Parkinson's disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms of Parkinson's disease are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. Parkinson's disease usually affects people over the age of 50. Early symptoms of PD are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of Parkinson's disease patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions. There are no blood or laboratory tests available to diagnose Parkinson's disease.

At present, there is no cure for Parkinson's disease, but a variety of medications provide dramatic relief from the symptoms. Usually, patients are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain's dwindling supply. Although levodopa helps at least three-quarters of parkinsonian cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced. Problems with balance and other symptoms may not be alleviated at all. Anticholinergics may help control tremor and rigidity. Other drugs, such as bromocriptine, pergolide, pramipexole, and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms.

In some cases, surgery may be appropriate if the disease doesn't respond to drugs. A therapy called deep brain stimulation (DBS) has now been approved by the U.S. Food and Drug Administration. In DBS, electrodes are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS can reduce the need for levodopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of levodopa. It also helps to alleviate fluctuations of symptoms and to reduce tremors, slowness of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work correctly.

Levodopa
Levodopa probably remains the 'gold-standard' treatment for Parkinson's although recent evidence suggests that levodopa is responsible for many long-term side effects seen in Parkinson's. Most patients notice an improvement almost immediately although some may not for months or years.
Short-term side effects are uncommon but include nausea, hallucinations, tiredness and light-headedness. Virtually all patients suffer long-term complications, with about 50- 75 per cent on the drug for 5-10 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
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 (domperidone) for at least the first two weeks of treatment.
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 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. 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
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 including the UK as it may rarely cause severe liver toxicity. Entacapone is available in the UK and is usually used in the early stages of Parkinson's when the effect of levodopa starts wearing off.

Selegiline
A report by the Parkinson's Disease Research Group of the UK suggested a 60 per cent increase in mortality among patients treated over a long period of time with selegiline. This has not been found in other studies and a recent study from Scotland has suggested that selegiline therapy does not increase mortality in Parkinson's.
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. A buccal low strength formulation of selegiline (zydis preparation) is now available.

Amantadine
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).

Anticholinergics
Common anticholinergics include benzhexol, procyclidine, benzatropine, orphenadrine and biperiden. Used with levodopa therapy, they can help control resting tremor and dystonia (abnormalities of posture). 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.

Parkinson's disease is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. Although some people become severely disabled, others experience only minor motor disruptions. Tremor is the major symptom for some patients, while for others tremor is only a minor complaint and other symptoms are more troublesome. No one can predict which symptoms will affect an individual patient, and the intensity of the symptoms also varies from person to person.

National Institute of Neurological Disorders and Stroke (NINDS)