Parkinsonism and Parkinson's Disease

• 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 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.²

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.³

Prevalence

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

Risk factors

• Increasing prevalence with age, and slightly commoner 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

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.
Main features are resting tremor, rigidity and bradykinesia. There are also impaired postural reflexes.⁷

• Tremor at 4-6 Hz 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. There may also be saliva drooling from the mouth, often due to impaired swallowing, and a quiet voice.

Typically, muscles are 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 a 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.

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.⁸

• Bradykinesia (slowness of initiation of voluntary movement with progressive reduction in speed and amplitude or repetitive actions)
• And at least one of the following:³
  • Muscular rigidity
  • 4-6 Hz rest tremor
  • Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction

• Multiple-system atrophy - 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, 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 Alzheimer's) and Parkinsonism is usually mild.
• Drug- or toxin-induced - numerous drugs or toxins may cause tremor, notably SSRIs, caffeine, amfetamines, 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 tumour, or multiple sclerosis.
• Pyschogenic tremor - the tremor is variable, increases under direct observation, decreases with distraction and changes with voluntary movement of contralateral limb.

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.⁹

The diagnosis is clinical and can be confirmed by a dopamine challenge.¹⁰ Other investigations are focused on excluding other causes of the presentation:¹¹

• 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 (i.e. supratentorial tumours and normal pressure hydrocephalus) and extensive subcortical vascular pathology.³Functional 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.¹²
• 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.

• Dementia (in over 20% of patients with Parkinson's disease).¹³
• Depression (50% of patients with Parkinson's disease).

See separate article Parkinson's Disease Management.

These include:

• Infections
• Aspiration pneumonia
• Bed sores
• Poor nutrition
• Falls
• Contractures
• Bowel and bladder disorders

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.¹⁴ 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.¹⁵