SMLE neurology questions

This patient presents within the 4.5-hour window with a disabling deficit (NIHSS 12), no hemorrhage on CT, normal coagulation, and no absolute contraindications, making him a candidate for IV thrombolysis. Blood pressure must be controlled to below 185/110 mmHg before and during alteplase administration to reduce the risk of hemorrhagic transformation. Time is brain: thrombolysis should proceed as soon as eligibility is confirmed rather than waiting for further imaging. Aspirin is deferred for 24 hours after thrombolysis to avoid increasing bleeding risk.

• A. Aspirin should be withheld before thrombolysis and only started 24 hours later after a follow-up scan excludes hemorrhage.
• B. MRI is not required to initiate thrombolysis within the window and would only delay time-critical treatment.
• D. Waiting 24 hours would place the patient far outside the therapeutic window, losing the chance for reperfusion therapy.

Major surgery within the preceding 14 days is an absolute contraindication to intravenous thrombolysis because of the high risk of catastrophic bleeding at the surgical site. This patient should instead be evaluated for mechanical thrombectomy if a large vessel occlusion is confirmed and she meets criteria. Dose reduction is not a recognized strategy to mitigate this risk. The location of surgery does not matter; any major surgery within this timeframe carries systemic bleeding risk with thrombolytics.

• A. There is no validated reduced-dose protocol for alteplase in patients with recent major surgery; the contraindication is absolute.
• B. Surgical clearance does not override the absolute contraindication; the time-sensitive nature of stroke care makes same-day clearance impractical and unsafe.
• C. The bleeding risk from thrombolysis is systemic, not limited to the brain, so an unrelated surgical site does not make it safe.

This patient has a confirmed large vessel occlusion (M1 segment) presenting beyond the 6-hour window but within 24 hours, with favorable perfusion imaging showing a small core and large penumbra, meeting extended-window criteria for mechanical thrombectomy per current guidelines. IV alteplase is not indicated because he is well beyond the 4.5-hour thrombolysis window. Heparin has no proven benefit in acute ischemic stroke and increases hemorrhage risk. Conservative management would forgo an effective reperfusion therapy in a patient who still qualifies based on imaging mismatch.

• A. IV alteplase is only approved within 4.5 hours of onset; this patient is well beyond that window.
• C. Therapeutic anticoagulation is not recommended in acute ischemic stroke and raises hemorrhagic transformation risk.
• D. Conservative management misses the opportunity for mechanical thrombectomy, which improves outcomes in eligible large vessel occlusion patients up to 24 hours when perfusion mismatch is favorable.

A linear hyperdensity following the course of the middle cerebral artery on non-contrast CT is the hyperdense MCA sign, representing an acute thrombus or embolus within the vessel lumen. It is an early and specific, though not highly sensitive, sign of large vessel occlusion and does not exclude the patient from thrombolysis. It must be distinguished from parenchymal hypodensity, which indicates established infarction, and from hemorrhage, which would appear as a different distribution of hyperdensity. Vascular calcification is typically bilateral, nodular, and seen in older patients without correlating acute symptoms.

• A. Vascular calcification is typically seen as symmetric, nodular densities in older or atherosclerotic vessels and does not correspond acutely to a new focal neurological deficit.
• B. Early infarction appears as parenchymal hypodensity with loss of grey-white differentiation, not as a linear intraluminal hyperdensity.
• C. Subarachnoid hemorrhage appears as hyperdensity within the basal cisterns and sulci, not as a linear tubular density following a single artery.

Pure motor hemiparesis affecting the face, arm, and leg equally without cortical signs (aphasia, neglect, visual field defect) or sensory loss is the classic lacunar syndrome caused by a small-vessel infarct in the posterior limb of the internal capsule. This region carries densely packed corticospinal fibers, so even a small lacunar infarct produces a disproportionately large and uniform deficit. Cortical lesions would be expected to produce face/arm or leg predominant weakness along with cortical signs such as aphasia or neglect depending on laterality. Thalamic lesions classically cause pure sensory, not motor, deficits, and pontine involvement sufficient to cause bilateral tract dysfunction would typically also affect consciousness or cause crossed signs.

• B. The thalamus is classically associated with pure sensory stroke, not pure motor hemiparesis.
• C. Unilateral pontine lesions cause contralateral hemiparesis often with ipsilateral cranial nerve signs or ataxia, not isolated pure motor hemiparesis without other brainstem findings.
• D. Cortical lesions typically produce face/arm or leg-predominant weakness along with cortical signs such as aphasia, neglect, or visual field defects, which are absent here.

In a stroke patient without identifiable atherosclerotic risk factors or carotid disease, paroxysmal atrial fibrillation is an important and common occult cause that can be missed on a single admission ECG. Prolonged rhythm monitoring (24-72 hour Holter or longer, including implantable loop recorders in cryptogenic cases) significantly increases detection of intermittent atrial fibrillation, which has major implications for secondary prevention with anticoagulation. Repeating carotid duplex would not add new information since the study was already normal. Lumbar puncture and autoimmune serologies are reserved for suspected specific etiologies such as infection, vasculitis, or CNS inflammatory disease, which are not suggested by this presentation.

• A. Lumbar puncture is not indicated without features suggesting infection, subarachnoid hemorrhage, or inflammatory CNS disease.
• C. Autoimmune serologies are reserved for cases with specific clinical features suggesting vasculitis or connective tissue disease, which are absent here.
• D. A normal carotid duplex does not need to be repeated in one week without a new clinical indication; it does not explain a cryptogenic cardioembolic-pattern stroke.

Secondary prevention after non-cardioembolic ischemic stroke includes long-term antiplatelet therapy (commonly aspirin or clopidogrel) combined with a high-intensity statin, which is recommended regardless of baseline LDL level because statins reduce recurrent stroke risk through plaque-stabilizing and anti-inflammatory effects beyond lipid lowering alone. Deferring the statin because LDL is not elevated ignores this guideline-based benefit independent of baseline lipid levels. Warfarin is reserved for cardioembolic sources such as atrial fibrillation or mechanical valves, not small vessel disease. Dual antiplatelet therapy is typically limited to a short course of 21-90 days after minor stroke or high-risk TIA, not continued indefinitely, due to increased bleeding risk without added long-term benefit.

