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May 2007: Managing patients with Parkinson's disease

How is Parkinson's disease diagnosed?

Can other diseases cause parkinsonian symptoms?

What treatment strategies are available?

How is Parkinson's disease diagnosed?

Can other diseases cause parkinsonian symptoms?

What treatment strategies are available?

Parkinson's disease (PD) is the second most common neurodegenerative condition after Alzheimer's disease. In the UK the disease affects at least one in 1000 of the population.1

Diagnosis and clinical features of PD

The diagnosis of PD is a clinical diagnosis. The differential diagnosis includes several similar but prognostically distinct disorders (see table 1, below). Only 59% of people diagnosed with PD in the community are correctly diagnosed. For this reason the 2006 NICE guideline on diagnosis and management of PD recommends that all patients with suspected PD should be referred quickly and untreated to a specialist with expertise in the differential diagnosis of PD, and that the diagnosis be reviewed on a regular basis within the specialist setting.2


Since the diagnosis is based on clinical examination findings no particular pre-referral ‘work-up' is necessary, although where tremor is the most prominent symptom exclusion of underlying thyroid disease can be helpful.

Motor features

The core clinical features on which the diagnosis of PD is based are extrapyramidal motor features; these are defined by the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria (see table 2, attached). Paucity and slowness of movement (akinesia and bradykinesia) must be present in order to make the diagnosis. This can be tested by observing the patient perform rapid but repetitive movements with the hands, such as clenching and unclenching a fist or tapping a finger against the thumb. The patient must also have muscular rigidity, rest tremor or postural instability in order to make the diagnosis of parkinsonian syndrome.

Classic idiopathic PD is usually asymmetrical, progresses slowly and responds well (at least initially) to dopaminergic replacement. Red flags suggestive of an atypical parkinsonian syndrome are shown in box 1, below.


Distinguishing essential tremor from tremor-dominant PD can be particularly difficult. Subjects with essential tremor do not have any underlying rigidity or slowness of movement, but for those with very severe tremor assessment of bradykinesia can be difficult.

Non-motor features

Depression affects around 40–50% of people with PD and can predate the motor symptoms. Dementia develops in 48–80% of people with PD. Visual hallucinations may occur as part of the dementia, but may also be precipitated by medication used to treat the disease.

Autonomic impairment results in postural hypotension, urinary frequency and incontinence, drooling of saliva, constipation, erectile problems and abnormalities of sweating.

Sleep can be disturbed by night cramps and nocturnal akinesia. Rapid eye movement sleep behaviour disorder (RBD) can cause patients to act out their dreams, sometimes violently. Restless leg syndrome (RLS) is also common.

Investigation of PD

A radiolabelled tracer that binds to presynaptic dopamine re-uptake receptors (123I-FP-CIT) can be used with single photon emission computed tomography (SPECT) scanning to produce images of the basal ganglia. In normal subjects the caudate and putamen are seen as two comma-shaped highlighted images, whereas in PD loss of the presynaptic projections to the basal ganglia result in a characteristic ‘full stop' appearance on the scan.

123I-FP-CIT can be useful for distinguishing tremor-dominant PD from essential tremor, and idiopathic from drug-induced parkinsonism.

123I-FP-CIT cannot, with high accuracy, differentiate PD from other parkinsonian syndromes. Currently, 123I-FP-CIT is confined to larger hospitals, as the radioisotope used is expensive (£500 per scan) and the scan needs interpretation by a specialist.

Treatment options

Management of early PD

Levodopa: Levodopa is the treatment of choice for patients over the age of 75, or for younger patients with evidence of neuropsychiatric involvement (cognitive impairment or hallucinations). A starting regimen of 62.5mg standard-release co-careldopa or co-beneldopa is appropriate and can be up-titrated after four to six weeks if required. Slow-release preparations can be useful to cover the night-time hours, but have reduced and more unpredictable bioavailability than standard-release preparations and so are not the treatment of choice for daytime symptoms.

Dopamine agonists: Dopamine receptor agonists mimic the effect of dopamine by binding to post-synaptic dopamine receptors and are effective at controlling symptoms in early PD.

