Parkinson's Disease for USMLE Step 1 / COMLEX-USA Level 1
FREE ONE-MONTH ACCESS
Institutional (.edu or .org) Email Required
Register Now!
No institutional email?
Start your 1-week free trial, now!
Basic Pathophysiology
- Neurodegeneration: Loss of dopaminergic neurons in the substantia nigra pars compacta leads to hallmark motor symptoms.
- Lewy Bodies: Presence of intracellular protein aggregates primarily composed of alpha-synuclein.
Clinical Features
- Cardinal Motor Symptoms:
- Bradykinesia: Marked slowness of movement and reduction in spontaneous motion.
- Rigidity: "Lead-pipe" or "cogwheel" rigidity affecting limbs and trunk.
- Resting Tremor: Characteristic "pill-rolling" tremor, most prominent at rest.
- Postural Instability: Impaired balance, leading to falls in later stages.
Pathogenesis
- Dopamine-Acetylcholine Imbalance: Decrease in dopamine results in unopposed acetylcholine activity in the basal ganglia.
- Genetic and Environmental Factors: Mutations in genes such as SNCA (alpha-synuclein) and exposure to environmental toxins.
Diagnostic Approach
- Clinical Diagnosis: Predominantly based on the presence of bradykinesia plus either rigidity, resting tremor, or both.
- Response to Dopaminergic Therapy: Improvement with levodopa supports the diagnosis but is not definitive.
Pharmacology
- Levodopa/Carbidopa: Enhances dopamine availability in the brain; Carbidopa prevents peripheral degradation of Levodopa.
- Dopamine Agonists: Alternative or adjunct to Levodopa in younger patients or in those experiencing Levodopa-related complications.
- MAO-B Inhibitors: Increase dopamine availability by inhibiting its breakdown.
Histology and Imaging
- Substantia Nigra: Loss of dopaminergic neurons and presence of Lewy bodies in remaining neurons.
- Imaging: Not typically used for diagnosis but can help rule out other causes of parkinsonism.
High-Yield Items for Step 1
1. Lewy Bodies: Composed of alpha-synuclein; a key histological finding in PD.
2. Pathophysiology of Motor Symptoms: Focus on the role of the basal ganglia and the effects of dopamine depletion.
3. Pharmacology of PD: Mechanisms of action and side effects of Levodopa, dopamine agonists, and MAO-B inhibitors.
4. Differential Diagnosis:
- Essential Tremor: Differentiated by its action tremor vs. the resting tremor of PD.
- Drug-Induced Parkinsonism: Caused by drugs like metoclopramide or antipsychotic medications.
- Other Parkinsonian Syndromes: Atypical features and poor response to Levodopa.