• A. Indefinite dual antiplatelet therapy increases bleeding risk without added benefit; it is used only for a limited short course after minor stroke or high-risk TIA.
• B. Current guidelines recommend statin therapy for secondary stroke prevention regardless of baseline LDL level, not only when LDL is elevated.
• C. Warfarin is indicated for cardioembolic stroke sources such as atrial fibrillation, not for small vessel non-cardioembolic stroke.

This patient had a symptomatic transient ischemic event referable to a carotid artery with 70-99% stenosis, which is a strong indication for carotid endarterectomy, ideally performed within 2 weeks of the event to maximize benefit in preventing recurrent stroke. Delaying intervention or merely waiting for further symptoms increases the risk of a disabling stroke during the high-risk early period after a TIA. Medical therapy alone is insufficient for high-grade symptomatic stenosis, as surgical revascularization has been shown to reduce stroke risk more than antiplatelet therapy alone in this population. Simply monitoring with repeat imaging would also delay definitive treatment in a patient who already meets a clear surgical indication.

• A. Antiplatelet therapy alone is inferior to carotid endarterectomy for symptomatic high-grade carotid stenosis in a fit surgical candidate.
• C. Delaying definitive treatment for repeat imaging misses the early high-risk window after a TIA when intervention provides the greatest benefit.
• D. Stenting is generally reserved for patients at high surgical risk or when endarterectomy is technically unsuitable, and waiting for further symptoms exposes the patient to a high risk of recurrent, potentially disabling stroke.

When a non-contrast CT is performed more than 6 hours after headache onset and is negative, a lumbar puncture is required to exclude subarachnoid hemorrhage, looking for xanthochromia (from red cell breakdown products) which distinguishes true SAH from a traumatic tap. Xanthochromia is best detected by spectrophotometry and is most reliable when the LP is performed at least 12 hours after symptom onset. CT within 6 hours has very high sensitivity, but beyond that window LP remains the standard next step. Discharge without further workup risks missing a potentially fatal aneurysmal bleed.

• A. Discharging without excluding SAH is unsafe given the classic thunderclap presentation and the CT being outside the highly sensitive 6-hour window.
• B. Nimodipine is used for vasospasm prevention after a confirmed aneurysmal SAH, not as a diagnostic or empirical step before diagnosis.
• D. Repeating the CT adds delay and is less sensitive than lumbar puncture for detecting a small subarachnoid bleed at this stage.

After a first unprovoked seizure in an adult who has returned to normal baseline, the standard evaluation includes brain MRI to look for a structural cause (such as a tumor, vascular malformation, or old infarct) and an EEG, ideally within 24-48 hours but otherwise as a timely outpatient study, since EEG abnormalities help assess recurrence risk and identify an epilepsy syndrome. Antiepileptic drugs are not started routinely after a single unprovoked seizure unless the EEG shows epileptiform discharges, there is a structural brain lesion, or a nocturnal seizure is clinically concerning, because recurrence risk after a truly unprovoked first seizure with normal workup is only around 30-40%. There is no indication for lumbar puncture in the absence of fever, meningism, or immunocompromise.

• A. Lumbar puncture is not indicated here in the absence of fever, meningeal signs, or risk factors for CNS infection.
• B. Antiepileptic therapy is not routinely started after a single first unprovoked seizure unless imaging or EEG reveals a high-risk abnormality.
• C. Reassurance without imaging and EEG risks missing a structural or epileptiform cause that would change management and counseling.

In status epilepticus (seizure activity lasting 5 minutes or more, or recurrent seizures without recovery), the first-line treatment is a benzodiazepine, and when intravenous access is not immediately available, intramuscular midazolam is the preferred route because it has reliable absorption and onset of action comparable to intravenous lorazepam, as demonstrated in randomized trials (RAMPART). Waiting to secure intravenous access before treating delays seizure termination and increases the risk of neuronal injury and systemic complications. Oral or nasogastric phenytoin is inappropriate in an actively seizing patient due to aspiration risk and slow absorption, and levetiracetam is a second-line agent used after benzodiazepine failure, not a first-line choice.

• A. Levetiracetam is a second-line agent given after benzodiazepines fail to terminate the seizure, not the initial treatment.
• B. Delaying treatment to wait for intravenous access is unsafe when intramuscular midazolam can be given immediately with proven efficacy.
• C. Oral or nasogastric medication is unsafe in an actively convulsing patient due to aspiration risk and unpredictable absorption.

This child's presentation of brief staring spells with abrupt onset and offset, no postictal confusion, and an EEG showing generalized 3 Hz spike-and-wave discharges is classic for childhood absence epilepsy, which results from abnormal thalamocortical oscillatory circuits. Ethosuximide, which blocks T-type calcium channels in thalamic neurons, is a first-line agent for absence seizures when they occur in isolation, alongside valproate, which is preferred if the child also has generalized tonic-clonic seizures. Carbamazepine and phenytoin, which act on sodium channels, are not only ineffective but can worsen absence seizures. Lamotrigine is an alternative option but is generally considered less effective than ethosuximide or valproate as first-line monotherapy for pure absence epilepsy.

• A. Lamotrigine is a reasonable alternative but is not considered superior to ethosuximide as first-line therapy for isolated absence seizures.
• B. Carbamazepine can exacerbate absence seizures and is not used in this syndrome.
• D. Phenytoin is ineffective for absence seizures and can worsen them.

The clinical picture (myoclonic jerks on awakening, generalized tonic-clonic seizures, generalized spike-wave discharges on EEG) is classic for juvenile myoclonic epilepsy. Although valproate is highly effective for this syndrome, it is a major teratogen (neural tube defects, cognitive impairment) and is avoided in women of childbearing potential unless no other option is suitable. Levetiracetam has an established efficacy profile in generalized epilepsies and a much safer reproductive profile, making it the preferred first-line choice in this patient. Guidelines from SCFHS-aligned neurology practice and international bodies recommend avoiding valproate in girls/women who could become pregnant whenever alternatives exist.

