Brain : a journal of neurology
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Review Case Reports
Variably protease-sensitive prionopathy in the UK: a retrospective review 1991-2008.
Variably protease-sensitive prionopathy is a newly described human prion disease of unknown aetiology lying out with the hitherto recognized phenotypic spectrum of Creutzfeldt-Jakob disease. Two cases that conform to the variably protease-sensitive prionopathy phenotype have been identified prospectively in the U. K. since the first description of the condition in 2008 in the U. ⋯ K. Assuming ascertainment levels equivalent to that of other human prion diseases, these data indicate that variably protease-sensitive prionopathy is a rare phenotype within human prion diseases, which are themselves rare. Biochemical investigation indicates that the abnormal protease-resistant prion protein fragment that characterizes variably protease-sensitive prionopathy is detectable at low levels in some cases of sporadic Creutzfeldt-Jakob disease and conversely, that the form of abnormal prion protein that characterizes sporadic Creutzfeldt-Jakob disease can be found in certain brain regions of cases of variably protease-sensitive prionopathy, indicating molecular overlaps between these two disorders.
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Multiple avenues of research including epidemiology, molecular genetics and cell biology have identified links between Parkinson's disease and type 2 diabetes mellitus. Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism. This includes converging evidence identifying that peroxisome proliferator activated receptor gamma coactivator 1-α, a key regulator of enzymes involved in mitochondrial respiration and insulin resistance, is potentially pivotal in the pathogenesis of neurodegeneration in Parkinson's disease. ⋯ In parallel with these advances, there are already randomized trials evaluating several established treatments for insulin resistance (pioglitazone and exenatide) as possible disease modifying drugs in Parkinson's disease, with only preliminary insights regarding their mechanisms of action in neurodegeneration, which may be effective in both disease processes through an action on mitochondrial function. Furthermore, parallels are also emerging between these same pathways and neurodegeneration associated with Alzheimer's disease and Huntington's disease. Our aim is to highlight this converging evidence and stimulate further hypothesis-testing studies specifically with reference to the potential development of novel neuroprotective agents in Parkinson's disease.
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The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. ⋯ This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors.
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In a previous paper, we reviewed the range of therapies available for the treatment of super-refractory status epilepticus. Here we report a review of the outcome of therapies in refractory and super-refractory status epilepticus. Patients (n = 1168) are reported who had therapy with: thiopental, pentobarbital, midazolam, propofol, ketamine, inhalational anaesthetics (isoflurane, desflurane), antiepileptic drugs (topiramate, lacosamide, pregabalin, levetiracetam), hypothermia, magnesium, pyridoxine, immunotherapy, ketogenic diet, emergency neurosurgery, electroconvulsive therapy, cerebrospinal fluid drainage, vagal nerve stimulation and deep brain stimulation. ⋯ Given these deficits, only broad recommendations can be made regarding optimal therapy. An approach to therapy, divided into first-line, second-line and third-line therapy, is suggested on the basis of this outcome evaluation. The importance of treatments directed at the cause of the status epilepticus, and of supportive ITU care is also emphasized.
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Review Historical Article
A developmental and genetic classification for malformations of cortical development: update 2012.
Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. ⋯ These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development.