Lancet neurology
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Randomized Controlled Trial Multicenter Study
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.
Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. ⋯ BallouSkies, Parent Project for Muscular Dystrophy, US National Center for Advancing Translational Sciences, and US National Institutes of Health.
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Constraint-induced movement therapy (CIMT) was developed to overcome upper limb impairments after stroke and is the most investigated intervention for the rehabilitation of patients. Original CIMT includes constraining of the non-paretic arm and task-oriented training. Modified versions also apply constraining of the non-paretic arm, but not as intensive as original CIMT. ⋯ The original and modified types of CIMT have beneficial effects on motor function, arm-hand activities, and self-reported arm-hand functioning in daily life, immediately after treatment and at long-term follow-up, whereas there is no evidence for the efficacy of constraint alone (as used in forced use therapy). The type of CIMT, timing, or intensity of practice do not seem to affect patient outcomes. Although the underlying mechanisms that drive modified and original CIMT are still poorly understood, findings from kinematic studies suggest that improvements are mainly based on adaptations through learning to optimise the use of intact end-effectors in patients with some voluntary motor control of wrist and finger extensors after stroke.
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Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. ⋯ Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis.
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A better understanding of the pathological mechanisms that drive neurodegeneration in individuals with multiple sclerosis is needed to develop therapies that will effectively treat patients in the primary and secondary progressive stages of the disease. We propose that the inflammatory demyelinating disease process in early multiple sclerosis triggers a cascade of events that lead to neurodegeneration and are amplified by pathogenic mechanisms related to brain ageing and accumulated disease burden. ⋯ This process leads to chronic cell stress and imbalance of ionic homoeostasis, resulting in axonal and neuronal death. The evidence suggests that treatment of progressive multiple sclerosis should be based on a combination of anti-inflammatory, regenerative, and neuroprotective strategies.
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Biography Historical Article
Hans Lassmann: still determined to solve the puzzle.