Neurology USMLE Practice Questions
Understand the nervous system from neuroanatomy to clinical presentations.
5 free neurology practice questions
Pick an answer and check it. After each question you get the same explanation StepGenie students see: the stem decoded clue by clue, the reasoning chain with its infographic, why every wrong option is wrong, and the trap the question was built around. Step 1 questions test mechanism; Step 2 CK questions ask for the next step.
A 27-year-old man is brought to the emergency department 40 minutes after the onset of weakness, headache, and vomiting. He is an amateur chef, and his symptoms began about 10 minutes after he ate pufferfish that he had prepared himself. On arrival, he is lethargic. Temperature is 37°C (98.6°F), pulse is 120/min, respirations are 8/min, and blood pressure is 92/64 mm Hg. He is intubated, started on mechanical ventilation, and given intravenous fluids. The toxin responsible for this patient’s condition most likely acts by which of the following mechanisms?
Correct answer · A
Decrease in cell membrane permeability to sodium ions
Decoding the stem
Step-by-step reasoning
Step 1 of 5
Pufferfish ingestion → think tetrodotoxin, a well-known marine neurotoxin from Tetraodontidae fish.
Step 2 of 5
Tetrodotoxin binds to voltage-gated Na⁺ channels on nerve and cardiac cell membranes.
Step 3 of 5
Binding blocks Na⁺ influx through these channels → functionally decreases cell membrane permeability to Na⁺ ions.
Step 4 of 5
Without Na⁺ influx, action potentials cannot be generated or propagated along nerves and muscle fibers.
Step 5 of 5
Failure of neural transmission to respiratory muscles → weakness, respiratory depression, and need for mechanical ventilation, as seen in this patient.
Why not the others?
B. Increase in cell membrane permeability to chloride ions
This option implies GABA_A or glycine-related mechanisms (e.g., sedatives), which enhance inhibitory Cl⁻ currents, BUT tetrodotoxin classically targets Na⁺ channels, not Cl⁻ conductance.
C. Decrease in cell membrane permeability to calcium ions
This suggests blockade of voltage-gated Ca²⁺ channels (e.g., some neurotoxins, calcium-channel blockers) affecting neurotransmitter release, BUT the canonical pufferfish toxin effect is on Na⁺ channels, not Ca²⁺ channels.
D. Decrease in cell membrane permeability to potassium ions
Blocking K⁺ channels would impair repolarization, potentially prolonging action potentials and causing arrhythmias, BUT tetrodotoxin causes failure to initiate action potentials via Na⁺ blockade, not altered K⁺ efflux.
E. Increase in cell membrane permeability to calcium ions
Increased Ca²⁺ permeability would enhance neurotransmitter release and contraction, which would cause hyperexcitability, BUT this patient has flaccid paralysis and respiratory depression from blocked Na⁺ channels.
Exam trap
Students may see “acute neurotoxicity after seafood” and think of saxitoxin or ciguatoxin, which can alter Na⁺ channel gating differently. For pufferfish, specifically recall tetrodotoxin, which blocks voltage-gated Na⁺ channels and thus decreases Na⁺ permeability rather than increasing it or affecting other ions.
The bottom line
Tetrodotoxin from pufferfish blocks fast voltage-gated Na⁺ channels, preventing action potential propagation and causing rapid flaccid paralysis and respiratory failure.
A 47-year-old woman presents to the emergency department with worsening back pain over the past 2 weeks that has progressed to the point that she cannot perform her usual daily activities. One month ago, she fell and injured her back while gardening; at that time, the pain improved with over-the-counter acetaminophen. Her medical history is significant for type 2 diabetes mellitus and breast cancer treated with left mastectomy 1 year ago. Current medications include metformin, sitagliptin, and a multivitamin. She appears uncomfortable. Temperature is 38.9°C (102.0°F), pulse is 101/min, and blood pressure is 110/80 mm Hg. Examination of the spine reveals thoracic vertebral tenderness. She has mild stiffness on neck flexion. Muscle strength is decreased in the lower extremities, but deep tendon reflexes are 2+ bilaterally. Sensation to pain, light touch, temperature, and proprioception is intact. Her hemoglobin concentration is 13.1 g/dL, and leukocyte count is 19,300/mm³. Which of the following is the most appropriate next step in management?
Correct answer · F
MRI of the spine
Decoding the stem
Step-by-step reasoning
- 1
This patient has red flag back pain: progressive, severe, function-limiting, with focal vertebral tenderness and systemic signs (fever, tachycardia, leukocytosis).
- 2
Her history of breast cancer makes vertebral metastases with epidural spinal cord compression a major concern; fever and leukocytosis also raise concern for spinal epidural abscess or osteomyelitis.
