Note On Pathophysiology

Parkinson's disease9 affects about 1 in 200 of the elderly population. In broad terms, it is caused by degeneration of the substantia nigra10 in the midbrain, and consequent loss of dopamine-containing neurons in the nigrostriatal pathway (see Fig. 19.3, p. 382). There is no known cure but drug treatment can, if properly managed, dramatically improve quality of life in this progressive disease.

Two balanced systems are important in the extrapyramidal control of motor activity at the level of the corpus striatum and substantia nigra: in one the neurotransmitter is acetylcholine; in the other it is a dopamine. In Parkinson's disease there is degenerative loss of nigrostriatal dopaminergic neurons and the symptoms and signs of the disease are due to dopamine depletion.

Certain drugs also produce the features of Parkinson's disease (see below) and the general term 'parkinsonism' is used to cover both the disease and the drug-induced states. The symptom triad of the disease is bradykinesia, rigidity and tremor. Patients who have received levodopa for a long time may exhibit the 'on-off' phenomenon in which, abruptly and distressingly, dyskinesia (the 'on' phase) alternates with hypokinesia (the 'off' phase). One sufferer, a physician, wrote about his condition:

9 James Parkinson (1755-1824), physician; he described paralysis agitans in 1817.

10 Substantia nigra is (Latin) black substance. A coronal section at this point in the brain shows the distinctive black areas, visible with the naked eye in the normal brain, but absent from the brains of patients with Parkinson's disease.

'One of its most trying aspects is the extent to which it interferes with the trivial events in daily life. Nothing is easy in Parkinson's disease. There is no feature of any task that is not potentially out of control. A cuff-link refuses to find its way into a tuxedo shirt, my wife is out of town, and I miss the annual dinner. I am unable to stuff change from a $5 bill into my wallet, and the patrons in line behind the cash register fume. Bow ties won't tie and shoelaces won't lace. A cube of beef obstructs the glottis. In Parkinson's disease one must expect the unexpected ... About five years ago, my disease began to close in on me, becoming more aggressive and difficult to handle. I had increasing discomfort from hyperkinesias. My voice was almost inaudible, and periods when my feet felt frozen to the floor became commonplace. I lost the advantage I had previously enjoyed of a comfortable margin between the effective dose and the dose with intolerable side effects. I had an "off" spell... in a telephone booth.. ,'n

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