Parkinson's Disease

Parkinson's disease (PD) is a movement disorder characterised by:1

The diagnosis is almost entirely based on clinical examination. It is caused by degeneration of the dopaminergic pathways in the substantia nigra.

Pathogenesis

  • The ventral tier of the zona compacta of the substantia nigra is particularly affected with reduction of dopamine in the striatum.
  • Parkinson's disease 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, e.g. metoclopramide.2
  • Parkinsonism may also occur following encephalitis or exposure to certain toxins, e.g. manganese dust, carbon disulfide, severe carbon monoxide (CO) poisoning.

Epidemiology

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.3 Unusually, it appears to be more common in affluent areas.

Incidence

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.1

Prevalence

65.6 per 100,000 to 125 per 100,000.

Risk factors

  • Increasing prevalence with age, and slightly more common in men.
  • A Canadian study has shown increased prevalence in healthcare workers, teachers and people living in close proximity to others - in crowded conditions (suggests possible viral involvement).4
  • Other recognised factors include smoking and pesticide exposure.5
  • Small-scale studies have suggested that patients born in the spring have a higher incidence of Parkinson's disease.6

Presentation

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:7

  • Tremor at 4-6 Hz is seen at rest and, if not immediately apparent, may be induced by concentration, e.g. asking the patient to recite months of the year backwards. It is absent during activity, e.g. 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, e.g. 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.

Later features

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.

Long-term problems

After an initial 'honeymoon period' 50-90% of people who have received levodopa 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:

Motor fluctuations

When Parkinson's disease (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 (i.e 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 1 year after diagnosis of PD. It is similar to Alzheimer-type dementia but has 3 typical features:

  • Presence of Parkinsonism in the limbs.
  • Frequent visual hallucinations.
  • Frequent fluctuations in lucidity.

Sudden deteriorations may be mistaken for intercurrent illness, e.g. 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, e.g.quetiapine, are effective without worsening the Parkinsonism.

Differential diagnosis

  • Benign essential tremor - far more common; tremor is worse on movement (e.g. 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, e.g.haloperidol, chlorpromazine, and anti-emetics, e.g. prochlorperazine, can cause Parkinsonian features which look identical to Parkinson's disease (PD).
  • Huntington's disease - can present earlier with rigidity instead of chorea when Parkinsonism 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, e.g. 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 extra-pyramidal 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 'Parkinson plus' disorders 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 - initially appears as Parkinsonism but has more rapid pulse and is characterised by an inability to look down voluntarily.
  • 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.

Referral

Refer people with suspected Parkinson's disease quickly (and untreated) to a specialist (with expertise in the differential diagnosis of this condition) for diagnosis.

The National Institute for Health and Clinical Excellence (NICE) states that people with suspected mild Parkinson's disease should be seen within 6 weeks, but new referrals in later disease with more complex problems require an appointment within 2 weeks.8

Investigations

The diagnosis is clinical and can be confirmed by a dopamine challenge.9 Other investigations focus on excluding other causes of the presentation:10

  • 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 (e.g. supratentorial tumours and normal pressure hydrocephalus) and extensive subcortical vascular pathology.1Functional 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 Parkinson's Disease.11
  • 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.
  • Further investigations for young-onset or atypical disease may include measurement of ceruloplasmin levels (Wilson's disease), tests for the Huntington gene and syphilis serology.

Associated diseases

  • Dementia (in over 20% of patients with Parkinson's disease).12
  • 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.13

Management

See separate article Parkinson's Disease Management.


Complications

These include:

Prognosis

Slowly progressive with a mean duration of 15 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 life spans than those with later-onset disease.14



Document references

  1. Lees AJ, Hardy J, Revesz T; Parkinson's disease. Lancet. 2009 Jun 13;373(9680):2055-66. [abstract]
  2. Drug-Induced Parkinsonism; Parkinson's Disease Society Information Sheet (Revised 2008)
  3. von Campenhausen S, Bornschein B, Wick R, et al; Prevalence and incidence of Parkinson's disease in Europe. Eur Neuropsychopharmacol. 2005 Aug;15(4):473-90. [abstract]
  4. Tsui JK, Calne DB, Wang Y, et al; Occupational risk factors in Parkinson's disease. Can J Public Health. 1999 Sep-Oct;90(5):334-7. [abstract]
  5. Elbaz A, Tranchant C; Epidemiologic studies of environmental exposures in Parkinson's disease. J Neurol Sci. 2007 Nov 15;262(1-2):37-44. Epub 2007 Jul 27. [abstract]
  6. Postuma RB, Wolfson C, Rajput A, et al; Is there seasonal variation in risk of Parkinson's disease? Mov Disord. 2007 Jun 15;22(8):1097-101. [abstract]
  7. Diagnosis and pharmacological management of Parkinson's disease, Scottish Intercollegiate Guidelines Network - SIGN (January 2010)
  8. Parkinson's disease: diagnosis and management in primary and secondary care, NICE (2006)
  9. Albanese A, Bonuccelli U, Brefel C, et al; Consensus statement on the role of acute dopaminergic challenge in Parkinson's disease. Mov Disord. 2001 Mar;16(2):197-201. [abstract]
  10. Smaga S; Tremor. Am Fam Physician. 2003 Oct 15;68(8):1545-52. [abstract]
  11. Shagam JY; Unlocking the secrets of Parkinson disease. Radiol Technol. 2008 Jan-Feb;79(3):227-39. [abstract]
  12. Conley SC, Kirchner JT; Parkinson's disease--the shaking palsy. Underlying factors, diagnostic considerations, and clinical course. Postgrad Med. 1999 Jul;106(1):39-42, 45-6, 49-50 passim. [abstract]
  13. Lemke MR; Depressive symptoms in Parkinson's disease. Eur J Neurol. 2008 Apr;15 Suppl 1:21-5. [abstract]
  14. Ishihara LS, Cheesbrough A, Brayne C, et al; Estimated life expectancy of Parkinson's patients compared with the UK population. J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):1304-9. Epub 2007 Mar 30. [abstract]

Internet and further reading

The clinicians responsible for the production of this document are:
Original Author: Dr Laurence Knott
Last Checked: 6 Apr 2011
Current Version: Dr Hayley Willacy
Document ID: 2574  Version: 25
Peer Reviewer: Dr Huw Thomas
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