• A. Carbamazepine can exacerbate myoclonic and absence seizures in generalized epilepsy syndromes.
• B. Valproate is effective but teratogenic and should be avoided in women of childbearing age when alternatives exist.
• D. Phenytoin is not effective for generalized epilepsies and can worsen myoclonic seizures.

The epigastric rising sensation and olfactory aura followed by oral and manual automatisms (lip-smacking, picking at clothing) with impaired awareness are characteristic of mesial temporal lobe epilepsy, often arising from the hippocampus or amygdala. Secondary generalization to a tonic-clonic seizure with subsequent prolonged postictal confusion is common. Frontal lobe seizures typically present with brief, bizarre motor automatisms and minimal postictal confusion. This semiology pattern is a key teaching point for localizing focal epilepsy clinically before EEG or MRI confirmation.

• B. Frontal lobe seizures are typically brief with bizarre hypermotor activity and rapid recovery, not prolonged automatisms with an aura.
• C. Occipital lobe seizures usually present with visual phenomena such as flashing lights.
• D. Parietal lobe seizures typically cause sensory symptoms such as tingling or distorted body perception.

The patient has classic phenytoin toxicity: cerebellar signs (nystagmus, ataxia, dysarthria) with a supratherapeutic level and chronic gingival hyperplasia, a known dose-related adverse effect. Management of dose-related phenytoin toxicity is to reduce or temporarily withhold the dose and monitor levels, rather than switching agents acutely or adding sedating drugs. Phenytoin has nonlinear (zero-order) kinetics at higher doses, so small dose increases can cause disproportionate rises in serum level and toxicity. Folic acid addresses megaloblastic anemia, a separate chronic adverse effect, not acute cerebellar toxicity.

• A. Folic acid supplementation treats phenytoin-associated folate deficiency, not acute cerebellar toxicity.
• B. Switching to another antiseizure drug is not the immediate priority; the toxicity should first be corrected by dose reduction.
• C. Adding another sedating antiseizure drug would worsen toxicity and is not indicated.

The patient has developed Stevens-Johnson syndrome/toxic epidermal necrolysis, a severe cutaneous adverse reaction strongly associated with carbamazepine in individuals carrying the HLA-B*1502 allele, which is common in Han Chinese, Thai, Malaysian, and other Southeast Asian populations. International guidelines recommend HLA-B*1502 screening before starting carbamazepine in patients from these high-risk ethnic groups, and avoiding the drug in those who test positive. G6PD deficiency is relevant to hemolysis risk with oxidative drugs, not SJS/TEN. TPMT activity guides thiopurine dosing, and CYP2C9 genotype is relevant to warfarin and phenytoin metabolism, not carbamazepine hypersensitivity.

• A. CYP2C9 genotype affects warfarin and phenytoin metabolism, not carbamazepine-associated SJS/TEN risk.
• C. TPMT activity is relevant to thiopurine drug toxicity, not carbamazepine hypersensitivity.
• D. G6PD deficiency predicts hemolysis with oxidant drugs, not carbamazepine-induced SJS/TEN.

Most licensing authorities, including guidance followed in Saudi practice, require a defined seizure-free interval, typically 6-12 months depending on jurisdiction and whether the license is for private or commercial/professional driving, before a person with epilepsy may resume driving. Commercial drivers such as taxi or truck drivers are usually held to stricter criteria than private drivers because of the greater risk to public safety. Immediate resumption of driving poses an unacceptable risk of a seizure causing a road traffic accident. A permanent driving ban is not appropriate if the patient achieves sustained seizure control, as this would be overly restrictive and not evidence-based.

• A. Driving immediately after a seizure poses significant risk to the patient and the public regardless of medication adherence.
• C. A permanent ban is not warranted if the patient achieves sustained seizure freedom on treatment.
• D. A normal EEG does not shorten the required seizure-free interval before driving is permitted.

According to the International Classification of Headache Disorders (ICHD-3) criteria, migraine without aura requires at least 5 attacks lasting 4-72 hours with at least two of unilateral location, pulsating quality, moderate-to-severe intensity, or aggravation by routine physical activity, plus at least one of nausea/vomiting or photophobia/phonophobia. This patient's headaches fulfill these criteria: unilateral, throbbing, aggravated by exertion, with nausea and photophobia/phonophobia-seeking behavior. Tension-type headache is typically bilateral, pressing, and not aggravated by activity. Cluster headache is characteristically much shorter (15-180 minutes), associated with ipsilateral autonomic features, and occurs in clusters.

• A. Tension-type headache is usually bilateral and pressing, without aggravation by physical activity.
• C. Chronic paroxysmal hemicrania involves very frequent, short-lasting attacks with autonomic features, not prolonged throbbing headaches.
• D. Cluster headache attacks are much shorter in duration and associated with ipsilateral autonomic features such as lacrimation or ptosis.

Triptans are selective 5-HT1B/1D receptor agonists. Activation of 5-HT1B receptors on vascular smooth muscle causes vasoconstriction, which is therapeutic in cranial vessels during migraine but can also constrict coronary arteries. This makes triptans contraindicated in patients with established coronary artery disease, prior myocardial infarction, or uncontrolled hypertension due to the risk of precipitating myocardial ischemia or infarction. Alternative acute therapies such as NSAIDs, antiemetics, or non-vasoconstrictive agents (e.g., gepants) should be considered in these patients.

• B. This is not the mechanism of triptans; this describes effects of agents like reserpine.
• C. Triptans do not have a clinically significant antiplatelet effect.
• D. QT prolongation is not a recognized mechanism of triptan-related cardiac risk.

