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.

Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C

“…Cortical myoclonus is thought to result from increased excitability of the sensorimotor cortex due to decreased inhibition through the cerebellar-thalamic-cortical loop [27]. The combination of cortical myoclonus and cerebella ataxia is also seen in disorders with prominent Purkinje cell loss, for example celiac disease [28, 29].…”

Propofol effects on cerebellar long-term depression

“…Movement disorders including dystonia, myoculus, and ataxia, are often associated with alterations in cerebellar function in which PCs play a principal role in [9,10]. This is the first study to describe electrophysiological changes induced by propofol in the cerebellar cortex.…”

“…Sincethe cerebellum is important for coordinating motor activities and the acquisition of novel motor skills,propofol-induced movement disordersmay be a result of cerebellar dysfunction [9,10].Purkinje cells (PCs) are the sole output ofthe cerebellar cortex and provide signals required for motor planning, execution, and coordination in their neuronal activity [12,24].Granule cell axons, known as parallel fibers (PFs), synapse onto PCs and changes in the strength of PF-PC synapses can influence appropriate motor outputs [12,20,24]. LTD at PF-PC synapse (PF-LTD) is one of the mechanisms underlying motor learning in the cerebellum [4,12,24].…”

Combined focal myoclonus and dystonia secondary to a cerebellar hemorrhage: a case report

“…This paradoxical absence of cortical pathology and cortical myoclonus in patients with cerebellar pathology has promoted the authors to suggest that enhanced excitability of the sensorimotor cortex may arise as a distant effect of cerebellar pathology [10]. This has further been explored in the review by Ganos et al [11]. …”