Wednesday, March 18, 2009

Parkinsonism and Parkinson's Disease

Movement disorder characterised by degeneration of the dopaminergic nigrostriatal pathway in the brain. 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.1

Parkinsonism may also occur following encephalitis or exposure to certain toxins, e.g. manganese dust, carbon disulfide, severe CO poisoning.

Epidemiology2

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.

Incidence

5-346 per 100,000 per year.

Prevalence

65.6 per 100,000 to 12,500 per 100,000

Risk factors

Increasing prevalence with age and slightly commoner in men. A Canadian study has shown that increased prevalence in healthcare workers, teachers and people living in close proximity to others, crowded conditions (suggest possible viral involvement).3 Other recognised factors include smoking and pesticide exposure.4Small-scale studies have suggested that patients born in the spring have a higher incidence of Parkinson's Disease.5

Presentation6

Onset is insidious with peak age of onset at 55-65 years. Main features are resting tremor, rigidity andbradykinesia. There are also impaired postural reflexes.

  • Tremor at 4-6 cps is seen mainly at rest and is exacerbated by stress and relieved by voluntary activity. 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.
  • Bradykinesia presents as a slowness of voluntary movement and reduced automatic movements, e.g. swinging of arms while walking.

Patients may still retain the ability to move quickly in an emergency situation. A fixed facial expression is characteristic with infrequent blinking. May also be saliva drooling from the mouth often due to impaired swallowing and a quiet voice.

Typically, muscles of normal strength if given time to develop power and there is no alteration in tendon reflexes or plantar responses. Patient may have difficulty in rising from sitting position and starting to walk. Gait is characterised by small shuffling steps with unsteadiness on turning and difficulty in stopping ("festinating"). There may be a tendency to fall.

Differential diagnosis6
  • Multiple system atrophies - initially appears as parkinsonism but has more rapid pulse and is characterised by an inability to look down voluntarily.
  • Benign essential tremor - far more common, tremor is worse on movement and rare while at rest. No rigidity or bradykinesia.
  • Huntington’s disease - can present earlier with rigidity instead of chorea when parkinsonism not expected. Normally family history.
  • Wilson’s disease - earlier onset with characteristic Kayser-Fleischer rings and hepatitis.
  • 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.
  • Corticobasal degeneration - manifest by obvious signs of cortical dysfunction, e.g. apraxia, dementiaand aphasia.
  • 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.
  • Pick Disease - affects the frontal and/or temporal lobes. Level of consciousness is not affected, unlikeAlzheimer's, and Parkinsonism is usually mild.
  • Drug or toxin induced - numerous drugs or toxins may cause tremor, notably SSRIs, caffeine, amphetamines, beta-adrenergic blockers, tricyclics, and lithium.
  • Cerebellar tremor - this presents as a unilateral or bilateral, low-frequency intention tremor. It may be caused by stroke, brainstem tumor, or multiple sclerosis.
  • Pyschogenic tremor - the tremor is variable, increases under direct observation, decreases with distraction, and changes with voluntary movement of contralateral limb.
Investigations

The diagnosis is clinical and can be confirmed by a dopamine challenge.7 Other investigations are focused on excluding other causes of the presentation:8

  • CT or MRI brain scan: not usually needed for diagnosis but should be performed if parkinsonism is purely unilateral, atypical or if additional signs are present. A scan also rules out a space-occupying lesion, hydrocephalus and vascular disease.
    Functional MRI and CT imaging is a useful research tool. 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.9
  • 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 ceruloplasminlevels (Wilson's disease), tests for the Huntington gene and syphilis serology.
Associated diseases10
  • Dementia (in over 20% of patients with Parkinson's disease).
  • Depression (50% of patients with Parkinson's disease).
Management

See related 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.6 A recent study suggests, perhaps not surprisingly, that patients whose condition develops at an early age have shorter live spans than those with later-onset disease.11

Document references
  1. Drug-Induced Parkinsonism; Parkison's Disease Society Information Sheetn 2006
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Parkinson's disease, Clinical Knowledge Summaries (2007)
  7. 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]
  8. Smaga S; Tremor. Am Fam Physician. 2003 Oct 15;68(8):1545-52. [abstract]
  9. Shagam JY; Unlocking the secrets of Parkinson disease. Radiol Technol. 2008 Jan-Feb;79(3):227-39. [abstract]
  10. 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]
  11. 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
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