion has emerged as an attractive therapeutic approach. In this review we have discussed the current state of bifunctional RNAs as a viable therapy, concentrating on recent advances and overall implications of this research on SMA.
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The cause of multiple sclerosis is unknown although it is recognised to involve an inflammatory process associated with demyelinating plaques and more widespread neurodegeneration. It appears to have become progressively more common in females which is further discussed in this issue, and genetic factors, as identified to date, appear to play only a moderate role. One curious observation is that Leber's Hereditary Optic Neuropathy (LHON), a rare genetic syndrome, presents clinically overwhelmingly in males, but can be associated with an MS-like illness and when it does it occurs mainly in females. It is interesting to examine this further to assess if this could give us any clues as to the pathogenesis of MS.
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Antiplatelet therapy is an integral component of effective secondary prevention after non-cardioembolic ischemic stroke. Numerous clinical trials have tested the efficacy and safety of different antiplatelet regimens, including aspirin monotherapy, clopidogrel monotherapy, the combination of aspirin plus clopidogrel, and the combination of aspirin plus dipyridamole, in patients with a history of arterial ischemic stroke and transient ischemic attack (TIA). Although competing, head-to-head comparisons between aspirin plus dipyridamole and clopidogrel were not previously available, various professional societies have outlined evidence-based recommendations for antiplatelet therapy in patients with ischemic stroke or TIA. ⋯ The results of PRoFESS thus highlight the pitfalls of making conclusions of relative therapy efficacy in the absence of head-to-head comparisons. This article presents an overview of the factors that differ between clinical trials and "real-world" patient populations, as well as factors that differ among clinical trials themselves. The article also addresses the potential impact these differences may have on clinical trial results and subsequent clinical decision making.