Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Parkinson's disease (PD) is a movement disorder characterised by:
- Tremor at rest
The diagnosis is almost entirely based on clinical examination. It is caused by degeneration of the dopaminergic pathways in the substantia nigra.
- The ventral tier of the zona compacta of the substantia nigra is particularly affected with reduction of dopamine in the striatum.
- Parkinson's disease (PD) is used to describe the idiopathic syndrome of Parkinsonism.
- Drug-induced Parkinsonism is caused by drugs that block the dopamine receptors or reduce storage of dopamine. This is mainly the major tranquilisers used to treat psychosis but the condition can also be seen with drugs used to treat nausea - eg, metoclopramide.
- Parkinsonism may also occur following encephalitis or exposure to certain toxins - eg, manganese dust, carbon disulfide, severe carbon monoxide (CO) poisoning.
A systematic review of European studies reports wide variation in incidence and prevalence, possibly due to genetic and environmental factors, but also due to differences in methodology.
The incidence of the disease rises steeply with age; from 17.4 in 100,000 person years between 50 and 59 years of age to 93.1 in 100,000 person years between 70 and 79 years.
65.6 per 100,000 to 125 per 100,000.
- Increasing prevalence with age, and slightly more common in men.
- Another recognised factor includes pesticide exposure.
- Small-scale studies have suggested that patients born in the spring have a higher incidence of PD.
Onset is insidious with peak age of onset at 55-65 years. It commonly presents with impairment of dexterity or, less commonly, with a slight dragging of one foot. A fixed facial expression is characteristic with infrequent blinking. There may also be saliva drooling from the mouth, often due to impaired swallowing, and a quiet voice.
Main features are resting tremor, rigidity and bradykinesia:
- Tremor at 4-6 Hz is seen at rest and, if not immediately apparent, may be induced by concentration - eg, asking the patient to recite months of the year backwards. It is absent during activity - eg, tipping water from cup to cup. Tremor is usually apparent in one limb or the limbs on one side for months or even years before becoming generalised.
- Rigidity presents as an increase in resistance to passive movement that can produce a characteristic flexed posture in many patients. It may be increased by asking the patient to perform an action in the opposite limb - contralateral synkinesis.
- Bradykinesia presents as a slowness of voluntary movement and reduced automatic movements. It is particularly noticeable in a reduced arm swing whilst walking. It can also be seen as a progressive reduction in the amplitude of repetitive movements - eg, asking the patient to repeatedly oppose middle finger and thumb. Patients may still retain the ability to move quickly in an emergency situation.
Typically, muscles are of normal strength if given time to develop power. There is no alteration in tendon reflexes or plantar responses.
Gait disturbance: the patient may have difficulty in rising from a sitting position and starting to walk. Gait is characterised by small shuffling steps with unsteadiness on turning (taking several steps to turn) and difficulty in stopping ('festination'). There may be a tendency to fall.
When patients have a gait disorder without other Parkinsonian features, the most likely diagnosis is gait apraxia, which is more common and usually caused by small-vessel cerebrovascular disease.
Criteria for the diagnosis of Parkinson's disease
The National Institute for Health and Clinical Excellence (NICE) recommends using the UK Parkinson's Disease Society (PDS) Brain Bank Criteria for diagnosis:
Step 1: diagnosis of Parkinsonian syndrome
Bradykinesia (slowness of initiation of voluntary movement with progressive reduction in speed and amplitude or repetitive actions) and at least one of the following:
- Muscular rigidity.
- 4- to 6-Hz resting tremor.
- Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction.
Step 2: exclusion criteria for Parkinson's disease
- History of repeated strokes with stepwise progression of Parkinsonian features.
- History of repeated head injury.
- History of definite encephalitis.
- Oculogyric crises.
- Neuroleptic treatment at onset of symptoms.
- More than one affected relative.
- Sustained remission.
- Strictly unilateral features after three years.
- Supranuclear gaze palsy.
- Cerebellar signs.
- Early severe autonomic involvement.
- Early severe dementia with disturbances of memory, language and praxis.
- Babinski's sign.
- Presence of a cerebral tumour or communicating hydrocephalus on CT scan.
- Negative response to large doses of L-dopa (if malabsorption excluded).
- Exposure to MPTP.
Step 3: supportive prospective positive criteria of Parkinson's disease
Three or more are required for the diagnosis of definite PD:
- Unilateral onset.
- Rest tremor present.
- Progressive disorder.
- Persistent asymmetry affecting the side of onset most.
- Excellent response (70-100%) to L-dopa.
- Severe L-dopa-induced chorea.
- L-dopa response for five years or more.
- Clinical course of ten years or more.
- Visual hallucinations.
After an initial 'honeymoon period', 50-90% of people who have received L-dopa for 5-10 years may experience the following; however, they are less likely to occur in those whose symptoms begin after the age of 70 years:
- When PD patients are moving well, they say they are 'on'. When they are stiff and bradykinetic, they say they are 'off'.
- Wearing off of the treatment (before the next dose is due) may start to occur as well as 'on-off' fluctuations, which occur randomly.
- Patients may also experience involuntary movements whilst 'on'. These are dyskinesias.
- Motor fluctuations are difficult to treat and are best managed by a specialist.
Axial problems not responding to treatment
- Axial problems are balance, speech and gait disturbance which do not respond to PD medication.
