Parkinson syndrome

Parkinsonism (akinetic rigid syndromes)

There are many causes of Parkinsonism, including idiopathic Parkinson's disease, post-encephalitis (encephalitis lethargica) and diffuse damage to the white matter of the brain as in hydrocephalus or cerebrovascular disease. Some neurodegenerative disorders such as multiple system atrophy and progressive supranuclear palsy can produce Parkinsonism. Parkinsonian features are also seen in manganese poisoning and after repeated head injury in boxers.

Idiopathic Parkinson's disease

Epidemiology

The incidence of idiopathic Parkinson's disease is approximately 20 per 100 000 per year with a prevalence of 150 per 100 000. The prevalence increases with age. The disease usually presents between the ages of 50 and 70. Both men and women are equally affected.

Pathology

Idiopathic Parkinson's disease is associated with loss of pigmented neurones in the substantia nigra and locus caeruleus with degeneration of the dopaminergic pathway. There are also Lewy bodies (eosinophilic cytoplasmic inclusions) in other parts of the brain. It is probably the only disease that is less common in smokers but a pathological explanation for this is not yet available. Drugs that block dopaminergic receptors (antipsychotics, antiemetics) can cause a Parkinsonian syndrome.

Scope of disease

Impairment of mobility and loss of postural reflexes often lead to falls and injuries. The disease has a higher prevalence of dementia when compared to healthy control populations. The complications of treatment include postural hypotension, hallucinations and troublesome on/off phenomena including dyskinesias.

Clinical features

Patients complain of generalized slowness of movement (bradykinesia) during everyday activities and at work. In addition they may complain of stiffness (rigidity) and tremor, which is prominent at rest and may disappear with movement. The triad of bradykinesia, rigidity and tremor forms the main features of this disease. These features are usually asymmetrical but gradually progress to affect all four limbs. Additional symptoms include hypersalivation.

Drug enquiry (neuroleptic medication, antiemetics) is essential in excluding drug-induced Parkinsonism. Several risk factors for cerebrovascular disease may suggest a vascular aetiology.

On examination, patients usually have an expressionless face and soft monotonous speech. They adopt a flexed posture and have a slow and festinant gait. Initiation of walking may be difficult and there is absence of arm swinging. Examination of the limbs often reveals a resting tremor (frequency of 4-6 Hz), cogwheel rigidity on passive movement and slowness of repetitive movements.

Initial investigations

The diagnosis is clinical, and confirmation of the disease usually follows from evidence of response to treatment which distinguishes idiopathic Parkinson's disease from other Parkinsonian syndromes.

Further investigations

CT or MRI of the head

Imaging is required for patients with symptoms or signs of secondary disease. Other structural pathologies that can lead to symptoms of Parkinsonism include basal ganglia tumours, extensive ischaemic damage and hydrocephalus.

Copper studies

Wilson's disease can mimic Parkinsonism, and copper studies should be performed for young patients with Parkinsonian features.

Autonomic function tests

Autonomic function tests may help distinguish idiopathic Parkinson's disease from multiple system atrophy. The latter is characterized by additional evidence of autonomic dysfunction and symmetrical signs, often without tremor.

Apomorphine challenge

Apomorphine is the most powerful dopamine agonist but can only be administered intradermally. Its effects are almost immediate and thus it can be used as a diagnostic tool in demonstrating clinical responsiveness where idiopathic Parkinson's disease is suspected clinically. Some clinicians prefer a challenge with oral l-dopa preparations over a period of several weeks.

Medical management

Drug treatment does not alter the progression of the disease but can significantly alleviate the symptoms, particularly earlier on in the disease process.

l-DOPA and a dopa-decarboxylase inhibitor

l-dopa is a precursor of dopamine that is able to cross the blood-brain barrier. To avoid the peripheral dopaminergic adverse effects (nausea, vomiting, cardiac arrhythmias), l-dopa is administered in conjunction with a dopa-decarboxylase inhibitor (benserazide, carbidopa) that remains in the systemic circulation and does not cross the blood-brain barrier. l-dopa is the most powerful drug in the treatment of idiopathic Parkinson's disease.

Dopamine agonists

Dopamine agonists (bromocriptine, pergolide, ropinirole, pramipexole, cabergoline, apomorphine) can be used alone or in combination with l-dopa. They are less effective than l-dopa but can be used as the first line (particularly in young individuals) when treatment is clinically indicated or in combination with l-dopa in more advanced disease.

Monoamine oxidase inhibitors

Selegiline is a selective inhibitor of the enzyme monoamine oxidase B that results in an increase in cerebral dopamine. It is a useful agent in reducing dyskinesias.

Parenteral apomorphine

Parenteral apomorphine (a direct acting agonist) is useful in sparing the use of l-dopa and other dopamine agonists in dopa-induced psychosis and for advanced disease with severe fluctuations. It is intensely emetic and is therefore co-administered with an antiemetic which does not cross the blood-brain barrier (domperidone).

Anticholinergic agents
Anticholinergic drugs (trihexphenidyl) are less effective and limited by their extensive side effect profile (dry mouth, memory loss, etc.).

Surgical management

Stereotactic ablation and deep brain stimulation

Neurosurgical intervention is targeted at three sites: the thalamus, globus pallidus and subthalamic nucleus. Surgery involves either ablation or deep brain stimulation, with an aim to reduce or eliminate the abnormal output discharges from the basal ganglia to the cortex and brainstem. Therefore, surgery attempts to control the disease, and does not modify the underlying neurodegenerative process.

Surgery can be of benefit in severe disease when optimal medical therapy cannot provide acceptable disease control. Further studies are currently underway to evaluate the effects of surgical intervention.

Prognosis

Patients with idiopathic Parkinson's disease have a reduced lifespan as a result of the disease. Patients eventually become bed bound and the cause of death is usually pneumonia.

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