This presentation is classic for cluster headache: severe unilateral periorbital pain with ipsilateral autonomic features (lacrimation, conjunctival injection, ptosis), occurring in bouts with a circadian pattern. High-flow oxygen (100% at 12-15 L/min via non-rebreather mask for 15-20 minutes) is a first-line abortive treatment, with response rates over 70%. Subcutaneous or intranasal triptans are the other first-line abortive option. Oxygen therapy acts rapidly and has an excellent safety profile, making it ideal for repeated daily attacks.

• A. Corticosteroids are used as a bridging prophylactic therapy for cluster periods, not for aborting an individual acute attack.
• C. Propranolol is used for migraine prophylaxis, not for acute cluster headache attacks.
• D. Dihydroergotamine can be used but is not first-line compared to oxygen or subcutaneous triptans and carries more side effects.

Tension-type headache is characterized by bilateral, pressing or tightening (non-pulsatile) pain of mild to moderate intensity that does not worsen with routine physical activity, and is not associated with nausea or more than one of photophobia/phonophobia. This distinguishes it from migraine, which typically features unilateral, pulsatile pain, moderate-severe intensity, aggravation by activity, and associated nausea or photophobia/phonophobia. The absence of aggravating activity and associated autonomic or gastrointestinal symptoms here supports tension-type headache over migraine.

• A. There is no mention of frequent analgesic use that would suggest medication-overuse headache.
• C. Migraine typically presents with unilateral, pulsatile pain, is worsened by physical activity, and is often accompanied by nausea or photophobia/phonophobia, none of which are present here.
• D. Cervicogenic headache typically has a unilateral distribution related to neck movement or posture, which is not described here.

A sudden-onset, severe 'thunderclap' headache reaching maximal intensity within one minute is a red-flag feature requiring urgent evaluation for subarachnoid hemorrhage. Non-contrast CT of the head is the most appropriate initial investigation, with very high sensitivity (over 95%) for detecting subarachnoid hemorrhage when performed within 6 hours of symptom onset. If CT is negative but clinical suspicion remains high, lumbar puncture to look for xanthochromia is the next step. Prompt imaging is essential because missed subarachnoid hemorrhage carries high morbidity and mortality from rebleeding.

• A. Lumbar puncture is performed only after a non-contrast CT, typically if CT is negative and suspicion remains.
• C. MRI is not the first-line investigation and is slower to obtain acutely compared to non-contrast CT.
• D. Treating as migraine without first excluding subarachnoid hemorrhage in a thunderclap headache would be dangerous and inappropriate.

This patient meets the modified Dandy criteria for idiopathic intracranial hypertension: raised intracranial pressure (opening pressure greater than 25 cmH2O) with normal CSF composition, normal neuroimaging, and no other identifiable cause, occurring in a young obese woman. Acetazolamide, a carbonic anhydrase inhibitor, is the first-line medical treatment because it reduces cerebrospinal fluid production, thereby lowering intracranial pressure. Weight loss is also a key component of long-term management. Regular visual field testing is essential to monitor for progression to permanent visual loss, and surgical options such as optic nerve sheath fenestration or CSF shunting are reserved for refractory cases or impending visual loss.

• B. Mannitol is used for acute severe elevations in intracranial pressure, not for long-term outpatient management of idiopathic intracranial hypertension.
• C. Corticosteroids are not standard first-line therapy for idiopathic intracranial hypertension and can cause weight gain, worsening the condition.
• D. Furosemide is not an established first-line treatment for reducing cerebrospinal fluid production in this condition.

This presentation, with jaw claudication, temporal artery tenderness, and markedly elevated ESR in an elderly patient, is classic for giant cell arteritis, and the new visual symptoms indicate imminent risk of irreversible blindness from ophthalmic artery involvement. High-dose corticosteroids (e.g., oral prednisolone 60 mg daily, or intravenous methylprednisolone if visual loss is present) must be started immediately without waiting for biopsy confirmation, since treatment delay risks permanent vision loss. Temporal artery biopsy should still be performed, ideally within 1-2 weeks of starting steroids, as the histological changes persist for some time despite treatment, and biopsy confirms the diagnosis for long-term management decisions. Delaying steroids for biopsy results is a critical error in suspected giant cell arteritis with visual symptoms.

• B. Delaying corticosteroids until biopsy confirmation risks progression to permanent blindness and is not recommended.
• C. Waiting for biopsy results before starting steroids is unsafe given the risk of irreversible vision loss.
• D. Aspirin alone does not treat the underlying vasculitis and does not prevent visual loss in giant cell arteritis.

This patient demonstrates the cardinal features of Parkinson disease: resting tremor that diminishes with voluntary movement, cogwheel rigidity, and bradykinesia with shuffling gait and reduced arm swing, typically beginning asymmetrically as seen here on the right side. These motor features result from progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced dopaminergic input to the striatum and disruption of basal ganglia motor circuits. Diagnosis is clinical, based on bradykinesia plus at least one of rest tremor or rigidity, with asymmetric onset supporting the diagnosis over other parkinsonian syndromes. Response to levodopa further supports the diagnosis.

• A. Amyloid plaque accumulation is characteristic of Alzheimer disease, not the motor syndrome described here.
• B. Anterior horn cell degeneration occurs in motor neuron disease, which presents with weakness and muscle wasting, not the described tremor and rigidity.
• D. Autoimmune demyelination of corticospinal tracts describes conditions like multiple sclerosis, not Parkinson disease.

As nigrostriatal dopaminergic neurons continue to degenerate, the striatum loses its capacity to buffer and store dopamine from exogenous levodopa, so the clinical response increasingly mirrors plasma drug levels. This produces 'wearing-off' fluctuations, where motor benefit fades before the next scheduled dose because the short half-life of levodopa is no longer compensated by presynaptic storage. This is one of the most common long-term motor complications of levodopa therapy, occurring in a large proportion of patients after 5 years of treatment. Management includes shortening dosing intervals, adding a COMT inhibitor, or using a dopamine agonist.