Dopamine agonists are suitable first-line therapy for younger patients (<70 years) without neuropsychiatric symptoms, because treatment with these agents delays the onset of motor fluctuations usually associated with long-term levodopa therapy.3,4

Dopamine agonists may also be useful as incremental treatment for patients whose PD is inadequately relieved by levodopa alone. These agents are available in tablet form and also in the form of a skin patch (rotigotine).

Nausea, anorexia, vomiting and dizziness are early side-effects of dopamine agonist treatment, but tolerance usually develops over a four to six-week period without the need to stop treatment. Daytime somnolence can be a problem. As some patients experience sudden onset ‘sleep attacks', drivers with PD are warned to refrain from driving during dose escalation. Dopamine agonists can also precipitate confusion and visual hallucinations.

Ergot-derived dopamine agonists (bromocriptine, cabergoline, lisuride and pergolide) can cause serosal reactions such as pleural, pericardial and peritoneal effusions and retroperitoneal fibrosis. These agents have also been associated with cardiac valvulopathy.5 Non-ergot dopamine agonists (pramipexole and ropinirole) do not appear to be associated with this risk.

MAO-B inhibitors: The MAO-B inhibitors selegiline and rasagiline block the metabolism of dopamine, thereby increasing its level in the striatum.

These agents are effective for reducing motor symptoms in PD, but less effective than levodopa or dopamine agonists, and can delay the need for treatment with levodopa.

In practice MAO-B inhibitors are used as first-line therapy in young patients with PD who cannot tolerate dopamine agonists but who wish to delay treatment with levodopa, and as ‘add-on' therapy in subjects already taking levodopa who are experiencing motor fluctuations.

Neuropsychiatric side-effects can occur and are often attributed to the amphetamine-like byproducts of selegiline metabolism. It is not yet clear whether lack of amphetamine metabolites with rasagiline confers any clinical benefit over selegiline.

Serious drug interactions can occur with MAO-B inhibitors. The interaction of MAO-B inhibitors with antidepressants (tricyclics and SSRIs) is particularly important as this can result in a fatal serotonin syndrome.

Management of non-motor complications of PD


SSRIs are the treatment of choice for depression in PD. MAO-B inhibitors should be stopped for at least two weeks before an SSRI is prescribed. Tricylic antidepressants should be avoided if possible as the anticholinergic effects can exacerbate neuropsychiatric symptoms.

Confusion, hallucinations and dementia

Simplification of the drug regimen and exclusion of other organic causes, such as infection or electrolyte imbalance, is the starting point when patients develop confusion and hallucinations.

Dopamine agonists and anticholinergic medication should be reduced or withdrawn if required. It may be necessary to up-titrate levodopa in this situation, and ideally these complex alterations in medication should be overseen by a specialist clinic.

The acetylcholinesterase inhibitor rivastigmine is licensed for the treatment of dementia in PD, treatment must be initiated and monitored by a specialist (old age psychiatrist, neurologist or elderly care physician). When behavioural disturbance accompanies cognitive decline an atypical antipsychotic such as quetiapine may be required.

Management of later stages of PD motor complications

The motor complications of the later stages of PD – ‘on/off' phenomena, freezing and dyskinesias – appear to result from the fluctuation of dopamine levels in the brain. Treatment of motor complications is therefore focused on ‘smoothing out' the pharmacokinetic profile of dopamine replacement. This can be achieved in a number of ways.

Fragmentation of existing drug regimen: Splitting levodopa into smaller doses with more frequent drug administration can be helpful in reducing off times while not exacerbating peak dose dyskinesias.

Catechol-O-methyltransferase inhibition: Catechol-O-methyl transferase (COMT) inhibitors (entacapone or tolcapone) inhibit the peripheral metabolism of dopamine, leading to a 30–50% increase in levodopa half-life. COMT inhibitors reduce off time and improve on time, motor impairments and disability.6

Tolcapone can cause fatal hepatic toxicity. Its European licence was withdrawn in 1998, but it has recently been reintroduced as a second-line agent for people who do not tolerate entacapone. Fortnightly liver function tests are mandatory for the first year of treatment with tolcapone.

