The Department of Neurology
Extrapyramidal conditions cause disorders of movement which can be broadly divided into two categories: ※ Those where there is diminished movement with an increase in ton----akinetic-rigid sydrome. ※ Those in which there are added movements outside voluntary control----dyskinesias.
These conditions involve lesions of the basal ganglia and their connections.
Parkinson’s disease was first described by James Parkinson in 1817, who named it the “shaking palsy”. It is the commonest of all the movement disorders. The disease is seen worldwide, with increasing incidence with age. The prevalence is 1 in 200 in those over 70 years. It is more common in men than in women.
There is progressive degeneration of cells within the pars compacta of the substantia nigra in the midbrain, with the appearance of eosinophilic inclusions (Lewy bodies). Minor changes may also be seen in other brainstem nuclei. As a result, there is a reduction in dopamine in the striatum, disrupting the normal dopamine: acetylcholine ratio.
The cause of Parkinson’s disease is unknown. Discordance in identical twins suggests that genetic factors are not paramount. However, a consistent environmental factor has not been elucidated. Increased interest in exogenous toxins as a cause arose with the finding that drug addicts taking heroin contaminated with MPTP developed a similar condition, with selective destruction of the nigral cells and their striatal connections.
A distinction must be made between “idiopathic Parkinson’s disease” and “Parkinsonism”. Parkinsonism denotes a syndrome that appears clinically similar to idiopathic Parkinson’s disease but has a different pathological or etiological basis.
Cause of parkinsonism include: ►Drugs ----especially dopamine antagonists ►Trauma ----especially repetitive head injury ►Cerebrovascular disease----especially lacunar infarcts of the basal ganglia ►Toxins such as MPTP
Clinical features of Parkinson’s disease comprise the classical triad of tremor, rigidity, and bradykinesia, in association with important changes in posture and a mask-like, expressionless face.
There is usually striking asymmetry in tremor and rigidity, such that a symmetrical onset should make one doubt a diagnosis of idiopatic Parkinson’s disease.
This is a characteristic coarse resting tremor(47HZ), which is usually decreased by action, increased with emotion, and disappears during sleep. The tremor is often “pill-rolling”, the thumb moving rhythmically backwards and forwards on the palmar surface of the fingers.
There is stiffness of the limbs which can be fell throughout the range of movement and equally in the flexors and extensors. This is termed “lead-pipe” rigidity. When combined with the tremor, there is a jerky element ,which is termed “cog-wheel” rigidity. The increase in tone can be fell most easily when the joint is moved slowly and steadily, and can be made more apparent when the patient is asked to voluntarily move the opposite limb. The rigidity is often asymmetrical and may be very markde in the trunk.
Slowing and paucity of movement also occurs. In addition to the limbs, this affects the muscles of facial expression (mask-like facies),the muscles of mastication, speech, and voluntary swallowing, and the axial muscles. There is difficulty in initiating movements and alternating movement.
The posture is characteristically stooped, with a shuffling, festinant gait with poor arm swing. Falls are common, as the normal righting reflexes are affected. The patient falls stiffly, “like a telegraph pole”.
Speech is altered, producing a monotonous, hypophonic dysarthria, due to a combination of bradykinesia, rigidity, and tremor. Power is normal, however in advanced disease, the slowness and rigidity makes testing power difficult. Sensory examination is also normal, although patients describe discomfort in legs. Handwriting reduces in size and becomes spidery. Constipation is usual and urinary difficulties are common, especially in men. Depression is common. Cognitive function is preserved in the early stages, although dementia may occur late.
The diagnosis of Parkinson’s disease is a clinical one. It must be differentiated from the other akinetic-rigid syndromes, secondary cause of parkinsonism, and diffuse multifocal brain diseases that may have some of the features of parkinsonism.
Drug treatment is aimed at restoring the dopamine acetylcholine balance caused by the dopamine deficiency and therefore either involves restoring dopamine or reducing acetylcholine.
Levodopa forms the mainstay for the treatment of most patients with Parkinson’s disease. It is given in a combined form with a peripheral decarboxylase inhibitor to provent peripheral breakdown of the drug and to reduce the perpheral side effects. Treatment is commenced gradually and increased slowly until either an adequate effect is achieved or side effect limit further increases. Levodopa improves bradykinesia and rigidity, but has a lesser effect on tremor.
The majority of patients with Parkinson’s disease initially improve with levodoap. However , with time the effect becomes diminished, the duration of action of the drug contracts, there are marked fluctuations in symptoms, and patients experience the on-off syndrome. In the latter, there are marked swings between dopa-induced dysdinesias and sever and often suden periods of immobility, which may bear no relationship to the timing of the levodopa dose. Consequently , levodopa therapy should not be started until necessary.
Dopamine agonists are analogues of dopamine and directly stimulate the dopamine receptors. The most effective antiparkinsonian dopamine agonists stimulate D2 receptors predominantly. These can be used alone, especially in younger patients(aged less than 60 years) or to delay levodopa use, or as an adjunct to levodopa.
Anticholinergic drugs include benzhexol and bentropine, which are antimuscarinic agents that penetrate the central nervous system. They are most effective in reducing tremor, though not so effective for rigidity and bradykinesia. Side effects often prevent their use, especially in the elderly.
Selegiline is an inhibitor of monoamine oxidase B, so blocking the metabolism of central dopamine. Early use can delay the need for levodopa, but there may be an increased risk of cardiovascular morbidity in advanced cases.
Surgery is not extensively carried out but dose have a place in sever cases and young patients. The techniques used include stereotactic thalamotomy for sever tremor, pallidotomy, transplantation of fetal substantia nigra, and subthalamic neurostimulators.