, Question 1
In a neuron undergoing sustained glutamate exposure, which sequence best
explains delayed calcium-dependent necrosis rather than apoptosis?
A. NMDA receptor overactivation -> Ca² influx -> calpain and nNOS
activation -> mitochondrial permeability transition pore opening
B. AMPA receptor desensitization -> Na/K ATPase failure -> cytochrome
c release -> caspase-3 cleavage
C. Metabotropic glutamate receptor activation -> IP-mediated Ca² release
-> Bcl-2 upregulation -> lysosomal rupture
D. Reverse Na/Ca² exchanger operation -> cytosolic Ca² clearance ->
caspase-independent PARP inhibition
Correct Answer: A - NMDA receptor overactivation -> Ca²
influx -> calpain and nNOS activation -> mitochondrial
permeability transition pore opening
RATIONALE
Excitotoxic necrosis is driven by NMDA-mediated Ca² overload,
activating calpains and nNOS; mitochondrial permeability transition
pore opening dissipates m and causes ATP collapse, favoring necrosis
over caspase-dependent apoptosis. Distractors misassign receptor
subtypes, ion gradients, or downstream effectors.
Question 2
A patient with anti-NMDA receptor encephalitis is most likely to exhibit which
pathophysiologic mechanism underlying the psychiatric and seizure
manifestations?
A. Antibody-mediated internalization of NMDA receptors, reducing
synaptic currents and disrupting glutamatergic signaling
B. Complement-mediated destruction of GABAergic interneurons in the
hippocampus
C. Direct antibody blockade of voltage-gated potassium channels causing
Page 2
, hyperexcitability
D. Antibody-induced upregulation of AMPA receptors leading to
excitotoxic injury
Correct Answer: A - Antibody-mediated internalization of
NMDA receptors, reducing synaptic currents and disrupting
glutamatergic signaling
RATIONALE
Anti-NMDAR encephalitis involves IgG antibodies against the GluN1
subunit, causing receptor crosslinking and internalization, which
reduces NMDAR-mediated currents and produces neuropsychiatric
symptoms and seizures. Other options incorrectly implicate
GABAergic loss, potassium channels, or AMPA upregulation.
Question 3
Which finding best localizes a lesion to the medial longitudinal fasciculus
(MLF) rather than the abducens nucleus?
A. Impaired adduction of the ipsilateral eye with preserved convergence
B. Impaired abduction of the ipsilateral eye with diplopia on lateral gaze
C. Downbeat nystagmus on upward gaze with vertigo
D. Bilateral ptosis with impaired upward gaze
Correct Answer: A - Impaired adduction of the ipsilateral eye
with preserved convergence
RATIONALE
MLF lesions cause internuclear ophthalmoplegia: failure of adduction
in the ipsilateral eye with intact convergence, because the MLF carries
signals from the abducens internuclear neurons to the contralateral
oculomotor nucleus. Abducens nuclear lesions cause abduction deficit;
other options reflect different brainstem/cerebellar sites.
Page 3
, Question 4
A lumbar puncture in a patient with suspected Guillain-Barré syndrome is most
likely to show which cerebrospinal fluid profile, and what is the
pathophysiologic basis?
A. Elevated protein with normal white blood cell count due to
autoimmune demyelination and blood-nerve barrier disruption
B. Elevated white blood cells with normal protein due to viral meningitis
C. Low glucose with elevated neutrophils due to bacterial meningitis
D. Xanthochromia with elevated red blood cells due to subarachnoid
hemorrhage
Correct Answer: A - Elevated protein with normal white blood
cell count due to autoimmune demyelination and blood-nerve
barrier disruption
RATIONALE
GBS classically demonstrates albuminocytologic dissociation:
elevated protein with normal cell count, resulting from
autoimmune-mediated demyelination and increased permeability of
the blood-nerve barrier. The other profiles correspond to infectious or
hemorrhagic processes, not GBS.
Question 5
Which molecular alteration is most directly linked to the pathogenesis of
Alzheimer disease via impaired amyloid-beta clearance?
A. Presenilin mutations increasing A42 production
B. APOE 4 allele enhancing A aggregation and reducing clearance
C. Tau hyperphosphorylation destabilizing microtubules
D. Alpha-synuclein aggregation forming Lewy bodies
Correct Answer: B - APOE 4 allele enhancing A aggregation and
reducing clearance
Page 4
In a neuron undergoing sustained glutamate exposure, which sequence best
explains delayed calcium-dependent necrosis rather than apoptosis?
