![]() Early studies showed that applying a GABA A antagonist to the striatum induced dystonia in cats or rats, indicating that impaired inhibition of the striatum is important in this disorder 22– 24. Finally, many dystonic patients experience an alleviation of symptoms after lesions or deep brain stimulation (DBS) of nuclei in the basal ganglia 17– 21.Īnimal models have demonstrated that a number of manipulations to the basal ganglia can result in dystonia. Since normal dopamine signaling is vital to basal ganglia function, dopamine involvement suggests an important link between the basal ganglia and dystonia 15, 16. In addition, some patients with Parkinson’s disease present initially with dystonia 13, 14. Dystonia can be associated with abnormalities in dopamine as seen in patients with DYT5 who are highly responsive to treatment with levodopa 12. Because damage to the basal ganglia can lead to secondary dystonia in human patients, this area is traditionally considered to underlie this disorder. Multiple lines of reasoning suggest that the basal ganglia are involved in dystonia. The Basal Ganglia in movement and movement disordersĬlinically, it has been known for a number of years that dysfunction in the basal ganglia can cause movement disorders 11. Finally, we will address how these results can improve our therapeutic approach to dystonia. and how they add to our understanding of the pathophysiology underlying dystonia. We will also discuss the implications of the paper by Chen et al. In this perspective, we will address the evidence for a role of the cerebellum and cerebello-basal ganglia communication in dystonia. In 2014, Chen et al., showed that basal ganglia activity can be modulated by input from the cerebellum via this direct cerebello-thalamo-basal ganglia pathway 10. Further, it was suggested that abnormal cerebellar output may cause dystonia by altering basal ganglia activity through a di-synaptic pathway connecting these two brain areas ( Figure 1). It was also shown that the most common inherited dystonia, DYT1, can be modeled in the mouse by targeting only the cerebellum 9. Importantly, two recent studies have provided compelling evidence for a cerebello-thalamo basal ganglia pathway.Ī 2011 study by Calderon et al., demonstrated that the rare genetic dystonia Rapid-onset dystonia Parkinsonism (RDP) can be pharmacologically modeled in the rodent by targeting both the cerebellum and basal ganglia 8. While dystonia has been considered a disorder of the basal ganglia, there is evidence to suggest that other brain areas may also play a role 5– 7. Unfortunately, the neural substrates of dystonia are not completely understood and therefore therapeutic options available to patients remain limited 4. ![]() Further, they are usually exaggerated by voluntary movement and are associated with muscle activation overflow, resulting in the characteristic co-contraction of agonist-antagonist muscle pairs 3. The movements are often patterned and twisting but may be tremulous as well. In dystonia abnormal muscle contractions result in unwanted movements or postures 2. We conclude that there is ample evidence to suggest that the cerebellum plays a role in some dystonias, including the early-onset primary torsion dystonia DYT1 and that further studies examining the role of this brain region and its interaction with the basal ganglia in dystonia are warranted.ĭystonia is the third most common movement disorder behind only Parkinson’s disease and essential tremor 1. In this review we examine the evidence for the involvement of the cerebellum and cerebello-basal ganglia interactions in dystonia. Further, this paper and others have provided evidence that in some cases, aberrant cerebello-basal ganglia communication can be involved in dystonia. They showed that the cerebellum can directly modulate basal ganglia activity through a short latency cerebello-thalamo-basal ganglia pathway. Can different types of dystonia be classified as either a basal ganglia disorder or a cerebellar disorder? Is dystonia a network disorder that involves the cerebellum and basal ganglia? If dystonia is a network disorder, how can we target treatments to alleviate symptoms in patients? A recent study by Chen et al., using the pharmacological mouse model of Rapid-onset dystonia Parkinsonism (RDP), has provided some insight into these important questions. However, growing evidence suggests that the cerebellum may be involved in certain types of dystonia raising several questions. Dystonia has traditionally been considered a disorder of the basal ganglia. Dystonia is a common movement disorder that devastates the lives of many patients but the etiology of this disorder remains poorly understood.
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