Amantadine: Several small trials have shown that amantadine (100–400mg/day) may be helpful in reducing dyskinesias in the later stages of PD. Side-effects of amantadine include confusion, worsening of hallucinations, palpitations, dry mouth and constipation.

Apomorphine: Apomorphine is a dopamine agonist that is not effective orally owing to extensive first-pass metabolism in the liver. It can be given by subcutaneous injection, either as intermittent injections as ‘rescue therapy' for patients with unpredictable off periods, or as a continuous daytime subcutaneous infusion.

To be suitable for apomorphine treatment, patients must ideally be cognitively unimpaired and without visual hallucinations. Ideally the patient should have a carer who can assist with setting up the pump on a daily basis. Support from a PD nurse specialist is also important.

Local injection site reactions with the formation of subcutaneous nodules can lead to cessation of apomorphine treatment. Neuropsychiatric problems may be exacerbated by apomorphine. Systemic side-effects such as nausea and vomiting can be managed with domperidone.

Apomorphine is an expensive treatment, costing around £500–1,000 per month, but can allow selected patients to maintain their independence and avoid admission to a nursing home.

Co-careldopa: This is now available as an intestinal gel. The preparation is given continuously through an enterostomy tube into the jejunum (similar to a PEG tube but longer). This overcomes fluctuations in plasma levels of dopamine caused by unpredictable gastric emptying and high-protein meals. Treatment with this preparation can be effective in reducing on/off motor symptoms, but involves an invasive procedure to site the jejunostomy tube and costs around £2,000 per month.

While there is significant experience with this product in Scandanavia, there is little experience with it in the UK at present and referral is currently on a named patient basis instituted by a PD specialist.

Surgery: Patients who develop motor complications that are refractory to the medical options outlined above may benefit from neurosurgery. These patients must be ‘young' (usually <70 years), biologically fit and must not have any evidence of active mental health problems such as dementia or depression.

Bilateral deep brain stimulation of the subthalamic nuclei is the most common procedure and is effective at reducing off time, dyskinesia and levodopa dose, while improving quality of life. There is a risk of permanent neurological damage as a result of the procedure, and neuropsychiatric complications, particularly severe depression and suicide, may occur. This approach is expensive, costing around £19,500 per quality-adjusted life year.


• Parkinson's disease can be difficult to diagnose and referral to a specialist clinic is advised.

• Medication should not be commenced before specialist diagnosis as this can mask symptoms and make accurate diagnosis more difficult.

123I-FP-CIT scanning can be used to distinguish PD from essential tremor, but is unhelpful in distinguishing PD from other parkinsonian disorders.

• Treatment of PD should be tailored to the individual patient and will depend on the patient's age, disease severity and neuropsychiatric comorbidity.

Useful information

The Parkinson's Disease Society offers support, advice and information for people with Parkinson's disease, their carers, families and health professionals.
helpline: 0808 800 0303


Dr Liesl M Allcock
consultant geriatrician with an interest in Parkinson's disease, Rehabilitation and Intermediate Care Services, Newcastle General Hospital, and honorary senior lecturer, Institute for Ageing and Health, University of Newcastle upon Tyne

key points park Key points Table 2: UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria Table 2: UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria

Table 2: UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria

Figure 3: Interventions for people with PD Figure 3: Interventions for people with PD

Figure 3: Interventions for people with PD

Table 1 Parkinson's table 3 Table 3: Common causes of tremor Parkinson's disease box 1 Box 1 Parkinson's table 4 Table 4: Key points for supporting patients with Parkinson's disease Parkinson's disease Normal 123I-FP-CIT scan. The caudate and putamen appear as two comma-shaped highlighted images.

Scan courtesy of Birmingham City Hospital, Birmingham Figure 1: Normal scan 123I-FP-CIT scan in

a patient with Parkinson's disease. Loss of the presynaptic projections to the basal ganglia result in a characteristic full stop appearance.

Scan courtesy of Birmingham City Hospital, Birmingham Figure 2: Parkinson's disease scan Repetitive hand movements, such as clenching and unclenching a fist, test for akinesia and bradykinesia. These must be present to make a diagnosis of Parkinson's disease Figure 4

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