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Parkinson's disease
Written by Dr G Hotton, King's College and Lewisham Hospitals, London and Dr K Ray Chaudhuri, King's College and Lewisham Hospitals, London
What can my doctor do?
All patients should see a neurologist or a geriatrician with an interest in Parkinson's to confirm the diagnosis and discuss treatment options. Those whose care is taken on by a GP should be referred back to the specialist if their medication is not effective.
What drug treatment is available?
Parkinson's is incurable but the symptoms can be controlled for many years. Treatment is primarily based on dopamine replacement using dopamine-enhancing drugs such as levodopa. This improves disability in most patients and reduces the risk of fatal complications.
Short-term side effects are uncommon but include nausea, hallucinations, tiredness and light-headedness. Virtually all patients suffer long-term complications, with about 50 to 75 per cent on the drug for 5 to 10 years developing abnormal excessive and involuntary movements called dyskinesias. The short half-life of levodopa (1.5 hrs) is implicated in the development of disabling dyskinesias.
Dopamine agonists
The side effects of dopamine agonists are similar to levodopa although nausea and mental problems such as hallucinations usually occur more often.
Recently, clinical studies have shown that in early untreated Parkinson's, initiation of treatment with a dopamine agonists such as ropinirole, canergoline, pramipexole or pergolide reduces the chance of dyskinesias (normally caused by levodopa therapy) by about 50 per cent.
These observations suggest that there may be strong consideration for starting treatment with a dopamine agonist in younger parkinson's patients till levodopa is required. The long half-life of drugs such as cabergoline suggest that this may be an useful treatment for night-time problems faced by many patients with Parkinson's.
Apomorphine
Apomorphine is usually reserved for patients in whom oral treatment is no longer effective. A pen device is available, which allows patients to inject themselves - similar to insulin injections used by diabetics.
COMT inhibitors
Other drugs
Side effects include hallucinations, sleep disorder, agitation, postural hypotension (a drop in blood pressure on standing) and problems associated with the withdrawal of the medicine.
Amantadine
Anticholinergics
In older patients they may cause confusion and aggravate dementia. Other side effects include difficulty in passing urine, constipation, blurred vision, dry mouth and the onset of narrow angle glaucoma.
Anticholinergics are rarely used in Parkinson's treatment.
Other drugs in development
Other non-drug treatment
Subthalamic nucleus deep brain stimulation
Pallidal deep brain stimulation
The benefits of deep brain stimulation include the fact it is not necessary to make a lesion (burn a hole) in the target and stimulation can be adjusted if necessary. However, the pacemaker battery has to be replaced under anaesthetic and the procedure is extremely expensive and is only available at some regional centres in the UK.
Neurotransplantation
Transplantation therefore, holds hope for the future. Furthermore, in future transplantation may be attempted using neural stem cell or growth factors which enhance nerve cell growth. The experience from the US, however, highlights the dangers of performing clinical trails before extensive experimental studies are undertaken.
Good advice
Nutrition
Exercise
What is the likely outcome?
Patients experience involuntary movements between doses of medication, which are initially mild but may become progressively problematic. Parkinson's is a complicated disorder and modern management is essential. Patients should therefore seek referral to a specialist with an interest in Parkinson's and also contact their local or central Parkinson's Disease Society. With modern treatment, specialist centre care and support most patients have a normal life span with a reasonable quality of life.
Dopamine agonists work by directly stimulating the dopamine receptors to bypass the degenerating brain cells. These drugs include bromocriptine, lisuride, pergolide, cabergoline, ropinirole, talipexole (only available in Japan), pramipexole
and apomorphine. However, they appear less effective at controlling symptoms than levodopa, particularly in advanced Parkinson's disease. Patients are advised to take an anti-sickness tablet) for at least the first two weeks of treatment.
Apomorphine is usually administered under the skin by injection or via an infusion pump over 12, 18 or 24 hours. The main side effects are the formation of skin nodules, nausea, yawning and drowsiness.
Catechol-O-methyl-transferase (COMT) prolongs the beneficial effect of levodopa. Two COMT inhibitors exist, tolcapone and entacapone. However, tolcapone is not in use in many countries as it may rarely cause severe liver toxicity. Entacapone is usually used in the early stages of Parkinson's when the effect of levodopa starts wearing off.
Amantadine
is a mild antiviral agent and used in young patients to delay the need to use levodopa. In high doses, amantadine can act as an anti-dyskinetic drug. Amantadine can cause visual hallucinations, confusion and agitation. It should be given as a single dose in the morning to prevent sleep problems. It can cause a specific discolouration of the legs (livido reticularis).
Common anticholinergics include trihexyphenidyl, procyclidine, benzatropine and orphenadrine. Used with levodopa therapy, they can help control resting tremor and dystonia (abnormalities of posture).
Many drugs are being developed for treatment of Parkinson's disease. Some of these drugs spare dopamine and work on different brain chemicals. Examples are riluzole, adenosine antagonists, canabinoids and neuroimmunophilins. Some drugs are being developed so that they can be adminstered in the form of a skin patch.
Counselling, physiotherapy (aerobic exercise) and speech therapy can also help patients to manage their symptoms and enjoy a better quality of life. A dietitian can also advise on better nutrition to avoid constipation. Depression, sleep problems and urinary difficulties are common in Parkinson's and may need specific treatment.
This operation involves putting an electrode into a specific cluster of nerve cells in an area known as the subthalamic nucleus. The stimulation can be controlled by the patient using a switch that can turn the stimulator 'on' or 'off'. This operation is effective at controlling all the features of Parkinson's but the procedure is complex. Operation can be safely performed on both subthlamic nucleus unlike pallidotomy.
Like subthalamic nucleus deep brain stimulation, this operation involves putting an electrode into a specific (but different) cluster of nerve cells. However, its effects are closer to that of pallidotomy in that it is particularly effective for dyskinesias.
Researchers have found that tissue from a foetus can survive being transplanted into adult brain cells that have died as a result of Parkinson's disease. However, this procedure remains experimental and controversial. A recent study form the US suggested that transplanted Parkinson's patients may sometimes develop a disabling 'runaway' dyskinesias possibly due to overgrowth of grafts. However, the Swedish experience is more positive and they have shown that properly harvested and implanted grafts can survive within the brain and establish connections with surviving cells.
Patients should educate themselves about the disease. Referral to a specialist centre is important. Further information may be obtained from hospitals and support groups.
Patients should follow a high-fibre diet as constipation is a common symptom - and can be a side effect of medication. They should also wait until an hour after eating a large meal before taking a dose of medication, to improve the absorption of the medicine from the digestive system.
Gentle exercise is important in maximising a patient's general mobility. Regular physiotherapy may help patients exercise effectively as the disease advances.
Most patients eventually find their medication becomes less effective. This may occur as early as two years into treatment or not until 8 to 10 years later.
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