• B. Receptor downregulation is not the mechanism of wearing-off; it relates more to dyskinesia pathophysiology from pulsatile receptor stimulation.
• C. Levodopa does not cause autoimmune destruction of nigral neurons; disease progression is intrinsic to the underlying neurodegenerative process.
• D. Levodopa metabolites do not cause this clinical picture; the symptoms described are motor, not sensory or neuropathic.

Drug-induced parkinsonism from dopamine receptor-blocking agents (typical antipsychotics, metoclopramide) typically presents with symmetric bradykinesia, rigidity, and tremor because the pathophysiology is diffuse striatal D2 receptor blockade rather than focal nigral degeneration. Idiopathic Parkinson disease classically begins asymmetrically. The drug-induced form is reversible, usually resolving over weeks to a few months after withdrawal of the offending agent, though resolution can occasionally take longer in older patients. This temporal and symmetry pattern is the key distinguishing clinical clue.

• A. A classic rest tremor that diminishes, not worsens, with action is seen in idiopathic Parkinson disease; this phrasing describes action tremor, which is less typical of either condition and not the distinguishing feature here.
• B. Early falls and postural instability within the first year suggest an atypical parkinsonian syndrome such as progressive supranuclear palsy, not drug-induced parkinsonism.
• D. Levodopa response is often poor or inconsistent in drug-induced parkinsonism since the problem is receptor blockade, not dopamine deficiency, so this does not reliably distinguish the two.

Huntington disease is caused by an autosomal dominant CAG trinucleotide repeat expansion in the HTT gene on chromosome 4, producing a mutant huntingtin protein with toxic gain of function that selectively damages GABAergic medium spiny neurons in the caudate nucleus. This causes the characteristic caudate atrophy and secondary ex-vacuo enlargement of the frontal horns of the lateral ventricles seen on imaging. The disease shows genetic anticipation, with earlier onset and longer repeats in successive generations, particularly with paternal transmission. Clinical features include chorea, cognitive decline, and psychiatric disturbance, consistent with this patient's presentation and family history.

• A. Mitochondrial point mutations cause diseases like MELAS or Leigh syndrome, not the autosomal dominant pattern and caudate atrophy seen in Huntington disease.
• B. This describes Wilson disease, which causes hepatolenticular degeneration, not the chorea and caudate atrophy pattern described here.
• C. This describes fragile X syndrome, which causes intellectual disability, not adult-onset chorea with autosomal dominant inheritance.

This presentation of fever, rigidity, autonomic instability, altered mental status, and markedly elevated creatine kinase following antipsychotic initiation is classic for neuroleptic malignant syndrome, caused by dopamine receptor blockade in the hypothalamus and nigrostriatal pathways. The first and most critical step is to stop the offending dopamine-blocking agent immediately, combined with supportive care including aggressive cooling, intravenous fluids, and correction of electrolyte abnormalities to prevent rhabdomyolysis-induced renal failure. Dantrolene or bromocriptine may be added for severe or refractory cases, but discontinuing the drug and starting supportive management take priority. Electroconvulsive therapy and benzodiazepines are used mainly in catatonia or serotonin syndrome, not as first-line therapy here.

• A. The clinical picture fits NMS, not meningitis; there are no signs such as neck stiffness or photophobia described, and antibiotics would delay correct management.
• C. Switching antipsychotics is inappropriate during an acute NMS episode; all dopamine-blocking agents should be avoided until the episode resolves.
• D. Electroconvulsive therapy is not an immediate first step for NMS and benzodiazepines alone do not address the underlying cause; the priority is stopping the causative drug and supportive care.

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy typically triggered by a preceding infection, classically Campylobacter jejuni gastroenteritis, through molecular mimicry between microbial lipo-oligosaccharides and peripheral nerve gangliosides. It presents with rapidly progressive, symmetric ascending weakness and loss of deep tendon reflexes (areflexia), usually without significant sensory loss. The time course (days after a diarrheal illness) and the symmetric ascending pattern with areflexia are the clinical hallmarks. Sensation and cranial nerves may be involved later, but early areflexic ascending weakness after diarrhea is classic for GBS.

• B. Transverse myelitis usually causes a sensory level and upper motor neuron signs (hyperreflexia, sphincter involvement), not areflexia.
• C. Myasthenia gravis causes fatigable weakness with preserved or brisk reflexes, not areflexia, and typically affects ocular/bulbar muscles first.
• D. Periodic paralysis causes episodic weakness related to serum potassium shifts, not a progressive ascending course after an infection.

The classic cerebrospinal fluid (CSF) finding in Guillain-Barré syndrome is albuminocytologic dissociation: markedly elevated protein with a normal or only mildly elevated white cell count (typically fewer than 10 cells/µL). This reflects inflammation and increased permeability along the nerve roots without significant meningeal cellular infiltration. The finding may be absent in the first week of symptoms, so a normal CSF protein early on does not exclude the diagnosis, and nerve conduction studies showing demyelinating features (prolonged distal latencies, conduction block, reduced conduction velocity) support the diagnosis. Low CSF glucose suggests bacterial or fungal infection, not GBS.

• A. Low CSF glucose relative to serum suggests bacterial, fungal, or tuberculous meningitis, not GBS.
• B. Lymphocytosis with atypical lymphocytes suggests a viral or lymphoproliferative process, not the characteristic CSF profile of GBS.
• C. Markedly elevated creatine kinase suggests a myopathic process, not a demyelinating polyneuropathy.

In Guillain-Barré syndrome, respiratory failure results from progressive weakness of the diaphragm and intercostal muscles, which can occur before hypoxemia or tachypnea develop because patients compensate until muscles fatigue markedly. Serial forced vital capacity (FVC) measurement is the standard bedside test to track respiratory muscle strength; a FVC below approximately 20 mL/kg, or a rapid decline, signals impending ventilatory failure and is an indication for elective intubation and consideration of intravenous immunoglobulin (IVIG) or plasma exchange if not already started. Pulse oximetry and respiratory rate are insensitive and often remain normal until decompensation is advanced.

