Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

Abstract

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

Sensorimotor Integration and GABA-ergic Activity in Embouchure Dystonia: An Assessment with Magnetoencephalography

“…14,15 Our study shows increased coherence in the contralateral cerebellum during and post-dystonic tremor, thereby adding to the literature on the topic.…”

Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

“…Anatomically, a topographical, disynaptic, reciprocal connection from the subthalamic nucleus to the cerebellar cortex and cerebellar dentate nucleus to the striatum links both structures . Evidence for a functional role of the cerebellum has been collected most consistently for dystonia; data from expression levels of genes involved in monogenic forms of dystonia, mechanisms in animal models of the disease, human electrophysiology, and structural and functional imaging point to cerebellar involvement in addition to changes in the basal ganglia and motor cortex . Similarly, myoclonus has been associated with cerebellar dysfunction in a number of conditions .…”

“…Similarly, myoclonus has been associated with cerebellar dysfunction in a number of conditions . A loss of inhibitory cerebellar control over the cortex has been proposed for both etiologies . In both Huntington disease and PD, functional imaging data suggest cerebellar hyper‐metabolism, which has been interpreted as a compensatory mechanism to balance basal ganglia dysfunction …”

Dystonia and ataxia progression in spinocerebellar ataxias

“…Dystonia in SCAs could result from the cerebellar pathology and extra-cerebellar involvement [24–28]. The brain circuitry involved in dystonia has been reported in the cerebellum and its connection to the brainstem, cervical spinal cord, thalamus, and motor cortex [5,24–29].…”