Parkinson s disease

Described by James Parkinson (1817) in 'An essay on the shaking palsy'. Recognised as an extrapyramidal disorder by Kinnier Wilson (1912). Annual incidence: 20 per 100 000. Prevalence: 190 per 100000. Sex incidence: male:female - 3:2

Age of onset: 50 years upwards. Incidence peaks in mid-70s then declines. Familial incidence occurs in 5%.

AETIOLOGY

The cause of Parkinson's disease is unknown. Discordance in identical twins suggests that genetic factors are not important and environmental mechanisms appear to play a role.

Increased interest in the role of exogenous toxins has arisen through the recent observation that, in drug abusers, l-methyl-4-phenyl 1236 tetrahydropyridine (MPTP) produces parkinsonism by selectively destroying nigral cells and their striatal projections.

Observations of altered iron metabolism, increased oxidative stress, reduced glutathione and mitochrondrial complex I deficiency indicate a widespread biochemical abnormality. Features of Parkinson's disease occur in many disorders (Akinetic rigid syndromes)

- idiopathic Parkinson's disease

- secondary Parkinsonism

- drug induced e.g. haloperidol

- post encephalitic

- toxic e.g. Carbon monoxide

- toxic (endogenous) e.g. Wilson's disease

- Multiple System Atrophy (MSA)

- Progressive supranuclear palsy

- Corticobasal degeneration

- Diffuse Lewy body disease

- Alzheimer's disease

The substantia nigra contains pigmented cells (neuromelanin) which give it a characteristic 'black' appearance (macroscopic). These cells are lost in Parkinson's disease and the substantia nigra becomes pale. Remaining cells contain atypical eosinophilic inclusions in the cytoplasm - Lewy bodies - although these are not specific to Parkinson's disease. Lewy bodies may be found in the cerebral cortex especially when dementia is present (Diffuse Lewy body disease).

Minor changes are seen in other basal nuclei - striatum and globus pallidus. Radiolabelied ligand studies have identified two dopamine receptors on striatal cell membranes - D j - D5 receptors.

The D2 receptor correlates with Parkinson's disease. When blocked by phenothiazines it enhances symptoms; when activated by dopamine or dopamine agonists it reduces symptoms. 351

PATHOLOGY of idiopathic

Parkinson's disease

Superior colliculus

Red -nucleus nerve MIDBRAIN

Superior colliculus

Red -nucleus

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