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

Vikram G. Shakkottai, Amit Batla, Kailash Bhatia, William T Dauer, Christian Dresel, Martin Niethammer, David Eidelberg, Robert S. Raike, Yoland Smith, H. A. Jinnah, Ellen J. Hess, Sabine Meunier (+9 others)
2016 Cerebellum  
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
more » ... 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. network [4] . It may arise from dysfunction of a single node in the network, simultaneous dysfunction of more than one node, or abnormal communication between the nodes. One such additional node that has recently been implicated in dystonia is the cerebellum. In this manuscript, animal studies linking the cerebellum to dystonia are summarized. This is followed by a summary of the role of the cerebellum in human dystonia. A consensus opinion of the role of the cerebellum in dystonia is presented, in addition to areas for future research. Motor Pathways Involved in Dystonia (H.A. Jinnah, Yoland Smith, Ellen Hess) Some of the strongest evidence for involvement of nodes other than the basal ganglia in dystonia has come from animal studies, and particularly rodents. This evidence must be interpreted in view of potential species differences. Species differences in motor behavior The normal motor behavior of humans and rodents is quite different, so the first question to address is whether or not dystonia can occur in rodents. Dystonia is defined by the quality of abnormal movements, with excessive contraction of muscles that lead to twisting or repetitive movements or postures [1]. By definition, any abnormal movements with these qualities are "dystonic". Co-contraction of antagonistic muscle pairs is said to be characteristic of dystonia, but this phenomenon is not universal [5] . Electromyography can be helpful in confirming some of the electrophysiological dopamine, acetylcholine, norepinephrine, serotonin), intrinsic connections (glutamate, GABA, acetylcholine, adenosine), and efferents (mostly GABA). Cerebellum. The gross anatomy of the rodent cerebellum is different from humans; it is smaller with relatively less prominent hemispheres. However, the major efferent and efferent connections are similar in rodents in humans, with entry and exit through three very similar peduncles. Once again, however, the relative contribution of afferent and efferent pathways differs between rodents and humans. The cytoarchitectonics are strikingly similar across species with a cerebellar cortex divided into 3 layers (molecular layer, Purkinje layer, granule layer) and distinct cerebellar nuclei deep in the white matter (dentate, globose, fastigial, emboliform). The intrinsic circuitry of the cerebellum also is identical across species, with a highly characteristic layout of climbing fibers, mossy fibers, parallel fibers, and Purkinje neuron output. Are species differences relevant for dystonia? With regards to both motor behavior and neuroanatomy, there are clear differences between rodents and humans that must be acknowledged. Regarding motor behavior, some subtypes of dystonia such as writer's cramp may not occur in rodents; but there is no reason to suspect that other types of dystonia do not occur. Regarding the neuroanatomy, species differences are obvious, but the similarities are more extensive. The critical issue is not whether there are differences between humans and rodents, but whether these differences are sufficiently critical to dismiss the rodent literature. The answer to this question is unknown. However, there is presently no clear evidence that dystonia in rodents and humans is mediated by different anatomical
doi:10.1007/s12311-016-0825-6 pmid:27734238 pmcid:PMC5336511 fatcat:ejky6yfwwngnxp6rfd6d3xb5xa