title: The role of the cerebellum in the pathogenesis of cortical myoclonus.
abstract: The putative involvement of the cerebellum in the pathogenesis of cortical myoclonic syndromes has been long hypothesized, as neuropathological changes in patients with cortical myoclonus have most commonly been found in the cerebellum rather than in the suspected culprit, the primary somatosensory cortex. A model of increased cortical excitability due to loss of cerebellar inhibitory control via cerebello-thalamo-cortical connections has been proposed, but evidence remains equivocal. Here, we explore this hypothesis by examining syndromes that present with cortical myoclonus and ataxia. We first describe common clinical characteristics and underlying neuropathology. We critically view information on cerebellar physiology with regard to motorcortical output and compare findings between hypothesized and reported neurophysiological changes in conditions with cortical myoclonus and ataxia. We synthesize knowledge and focus on neurochemical changes in these conditions. Finally, we propose that the combination of alterations in inhibitory neurotransmission and the presence of cerebellar pathology are important elements in the pathogenesis of cortical myoclonus.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, United Kingdom; Department of Neurology, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany; Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Ganos
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kassavetis
authors.forename: Roberto
authors.initials: R
authors.lastname: Erro
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: John
authors.initials: J
authors.lastname: Rothwell
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
mesh_terms: D001259:Ataxia / Q000473:pathology* / Q000503:physiopathology; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D004569:Electroencephalography; D006801:Humans; D009207:Myoclonus / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
keywords: GABA; ataxia; cortical myoclonus; motorcortical disinhibition; progressive myoclonus epilepsy