Pathophysiological and diagnostic implications of cortical dysfunction in ALS

Nimeshan Geevasinga, Parvathi Menon, Pembe Hande Ozdinler, Matthew C. Kiernan, Steve Vucic*

*Corresponding author for this work

Research output: Contribution to journalReview article

58 Scopus citations

Abstract

Cortical dysfunction-specifically, the development of hyperexcitability-seems to be an early and intrinsic feature of sporadic and familial amyotrophic lateral sclerosis (ALS) phenotypes, preceding the onset of lower motor neuron dysfunction and correlating with ensuing lower motor neuron dysfunction and degeneration. In fact, cortical dysfunction could provide a pathogenic basis for ALS, with corticomotor neuronal hyperexcitability mediating motor neuron degeneration via a trans-synaptic, glutamate-mediated, excitotoxic mechanism. The recent identification of C9orf72 repeat expansion as an important genetic risk factor for both ALS and frontotemporal dementia has underscored the importance of cortical function in ALS pathogenesis, and has helped to confirm that the disease forms part of a spectrum of central neurodegenerative processes. Changes in cortical function that develop in ALS could prove useful as diagnostic biomarkers, potentially enhancing the diagnosis of ALS at an early stage of the disease process. Pathophysiological and diagnostic biomarkers of cortical function might also provide insights to guide the development of future therapeutic approaches, including stem cell and genetic interventions, thereby providing potential for more-effective management of patients with ALS.

Original languageEnglish (US)
Pages (from-to)651-661
Number of pages11
JournalNature Reviews Neurology
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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