Lancet neurology
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Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. ⋯ Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance.
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New research criteria for preclinical Alzheimer's disease have been proposed, which include stages for cognitively normal individuals with abnormal amyloid markers (stage 1), abnormal amyloid and neuronal injury markers (stage 2), or abnormal amyloid and neuronal injury markers and subtle cognitive changes (stage 3). We aimed to investigate the prevalence and long-term outcome of preclinical Alzheimer's disease according to these criteria. ⋯ National Institute of Aging of the National Institutes of Health (P01-AG003991, P50-AG05681, P01-AG02676), Internationale Stichting Alzheimer Onderzoek, the Center for Translational Molecular Medicine project LeARN, the EU/EFPIA Innovative Medicines Initiative Joint Undertaking, and the Charles and Joanne Knight Alzheimer Research Initiative.
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Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are the most common known genetic cause of frontotemporal dementia (FTD) and motor neuron disease (MND). We assessed whether expansion size is associated with disease severity or phenotype. ⋯ The ALS Therapy Alliance, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Arizona Department of Health Services, the Arizona Biomedical Research Commission, and the Michael J Fox Foundation for Parkinson's Research.
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Review Meta Analysis
Subthalamic neurostimulation for Parkinson's disease with early fluctuations: balancing the risks and benefits.
Electrical stimulation of the subthalamic nucleus is an established treatment for patients with advanced Parkinson's disease with pharmacologically unresponsive fluctuations. Compared with pharmacological treatment, subthalamic neurostimulation significantly improves motor symptoms, particularly during the phases of poor response to drug treatment, and reduces the severity of dyskinesias. Importantly, it also significantly improves quality of life and other integral measures of disease severity. ⋯ In a recent study (EARLYSTIM) in patients with a disease duration of 7·5 years and fluctuations for 1·5 years, similar improvements in clinical outcomes were reported. These findings suggest that neurostimulation of the subthalamic nucleus could be used earlier in the disease course for carefully selected patients if the benefits of the treatment are weighed against the surgical risks and the lifelong need for specialised care by an experienced team. As mobility is consistently improved during the times with poor mobility by reducing fluctuations and delaying levodopa-sensitive complications, we propose that this treatment changes the disease course.
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A fifth of all strokes and transient ischaemic attacks occur in the posterior circulation arterial territory. Diagnosis can be challenging, in part because of substantial overlap in symptoms and signs with ischaemia in the anterior circulation. Improved methods of non-invasive imaging of the vertebrobasilar arterial tree have been used in recent prospective follow-up studies, which have shown a high risk of early recurrent stroke, particularly when there is associated vertebrobasilar stenosis. This finding emphasises the importance of urgent secondary prevention, and the role of stenting for vertebral stenosis is being investigated.