Parkinson's Disease for USMLE Step 1 / COMLEX-USA Level 1

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

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.