Cortical hyperexcitability: Diagnostic and pathogenic biomarker of ALS

Abstract

Cortical hyperexcitability is an early and intrinsic feature of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS).. Importantly, cortical hyperexcitability appears to be associated with motor neuron degeneration, possibly via an anterograde glutamate-mediated excitotoxic process, thereby forming a pathogenic basis for ALS. The presence of cortical hyperexcitability in ALS patients may be readily determined by transcranial magnetic stimulation (TMS), a neurophysiological tool that provides a non-invasive and painless method for assessing cortical function. Utilising the threshold tracking TMS technique, cortical hyperexcitability has been established as a robust diagnostic biomarker that distinguished ALS from mimicking disorders at early stages of the disease process. The present review discusses the pathophysiological and diagnostic utility of cortical hyperexcitability in ALS.