ABSTRACT
Introduction: Patients with Parkinson’s disease are known to develop motor complications after a few years of therapy. Motor fluctuations and dyskinesias develop with increasing severity of disease, and were formerly thought to be an inevitable consequence of the disease. Methods: Literature review of articles on the aetiopathogenesis of Parkinson’s disease, the mechanisms underlying the development of motor fluctuations and dyskinesias, and strategies for delaying the onset of dyskinesias. Result: Motor fluctuations develop with increasing severity of the disease, owing to loss of dopaminergic neurons and loss of the buffering capacity of the neurons to fluctuating dopamine levels. Dyskinesias develop as a result of pulsatile stimulation of the receptors, causing changes in plasticity, dysregulation in gene and protein expression and alterations in neuronal firing patterns. Continuous dopaminergic stimulation, through long-acting dopa agonists and frequent administration of levodopa, is known to delay the development of dyskinesias. The use of catechol-O-methyl transferase (COMT) inhibitors likewise increases the bioavailability and brings about a smooth drug profile. The use of dopa agonists is associated with sedation and confusion, particularly in the elderly. Conclusions: Initiation of therapy in Parkinson’s disease should begin with a dopa agonist agent, unless the patient is elderly or has cognitive impairment, in which case levodopa therapy should be given.
The management of idiopathic Parkinson’s disease is deceptively simple. Current practice, which consists of replacing dopamine on a twice or thrice daily regime may actually be responsible for causing the involuntary movements (dyskinesias) which were formerly thought to be inevitable in the disease and which occur in association with levodopa administration. These dyskinesias are usually choreiform, but may also be dystonic or even ballistic. This paper hopes to examine the evidence advocating continuous stimulation of the dopaminergic receptors by means of more frequent dosing of levodopa. Finally, it advises physicians to initiate therapy with a non-ergot dopa agonist in the young and mentally alert, in order to delay the development of dyskinesias. In elderly patients, treatment with levodopa 4 to 5 times a day, in order to achieve continuous dopaminergic stimulation, is recommended.
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