Pathogenesis of dystonia: is it of cerebellar or basal ganglia origin?

Abstract

Dystonia is a disorder of motor programmes controlling semiautomatic movements or postures, with clinical features such as sensory trick, which suggests sensorimotor mismatch as the basis. Dystonia was originally classified as a basal ganglia disease. It is now regarded as a 'network' disorder including the cerebellum, but the exact pathogenesis being unknown. Rare autopsy studies have found pathology both in the striatum and the cerebellum, and functional disorganisation was reported in the somatosensory cortex in patients. Recent animal studies showed physiologically tight disynaptic connections between the cerebellum and the striatum. We review clinical evidence in light of this new functional interaction between the cerebellum and basal ganglia, and put forward a hypothesis that dystonia is a basal ganglia disorder that can be induced by aberrant afferent inputs from the cerebellum.

Keywords: cerebellar disease; dystonia; functional imaging; movement disorders; neurophysiology.

Figure 1

A classical picture of sensory trick (geste antagoniste) in spasmodic torticollis. Left: without trick. Right: abnormal posture is corrected by placing the right hand on the hip bone and touching the chin with the left hand.

Figure 2

Scheme of hypothetical pathways for sensory versus motor output in dystonia. Dystonic movements are reproduced with high-frequency vibration (TVR) and blocked by desensitising the muscle spindle with diluted local anaesthetics (MAB). Spindle afferents are projected to the cerebellum, and disynaptic projection of cerebello-thalamo-striatal pathway affects the neuroplasticity at the corticostriatal synapse, where rhythmic activity is essential. Subcortical route is assumed for TVR. ACh, acethylcholine; DA, dopamine; MAB, muscle afferent block; TVR, tonic vibration reflex.

Figure 3

Striosomes (S) and direct versus indirect pathways in the matrix (M) in normal (left) and XDP dystonia (right). The lower left subset indicates activated (red) and inhibited (blue) muscles for the task (surround inhibition). The loss of striosomal neurons in XDP disinhibits dopaminergic release by substantia nigra pars compacta (SNc, dotted arrow), which in turn makes direct pathway predominant over indirect pathway, resulting in disruption of surround inhibition. GABA; gamma-aminobutyric acid; XDP, X-linked dystonia-parkinsonism.