Physiologic changes associated with cerebellar dystonia

Abstract

Dystonia is a neurologic disorder characterized by sustained involuntary muscle contractions. Lesions responsible for unilateral secondary dystonia are confined to the putamen, caudate, globus pallidus, and thalamus. Dysfunction of these structures is suspected to play a role in both primary and secondary dystonia. Recent evidence has suggested that the cerebellum may play a role in the pathophysiology of dystonia. The role of the cerebellum in ataxia, a disorder of motor incoordination is well established. How may the cerebellum contribute to two apparently very different movement disorders? This review will discuss the idea of whether in some cases, ataxia and dystonia lie in the same clinical spectrum and whether graded perturbations in cerebellar function may explain a similar causative role for the cerebellum in these two different motor disorders. The review also proposes a model for cerebellar dystonia based on the available animal models of this disorder.

Figure 1. Schematic patterns of muscle activity in normal, dystonic and ataxic subjects during flexion movements at the elbow

A. Normal subjects activate the biceps (agonist) followed by the antagonist (triceps). (Middle) B. In some subjects with cerebellar ataxia, agonist contraction is delayed and prolonged. Antagonist contraction is also delayed but is of normal duration. C. In other subjects with cerebellar ataxia, both agonist and antagonist activity is prolonged D. In dystonic subjects agonist contraction is prolonged. Antagonist contraction is premature resulting in co-contraction, as well as prolonged. Modified from [–47, 54].

Figure 2. Model for cerebellar dystonia

(Left) Normal cerebellar function relies on separation of signals for agonist and antagonist muscle groups at the level of the cerebellar cortex and cerebellar nuclei. (Right) Model for cerebellar dystonia. Dystonia would be expected to occur under conditions of lack of separation of signals intended for agonist and antagonist muscle groups at the level of the cerebellar nuclei, the sole motor output from the cerebellum. PC: Purkinje neuron, CN: Cerebellar nuclear neuron, GC: Granule cell, IN: Molecular layer interneuron, Sync: Increased synchrony, Green: Excitatory neurons and transmission, Red: Inhibitory neurons and transmission, Yellow: Hypothetical aberrant connections. Strength of connections is indicated by the thickness of the line.