(USMLE topics) Parkinson disease: pathology, symptoms, causes and treatments (medications and surgery).
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Parkinson's disease, or PD, is a neurodegenerative disorder in which DOPAMINE-producing neurons of a brain structure called the SUBSTANTIA NIGRA, are damaged and die over time, leading to a number of MOTOR problems and mental disabilities.
The substantia nigra is part of the basal ganglia, whose major function is to INHIBIT UNwanted motor activities. When a person intends to make a movement, this inhibition is removed by the action of dopamine. As dopaminergic neurons are progressively lost in PD patients, LOW levels of dopamine make it HARDER to INITIATE voluntary movements.
The events leading to neuronal cell death are poorly understood but the presence of so-called “Lewy bodies” in the neurons before they die may offer a clue and is currently the subject of intensive research.
Symptoms develop slowly over time; most prominent are MOTOR problems which include hand tremors, slow movements, limb rigidity and problems with gait and balance. These motor symptoms are collectively known as "PARKINSONISM". However, parkinsonism may also be caused by a variety of other factors, which must be excluded before a person can be diagnosed with PD. Other motor-related problems may include slurred speech and reduced facial expressions. In later stages, non-motor symptoms such as mood and behavioral changes, cognitive impairment and sleep disturbances… may be observed.
The cause of Parkinson's remains largely unknown but is likely to involve both genetic and environmental factors.
There is no cure for PD but current treatments are effective in managing motor symptoms:
First-line treatment involves medications which aim to INcrease dopamine levels in the brain. Major classes of medication include:
- Levodopa, a precursor of dopamine: levodopa can cross the blood brain barrier and is converted into dopamine inside the brain. Levodopa is the most effective of all medications but because it also produces dopamine elsewhere in the body, its side effects may become serious in the long-term. For this reason, levodopa is always administered together with some other drugs that inhibit its action OUTSIDE the brain.
- Dopamine agonists: substances that bind to dopamine receptors and mimic the action of dopamine.
- Another class of drugs includes INHIBITORS of enzymes that break down dopamine.
For people who do NOT respond to medications, surgery may be recommended. The most commonly performed procedure, deep brain stimulation, involves the implantation of a device called a neurostimulator, which sends electrical impulses to specific parts of the brain. By doing so, the device controls brain activities to relieve symptoms.

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