How does the cerebellum contribute to the pathophysiology of dystonia?

Dystonia has historically been considered a disorder of the basal ganglia. This notion comes from the observation that most lesions responsible for secondary dystonia involve the basal ganglia and from the clinical analogy between primary and secondary dystonia. However, recent evidence coming from neuroimaging, neurophysiological and behavioral studies suggested that the Cerebellum may be involved in the pathophysiology of dystonia. Structural and functional magnetic resonance imaging studies documented a widespread pattern of dysfunction in primary dystonia, thus leading us to reconsider it as a neurodevelopmental motor circuit disorder, characterized by an abnormal functioning of a network of cortical and subcortical areas including the Cerebellum. The most compelling neurophysiological evidence supporting the role of the Cerebellum in the pathophysiology of dystonia comes from studies of the eyeblink conditioning paradigm and of the cerebello-cortical interaction. Preliminary data from patients with primary cervical and focal hand adult-onset dystonia show that performance on the eyeblink conditioning paradigm, which is specifically dependent upon the olivo-cerebellar pathway, is abnormal. Cerebello-cortical interaction can be tested with transcranial magnetic stimulation by investigating how a conditioning stimulus over the Cerebellum influences a subsequent stimulus over the controlateral motor cortex. A reduced cerebellar modulation of motor cortex excitability has been reported in dystonia. At the behavioral level, the dystonia cerebellar function has been explored in a broader range of behaviors. Data present in the literature suggest that the Cerebellum may be involved in the impairment of different abilities in dystonic patients ranging from movement control to sensory perception and motor learning. Overall, this body of evidence suggests that in dystonia the Cerebellum has an abnormal activity; however whether this activity is compensatory, secondary to pathology elsewhere within the sensori-motor network, or plays a primary role in the pathophysiology of dystonia is still open to question. (C) 2012 Elsevier GmbH. All rights reserved.