Master Neuroscience
for USMLE Step 1

Core Concepts

Neuroscience for USMLE Step 1 encompasses the structure (anatomy), function (physiology), and pathology of the nervous system. Key anatomical structures include the cerebral cortex (localization of function: frontal-executive, temporal-auditory/memory, parietal-somatosensory, occipital-visual), brainstem (cranial nerve nuclei, ascending/descending tracts), spinal cord (dorsal columns-proprioception/vibration/fine touch; spinothalamic tract-pain/temperature; corticospinal tract-motor), cerebellum (coordination, balance), and basal ganglia (motor control, procedural memory). Neurophysiology centers on neuronal action potentials (Na+ influx, K+ efflux), synaptic transmission (neurotransmitters like acetylcholine for neuromuscular junction/PNS, dopamine for reward/motor, serotonin for mood, NE for arousal, GABA-inhibitory, glutamate-excitatory), and glial cell functions (astrocytes-BBB, oligodendrocytes/Schwann cells-myelination, microglia-immune). Pathology involves understanding lesion localization, ischemic events (stroke types, vascular territories), neurodegenerative diseases (protein aggregates in Alzheimer's, Parkinson's, Huntington's), demyelination (MS), and neuromuscular junction disorders. Embryology includes neural tube development (anencephaly, spina bifida) and neural crest derivatives.

Clinical Presentation

• **Stroke (Ischemic/Hemorrhagic):** Sudden onset focal neurological deficits (hemiparesis, aphasia, visual field defects) depending on vascular territory.
• **Parkinson's Disease:** Bradykinesia, rigidity (cogwheel), resting tremor (pill-rolling), postural instability (TRAP).
• **Multiple Sclerosis (MS):** Relapsing-remitting course with episodic neurological deficits (optic neuritis, internuclear ophthalmoplegia, sensory changes, motor weakness, bladder dysfunction, spasticity).
• **Myasthenia Gravis:** Fluctuating, fatigable muscle weakness, worse with activity, better with rest (ptosis, diplopia, dysphagia, generalized weakness).
• **Guillain-Barré Syndrome (GBS):** Ascending flaccid paralysis following infection, often with paresthesias and absent DTRs.
• **Amyotrophic Lateral Sclerosis (ALS):** Progressive degeneration of both upper (spasticity, hyperreflexia, Babinski) and lower (atrophy, fasciculations, weakness) motor neurons, typically sparing sensation and ocular movements.
• **Seizures:** Transient, abnormal neuronal activity (tonic-clonic, absence, focal with or without impaired awareness).
• **Meningitis:** Fever, headache, nuchal rigidity (Kernig's/Brudzinski's signs).

Diagnosis (Gold Standard)

Diagnosis often relies on a comprehensive clinical history and neurological examination. For stroke, head CT (to rule out hemorrhage) followed by MRI with diffusion-weighted imaging (DWI) for ischemia. For neurodegenerative diseases like Alzheimer's, clinical criteria with MRI (atrophy) and CSF biomarkers (amyloid-beta, tau) or PET scans (amyloid) can aid. MS diagnosis involves clinical presentation, MRI of brain/spine (dissemination in space and time), and sometimes CSF (oligoclonal bands). Myasthenia Gravis is diagnosed by clinical findings, positive AChR antibodies, and EMG (decremental response to repetitive stimulation). GBS is clinical with supporting EMG/NCS findings (demyelinating neuropathy) and CSF (albuminocytologic dissociation). Meningitis is diagnosed via CSF analysis (lumbar puncture) for cell count, protein, glucose, and culture.

Management (First Line)

Acute ischemic stroke: IV thrombolysis (alteplase) within 4.5 hours or mechanical thrombectomy within 24 hours in selected patients. Parkinson's Disease: Levodopa/Carbidopa. Multiple Sclerosis: Acute relapses treated with high-dose corticosteroids; disease-modifying therapies (e.g., interferon-beta, glatiramer acetate, monoclonal antibodies) for long-term management. Myasthenia Gravis: Pyridostigmine (acetylcholinesterase inhibitor); prednisone for immunosuppression, plasma exchange or IVIG for crisis. GBS: Plasma exchange or IVIG. ALS: Riluzole (glutamate inhibitor) to slow progression; symptomatic management. Seizures: Antiepileptic drugs (e.g., phenytoin, valproate, levetiracetam) based on seizure type. Bacterial Meningitis: Empiric broad-spectrum antibiotics (e.g., ceftriaxone, vancomycin) and often dexamethasone.

Exam Red Flags