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Parkinson’s Disease: Overview and Risk Factors

Parkinson’s disease (idiopathic paralysis agitans) is a progressive, degenerative disorder of the brain that is associated with a loss of dopaminergic neurons in the substantia nigra, neurodegeneration in other areas of the central nervous system (CNS), such as the locus ceruleus and the cerebral cortex, and the presence of Lewy bodies. Loss of dopamine stimulation causes an imbalance between excitation and inhibition pathways of the basal ganglia (that coordinate motor activity), resulting in impairment in the voluntary control of movement.

Hallmarks of the disease include muscular (“cogwheel”) rigidity, slowed initiation of movement (bradykinesia), and an unstable, flexed posture. Despite instability, the gait is narrow–based. A resting tremor that decreases with movement appears in about 2/3 of patients and most often manifests in a classic “pill–rolling” tremor of the thumb and forefinger. This tremor disappears with the initiation of movement, only to return with sustained postures or rest. Patients exhibit a shuffling gait and slowed movements and usually show progressive difficulties with activities of daily living (eg, eating, dressing, writing). Depression is common, and hallucinations may appear with more advanced disease, sometimes as an adverse side effect of medications used to treat the condition. Dementia occurs in about one–third of cases and often appears as Alzheimer’s disease. However, prominent hallucinations may indicate diffuse Lewy body disease. Autonomic dysfunction, including postural hypotension, is common late in the course of disease.

Most cases are idiopathic. However, there are many conditions that present as parkinsonism, most of which do not include tremor. Some of these are degenerations of the basal ganglia systems, but without dominant degeneration of substantia nigra seen in idiopathic Parkinson’s. Parkinsonism may also result from exposure to toxins (MPTP, a contaminant of poorly synthesized opioid narcotics; pesticides; manganese toxicity), head trauma, CNS infection, or postsynaptic dopamine–receptor blockers, such as antiemetics, antipsychotics, and reserpine. 

Risk Factors

Age. About 1% of Americans over age 50 are affected, and prevalence increases  with age. Typical age of onset is the late 50s, although 10% of cases present before age 40.

Genetics. Although genetics has been postulated to play a role, familial disease is rare.

 

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Parkinson’s Disease: Diagnosis and Treatment >>