Parkinson's Disease: Definition and Epidemiology

Study Notes

Parkinson's disease (PD) is a neurodegenerative condition that involves the progressive depletion of dopaminergic neurons in the basal ganglia, particularly the substantia nigra.
PD is the most common hypokinetic movement disorder.
Prevalence: 2nd most common neurodegenerative disorder following Alzheimer's disease.
Age of onset: ∼ 60 years in sporadic cases.
PD affects about 1-2% of the population aged 60+ years, with no significant gender bias.

Parkinson's disease is primarily associated with the gradual loss of cells in the substantia nigra of the brain.
Dopamine is a chemical messenger that transmits signals between two regions of the brain to coordinate activity.
If there is a deficiency of dopamine in the striatum, the nerve cells in this region "fire" out of control, leading to the initial symptoms of Parkinson's disease.

Macroscopically: atrophy of the substantia nigra in advanced Parkinson's disease is recognizable by loss of the characteristic melanin pigmentation of this region.
Microscopically: severe neuronal loss is demonstrable in the substantia nigra, remaining neurons often containing a distinctive intracellular inclusion, the Lewy body.
Lewy bodies (hyaline inclusion bodies) are a key neuronal finding in the brains of patients with Parkinson disease.

Parkinsonism, also known as "atypical Parkinson's" or "secondary Parkinson's," refers to symptoms and signs of Parkinson disease and can result from many conditions.
Parkinsonism is a syndrome comprising bradykinesia and either resting tremor or rigidity or both.

Overview: signs of PD gradually progress over time, usually > 10 years, with motor signs being unilateral at onset and asymmetrical.
Preclinical stage: may precede the onset of motor signs, characterized by non-motor signs such as constipation, anosmia, sleep disturbance, and mood disorders.
Clinical stage: motor signs, including parkinsonism, postural instability, gait abnormality, stooped posture, masked face, micrographia, and dementia in advanced stages.
Non-motor findings: autonomic symptoms, neuropsychiatric symptoms, disordered sleep, and hyposmia/anosmia.

Parkinson disease is a clinical diagnosis, evaluated based on detailed patient history and physical examination.
A diagnosis of PD requires the presence of parkinsonism (i.e., bradykinesia and either resting tremor, rigidity, or both).
Supportive findings: olfactory loss, clear benefit from dopaminergic medication.
Imaging is not routinely required for diagnosis but can be considered under specialist guidance if the diagnosis is unclear.

No cure, goals are to delay disease progression and relieve symptoms.
Best initial treatment: carbidopa-levodopa (Sinemet), which ameliorates all symptoms of Parkinson disease.
Dopamine-receptor agonists (e.g., bromocriptine, pramipexole) may be used in early stages of the disease.
Next best treatment: selegiline, which may be neuroprotective and may decrease the need for levodopa.