- 3
Neurologic exam shows new lower extremity weakness (motor deficit) despite preserved reflexes and sensation, suggesting early cord or nerve root compression.
- 4
Spinal cord compression and epidural abscess are true neurological emergencies; delays can lead to irreversible paralysis and loss of bowel/bladder function.
- 5
The best test to evaluate suspected epidural abscess or cord compression is MRI with contrast of the spine, which visualizes soft tissues, epidural space, and cord.
- 6
Therefore, the most appropriate next step is MRI of the spine to rapidly confirm diagnosis and guide urgent surgical/medical management.
Why not the others?
A. NSAIDs and bed rest
This option implies mechanical/benign back pain, which typically lacks fever, leukocytosis, focal vertebral tenderness, or neurologic deficits. BUT this patient has systemic signs and motor weakness, making simple symptomatic treatment unsafe and potentially dangerous.
B. Serum protein electrophoresis
This option implies evaluation for multiple myeloma, which causes bone pain, anemia, hypercalcemia, and lytic lesions. BUT the patient has normal hemoglobin, no hypercalcemia or renal failure described, and acute fever with leukocytosis pointing more toward infection or metastasis; urgent imaging cannot be delayed for myeloma workup.
C. X-rays of the spine
This option implies evaluation for bony abnormalities (fracture, gross metastasis), BUT plain radiographs are insensitive for early metastases, epidural abscess, and soft-tissue disease, and they do not adequately evaluate cord compression. With motor deficits and fever, higher-yield MRI is required immediately.
D. Methylprednisone therapy
This option implies empiric steroid treatment for spinal cord compression (e.g., trauma, metastasis). While steroids may be used after imaging confirms compression, starting them empirically without first obtaining MRI can mask infection (e.g., epidural abscess) and is not the most appropriate next step in undifferentiated back pain with fever.
E. Vancomycin and nafcillin therapy
This option implies empiric treatment for spinal epidural abscess/osteomyelitis, which is appropriate once diagnosis is strongly supported by imaging or blood cultures. BUT before committing to prolonged IV antibiotics and possible surgery, MRI is needed to confirm the presence, location, and extent of infection and cord compression.
Exam trap
The vignette mentions an old minor fall and prior cancer, which may tempt you to think ‘chronic back pain’ and pick NSAIDs or plain X-ray. However, the combination of fever, leukocytosis, focal vertebral tenderness, and new motor weakness are classic red flags demanding urgent MRI to evaluate for epidural abscess or metastatic cord compression.
The bottom line
Spinal epidural process (abscess or metastasis) suspected in cancer patient with fever, focal vertebral tenderness, and new weakness → urgent spine MRI.
A 3-year-old boy is brought to the emergency department with 1 day of nausea and vomiting. His mother reports that her brother had a seizure disorder and died in childhood. The child appears fatigued, and respirations are 32/min. Physical examination reveals diffuse weakness of the extremities. Serum studies demonstrate low pH, elevated lactate concentration, and normal blood glucose. A metabolic disorder due to a defect in oxidative phosphorylation is suspected. Which of the following findings is most likely to be seen on microscopic examination of this patient’s muscle biopsy?
Correct answer · E
Subsarcolemmal accumulation of mitochondria
Decoding the stem
Step-by-step reasoning
Step 1 of 6
Defect in oxidative phosphorylation implicates mitochondria, the site of the electron transport chain and ATP production.
Step 2 of 6
Mitochondrial disorders often present in childhood with neurologic (seizures) and muscle weakness, and show lactic acidosis from impaired aerobic metabolism.
Step 3 of 6
Mitochondria are inherited maternally; the history of a maternal relative (mother’s brother) affected in childhood supports mitochondrial disease.
Step 4 of 6
In mitochondrial myopathies, muscle fibers compensate by proliferating mitochondria, especially under the sarcolemma (muscle cell membrane).
Step 5 of 6
These subsarcolemmal mitochondrial accumulations create ragged-red fibers on biopsy (Gomori trichrome stain), described histologically as subsarcoplasmic accumulation of mitochondria.
Step 6 of 6
Therefore, the most likely biopsy finding is subsarcolemmal accumulation of mitochondria.
Why not the others?
A. Fibrofatty replacement of normal muscle fibers
This option implies Duchenne muscular dystrophy, which causes progressive proximal weakness and pseudohypertrophy, BUT it is an X-linked dystrophin defect, not a mitochondrial oxidative phosphorylation disorder with lactic acidosis.
B. Muscle atrophy with perimysial inflammation
This option implies dermatomyositis, which shows perimysial inflammation and skin findings (heliotrope rash, Gottron papules), BUT the vignette lacks skin changes and autoimmune context, and instead highlights lactic acidosis and maternal inheritance pattern.
