Lancet neurology
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Optical coherence tomography (OCT) is a new method that could aid analysis of neurodegeneration in multiple sclerosis (MS) by capturing thinning of the retinal nerve fibre layer (RNFL). Meta-analyses of data for time domain OCT show RNFL thinning of 20.38 microm (95% CI 17.91-22.86, n=2063, p<0.0001) after optic neuritis in MS, and of 7.08 microm (5.52-8.65, n=3154, p<0.0001) in MS without optic neuritis. ⋯ RNFL thickness correlates with visual and neurological functioning as well as with paraclinical data. Developments that could improve understanding of the relation between structure and function in MS pathophysiology include spectral or Fourier domain OCT technology, polarisation-sensitive OCT, fluorescence labelling, structural assessment of action-potential propagation, and segmentation algorithms allowing quantitative assessment of retinal layers.
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Randomized Controlled Trial
Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR.
In September, 2008, the European Acute Stroke Study III (ECASS III) randomised trial and the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) observational study reported the efficacy and safety of the extension of the time window for intravenous alteplase treatment from within 3 h to within 4.5 h after stroke onset. We aimed to assess the implementation of the wider time window, its effect on the admission-to-treatment time, and safety and functional outcome in patients recorded in SITS-ISTR. ⋯ Boehringer Ingelheim, Ferrer, the European Union Public Health Executive Authority, and Medical Training and Research (ALF) from Stockholm County Council and Karolinska Institutet.
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Cerebellar ataxias with autosomal dominant transmission are rare, but identification of the associated genes has provided insight into the mechanisms that could underlie other forms of genetic or non-genetic ataxias. In many instances, the phenotype is not restricted to cerebellar dysfunction but includes complex multisystemic neurological deficits. ⋯ All other SCAs are caused by either conventional mutations or large rearrangements in genes with different functions, including glutamate signalling (SCA5/SPTBN2) and calcium signalling (SCA15/16/ITPR1), channel function (SCA13/KCNC3, SCA14/PRKCG, SCA27/FGF14), tau regulation (SCA11/TTBK2), and mitochondrial activity (SCA28/AFG3L2) or RNA alteration (SCA31/BEAN-TK2). The diversity of underlying mechanisms that give rise to the dominant cerebellar ataxias need to be taken into account to identify therapeutic targets.
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Disruption of the most fundamental cellular energy process, the mitochondrial respiratory chain, results in a diverse and variable group of multisystem disorders known collectively as mitochondrial disease. The frequent involvement of the brain, nerves, and muscles, often in the same patient, places neurologists at the forefront of the interesting and challenging process of diagnosing and caring for these patients. Mitochondrial diseases are among the most frequently inherited neurological disorders, and can be caused by mutations in mitochondrial or nuclear DNA. Substantial progress has been made over the past decade in understanding the genetic basis of these disorders, with important implications for the general neurologist in terms of the diagnosis, investigation, and multidisciplinary management of these patients.
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Although the interaction between comorbidities and chronic diseases is strong, the effect of comorbidities receives little attention in many chronic diseases. In multiple sclerosis (MS), an increasing amount of evidence suggests that physical and mental comorbidities, and adverse health factors such as smoking and obesity, are common and can affect the disease. These comorbid diseases and lifestyle factors affect clinical phenotype, the diagnostic delay between symptom onset and diagnosis, disability progression, and health-related quality of life. ⋯ Studies of the frequency of comorbidities in patients with MS should be population based, incorporating appropriate comparator groups. These studies should expand the range of comorbidities assessed, and examine how the frequency of comorbidities is changing over time. Further research is needed to answer many other questions about comorbidities and their associations with MS, including the best way to measure and analyse comorbidities to understand these associations.