NCS Neurologic Pathophysiology 2 — Questions and Answers
Question 1: Uhthoff's phenomenon in multiple sclerosis is best explained by which pathophysiologic mechanism?
- Increased inflammatory cytokine release with fever
- Heat-induced conduction failure in demyelinated axons (Correct answer)
- Autoimmune attack triggered by elevated core temperature
- Increased cortisol suppressing myelin repair
Correct answer: Heat-induced conduction failure in demyelinated axons
Demyelinated axons have reduced safety factor for conduction, and even small rises in temperature further impair sodium channel function, causing transient neurologic deficits.
Question 2: Lewy bodies in Parkinson's disease are primarily composed of which misfolded protein?
- Tau
- Alpha-synuclein (Correct answer)
- TDP-43
- Beta-amyloid
Correct answer: Alpha-synuclein
Lewy bodies are intraneuronal inclusions predominantly composed of aggregated alpha-synuclein, a presynaptic protein implicated in dopaminergic neuron death.
Question 3: In Guillain-Barré syndrome (AIDP subtype), nerve conduction studies most characteristically show:
- Reduced CMAP amplitude with normal conduction velocity
- Prolonged distal latencies and slowed conduction velocity indicating demyelination (Correct answer)
- Fibrillation potentials on needle EMG as the earliest finding
- Absent F-waves only in lower extremity nerves
Correct answer: Prolonged distal latencies and slowed conduction velocity indicating demyelination
AIDP is an acute inflammatory demyelinating polyneuropathy, so NCS demonstrates slowed conduction velocity, prolonged distal latencies, conduction block, and temporal dispersion.
Question 4: A patient with ALS demonstrates both upper and lower motor neuron signs. The hallmark LMN finding that most strongly supports ALS over a structural lesion is:
- Hyperreflexia in the affected limb
- Fasciculations at rest in multiple body regions (Correct answer)
- Positive Babinski sign bilaterally
- Spastic gait pattern
Correct answer: Fasciculations at rest in multiple body regions
Widespread fasciculations at rest across multiple myotomal distributions indicate diffuse anterior horn cell involvement, a key LMN signature of ALS not explained by a focal structural lesion.
Question 5: The amyloid cascade hypothesis of Alzheimer's disease proposes that the initiating pathological event is:
- Hyperphosphorylation of tau forming neurofibrillary tangles
- Abnormal processing of APP leading to Aβ42 accumulation (Correct answer)
- Cholinergic neuron loss in the nucleus basalis of Meynert
- Neuroinflammation driven by activated microglia
Correct answer: Abnormal processing of APP leading to Aβ42 accumulation
The amyloid cascade hypothesis holds that accumulation of Aβ42 peptide from abnormal APP cleavage by beta- and gamma-secretases is the upstream trigger for downstream tau pathology and neurodegeneration.
Question 6: Huntington's disease causes preferential degeneration of which neuronal population, explaining the characteristic chorea?
- Dopaminergic neurons of the substantia nigra pars compacta
- GABAergic medium spiny neurons of the striatum (Correct answer)
- Purkinje cells of the cerebellar cortex
- Cholinergic neurons of the basal forebrain
Correct answer: GABAergic medium spiny neurons of the striatum
Loss of GABAergic medium spiny neurons in the striatum (caudate/putamen) disinhibits the thalamus via indirect pathway disruption, producing excessive involuntary movements.
Question 7: In myasthenia gravis (AChR-antibody positive), the primary pathophysiologic mechanism causing fatigable weakness is:
- Presynaptic failure to release acetylcholine vesicles
- Antibody-mediated destruction and blockade of postsynaptic AChR (Correct answer)
- Degeneration of the motor neuron axon terminal
- Impaired voltage-gated calcium channel function at the NMJ
Correct answer: Antibody-mediated destruction and blockade of postsynaptic AChR
AChR antibodies cause complement-mediated destruction of the postsynaptic membrane, receptor internalization, and direct blockade, reducing the end-plate potential below the threshold for action potential generation.
NCS Neurologic Pathophysiology 2
Uhthoff's phenomenon in multiple sclerosis is best explained by which pathophysiologic mechanism?