• B. Oxygen saturation typically stays normal until respiratory failure is advanced because of compensatory mechanisms, making it an insensitive early monitor.
• C. Peak expiratory flow reflects airway caliber more than overall respiratory muscle strength and is less validated for tracking GBS progression.
• D. Respiratory rate is an unreliable early indicator since patients can maintain a normal rate despite significant diaphragmatic weakness.

The clinical picture of fatigable, fluctuating ptosis and diplopia worsening with sustained activity and improving with rest, along with fatigable chewing, is classic for myasthenia gravis, an autoimmune disease caused by antibodies against postsynaptic acetylcholine receptors at the neuromuscular junction. Serum anti-acetylcholine receptor (anti-AChR) antibody testing is positive in about 80-85% of patients with generalized myasthenia gravis and is the most specific confirmatory test. The edrophonium (Tensilon) test and ice-pack test can support the diagnosis clinically but are less specific and have largely been replaced by antibody testing and electrophysiology (repetitive nerve stimulation, single-fiber EMG) where available.

• A. Anti-voltage-gated calcium channel antibodies are associated with Lambert-Eaton myasthenic syndrome, which improves with sustained contraction rather than worsening.
• B. Creatine kinase is a marker of muscle fiber injury and is normal in myasthenia gravis since the defect is at the neuromuscular junction, not the muscle fiber.
• C. Facial nerve conduction studies do not assess neuromuscular junction transmission and are not used to diagnose myasthenia gravis.

The combination of respiratory distress with cholinergic features (excessive salivation, sweating, abdominal cramps, miosis) in a patient on a cholinesterase inhibitor suggests cholinergic crisis from cholinergic excess rather than myasthenic crisis from undertreatment. The immediate priority regardless of the type of crisis is securing the airway and ensuring adequate ventilation, since respiratory failure can occur in either; pyridostigmine should be withheld because continuing or increasing it would worsen cholinergic toxicity if that is the cause, and the diagnosis should be clarified once the patient is stabilized. Giving more cholinesterase inhibitor empirically is dangerous if the picture is cholinergic crisis.

• A. Administering more pyridostigmine would worsen cholinergic crisis if that is the cause and risks further respiratory compromise.
• B. Atropine treats muscarinic symptoms but does not address the underlying respiratory failure and should not be given before securing the airway and stopping the offending drug.
• C. Immunoglobulin takes days to act and does not address the acute cholinergic toxicity or impending respiratory failure; airway management takes priority.

Lumbar puncture carries a risk of brain herniation in patients with raised intracranial pressure or a mass lesion. Indications for computed tomography (CT) of the head before lumbar puncture include new focal neurological deficits, papilledema, altered level of consciousness, immunocompromised state, history of CNS disease, or new-onset seizures. This patient has a focal deficit, papilledema, and is immunocompromised, all of which mandate CT imaging first to exclude a mass lesion, abscess, or significant edema before proceeding with lumbar puncture. If CT is delayed, empiric antibiotics should still be started without waiting.

• B. Empiric antifungal therapy is not indicated without confirmation of a fungal cause and does not address the immediate safety concern of lumbar puncture.
• C. Spinal MRI is not the modality used to assess for raised intracranial pressure or mass effect prior to lumbar puncture.
• D. EEG is used to evaluate seizure activity or encephalopathy but does not assess risk of herniation before lumbar puncture.

Tuberculous meningitis classically produces a CSF profile with lymphocytic pleocytosis (typically 100-500 cells/µL, predominantly lymphocytes), markedly elevated protein, and a low glucose with a reduced CSF-to-serum glucose ratio, reflecting a subacute inflammatory process with impaired glucose transport across the inflamed meninges. This combination, a subacute course over days with lymphocytic pleocytosis and hypoglycorrhachia, distinguishes tuberculous meningitis from viral meningitis, which usually has normal glucose, and from acute bacterial meningitis, which usually shows neutrophilic pleocytosis with a very high cell count. Raised opening pressure is also common in TB meningitis due to basal exudates and hydrocephalus.

• A. Cryptococcal meningitis typically occurs in immunocompromised patients and classically shows a lower cell count with a more insidious course; this scenario lacks mention of immunosuppression or cryptococcal risk factors.
• B. Viral meningitis usually shows lymphocytic pleocytosis with normal glucose, not the hypoglycorrhachia seen here.
• D. Acute bacterial meningitis typically shows a markedly elevated neutrophil-predominant white cell count, not lymphocyte predominance, and presents more acutely over hours.

Herpes simplex encephalitis is a medical emergency with high mortality if untreated, and the temporal lobe predilection on MRI together with the clinical picture of fever, confusion, and focal findings is highly suggestive. Current guidelines recommend starting empiric intravenous acyclovir immediately whenever HSE is suspected, without waiting for CSF PCR confirmation, because outcomes correlate strongly with time to treatment. If PCR is later negative and an alternative diagnosis is not found, acyclovir can be stopped. Delaying treatment pending confirmatory testing significantly increases the risk of permanent neurological damage or death.

• B. Oral valacyclovir has insufficient CNS penetration and delaying effective therapy by 48 hours is not acceptable in suspected HSE.
• C. This regimen targets bacterial meningitis, which does not explain the temporal lobe MRI findings and would delay appropriate antiviral therapy.
• D. Withholding therapy pending PCR confirmation risks irreversible neurological damage given the time-sensitive nature of HSE.

Close contacts of a confirmed meningococcal meningitis case, including household and dormitory roommates, require chemoprophylaxis as soon as possible, ideally within 24 hours of case identification, to eradicate nasopharyngeal carriage and prevent secondary cases. Oral rifampicin given twice daily for 2 days is a standard regimen, with ciprofloxacin as a single-dose alternative in adults. Prophylaxis is recommended regardless of vaccination status because vaccines do not cover all serogroups and take time to generate protective antibodies. Observation alone is inappropriate given the significant risk of secondary disease in close contacts.

