Lancet neurology
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Patients with neuropathic pain present with various pain-related sensory abnormalities. These sensory features form different patterns or mosaics-the sensory profile-in individual patients. One hypothesis for the development of sensory profiles is that distinct pathophysiological mechanisms of pain generation produce specific sensory abnormalities. Several controlled trials of promising new drugs have produced negative results, but these findings could have been a result of heterogeneity in the patient population. Subgrouping patients on the basis of individual sensory profiles could reduce this heterogeneity and improve trial design. ⋯ A statistical categorisation of patients with neuropathic pain showed that subgroups of patients with distinct sensory profiles who perceive their pain differently do exist across a range of neuropathic disorders, although some distinct disorder-specific profiles were also detected. Results of the first clinical trials to use the subgroup approach at baseline could show a superior effect of the study drugs in specific subgroups, rather than in the entire cohort of patients. WHERE NEXT?: A new classification of neuropathic pain should take into account subgroups of patients with different sensory profiles. Sensory phenotyping has the potential to improve clinical trial design by enriching the study population with potential treatment responders, and might lead to a stratified treatment approach and ultimately to personalised treatment.
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Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosomal enzyme that is deficient in Gaucher's disease, are important and common risk factors for Parkinson's disease and related disorders. This association was first recognised in the clinic, where parkinsonism was noted, albeit rarely, in patients with Gaucher's disease and more frequently in relatives who were obligate carriers. ⋯ Hypotheses proposed to explain this association include a gain-of-function due to mutations in glucocerebrosidase that promotes α-synuclein aggregation; substrate accumulation due to enzymatic loss-of-function, which affects α-synuclein processing and clearance; and a bidirectional feedback loop. Identification of the pathological mechanisms underlying GBA-associated parkinsonism will improve our understanding of the genetics, pathophysiology, and treatment for both rare and common neurological diseases.
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Comment Letter
Is the door open again for neuroprotection trials in stroke?
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Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. ⋯ Wellcome Trust, UK Medical Research Council (MRC), Australian National and Medical Health Research Council, National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Human Genome Research Institute (NHGRI), and the National Institute of Neurological Disorders and Stroke (NINDS).
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial.
Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. ⋯ NoNO Inc and Arbor Vita Corp.