Atlas of pathophysiology, 2 Edition

Part II - Disorders

Neurologic disorders

Parkinson's disease

Parkinson's disease is a neurodegenerative disorder of the extrapyramidal system. It characteristically produces progressive muscle rigidity, akinesia, and involuntary tremor. Death may result from complications, such as aspiration pneumonia or other infection.

Age Alert

Parkinson's disease is one of the most common crippling diseases in the United States. It strikes 1 in every 100 people over age 60 and affects men more often than women.

Causes

Exact cause unknown

Possible contributing factors

·   Advanced age

·   Genetics

·   Environment (rural residence with exposure to well water, herbicides, and pesticides)

·   Industrial chemicals (such metals as manganese, iron, and steel alloys)

Pathophysiology

Parkinson's disease is a degenerative process involving the dopaminergic neurons in the substantia nigra (the area of the basal ganglia that produces and stores the neurotransmitter dopamine). This area plays an important role in the extrapyramidal system, which controls posture and coordination of voluntary motor movements.

Normally, stimulation of the basal ganglia results in refined motor movement because acetylcholine (excitatory) and dopamine (inhibitory) release is balanced. Degeneration of the dopaminergic neurons and loss of available dopamine lead to an excess of excitatory acetylcholine at the synapse and consequent rigidity, tremors, and bradykinesia. Other nondopaminergic neurons may be affected, possibly contributing to depression and the other nonmotor symptoms associated with this disease. Also, the basal ganglia are interconnected to the hypothalamus, potentially affecting autonomic and endocrine function as well.

Current research on the pathogenesis of Parkinson's disease focuses on damage to the substantia nigra from oxidative stress. Oxidative stress is believed to diminish brain iron content, impair mitochondrial function, inhibit antioxidant and protective systems, reduce glutathione secretion, and damage lipids, proteins, and deoxyribonucleic acid. Brain cells are less capable of repairing oxidative damage than are other tissues.

Signs and symptoms

·   Muscle rigidity, akinesia, and an insidious tremor beginning in the fingers (unilateral pill-roll tremor) that increases during stress or anxiety and decreases with purposeful movement and sleep

·   Resistance to passive muscle stretching, which may be uniform (lead-pipe rigidity) or jerky (cogwheel rigidity)

·   Akinesia causing difficulty walking (gait lacks normal parallel motion and may be retropulsive or propulsive)

·   Loss of posture control

·   Drooling and excessive sweating

·   Masklike facial expression

·   Dysarthria, dysphagia, or both

·   Oculogyric crises or blepharospasm

·   Decreased motility of GI and genitourinary smooth muscle

·   Orthostatic hypotension

·   Oily skin

Diagnostic test results

Generally, diagnostic tests are of little value in identifying Parkinson's disease. Diagnosis is based on the patient's age and history and on the characteristic clinical picture. However, urinalysis may support the diagnosis by revealing decreased dopamine levels.

A conclusive diagnosis is possible only after ruling out other causes of tremor, involutional depression, cerebral arteriosclerosis, intracranial tumors, Wilson's disease, or phenothiazine or other drug toxicity.

Treatment

·   Levodopa, a dopamine replacement most effective during early stages and given in increasing doses until symptoms are relieved or adverse effects appear

·   Drugs that enhance the therapeutic effect of levodopa—anticholinergics such as trihexyphenidyl; antihistamines such as diphenhydramine; amantidine, an antiviral agent; selegiline, an enzyme-inhibiting agent

·   Stereotactic neurosurgery

·   Physical therapy, including active and passive range-of-motion exercises, routine daily activities, walking, baths, and massage

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NEUROTRANSMITTER ACTION IN PARKINSON'S DISEASE

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