• A. Close contacts require prophylactic antibiotics regardless of symptoms because secondary cases can occur rapidly and have high mortality.
• B. Waiting for symptoms to appear before treating defeats the purpose of prophylaxis, which is meant to prevent disease, not treat it after onset.
• C. Vaccination alone does not provide the immediate protection needed and does not replace chemoprophylaxis for close contacts.

The combination of subacute presentation, basal meningeal enhancement, hydrocephalus, cranial nerve palsy, and CSF showing lymphocytic pleocytosis with markedly raised protein and low glucose is classic for tuberculous meningitis, particularly in a patient from a TB-endemic country. Standard management is empiric four-drug antituberculous therapy (isoniazid, rifampicin, pyrazinamide, ethambutol) started promptly without waiting for culture confirmation, given the high mortality of delayed treatment, continued for a prolonged course of at least 9-12 months. Adjunctive corticosteroids reduce mortality and neurological morbidity by limiting inflammatory complications such as vasculitis and hydrocephalus. Monotherapy risks resistance and treatment failure.

• B. Isoniazid monotherapy is inadequate for active tuberculous meningitis and risks the development of drug resistance.
• C. There are no features suggesting fungal meningitis such as cryptococcal infection, and amphotericin B is not indicated here.
• D. The CSF profile and basal enhancement are not consistent with a bacterial process and empiric antibacterials alone would not treat tuberculosis.

The distribution of numbness in the thumb, index, and middle fingers, nocturnal worsening, relief with shaking the hand (flick sign), and positive Phalen's and Tinel's signs are characteristic of median nerve compression at the wrist. Hypothyroidism is a recognized risk factor due to tissue edema and mucopolysaccharide deposition narrowing the carpal tunnel. Other risk factors include pregnancy, diabetes mellitus, repetitive wrist movements, and rheumatoid arthritis. The diagnosis is usually clinical, with nerve conduction studies used for confirmation in atypical or severe cases.

• A. Thoracic outlet syndrome typically causes symptoms in the ulnar distribution and is associated with vascular symptoms or positional arm symptoms, not isolated nocturnal median nerve symptoms.
• C. Ulnar neuropathy affects the little and ring fingers, not the thumb, index, and middle fingers.
• D. Cervical radiculopathy typically causes neck pain radiating to the arm with dermatomal rather than median nerve distribution sensory loss.

The 10 g Semmes-Weinstein monofilament test is the standard bedside screening tool for diabetic peripheral neuropathy and is used to identify patients at high risk of foot ulceration and amputation. It is applied to standardized sites on the plantar surface of the foot, and loss of sensation is a strong predictor of future ulceration. It is simple, inexpensive, and recommended annually in diabetes guidelines for foot risk stratification. Nerve conduction studies are more sensitive but are not practical or necessary for routine screening.

• A. Nerve conduction studies are reserved for atypical cases or research, not routine annual screening in primary care.
• C. Ankle and knee reflexes can be reduced in neuropathy but are not sensitive or specific enough to be the screening test of choice for ulceration risk.
• D. Ankle-brachial index assesses peripheral arterial disease, not sensory neuropathy.

Saddle anesthesia, urinary retention, and reduced anal tone in the setting of bilateral leg pain and bilateral positive straight leg raise are red-flag features of cauda equina syndrome, a surgical emergency. Urgent MRI of the lumbosacral spine is the investigation of choice to confirm the diagnosis and localize the level of compression, and it should be obtained emergently so that decompressive surgery can proceed without delay. Delayed diagnosis and treatment beyond 24-48 hours of symptom onset is associated with worse recovery of bladder, bowel, and sexual function. Plain radiographs do not adequately visualize neural or disc tissue and are not sufficient for this diagnosis.

• B. This is a surgical emergency requiring urgent imaging and decompression, not outpatient referral, and steroids are not standard therapy for compressive cauda equina syndrome.
• C. Lumbar puncture is not indicated and could be hazardous if there is a space-occupying lesion causing cord or cauda equina compression.
• D. Plain radiographs cannot visualize the spinal canal, disc, or nerve roots adequately and would delay the correct emergent investigation.

Weakness of ankle plantar flexion (gastrocnemius-soleus), sensory loss over the posterolateral calf and lateral foot, and a diminished or absent ankle reflex localize to the S1 nerve root. This pattern typically results from a herniated L5-S1 intervertebral disc compressing the S1 root as it exits below the L5 vertebra. In contrast, L5 root lesions cause weakness of foot dorsiflexion and great toe extension with sensory loss over the dorsum of the foot and preserved ankle reflex. Correlating motor, sensory, and reflex findings allows accurate clinical localization of the affected nerve root before imaging.

• B. L3 root lesions cause anterior thigh pain and weakness of hip flexion and knee extension, unrelated to this distribution.
• C. L5 root lesions cause weakness of foot dorsiflexion and great toe extension with a normal ankle reflex, which does not match this presentation.
• D. L4 root lesions cause weakness of knee extension and a reduced patellar reflex, not ankle plantar flexion weakness or an absent ankle reflex.

Early morning headache that improves on arising, projectile vomiting without nausea, and bilateral papilledema with loss of venous pulsation form the classic triad of raised intracranial pressure. Morning worsening reflects nocturnal hypoventilation causing CO2 retention and cerebral vasodilation, compounded by recumbency reducing CSF and venous drainage. Loss of spontaneous venous pulsation on fundoscopy is an early and sensitive sign of elevated ICP. The absence of fever and meningismus argues against an infectious cause, and the pattern and papilledema argue against a primary headache disorder.

• A. Bacterial meningitis would be expected to cause fever and neck stiffness, both absent here.
• C. Tension-type headache is a bilateral band-like headache without papilledema or vomiting.
• D. Migraine typically causes throbbing unilateral headache with photophobia and does not cause papilledema or loss of venous pulsation.

Amenorrhea-galactorrhea syndrome with a markedly elevated prolactin level and a sellar mass compressing the optic chiasm (producing bitemporal hemianopia) is diagnostic of a prolactinoma, the most common type of functioning pituitary adenoma. Prolactin levels above 200 ng/mL strongly suggest a macroprolactinoma rather than a stalk effect from a nonfunctioning mass. First-line treatment is a dopamine agonist such as cabergoline, which shrinks the tumor and normalizes prolactin in most patients. In contrast, glioblastoma is the most common primary malignant brain tumor overall but arises in the cerebral hemispheres and does not cause this endocrine picture.

