Parkinson's disease

Parkinson's disease can be difficult to diagnose as other conditions mimic it, says Dr Louise Warburton.

Parkinson's disease results in progressive motor deterioration, with slowing of movement and a tremor. The prevalence of Parkinson's disease is around 200 to 300 per 100,000 people.

The incidence is 20 per 100,000 per year in the UK. Prevalence rises with age and is slightly more common in men.

The pathology of Parkinson's involves the selective degeneration of the dopaminergic nigrostriatal pathway. In most cases, Lewy bodies can be found in the substantia nigra.

The principal clinical features of Parkinson's disease are resting tremor, rigidity and bradykinesia.

Parkinson's disease starts several years before patients first notice symptoms. The loss of dopaminergic nigral cells is slow and some 50 per cent of the nigrostriatal pathway is lost when symptoms first become apparent.

Life expectancy is usually not affected but quality of life is affected profoundly.

The Parkinson's Disease Society has produced criteria for the diagnosis of Parkinson's. These can be applied to any patient with tremor and bradykinesia.

A parkinsonian syndrome is diagnosed with muscle rigidity, rest tremor (4-6Hz) and postural instability unrelated to primary visual, cerebellar or proprioceptive dysfunction.

A diagnosis of Parkinson's disease is unlikely if the patient has any of the following: repeated strokes with stepwise progression, repeated head injury, antipsychotic or dopamine-depleting drugs, definite encephalitis, more than one affected relative, sustained remission, negative response to levodopa if malabsorption excluded, strictly unilateral features after three years, cerebral tumour or other specific neurological signs.

Definite diagnosis of Parkinson's disease is supported by the presence of at least three of the following: unilateral onset, rest tremor present, progressive disorder, persistent asymmetry most affecting the side of onset, excellent response to levodopa, severe levodopa-induced chorea, levodopa response for over five years, and clinical course for over 10 years.

Parkinson's disease can be difficult to diagnose and many conditions mimic it; for example, other causes of tremor are essential tremor, hyperthyroidism, dystonia, cerebellar disease and drug-induced tremor from beta-agonists.

Many drugs can cause parkinsonism and distinguishing drug-induced from true parkinsonism can be difficult. The most common are antipsychotics such as haloperidol and chlorpromazine. Other drugs that block dopamine receptors can also cause parkinsonism, for example, prochlorperazine, metoclopramide, cinnarizine, amiodarone, lithium, methyldopa, tranylcypromine, SSRIs, ACE inhibitors and drugs used to treat dementia.

There is no evidence that any treatment slows down the progression of Parkinson's disease. Treatment is therefore symptomatic and aims to reduce the effects of the disease.

The standard therapy for years has been levodopa combined with a peripheral decarboxylase inhibitor, to prevent systemic side-effects.

In younger patients, the new artificial dopamine agonists give the best results. A recent study has shown advantages with ropinirole because of a substantially reduced incidence of dyskinesia.

Drugs that inhibit the enzyme catechol-O methyltransferase (COMT) are also useful in the management of Parkinson's disease because they extend the duration of action of levopdopa.

Most patients develop a fluctuating response to levodopa after three to six years. This may be a deterioration of symptoms at the end of the interval between doses or unpredictable loss of mobility (on-off reactions). COMT inhibitors smooth out wearing-off fluctuations.

The first COMT inhibitor, tolcapone helped many patients. Unfortunately it produced hepatic toxicity and has been replaced by entacapone, which is safer and has fewer side-effects.

Levodopa is prescribed in combination with a decarboxylase inhibitor that does not cross the blood-brain barrier.

The usual starting regimen for levodopa/carbidopa (co-careldopa) and levodopa/benserazide (co-beneldopa) is 50mg levodopa with 12.5mg decarboxylase inhibitor, administered twice daily, increasing at three to five day intervals to levodopa 150mg four times daily.

The main side-effects are nausea and hypotension and over a longer period, dyskinesia and fluctuations in mobility.

Sustained-release preparations have longer plasma half-lives, but higher doses have to be given to achieve the same effects as standard preparations. They are useful in patients who have wearing-off reactions.

Dopamine agonists
Ropinirole is a non-ergot dopamine agonist and is usually started in a dose of 0.25mg three times daily, and built up to 8mg daily. Ropinirole can cause nausea and hypotension.

Nausea can be reduced by giving after meals and using domperidone. Psychiatric reactions, in particular visual hallucinations, can be more common with ropinirole than levodopa. Ropinirole produces less dyskinesia than levodopa, but can cause sleepiness.

Bromocriptine was the first artificial dopamine agonist to be used for Parkinson's disease. It is an ergot derivative and can cause pulmonary fibrosis and pleural effusions. The usual starting dose is 1-1.25mg at night, increasing to 20-30mg daily.

Pergolide is another ergot derivative and is started at 0.15mg daily. Cabergoline is the newest ergot-derived dopamine agonist and is useful in that a once daily dosage can be given.

COMT inhibitors
Entacapone is a new COMT inhibitor given together with levodopa (plus a decarboxylase inhibitor) and the combination extends the half-life of levodopa. Patients with wearing-off reactions have a prolongation of the 'on' period.

Adjuvant treatments
In complicated disease adjuvant treatments such as apomorphine injections, apomorphine infusions and amantadine are used.

NICE recommends that patients with Parkinson's disease should be referred quickly and untreated to a specialist with expertise in diagnosing Parkinson's disease.

In early disease there is not usually a need to begin treatment immediately. One of the most difficult decisions is when and which drug to start with. Drug management becomes increasingly complex as the disease advances.

The average GP will only have two or three patients with Parkinson's disease, making it difficult to acquire sufficient expertise to manage the condition. The main areas of care for a GP are regular review (see box, left) and identification of complications.

Common complications include deteriorating function (for example communication difficulties); loss of drug effect, motor fluctuations and dyskinesias; depression, anxiety, hallucinations and memory changes; and constipation, incontinence, weight loss, postural hypotension and swallowing problems.

A person who has Parkinson's disease must inform the DVLA and their motor insurance company. The patient may continue to drive as long as medical assessment confirms their capabilities.

Dr Warburton is a GP in Ironbridge, Shropshire

Parkinson's Awareness Week is 7-13 April. For more information see

Quick assessment tool for Parkinson's disease
This is useful in the GP surgery when performing periodic reviews on a patient with Parkinson's disease; each of these areas must be asked about and assessed.

  • Activities of daily living: speech, salivation, swallowing, handwriting, cutting food/handling utensils, dressing, personal hygiene, turning in bed, freezing when walking, tremor, sensory complaints such as numbness, tingling and severe pain.
  • Mental activity, mood: dementia, thought disorder, depression, motivation, anxiety, fatigue and sleep disorder.
  • Motor performance: speech, facial expression, tremor at rest, action or postural tremor, rigidity, hand movements (opening and closing hands in rapid succession), rapidly alternating movements (pronating and supinating hands rapidly), leg agility, rising from chair with arms folded across chest, posture, gait, postural stability and body bradykinesia/hypokinesia.

Useful information
Parkinson's Disease Society

Helpline: (0808) 800 0303.

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