C. Intermyofibrillar accumulation of glycogen
This option implies a glycogen storage myopathy (e.g., McArdle disease), which causes exercise intolerance and myoglobinuria, BUT this patient has a known oxidative phosphorylation defect and lactic acidosis with normal glucose, not a primary glycogen accumulation disorder.
D. Endomysial inflammation with T cell infiltration
This option implies polymyositis, an autoimmune inflammatory myopathy seen in adults with elevated CK and proximal weakness, BUT the patient is a young child with lactic acidosis and a suspected mitochondrial defect, not an autoimmune T cell–mediated myositis.
Exam trap
Students may look for classic inflammatory myopathy or dystrophy patterns and ignore the key phrase defect in oxidative phosphorylation, which should immediately steer to mitochondrial myopathy with ragged-red fibers (subsarcoplasmic/ subsarcolemmal mitochondrial accumulation).
The bottom line
Mitochondrial myopathy (oxidative phosphorylation defect) shows ragged-red fibers from subsarcolemmal mitochondrial accumulation on muscle biopsy.
A 49-year-old man comes to the clinic with an 8-month history of progressive voice changes and difficulty swallowing. His dysphagia initially occurred with dry foods such as crackers but has progressed to include liquids such as smoothies and ice cream. He works as a newspaper editor and reports increasing difficulty writing with his dominant hand. His wife says that he snores and drools in his sleep. Medical history is notable for hypertension and a bicuspid aortic valve, for which he takes hydrochlorothiazide. On examination, there is atrophy of the right hand. His speech is slow. Cardiac auscultation reveals a systolic murmur at the right upper sternal border. Neurologic examination shows a brisk left patellar reflex, and stroking the lateral plantar surface of the left foot elicits extension of the toes. Which of the following therapies is most likely to slow progression of this patient’s symptoms?
Correct answer · E
Riluzole
Decoding the stem
Step-by-step reasoning
- 1
This patient has slowly progressive bulbar symptoms (dysarthria, dysphagia) plus limb weakness interfering with fine motor tasks (writing).
- 2
Exam shows LMN signs (hand atrophy) along with UMN signs (brisk reflexes, Babinski) in the absence of sensory deficits.
- 3
A mixed UMN + LMN motor syndrome with bulbar involvement and preserved sensation is characteristic of amyotrophic lateral sclerosis (ALS).
- 4
ALS pathophysiology involves degeneration of motor neurons and glutamate-mediated excitotoxicity in the corticospinal and anterior horn cells.
- 5
Riluzole inhibits glutamate release and/or its excitotoxic effects, modestly prolonging survival and slowing progression in ALS patients.
- 6
Therefore, the therapy most likely to slow progression of this patient’s symptoms is riluzole.
Why not the others?
A. Amantadine
This option implies therapy for Parkinson disease (increases dopamine, decreases reuptake, and has NMDA antagonism), which causes resting tremor, rigidity, and bradykinesia, BUT this patient has mixed UMN and LMN signs and bulbar symptoms without parkinsonian features.
B. Beta interferon
This option implies multiple sclerosis treatment (immune modulation for demyelinating disease) which presents with optic neuritis, internuclear ophthalmoplegia, and sensory deficits, BUT this patient’s presentation is purely motor (UMN + LMN) without sensory or classic MS visual/ocular signs.
C. Donepezil
This option implies Alzheimer disease management (acetylcholinesterase inhibition) which causes progressive memory loss and cognitive decline, BUT this patient’s main problems are motor (bulbar and limb) with no cognitive impairment described.
D. Reserpine
This option implies depletion of monoamines (historical antihypertensive, can treat hyperkinetic movement disorders), which might affect mood or cause parkinsonism, BUT it does not target motor neuron degeneration and would not slow ALS progression.
Exam trap
Bulbar symptoms and hand atrophy might make students think of stroke or peripheral neuropathy; the key is recognizing combined UMN + LMN findings without sensory loss as ALS, then recalling riluzole as the specific disease-modifying therapy.
The bottom line
Amyotrophic lateral sclerosis (ALS) causes mixed UMN/LMN signs and bulbar symptoms; riluzole reduces glutamate-mediated toxicity and modestly slows disease progression.
A 2-month-old boy is brought to the emergency department by his mother due to 3 hours of progressive lethargy. He had been behaving normally earlier in the day while under the care of a new nanny. On returning home this afternoon, the mother noticed that he was unusually sleepy and refused to breastfeed. The pregnancy and delivery were uncomplicated. At birth, the Apgar scores were 8 and 9, and birth weight was 2.8 kg (6.1 lb). Since then, his growth has tracked at the 90th percentile, and he has met all developmental milestones. Immunizations are up-to-date, and there is no significant past medical history. On examination, the infant is difficult to arouse. Ophthalmologic evaluation reveals multiple retinal hemorrhages. Which of the following findings would most likely be seen on a noncontrast CT scan of the head?
