In vivoassessment of neurological channelopathies: Application of peripheral nerve excitability studies

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With the rapid evolution of understanding of neurological channelopathies comes a need for sensitive tools to evaluate patients in clinical practice. Neurological channelopathies with a single-gene basis can manifest as seizures, headache, ataxia, vertigo, confusion, weakness and neuropathic pain and it is likely that other genetic factors contribute to the phenotype of many of these disorders. Ion channel dysfunction can result in abnormal cell membrane excitability but utilisation of advanced neurophysiology techniques has lagged behind developments in clinical, genetic and imaging evaluation of channelopathies. However, momentum in the application of in vivo axonal excitability testing sees these tests emerging as valuable tools, with the capacity to provide sensitive and specific insights into the mechanism of disease. While single-channel function cannot be directly measured in vivo, evaluation of subjects with single-gene channelopathies has provided insights into the effects of mutation-related alterations of membrane excitability, as well as compensatory adaptive changes. By showing how ion channel dysfunction can affect axonal excitability in vivo, studies of the excitability of peripheral nerve axons complement in vitro analysis of single channel activity. The interpretation of results is enhanced by mathematical modelling of axonal function and insights provided by in vitro work.This article is part of the Special Issue entitled ‘Channelopathies.’HighlightsIn vivo assessment of neuronal ion channelopathies is directed at assessment of membrane excitability.Excitability tests of peripheral nerve can identify changes reflecting single channel dysfunction and compensatory responses.Mechanistic inferences of single channel dysfunction can be made from excitability tests with guidance from in vitro findings.Mathematical models of axonal excitability corroborate channel dysfunction as the basis for a change in membrane potential in channelopathies.

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