Studies indicate that the gene responsible for the commonest form of idiopathic torsion dystonia is present in 0.5–1.0% of the general population. The gene is only 40% penetrant, such that six out of ten people never manifest the illness during life.  However, this gene may be a common influence in dystonic manifestations of EPS.

Lewy body formation
Neuropathological studies of psychiatric patients who develop antipsychotic induced extrapyramidal symptoms (EPS) are few in number, as studies have focused on chemical, rather than pathological, aspects of parkinsonism. Only one neuropathological study on drug-induced parkinsonism has been conducted. Upon investigation, three cases were attributed to Lewy body degeneration of the substantia nigra, which is the pathological substrate of idiopathic Parkinson’s disease (PD).

The prevalence of idiopathic Lewy-body PD in the general population over the age of 60 is approximately 0.5%.  For every patient with overt clinical PD, ten are found to have incidental Lewy bodies in their substantia nigra at post mortem.  One in 20 individuals over the age of 65 years carry Lewy bodies in their substantia nigra at the time of death and are believed to be at the pre-clinical stage of parkinsonism.  These individuals also show a 20–30% cell loss of substantia nigra neurones.

The question of Lewy-body parkinsonism also intrudes into orofacial dyskinesias. Limited post mortem studies of patients with spontaneous orofacial dyskinesias have found Lewy bodies in their substantia nigra.  The Lewy body seems to be a pathological substrate for isolated orofacial dyskinesia without PD.

The most common manifestation of a focal lesion in the caudate nucleus is abulia (inert apathy).  We performed a meta-analysis of all cases of focal lesions in basal ganglia recorded up to 1992 using techniques of neuroimaging or pathological analysis. The most common behavioral abnormality was abulia, which was centered very strongly on the caudate nucleus.  The most common movement disorder was dystonia, associated with lesions in the putamen or globus pallidus.

In PD itself, it is the putamen that bears the brunt of pathology and dopamine deprivation; in the early stages of the disease, the caudate is relatively spared from these ravages. Cognitive impairment and apathy is not a conspicuous feature.  As the disease progresses, the patient becomes increasingly abulic (bradyphrenic).

Studies of the neurochemistry of basal ganglia suggest that overactivity of the subthalamic nucleus plays a crucial role in PD, with overactivity of the excitatory drive into the internal segment of the globus pallidus producing massive overactivity.

This crude model partly explains Parkinson’s disease.  It is intriguing that tremor occurs in just 15% of cases of drug-induced parkinsonism, compared with 85% of idiopathic PD – a striking difference.  Classical parkinsonian tremor is probably not attributable to dopamine deficiency alone.  Those patients (15%) with drug-induced Parkinsonism who also have tremor have probably got PD.

In chorea and ballism, the neurochemistry is the opposite of that underlying PD.  Inhibition of the subthalamic nucleus and ‘switching off’ of the globus pallidus explain most of the abnormal movements that levodopa produces in patients with PD.  The mechanism of levodopa-induced dyskinesias in PD is of considerable relevance to many of the movements produced by antipsychotic drugs.

Summary
The models discussed above cannot explain dystonia.  We still have no rational explanation for dystonia, the commonest movement disorder produced by lesions of the basal ganglia.  It is likely that the pathophysiology of dystonias is different from those of chorea and ballism.

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