SPEX Exam Neurology 4

Question 1

A 58-year-old man presents with progressive gait ataxia, dysarthria, and vertical supranuclear gaze palsy. He has frequent falls due to backward postural instability. MRI shows midbrain atrophy with a 'hummingbird sign.' Which protein aggregate is most characteristic of this condition?

Accepted Answer

Tau (4-repeat isoform)

Answer

The clinical picture describes Progressive Supranuclear Palsy (PSP), characterized by vertical supranuclear gaze palsy, early postural instability with backward falls, midbrain atrophy ('hummingbird sign'), and parkinsonism. PSP is a 4-repeat tauopathy, meaning tau aggregates predominantly as 4-repeat (4R) isoforms in neurons and glia. Alpha-synuclein is seen in Parkinson's and MSA; TDP-43 in ALS and FTLD; beta-amyloid in Alzheimer's disease.

Question 2

A 34-year-old woman with a history of migraine with aura has a first unprovoked seizure. She is started on valproic acid. Six weeks later she presents with confusion, asterixis, and elevated ammonia with normal liver function tests. What is the most likely mechanism?

Accepted Answer

Occult ornithine transcarbamylase deficiency unmasked by valproate

Answer

Valproate can precipitate hyperammonemic encephalopathy in patients with previously undiagnosed partial ornithine transcarbamylase (OTC) deficiency — the most common urea cycle disorder, X-linked. OTC deficiency in heterozygous females may be clinically silent until valproate inhibits OTC directly, reduces carnitine (impairing ammonia detoxification), and increases nitrogen load, pushing a partially compensated patient into crisis. Normal LFTs exclude hepatotoxicity. This is a classic unmasking scenario rather than a primary drug toxicity.

Question 3

A 45-year-old man presents with episodic attacks of severe unilateral orbital pain lasting 15–20 minutes, occurring 10–20 times per day for 3 weeks, then remitting for months. He notes ipsilateral ptosis, lacrimation, and nasal congestion during attacks. He failed to respond to sumatriptan. Which of the following is the most appropriate treatment to ABORT acute attacks?

Accepted Answer

Intranasal lidocaine 4% ipsilateral to the pain

Answer

The clinical description is consistent with Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) or Short-lasting Unilateral Neuralgiform attacks with cranial Autonomic symptoms (SUNA), given attack duration of 15–20 minutes and very high frequency (10–20/day). SUNCT/SUNA does NOT respond to indomethacin (which is the hallmark treatment for paroxysmal hemicrania), nor reliably to triptans or oxygen. Intranasal lidocaine is the recommended acute abortive therapy for SUNCT. High-flow oxygen works for cluster headache; indomethacin is diagnostic for paroxysmal hemicrania (attacks last 2–30 minutes but typically fewer per day and respond absolutely to indomethacin).

Question 4

A 67-year-old woman develops subacute cognitive decline, cerebellar ataxia, and myoclonus over 4 months. CSF shows 14-3-3 protein positivity and elevated total tau. MRI DWI reveals cortical ribboning and basal ganglia hyperintensity. RT-QuIC of CSF is positive. Which prion protein gene (PRNP) codon 129 polymorphism is most strongly associated with the classical Heidenhain variant of this condition?

Accepted Answer

Methionine/Methionine (MM)

Answer

The clinical presentation is Creutzfeldt-Jakob disease (CJD), confirmed by positive RT-QuIC (highly sensitive and specific). The Heidenhain variant, characterized by prominent early visual disturbances and occipital cortical ribboning, is most strongly associated with MM homozygosity at PRNP codon 129. MM homozygotes account for approximately 70% of all sporadic CJD cases and tend to have more rapid progression. VV homozygosity is associated with the Brownell-Oppenheimer (ataxic) variant. MV heterozygotes often have a more protracted course.

Question 5

A 29-year-old woman develops bilateral lower extremity weakness, a sensory level at T6, and urinary retention over 36 hours. MRI spine shows a central T2 hyperintense lesion spanning C5 to T8. Serum AQP4-IgG is negative, but MOG-IgG is positive. Compared to AQP4-IgG-positive NMOSD, which of the following best characterizes MOG-IgG-associated disease (MOGAD) longitudinally extensive transverse myelitis?

Accepted Answer

Greater likelihood of complete or near-complete neurological recovery between attacks

Answer

MOGAD (MOG-IgG-associated disease) longitudinally extensive transverse myelitis (LETM) is associated with significantly better recovery between attacks compared to AQP4-IgG-positive NMOSD. While both can cause LETM, MOGAD tends to spare the gray matter less severely and has greater plasticity/remyelination capacity. In AQP4-IgG-positive disease, attacks cause more permanent astrocytopathy and axonal damage with worse residual disability. MOGAD does not have a periventricular MS-like pattern preferentially, and maintenance immunotherapy decisions are more nuanced — some patients have monophasic disease.

SPEX Exam Practice Test

SPEX Exam Practice Test

SPEX Exam Neurology 4