• B. Craniopharyngiomas occur more often in children and young adults and classically cause growth failure or diabetes insipidus, not this degree of hyperprolactinemia.
• C. Glioblastoma is the most common primary malignant brain tumor in adults but arises from glial cells in the cerebral hemispheres, not the sella, and does not cause hyperprolactinemia of this magnitude.
• D. Meningiomas are usually hormonally silent and would not produce such a markedly elevated prolactin level.

This patient has clinical and radiological signs of impending transtentorial herniation (dilated pupil, Cushing-like bradycardia relative to blood pressure, midline shift, effaced cisterns). Intravenous mannitol reduces intracranial pressure by creating an osmotic gradient that draws water out of brain tissue, and head elevation improves venous drainage; both serve as temporizing measures while definitive neurosurgical decompression is arranged. Lumbar puncture is contraindicated in the setting of a mass lesion with midline shift because the sudden pressure gradient can precipitate or worsen herniation. Aggressive hyperventilation to very low PaCO2 levels causes excessive cerebral vasoconstriction and risks ischemia, so it is reserved briefly for acute deterioration rather than used to this degree as routine management.

• A. Corticosteroids are useful for vasogenic edema around tumors but act too slowly and do not substitute for osmotic therapy in acute impending herniation.
• C. Hyperventilation to such a low PaCO2 causes excessive vasoconstriction and risks cerebral ischemia; it is used cautiously and briefly, not to this target as initial management.
• D. Lumbar puncture is contraindicated here because the pressure gradient between the spinal and cranial compartments can precipitate herniation.

This woman's gradual, progressive, memory-predominant cognitive decline with preserved early motor function and hippocampal-predominant atrophy is typical of Alzheimer disease. Cholinesterase inhibitors such as donepezil are first-line pharmacologic therapy for mild to moderate Alzheimer disease; they increase synaptic acetylcholine by inhibiting its breakdown, partially compensating for the cholinergic deficit caused by degeneration of basal forebrain cholinergic neurons. Memantine, an NMDA receptor antagonist, is typically reserved for moderate to severe disease or added later. Antipsychotics and antidepressants have no role as first-line treatment for the cognitive decline itself.

• A. Selegiline is a monoamine oxidase-B inhibitor used in Parkinson disease, not a standard treatment for Alzheimer disease.
• C. Risperidone is used for behavioral and psychotic symptoms in dementia, not as first-line treatment for the cognitive decline itself, and carries increased cardiovascular and mortality risk in elderly dementia patients.
• D. Memantine is generally reserved for moderate to severe Alzheimer disease, not as first-line therapy in mild disease.

A stepwise pattern of cognitive decline occurring in temporal relation to discrete ischemic events, in a patient with vascular risk factors and imaging evidence of multiple infarcts, is characteristic of vascular dementia. This contrasts with Alzheimer disease, which follows a smooth, gradually progressive course without abrupt stepwise drops tied to vascular events. Focal neurological signs such as the spasticity and hemiparesis seen here are common in vascular dementia because of the underlying infarcts, whereas early Alzheimer disease typically has a normal motor examination. Management focuses on aggressive control of vascular risk factors to prevent further infarcts, since cholinesterase inhibitors have only modest evidence in this condition.

• A. Dementia with Lewy bodies presents with fluctuating cognition, visual hallucinations, and parkinsonism, not a stepwise decline following discrete infarcts.
• B. Alzheimer disease follows a smooth, gradually progressive course and does not typically show focal neurological signs or an abrupt stepwise decline tied to strokes.
• C. Frontotemporal dementia presents with early personality and behavioral changes or language difficulty, not a stepwise decline linked to strokes.

The triad of gait disturbance (typically the earliest and most prominent feature), urinary incontinence, and cognitive decline, together with ventriculomegaly disproportionate to cortical atrophy, is classic for normal pressure hydrocephalus. The recommended next step is a large-volume (high-volume) lumbar puncture with objective assessment of gait before and after CSF removal; symptomatic improvement predicts a favorable response to ventriculoperitoneal shunting. Proceeding directly to shunt surgery without this tap test increases the risk of operating on patients who will not benefit. Cholinesterase inhibitors and levodopa are not appropriate first steps because the underlying problem is a CSF dynamics disorder, not a primary neurodegenerative or dopaminergic deficiency.

• A. Levodopa-carbidopa is used for Parkinson disease; this gait pattern and the ventricular findings are not consistent with a dopaminergic deficiency.
• B. Cholinesterase inhibitors are used for Alzheimer disease, not as the next diagnostic or therapeutic step in suspected NPH.
• C. Shunting is the definitive treatment but should be preceded by a tap test or trial of CSF drainage to predict responsiveness before committing to surgery.

The acute onset, fluctuating course, and inattention in a previously cognitively intact elderly man with fever and tachycardia during an acute infection are classic for delirium, which reflects acute diffuse cerebral dysfunction triggered by a reversible systemic insult such as infection, metabolic derangement, or medication effect. This differs fundamentally from dementia, which has an insidious onset and a chronic, generally non-fluctuating progressive course due to structural neurodegeneration. The priority in delirium is to identify and treat the underlying precipitant, in this case likely sepsis from pneumonia, rather than attributing the picture to an underlying degenerative process. Full or near-full recovery of cognition is expected once the precipitant is treated, unlike the irreversible decline seen in dementia.

• A. This describes Lewy body or Parkinson disease pathology, which causes a chronic progressive course, not an acute reversible confusional state.
• C. This describes the pathology of Alzheimer disease, which has an insidious, chronic course rather than this acute fluctuating presentation.
• D. This describes vascular dementia pathology, which produces a chronic stepwise decline rather than an acute fluctuating confusional state tied to an infection.