Free USMLE Step 1 Neurology and Behavioral Health practice questions

Recurrent stroke-like episodes with lesions that cross vascular territories, lactic acidosis, hearing loss and short stature in a young adult are classic for MELAS, most often caused by m.3243A>G in MT-TL1 (tRNA-Leu). Mitochondria, and therefore mtDNA, are inherited only from the egg. Each cell contains hundreds to thousands of mtDNA copies, and when mutant and normal genomes coexist (heteroplasmy), the mutant fraction can differ widely among siblings, between mother and child, and among tissues. Only a small number of mtDNA copies repopulate each developing oocyte (the bottleneck), and copies segregate randomly at each cell division. A tissue fails when its mutant load passes a threshold, so high-energy organs such as brain, muscle, retina and cochlea are affected first. At a low load, as in this mother, the same variant typically causes only maternally inherited diabetes and deafness.

A. Anticipation from repeat expansion explains increasing severity across generations in Huntington disease, myotonic dystrophy and fragile X, not mtDNA point variants. B. Genomic imprinting affects nuclear genes such as those at 15q11-q13 and does not apply to mtDNA. D. Skewed X-inactivation explains manifesting female carriers of X-linked disorders; mtDNA is not on the X chromosome. E. Locus heterogeneity describes different genes causing one phenotype, whereas this mother and daughter share the same variant.

Cutting an axon triggers the axonal reaction, also called central chromatolysis, in the parent cell body. The anterior horn cells whose axons run in the sciatic nerve respond by increasing protein synthesis to rebuild the axon. Within days, the soma swells and rounds, the nucleus is displaced to the periphery, the nucleolus enlarges, and the Nissl substance (rough endoplasmic reticulum and polyribosomes) breaks up and moves toward the edge of the cell, leaving a pale center on Nissl stain. The change is reversible if the axon regenerates.

Meanwhile, the part of the axon distal to the cut undergoes Wallerian degeneration: the axon and its myelin fragment and are cleared by macrophages, and Schwann cells line up to guide regrowth from the proximal stump at about 1 mm per day.

A. Shrunken, eosinophilic neurons with pyknotic nuclei (red neurons) mark irreversible hypoxic-ischemic injury 12 to 24 hours after the insult, not axotomy. B. Intracytoplasmic eosinophilic inclusions describe Lewy bodies, or Negri bodies in rabies. D. Large, pale astrocytic nuclei are Alzheimer type II astrocytes of hyperammonemia. E. Microglial nodules around dying neurons (neuronophagia) are seen in viral encephalitis, such as poliomyelitis.

A broad-spectrum antiseizure drug that is renally cleared, has few drug interactions, and is favored in liver disease is levetiracetam. Its signature adverse effects are behavioral: irritability, aggression, mood lowering and depression, and rarely psychosis, along with somnolence and fatigue. Levetiracetam binds synaptic vesicle glycoprotein 2A (SV2A), a membrane protein of presynaptic vesicles that modulates vesicle exocytosis, thereby reducing synchronized neurotransmitter release during high-frequency firing. Because it is excreted unchanged, its dose is reduced in renal failure. It is also available IV and is preferred in pregnancy because of its low malformation risk.

A is wrong because irreversible GABA transaminase inhibition is the mechanism of vigabatrin, which causes visual field loss rather than mood changes. C is wrong because NMDA blockade describes felbamate, which is hepatotoxic and causes aplastic anemia, making it a poor choice in cirrhosis. D is wrong because enhancement of slow Na+ channel inactivation is the mechanism of lacosamide, a focal seizure drug whose signature effect is PR interval prolongation. E is wrong because inhibition of glucuronidation is a drug interaction property of valproate, which is hepatically metabolized and hepatotoxic.

This man has his own unacceptable impulse, the wish to be unfaithful, and he attributes it to his wife, then reacts to her as if she had it. This is projection, an immature, unconscious defense in which a person disowns a feeling or impulse by locating it in someone else ("you want to cheat, not me"). Projection protects him from the anxiety and guilt of recognizing his own wish, but it distorts reality and damages the relationship, producing jealousy and checking behavior. Projection is prominent in paranoid thinking and paranoid personality disorder, in which people attribute their own hostility to others and then feel persecuted.