A. NMDA receptor overactivation -> Ca² influx -> calpain and nNOS
activation -> mitochondrial permeability transition pore opening
B. AMPA receptor desensitization -> Na/K ATPase failure -> cytochrome
c release -> caspase-3 cleavage
C. Metabotropic glutamate receptor activation -> IP-mediated Ca² release
-> Bcl-2 upregulation -> lysosomal rupture
D. Reverse Na/Ca² exchanger operation -> cytosolic Ca² clearance ->
caspase-independent PARP inhibition
Correct Answer: A - NMDA receptor overactivation -> Ca²
influx -> calpain and nNOS activation -> mitochondrial
permeability transition pore opening
RATIONALE
Excitotoxic necrosis is driven by NMDA-mediated Ca² overload,
activating calpains and nNOS; mitochondrial permeability transition
pore opening dissipates m and causes ATP collapse, favoring necrosis
over caspase-dependent apoptosis. Distractors misassign receptor
subtypes, ion gradients, or downstream effectors.
Question 2
A patient with anti-NMDA receptor encephalitis is most likely to exhibit which
pathophysiologic mechanism underlying the psychiatric and seizure
manifestations?
A. Antibody-mediated internalization of NMDA receptors, reducing
synaptic currents and disrupting glutamatergic signaling
B. Complement-mediated destruction of GABAergic interneurons in the
hippocampus
C. Direct antibody blockade of voltage-gated potassium channels causing
Page 2
, hyperexcitability
D. Antibody-induced upregulation of AMPA receptors leading to
excitotoxic injury
Correct Answer: A - Antibody-mediated internalization of
NMDA receptors, reducing synaptic currents and disrupting
glutamatergic signaling
RATIONALE
Anti-NMDAR encephalitis involves IgG antibodies against the GluN1
subunit, causing receptor crosslinking and internalization, which
reduces NMDAR-mediated currents and produces neuropsychiatric
symptoms and seizures. Other options incorrectly implicate
GABAergic loss, potassium channels, or AMPA upregulation.
Question 3
Which finding best localizes a lesion to the medial longitudinal fasciculus
(MLF) rather than the abducens nucleus?
A. Impaired adduction of the ipsilateral eye with preserved convergence
B. Impaired abduction of the ipsilateral eye with diplopia on lateral gaze
C. Downbeat nystagmus on upward gaze with vertigo
D. Bilateral ptosis with impaired upward gaze
Correct Answer: A - Impaired adduction of the ipsilateral eye
with preserved convergence
RATIONALE
MLF lesions cause internuclear ophthalmoplegia: failure of adduction
in the ipsilateral eye with intact convergence, because the MLF carries
signals from the abducens internuclear neurons to the contralateral
oculomotor nucleus. Abducens nuclear lesions cause abduction deficit;
other options reflect different brainstem/cerebellar sites.
Page 3
, Question 4
A lumbar puncture in a patient with suspected Guillain-Barré syndrome is most
likely to show which cerebrospinal fluid profile, and what is the
pathophysiologic basis?
A. Elevated protein with normal white blood cell count due to
autoimmune demyelination and blood-nerve barrier disruption
B. Elevated white blood cells with normal protein due to viral meningitis
C. Low glucose with elevated neutrophils due to bacterial meningitis
D. Xanthochromia with elevated red blood cells due to subarachnoid
hemorrhage
Correct Answer: A - Elevated protein with normal white blood
cell count due to autoimmune demyelination and blood-nerve
barrier disruption
RATIONALE
GBS classically demonstrates albuminocytologic dissociation:
elevated protein with normal cell count, resulting from
autoimmune-mediated demyelination and increased permeability of
the blood-nerve barrier. The other profiles correspond to infectious or
hemorrhagic processes, not GBS.
Question 5
Which molecular alteration is most directly linked to the pathogenesis of
Alzheimer disease via impaired amyloid-beta clearance?
A. Presenilin mutations increasing A42 production
B. APOE 4 allele enhancing A aggregation and reducing clearance
C. Tau hyperphosphorylation destabilizing microtubules
D. Alpha-synuclein aggregation forming Lewy bodies
Correct Answer: B - APOE 4 allele enhancing A aggregation and
reducing clearance
Page 4