Correct answer · A
Crescent-shaped hematoma
Decoding the stem
Step-by-step reasoning
Step 1 of 5
A previously healthy 2-month-old with sudden neurologic decline after being with a caregiver raises concern for nonaccidental trauma (shaken baby syndrome).
Step 2 of 5
Shaken baby syndrome results from acceleration–deceleration forces that tear bridging veins between the brain and dura.
Step 3 of 5
Tearing of bridging veins classically causes a subdural hematoma rather than epidural or subarachnoid hemorrhage.
Step 4 of 5
Subdural hematomas collect between dura and arachnoid and spread over the hemisphere, producing a crescent-shaped hyperdensity on noncontrast CT.
Step 5 of 5
Retinal hemorrhages plus lethargy in an infant strongly support abusive head trauma with subdural hematoma, matching a crescent-shaped hematoma on CT.
Why not the others?
B. Lens-shaped hematoma
This option implies an epidural hematoma from middle meningeal artery rupture after a skull fracture, BUT there is no trauma history (fall/blow) or lucid interval; the pattern here (retinal hemorrhages in an infant) fits subdural, not epidural.
C. Blood in the basal cisterns
This option implies subarachnoid hemorrhage, typically from a ruptured berry aneurysm or trauma, causing sudden thunderclap headache, BUT the infant cannot describe headache and has classic retinal hemorrhages and suspected shaking, which point to subdural bleeding instead.
D. Cortical atrophy
This option implies chronic neurodegeneration (e.g., Alzheimer disease, chronic trauma), which develops over years, BUT this infant had normal development and an acute 3-hour decline, making atrophy inconsistent with the timeline.
E. Multiple cortical and subcortical infarcts
This option implies multifocal ischemic strokes from embolic or vasculitic disease, BUT the stem lacks signs of vascular risk, seizures, or focal deficits; the key findings (retinal hemorrhages in a shaken infant) point to venous bleeding, not ischemic infarcts.
Exam trap
The presence of intracranial hemorrhage may tempt you to pick a familiar pattern like epidural (lens-shaped), but the infant + retinal hemorrhages + caregiver context specifically indicate subdural hematoma (crescent-shaped) from tearing of bridging veins in abusive head trauma.
The bottom line
Subdural hematoma from abusive head trauma in an infant → tearing of bridging veins → crescent-shaped hematoma on CT.
Source: StepGenie question bank. Questions are written by StepGenie, not taken from NBME or USMLE materials, and are chosen for this page by how students actually performed on them (first-attempt accuracy on StepGenie). Selection last refreshed September 5, 2026.
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In-depth coverage of neuroanatomy, neurophysiology, stroke syndromes, movement disorders, demyelinating diseases, and neuropharmacology. Our AI tutor helps you master complex neurological pathways and localize lesions accurately.
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Neurology — Frequently Asked Questions
What neurology topics are highest-yield for the USMLE?
Stroke syndromes and their vascular territories, cranial nerve lesions, spinal cord tracts and the classic cord syndromes, demyelinating disease, movement disorders, and seizure classification. Neuroanatomy is the backbone: most questions are really asking you to localise a lesion, so tract and blood supply knowledge converts directly into points.
How do you localise a lesion in a neurology vignette?
Start by separating upper from lower motor neuron findings, then ask whether deficits are unilateral or bilateral and whether they cross. Crossed findings, meaning cranial nerve signs on one side and body weakness on the other, point to the brainstem. A clear sensory level points to the spinal cord. Cortical signs like aphasia or neglect point above the brainstem.
What is the difference between upper and lower motor neuron signs?
Upper motor neuron lesions produce spasticity, hyperreflexia, an upgoing plantar response, and little muscle atrophy. Lower motor neuron lesions produce flaccid weakness, hyporeflexia, marked atrophy and fasciculations. A vignette showing both together, such as weakness with fasciculations plus a Babinski sign, is the classic pattern of amyotrophic lateral sclerosis.
Why do spinal cord questions describe deficits on opposite sides of the body?
Because the tracts cross at different levels. The dorsal columns carry vibration and proprioception up the same side and cross in the medulla, while the spinothalamic tract carries pain and temperature and crosses within a segment or two of entry. A hemisection therefore gives ipsilateral vibration and motor loss with contralateral pain and temperature loss.
Are the neurology practice questions on this page free?
Yes. The 5 questions above come from StepGenie's question bank and can be answered here without an account, with the full explanation shown after each one. From the link under the set you can try three more Neurology questions in the dashboard preview, also without an account; a free account is what lets you choose the system and keep going.