A (displacement) moves a feeling from its true target to a safer one; he would be redirecting his own anger toward, for example, his children, rather than assigning his impulse to his wife. Projection puts your feeling into someone else, whereas displacement moves your feeling onto a new target. B (reaction formation) replaces an unacceptable impulse with its exact opposite, for example becoming excessively devoted and moralistic about fidelity; he does not reverse his impulse but assigns it to someone else. C (identification) is modeling oneself on a powerful figure, such as an abused child becoming a bully. E (undoing) is trying to cancel an unacceptable act or thought with a symbolic opposite act, for example bringing his wife flowers after each flirtatious exchange.

A round lesion in the anterior roof of the third ventricle at the foramina of Monro in a young adult with positional, paroxysmal headaches is a colloid cyst. It can act like a ball valve that intermittently blocks CSF outflow from the lateral ventricles, so ICP rises suddenly; rarely this causes sudden death. The block is a noncommunicating (obstructive) hydrocephalus, and the rule is that only the ventricles upstream of the block enlarge. CSF made by the choroid plexus of the lateral ventricles cannot pass through the interventricular foramina, so both lateral ventricles dilate while the third and fourth ventricles stay normal or small.

A. Enlargement of all four ventricles indicates a communicating hydrocephalus from impaired resorption at the arachnoid granulations (after subarachnoid hemorrhage or meningitis, and in normal pressure hydrocephalus), or an obstruction at the fourth ventricular outlets. C. Lateral and third ventricular enlargement with a normal fourth ventricle is the pattern of aqueductal stenosis. D. Isolated enlargement of the fourth ventricle can occur with a trapped fourth ventricle, but it does not result from a block at the foramina of Monro. E. Enlarged ventricles with widened sulci describe hydrocephalus ex vacuo from brain atrophy, as in Alzheimer disease; pressure is normal and it is not true hydrocephalus.

A constipated, floppy infant with bilateral ptosis, bulbar weakness, and hyporeflexia after honey exposure has infant botulism. Unlike adults, who ingest preformed toxin in home-canned food, infants swallow Clostridium botulinum spores, which germinate in the immature colonic flora and produce toxin in situ. Botulinum toxin is a zinc-dependent protease that enters the presynaptic motor nerve terminal and cleaves SNARE proteins such as SNAP-25 and syntaxin, which are required for the synaptic vesicle to dock and fuse with the plasma membrane. Acetylcholine release fails, producing a symmetric descending flaccid paralysis that begins with cranial nerves (ptosis, diplopia, dysphagia, dysarthria, dysphonia) and autonomic features including constipation and dry mouth. Because the defect is presynaptic, high-frequency repetitive stimulation increases calcium accumulation in the terminal and produces facilitation, the incremental response described. Treatment is botulism immune globulin; antibiotics are avoided because bacterial lysis can release more toxin.

A. Autoantibodies to the postsynaptic acetylcholine receptor cause myasthenia gravis, which shows a decremental response and fatigable ocular weakness in older patients. B. Blockade of glycine and GABA release from spinal inhibitory interneurons is the action of tetanospasmin, which produces spastic paralysis with trismus and opisthotonus, the opposite of this picture, even though both toxins cleave SNARE proteins. C. ADP ribosylation of elongation factor 2 is the mechanism of diphtheria toxin and Pseudomonas exotoxin A, which halt protein synthesis and cause pseudomembranous pharyngitis and myocarditis. D. Persistent receptor channel activation describes depolarizing neuromuscular blockade by succinylcholine, which causes fasciculations followed by paralysis under anesthesia.

Summer clustering of fever, headache, and neck stiffness in children, with a lymphocytic CSF pleocytosis, normal glucose, mildly elevated protein, negative Gram stain, complete recovery, and a nonenveloped positive-sense ssRNA virus in CSF and stool, is enteroviral aseptic meningitis, most often from echoviruses or coxsackieviruses. These are picornaviruses.

The picornavirus family splits on acid stability. Enteroviruses (polio, coxsackie A and B, echovirus, EV-D68, EV-71) have a capsid that tolerates the acidic stomach and bile, so they are swallowed, replicate in the oropharynx and gut lymphoid tissue such as Peyer patches, are shed in stool, and spread fecal-orally in summer and fall. After viremia they reach the meninges, heart, skin and mucosa, or spinal cord. Rhinovirus is acid-labile: it is destroyed in the stomach, so it stays in the upper airway and spreads by droplets and hands.

A. Picornaviruses are nonenveloped; the absence of an envelope helps them survive drying and detergents, but an envelope would make a virus more fragile in the gut, not less.

