Welcome to USMLE practice question #141! Today’s topic is neuropathology.
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A 62-year-old man presents to the clinic with a 3-month history of progressive difficulty walking and intermittent numbness in his feet. He has a history of alcohol use disorder but denies recent alcohol intake. Neurological examination reveals decreased vibration and proprioception in the lower extremities, mild weakness in both legs, and hyperreflexia in the lower limbs. His gait is wide-based and unsteady. Laboratory findings show a hemoglobin level of 9.5 g/dL (normal: 13.5–17.5 g/dL) and a mean corpuscular volume of 115 fL. Which of the following best explains the underlying cause of this patient’s condition?
A) Loss of myelin in the corticospinal and dorsal column tracts
B) Demyelination of peripheral nerves
C) Axonal degeneration
D) Autoimmune demyelination of the dorsal roots and peripheral nerves
E) Neuronal apoptosis
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following best explains the underlying cause of this patient’s condition?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the problem, 2nd: Identify the most likely underlying cause
Step 3: Read the vignette carefully and ask yourself: “Based on the patient’s history and my diagnosis, the most likely underlying cause is ______________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This 62-year-old man presents with progressive difficulty walking, numbness in his feet, and neurological findings of decreased vibration and proprioception, mild leg weakness, and hyperreflexia. His gait is wide-based and unsteady, and laboratory findings show macrocytic anemia (MCV 115 fL). These findings are consistent with subacute combined degeneration of the spinal cord caused by vitamin B12 deficiency.
ANSWER CHOICES:
CHOICE A: Loss of myelin in the corticospinal and dorsal column tracts
Explanation: Vitamin B12 deficiency causes subacute combined degeneration (SCD) due to demyelination of the corticospinal tracts (spastic paresis, hyperreflexia, and weakness) and dorsal columns (impaired vibration sense, proprioception, and sensory ataxia)
CHOICE B: Demyelination of peripheral nerves
Explanation: Demyelination of peripheral nerves occurs in conditions like Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, leading to symptoms such as flaccid weakness, hyporeflexia, and sensory loss.
CHOICE C: Axonal degeneration
Explanation: Axonal degeneration is characteristic of alcoholic neuropathy or other toxic/metabolic neuropathies. These typically cause distal sensory loss, weakness, and hyporeflexia in a length-dependent pattern.
CHOICE D: Autoimmune demyelination of the dorsal roots and peripheral nerves
Explanation: Autoimmune demyelination occurs in conditions like Guillain-Barré syndrome or Miller Fisher syndrome, leading to acute flaccid paralysis or ataxia due to peripheral nerve involvement.
CHOICE E: Neuronal apoptosis
Explanation: Neuronal apoptosis occurs in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Alzheimer’s disease but does not explain this patient’s combination of macrocytic anemia and neurological findings.
FINAL VERDICT…
CORRECT ANSWER: A) Loss of myelin in the corticospinal and dorsal column tracts
The patient’s symptoms are best explained by subacute combined degeneration caused by vitamin B12 deficiency, which leads to demyelination of the corticospinal tracts (causing hyperreflexia and weakness) and dorsal columns (causing impaired vibration sense and proprioception).
KEY CONCEPTS:
Subacute Combined Degeneration (SCD):
Caused by vitamin B12 deficiency.
Leads to demyelination of:
Corticospinal tracts: Upper motor neuron signs (e.g., spasticity, hyperreflexia).
Dorsal columns: Loss of vibration sense, proprioception, sensory ataxia.
Symptoms include progressive weakness, sensory deficits, ataxia, and wide-based gait.
Vitamin B12 Deficiency Causes:
Poor dietary intake (e.g., vegan diet).
Malabsorption (e.g., pernicious anemia, chronic gastritis).
Alcohol use disorder with associated nutritional deficiencies.
Laboratory Findings in Vitamin B12 Deficiency:
Macrocytic anemia with elevated MCV.
Low serum vitamin B12 levels.
Elevated methylmalonic acid and homocysteine levels.
Differential Diagnosis for Ataxia with Hyperreflexia:
Subacute combined degeneration due to vitamin B12 deficiency.
Multiple sclerosis.
Cervical spondylotic myelopathy.
Management of SCD:
Vitamin B12 replacement therapy.
Early treatment can reverse symptoms; delayed treatment may result in permanent neurological damage.