Dystonia as a network disorder: What is the role of the cerebellum?

Abstract

The dystonias are a group of disorders defined by sustained or intermittent muscle contractions that result in involuntary posturing or repetitive movements. There are many different clinical manifestations and causes. Although they traditionally have been ascribed to dysfunction of the basal ganglia, recent evidence has suggested dysfunction may originate from other regions, particularly the cerebellum. This recent evidence has led to an emerging view that dystonia is a network disorder that involves multiple brain regions. The new network model for the pathogenesis of dystonia has raised many questions, particularly regarding the role of the cerebellum. For example, if dystonia may arise from cerebellar dysfunction, then why are there no cerebellar signs in dystonia? Why are focal cerebellar lesions or degenerative cerebellar disorders more commonly associated with ataxia rather than dystonia? Why is dystonia more commonly associated with basal ganglia lesions rather than cerebellar lesions? Can answers obtained from animals be extrapolated to humans? Is there any evidence that the cerebellum is not involved? Finally, what is the practical value of this new model of pathogenesis for the neuroscientist and clinician? This article explores potential answers to these questions.

Dissecting the Links Between Cerebellum and Dystonia

“…These lesions are likely to be focal hemorrhages or space-occupying lesions that compress and distort cerebellar functions, leading to an increase rather than a decrease in blood flow to the cerebellum [3,9]. The hypothesis is consistent with the relationship between dystonia and tremor because tremor is also viewed as a distortion of cerebellar functioning [2]. Neuroimaging studies have consistently shown above-normal cerebellar activation in dystonia [3].…”

“…In the present investigation, Hoffland explores the hypothesis that different adaptive learning may exist across three forms of dystonia (blepharospasm, writer's cramp, and cervical dystonia), suggesting that different networks may exist for different types of dystonia [2,3]. During baseline walking conditions, individuals with blepharospasm and cervical dystonia showed impairment of gait demonstrated by a slower preferred walking speed and reduced balance confidence compared to healthy controls and people with writer's cramp.…”

“…Much of this understanding is based on the findings of overt basal ganglia lesions in neuroimaging and autopsy studies [1]. This localization of dystonia to the basal ganglia does not accommodate a growing body of clinical and experimental evidence of the involvement of other structures, and the concept of dystonia as a network disorder involving multiple brain regions has been proposed [2,3]. The role of the cerebellum in the pathophysiology of dystonia was first noted by Fletcher et al [4] and there is strong evidence of abnormal cerebellar function from pathological, neuroimaging, and neurophysiological studies [2,3,5], particularly in forms of primary dystonia [6][7][8].…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…1). Thus, it appears that both the basal ganglia and cerebellum participate and interact under normal conductions in motor and nonmotor functions, and that they share pathologic activity in certain movement disorders, such as parkinsonian tremor and some types of dystonia [95][96][97][98].…”

“…In some types of dystonia, the cerebellum may also be involved, either alone or in conjunction with basal ganglia abnormalities [96,98,209,210]. For instance, gene carriers of the autosomal dominant DYT1 and DYT6 dystonias show functional disturbances of cerebellar connections.…”