B. A segmented dsRNA genome describes rotavirus (Reoviridae), the leading cause of dehydrating diarrhea in infants.

C. Reverse transcription belongs to retroviruses and hepadnaviruses; picornaviruses copy their genome with an RNA-dependent RNA polymerase in the cytoplasm.

E. Preference for 33°C is the property that confines rhinovirus to the cooler nasal mucosa; it describes the cold virus, not the enterovirus.

Photopsia and a shower of floaters followed by a curtain-like shadow in a highly myopic patient, with a horseshoe tear and gray elevated retina, is rhegmatogenous retinal detachment. The retina develops from the two layers of the optic cup: the inner layer becomes the neurosensory retina and the outer layer becomes the retinal pigment epithelium (RPE). The potential space between them (the remnant of the optic vesicle cavity) is held closed only by RPE pumping and the interdigitation of RPE microvilli with photoreceptor outer segments. When posterior vitreous detachment pulls on an area of firm vitreoretinal adhesion, it tears the retina (flashes from mechanical stimulation, floaters from released pigment or blood). Liquefied vitreous then passes through the break into the subretinal space and lifts the neurosensory retina off the RPE. Because the photoreceptors depend on the choriocapillaris and RPE for oxygen and visual pigment recycling, detached retina stops functioning and degenerates. A superior detachment produces an inferior field defect, and repair before the macula detaches preserves central vision.

A. Separation of the RPE from Bruch membrane is a pigment epithelial detachment, seen in macular degeneration and central serous disease. B. Posterior vitreous detachment alone causes flashes and floaters but no curtain or elevated retina; here it was the trigger, not the lesion. C. Choroidal detachment follows hypotony after surgery or trauma. D. The inner retinal layers do not separate from each other in retinal detachment.

This patient took far more pyridostigmine than prescribed and now has muscarinic toxicity (diarrhea, cramps, salivation, sweating, bradycardia and miosis, the SLUDGE picture) plus nicotinic signs (fasciculations and worsening weakness). This is cholinergic crisis. Pyridostigmine inhibits acetylcholinesterase, so ACh persists in the synaptic cleft. At therapeutic doses this extra ACh outcompetes anti-AChR antibodies; in excess it keeps nicotinic receptors at the motor end plate activated, causing sustained depolarization. The surrounding voltage-gated sodium channels become inactivated and cannot reset, so new action potentials fail: a depolarizing block similar to phase I succinylcholine block, preceded by fasciculations. Distinguishing it from myasthenic crisis matters because more cholinesterase inhibitor worsens cholinergic crisis; management is airway support and withdrawal of the drug, with atropine for muscarinic effects (atropine does not reverse the nicotinic weakness).

A. Antibody-mediated receptor internalization causes myasthenic crisis, weakness from the disease itself, which would not produce miosis, drooling, diarrhea and fasciculations. B. Complement-mediated postsynaptic injury is part of myasthenia pathogenesis and is the target of eculizumab, but it does not explain the cholinergic signs. C. Antibodies to presynaptic voltage-gated calcium channels cause Lambert-Eaton syndrome, with autonomic dryness rather than excess secretions. E. Cleavage of SNARE proteins by botulinum toxin blocks ACh release, causing descending paralysis with dilated pupils and dry mouth.

The drug is temozolomide, an oral methylating agent that crosses the blood-brain barrier and is given with radiation for glioblastoma. It places methyl groups on DNA, and the key cytotoxic lesion is O6-methylguanine, which mispairs with thymine; repeated futile mismatch repair cycles then cause strand breaks and apoptosis. The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes this methyl group directly, transferring it to its own cysteine in a single-use (suicide) reaction, and so undoes the drug's damage. When the MGMT promoter is methylated, the gene is epigenetically silenced, the tumor makes little MGMT, the adducts persist, and patients survive longer with temozolomide. MGMT promoter methylation is therefore the main predictive biomarker for this drug. Thrombocytopenia is its main toxicity.

A. EGFR amplification is common in IDH wild-type glioblastoma and supports the diagnosis but does not predict temozolomide benefit. C. Glutathione conjugation is a mechanism of resistance to alkylating agents, so high glutathione S-transferase would predict a worse, not better, response. D. PTEN loss activates PI3K-AKT signaling and is another common glioblastoma alteration without predictive value for temozolomide. E. TP53 mutations occur in many gliomas and would, if anything, reduce apoptosis after DNA damage.