Introduction

The Parkinson's-Reversing Breakthrough

Cure for Parkinsons

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Idiopathic Parkinson's disease was first described by James Parkinson in 1817 as paralysis agitans, or the ''shaking palsy''. It is a relatively common neurodegenerative disease afflicting approximately 1% of all adults over the age of 65. The primary neurological features of the disease include difficulty in walking, a mask-like facial expression, and impairment of speech and of skilled acts such as writing. Without effective treatment, these symptoms progress to a rigid akinetic state in which the patients are incapable of caring for themselves and which inevitably ends in death due to complications of immobility such as pneumonia. There have been major advances in the drug therapy of parkinsonism in recent years which have markedly reduced the morbidity from this disease. A brief history of the treatment of Parkinson's disease is shown in Table 13.1.

Parkinsonism is a clinical syndrome that comprises four main features: bradykinesia (a slowness and poverty of movement), muscular rigidity (increased resistance of muscles to passive movement), resting tremor, which usually disappears during voluntary movement, and abnormalities in posture and gait.

It is now widely accepted that the term Parkinson's syndrome refers to a collection of neurodegenerative diseases, all of which are characterized by movement disorders. It also applies to drug-induced disorders of the parkinsonian type. A schematic representation of this syndrome is shown in Figure 13.1.

Most of these disorders are related to degenerative processes that are confined to the neuromelanin-pigmented nuclei of the basal ganglia (the substantia nigra), the locus coeruleus and parts of the dorsal vagal nucleus and reticular formation. While the cause of idiopathic Parkinsonism is unknown, neuroleptics, viral infections and metals such as manganese are

Fundamentals of Psychopharmacology. Third Edition. By Brian E. Leonard 2003 John Wiley & Sons, Ltd. ISBN 0 471 52178 7

FUNDAMENTALS OF PSYCHOPHARMACOLOGY Table 13.1. Treatment of Parkinson's disease

Parkinsonian syndromes described in ancient Egyptian and Indian texts in 1200 BC and 2500 BC respectively. Latter describe the beneficial effect of a herb rich in L-dopa u 1817 - John Parkinson described the essential symptoms of the disease u Later Charcot described the beneficial effects of Belladona alkaloids known to precipitate non-degenerative forms of the disorder. In addition to defects of movement, Parkinsonian patients often show symptoms such as depression and lack of concentration, an inability to associate ideas, a tendency to perseveration and a general slowness of thought which may progress to a true dementia. Abnormal endocrine function, involving for example prolactin and growth hormone secretion, has also been reported to occur in this disorder. A summary of the possible causes of Parkinson's disease is shown in Table 13.2.

Idiopathic Parkinsonism is distinguished from the other syndromes by the presence of Lewy bodies in the substantia nigra and locus coeruleus, and to a lesser extent in the substantia innominata, hypothalamus, dorsal medulla and sympathetic ganglia (Figure 13.2).

While the aetiology of idiopathic Parkinsonism is unknown, the underlying pathology is established. In 1960, Hornykiewicz demonstrated that patients with the disease showed a deficit in the concentration of dopamine in the zona compacta and substantia nigra, the reduction in the concentration of this transmitter correlating with the severity of the symptoms. Genetic factors do not appear to play an important role, although familial forms of the disease have been described. The lack of genetic factors that predispose patients to the disease has prompted research into possible environmental causes. So far no specific environmental toxins have been identified, but there has been considerable interest in the discovery that N-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP), a toxic metabolite formed during the synthesis of pethidine, can

Table 13.2. Causes of Parkinson's syndromes

• Neurodegenerative changes in basal ganglia as in Parkinson's disease, Huntington's chorea, Wilson's disease

• Toxic damage as in manganese, cyanide, carbon monoxide, ethanol, MPTP induced changes

• Infections as in Jakob-Creutzfeldt disease and HIV

• Brain trauma as in head injury

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