- It is thought to be as a consequence of axonal degeneration outside the substantia nigra where dopamine is not the neurotransmitter.
- If a patient cannot walk or speak well, but has no limb Parkinsonism (ie is otherwise well medicated) they will not be improved by increasing their dose.
- Their treatment options include physiotherapy, occupational therapy and speech and language therapy (SALT).
Parkinson's disease dementia
This is dementia occurring more than one year after diagnosis of PD. It is similar to Alzheimer-type dementia but has three typical features:
- Presence of Parkinsonism in the limbs.
- Frequent visual hallucinations.
- Frequent fluctuations in lucidity.
Sudden deteriorations may be mistaken for intercurrent illness - eg, urinary tract infection - but the mid-stream specimen of urine is negative, and the patient becomes better.
PD dementia is difficult to treat, as confusion and hallucinations may be worsened by the treatment of PD - dopamine agonists. Atypical antipsychotics (eg, quetiapine), are effective without worsening the Parkinsonism.
- Benign essential tremor - far more common; tremor is worse on movement (eg, while trying to hold a cup of tea) and rare while at rest.
- Drug- or toxin-induced - numerous drugs or toxins may cause tremor, notably selective serotonin reuptake inhibitors (SSRIs), caffeine, amfetamines, beta-adrenergic blockers, tricyclics, and lithium. Neuroleptics (eg, haloperidol, chlorpromazine) and anti-emetics (eg, prochlorperazine) can cause Parkinsonian features which look identical to PD.
- Huntington's disease - can present earlier with rigidity instead of chorea when Parkinsonism is not expected. Normally, there is family history.
- Wilson's disease - earlier onset with characteristic Kayser-Fleischer rings and hepatitis.
- Corticobasal degeneration - manifest by obvious signs of cortical dysfunction - eg, apraxia, dementia and aphasia.
- Creutzfeldt-Jakob disease (CJD) - dementia usually apparent with myoclonic jerking, ataxia and pyramidal signs common.
- Multi-infarct dementia - this is characterised by cognitive impairment, spasticity, and extrapyramidal signs.
- Lewy body dementia - often mimics Parkinsonian features.
- Pick's disease - affects the frontal and/or temporal lobes. Level of consciousness is not affected (unlike in Alzheimer's disease) and Parkinsonism is usually mild.
- Cerebellar tremor - this presents as a unilateral or bilateral, low-frequency intention tremor. It may be caused by stroke, brainstem tumour, or multiple sclerosis.
- Pyschogenic tremor - the tremor is variable, increases under direct observation, decreases with distraction and changes with voluntary movement of the contralateral limb.
The 'atypical Parkinsonism syndromes' are a group which look like PD but are much more severe. Median survival is only seven years compared with the normal lifespan in PD. They include:
- Multiple system atrophy - may also present with Parkinsonian symptoms, often with a poor or temporary response to levodopa therapy. See separate Multiple System Atrophy article.
- Progressive supranuclear palsy - characterised by paresis of conjugate gaze with initially problems looking up and down on request, advancing to difficulty in following objects up and down.
Refer people with suspected PD quickly (and untreated) to a specialist (with expertise in the differential diagnosis of this condition) for diagnosis.
NICE states that people with suspected mild PD should be seen within six weeks, but new referrals in later disease with more complex problems require an appointment within two weeks.
The diagnosis is clinical. Other investigations focus on excluding other causes of the presentation:
- CT or MRI brain scan:
- For patients who fail to respond to therapeutic doses of L-dopa (at least 600 mg/day) administered for 12 weeks.
- MRI scanning is needed to exclude rare secondary causes (eg, supratentorial tumours and normal pressure hydrocephalus) and extensive subcortical vascular pathology.
- Functional MRI and CT imaging are useful research tools. Blood flow changes monitored by these methods and correlated with functional disability are providing useful clues as to the structural abnormalities which cause Parkinsonism and PD.
- Transcranial sonography has been recommended for the differentiation of PD from atypical and secondary Parkinsonian disorders, for the early diagnosis of PD and for the detection of subjects at risk for PD. However, the technique is not universally available and requires some expertise.
- Positron emission tomography (PET) scanning with fluorodopa can localise dopamine deficiency in the basal ganglia, while autonomic tests and sphincter electromyography may support a diagnosis of multiple system atrophy.
- Genetic testing may be required - eg, Huntington's gene. Fewer than 5% of all PD cases are caused by known single-gene mutations.
- Olfactory testing to help differentiate PD from other Parkinsonian disorders.
- Further investigations for young-onset or atypical disease may include measurement of ceruloplasmin levels (Wilson's disease) and syphilis serology.
- Dementia: the prevalence of dementia in PD ranges from 20-40%, with a 2- to 6-fold increased risk compared with control populations.
- Depression: occurs in approximately 45% of all patients with Parkinson's disease, does not correlate with the stage of motor deficits and reduces the quality of life independently of motor symptoms.
See separate article Parkinson's Disease Management.
Slowly progressive with a mean duration of fifteen years. Severity, however, varies widely. It follows a relatively benign course in some patients, who may show little disability after twenty years. Others may be severely disabled after ten years. A recent study suggests, perhaps not surprisingly, that patients whose condition develops at an early age have shorter lifespans than those with later-onset disease.
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Further reading & references
- Parkinson's disease; NICE CKS, December 2014 (UK access only)
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