From The Times
February 28, 2008

Parkinson's disease: when fatigue rings alarm bells

Classic signs of Parkinson's are often preceded by less obvious symptoms such as daytime sleepiness

Dr Thomas Stuttaford

Until Brussels became famous for its diminutive Mannequin Pis fountain and as the fount of the laws that flow as continuously as the small boy's urine, the city made little impact on most Britons.

As tourists we admired its main square, enjoyed eating chips and mayonnaise, chanced the moules and drank the beer. Now Brussels is at the centre of Europe. Not only does it house the headquarters of the EU; it also provides a home for many other European organisations including the European Brain Council, the EBC.

This week the EBC has been discussing the impact of Parkinson's disease on health services within the European community as well as on patients and families. The extent to which the subtleties of the treatment of Parkinson's disease were understood by the medical profession, patients, media and public was also discussed. The greater the knowledge of the effects of Parkinson's symptoms, the more likely they will be relieved. Patients need access to specialised nursing and medical services as well as a source of information such as the Parkinson's Disease Society and its European equivalent. Both can also keep the medical and nursing profession aware of the latest advances in the treatment of the disease, such as deep brain stimulation, stem cell therapy and advances in medication.

Increasingly, research reveals that the classic signs and symptoms of tremor (shake), muscle rigidity, slowness of movement, fixed expression and characteristic gait are preceded by less obvious troubles. Insomnia and other disturbances of sleep patterns, especially excessive daytime sleepiness, often precede the muscle and movement symptoms by several years. Inexplicable depression is often an early sign, long before there are muscular problems. A slight tremor, usually initially only on one side, is frequently preceded by a loss of a sense of smell, so that a patient's palate no longer enables them to select the best wine. The combination of inexplic- able insomnia, excessive daytime sleepiness and depression is a frequent warning of trouble ahead.

Similarly, constipation - the last Pope suffered it so severely that he had exploratory surgery before he was crippled by Parkinson's - and an unreliable bladder (often associated with declining sexual ability) may precede classic symptoms of Parkinson's.

Research in the past 40 years has revolutionised the treatment of Parkinson's. Once the importance of the lack of dopamine, a chemical found in the brain, in causing symptoms of Parkinson's was understood, and from the 1960s means of substitution were introduced, patients were able to continue a normal life for years. However, no effective treatment is ever without side-effects. Unfortunately dopamine is not only essential for neuromuscular co-ordination but has an important psychological role. It enables the brain to react to potentially pleasurable stimulation. The restoration of a patient's dopamine state by taking dopamine agonists doesn't only ease the tremor, lighten the blank stare and improve movement but, for one in ten people with Parkinson's disease, it may induce or resurrect an enthusiasm for gambling. The influence of increased dopamine isn't confined to neuromuscular control but permeates those neighbouring parts of the brain that react to thrills and give someone a high.

Although it had always been realised that altering the body's dopamine levels would be as likely to have an effect on the psyche of someone with Parkinson's disease as on their neuromuscular function, the number who show an increase in gambling, sometimes excessive gambling, has been a surprise. The initial research in 1983 studied gambling in 1,281 patients treated with dopamine agonists and showed that about one in 100 became gamblers as a result. When one drug, pra- mipexole, was used, the proportion was slightly higher: 1.5 per cent.

At first it was thought that this was only likely to be a problem in the United States. Apparently gambling is unusually well catered for there, but now it is known that this side-effect is international. It doesn't influence only previous gamblers; patients who would have stuck to bridge and thought twice about buying a ticket for the Derby sweep can become addicted.

Other people liable to suffer from difficulties in controlling their impulses and a love of thrills may find that these get out of hand when taking some treatment for Parkinson's. A few women become shopaholics. There is a subgroup of these who become addicted to cruising charity shops as these provide the additional high of snapping up a bargain.

The effect of dopamine agonists on sexual drive was noticed within the first ten years of the use of levodopa. This drug was used clinically from 1960 and widely prescribed by 1967. In 1969 a study reported that although it caused a seemingly miraculous improvement in the patient's physical state, it also increased the libido in more than half the male patients treated. Unfortunately there was not much improvement in their sexual performance but fortunately only very occasionally could the patient's response be described as hypersexual, excessively and antisocially randy.