Annals of neurology
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Annals of neurology · Jul 2014
Meta AnalysisC9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: a genome-wide meta-analysis.
Substantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant in a proportion of ALS and FTD cases. We sought to identify additional evidence for a common genetic basis for the spectrum of ALS-FTD. ⋯ We identified common genetic variants in C9orf72, but in addition in UNC13A that are shared between ALS and FTD. UNC13A provides a novel link between ALS and FTD-TDP, and identifies changes in neurotransmitter release and synaptic function as a converging mechanism in the pathogenesis of ALS and FTD-TDP.
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Annals of neurology · Jun 2014
Stroke risk after nonstroke emergency department dizziness presentations: a population-based cohort study.
Acute stroke is a serious concern in emergency department (ED) dizziness presentations. Prior studies, however, suggest that stroke is actually an unlikely cause of these presentations. Lacking are data on short- and long-term follow-up from population-based studies to establish stroke risk after presumed nonstroke ED dizziness presentations. ⋯ Using rigorous case ascertainment and outcome assessment in a population-based design, we found that the risk of stroke after presumed nonstroke ED dizziness presentations is very low, supporting a nonstroke etiology to the overwhelming majority of original events. High-risk subgroups likely exist, however, because most of the 90-day stroke risk occurred within 2 days. Vascular risk stratification was insufficient to identify these cases.
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Annals of neurology · Jun 2014
JC virus reactivation during prolonged natalizumab monotherapy for multiple sclerosis.
To determine the prevalence of JC virus (JCV) reactivation and JCV-specific cellular immune response during prolonged natalizumab treatment for multiple sclerosis (MS). ⋯ Asymptomatic JCV reactivation may occur in CSF of natalizumab-treated MS patients. JCV DNA load is higher in circulating CD34(+) cells and monocytes compared to other mononuclear cells, and JCV in blood might trigger a JCV-specific CD4(+) T-cell response. JCV-specific cellular immune response is highly prevalent in all JCV-seropositive MS patients, regardless of treatment.
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Annals of neurology · Jun 2014
Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions.
Serum antibodies against the glial potassium channel KIR4.1 are found in a subpopulation of multiple sclerosis (MS) patients. Little is known about the expression of KIR4.1 in human normal brain tissue and in MS lesions. ⋯ The expression profile of KIR4.1 in glial cells and stage-dependent alterations of KIR4.1 IR in MS lesions are compatible with an immune response against KIR4.1 at least in a subset of MS patients.