Parkinsonism and other extrapyramidal diseases

Parkinson’s disease

Parkinson’s disease affects about 0.2% of the population, including 2% of those over 80 years of age. The main pathological feature is degeneration of neuromelanin-containing neurons in the pars compacta of the substantia nigra, which leads directly and indirectly to excessive inhibition of the thalamus and consequent bradikinesia.

Clinical features—these include (1) bradykinesia—the most disabling and progressive motor symptom; (2) resting tremor (4–7 Hz)—often the presenting symptom/sign, and often unilateral; (3) rigidity—cogwheel or lead pipe; (4) postural imbalance; fixed and stooped posture; (5) gait difficulty—shuffling and small steps, with or without festination; (6) other features—hypomimia (‘masked’ face), freezing episodes (sudden failure of movement), seborrhoea of the scalp, mental/cognitive disturbance; (7) Hyposmia (impaired olfaction ).

Investigation and treatment—there are no specific tests for Parkinson’s disease and diagnosis remains clinical. However SPECT imaging with DAT Scan is a valuable adjunct to clinical suspicion of diagnosis. First-line drug treatment is with levodopa (in combination with a decarboxylase inhibitor), dopamine agonists or monoamine oxidase-B inhibitors.

Other Parkinsonian and extrapyramidal diseases

Drug-induced Parkinsonism—dopamine-blocking agents (neuroleptics) such as prochlorperazine or chlorpromazine are the most common offending agents. Vestibular sedatives (used for motion sickness) are also implicated.

Progressive supranuclear palsy—typically presents with gait disturbance and falls (backwards predominantly). Examination reveals supranuclear gaze palsy, particularly of down-gaze, with extension and rigidity of neck, a staring look due to lid retraction, and bradykinesia/akinesia.

Multiple-system atrophy—comprises a variable combination of Parkinsonism with autonomic (postural hypotension), pyramidal or cerebellar symptoms and signs. Any response to levodopa is commonly incomplete and short-lived.

Dementia with Lewy bodies—manifestations include fluctuations in cognition and attention, recurrent and persistent visual hallucinations, and Parkinsonian motor signs.

Corticobasal ganglionic degeneration—characterized by progressive gait disturbances, cortical sensory loss and stimulus-sensitive myoclonus which results in a jerky, useless hand.

Dopa-responsive dystonia—characteristically shows marked diurnal variation; may start in childhood with an odd and unusual gait; diagnosed by finding mutation in the GTP-cyclohydrolase gene; excellent and sustained response to low-dose levodopa.

Other conditions—these include Wilson’s disease, neuroacanthocytosis, vascular pseudo Parkinsonism, and neuro ferritinopathy.

Other movement disorders

Dystonia—a syndrome of sustained muscle contractions, which may be focal, multifocal or generalized genetic or idiopathic. Particular causes include (1) generalized idiopathic torsion dystonia; (2) tardive dyskinesia—induced by long-term exposure to dopamine-blocking drugs; involuntary movements usually begin with the face and mouth. See Chapter 24.7.3 for further discussion.

Chorea and related disorders—chorea is an irregular, rapid, uncontrolled, involuntary, excessive movement that seems to move randomly from one part of the body to another; athetosis is a slower writhing and twisting movement. Causes include Huntington’s disease and Sydenham’s chorea (associated with rheumatic fever). See Chapter 24.7.3 for further discussion.

Tics—these are sudden, repetitive, stereotyped, nonrhythmic, involuntary movement (motor tic) or sound (phonic tic); when treatment is required, they generally respond to drugs that decrease dopaminergic transmission.