USMLE PRACTICE QUESTION #130
TOPIC: Neuropathology
USMLE practice question #130 will test your knowledge of a commonly tested neurological disorder.
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A 24-year-old man presents to the emergency department with progressive weakness in his legs for the past 5 days. He reports difficulty climbing stairs and mild numbness in his feet. One week ago, he had a diarrheal illness that resolved spontaneously. On physical examination, there is symmetric weakness in the lower extremities with absent deep tendon reflexes. Sensory examination is intact. Nerve conduction studies reveal decreased conduction velocity. Which of the following best describes the primary mechanism responsible for his condition?
A) Autoimmune destruction of presynaptic calcium channels in motor neurons
B) Autoimmune demyelination of peripheral nerves by activated T cells and macrophages
C) Antibody-mediated destruction of Schwann cells via complement activation
D) Inhibition of acetylcholine release from motor nerve terminals by a bacterial exotoxin
E) Ischemic damage to peripheral nerves due to microvascular inflammation
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 describes the primary mechanism responsible for his condition?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Identify/diagnose the condition; 2nd: Identify the primary mechanism responsible for the condition.
Step 3: Read the vignette carefully and ask yourself: “Based on my diagnosis of __________________, I know that the primary mechanism responsible 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 24-year-old man presents with progressive symmetric weakness in the lower extremities, absent deep tendon reflexes, and a history of a preceding diarrheal illness. Nerve conduction studies reveal decreased conduction velocity, which is consistent with demyelination of peripheral nerves. These findings strongly suggest Guillain-Barré syndrome—an acute inflammatory demyelinating polyneuropathy.
ANSWER CHOICES:
CHOICE A: Autoimmune destruction of presynaptic calcium channels in motor neurons
Explanation: This mechanism describes Lambert-Eaton myasthenic syndrome (LEMS), in which autoantibodies target presynaptic voltage-gated calcium channels, impairing acetylcholine release and causing proximal muscle weakness. LEMS typically presents with proximal muscle weakness that improves with activity, not the ascending weakness and hyporeflexia seen in GBS. Additionally, LEMS is associated with paraneoplastic syndromes (e.g., small cell lung cancer), not a recent diarrheal illness.
CHOICE B: Autoimmune demyelination of peripheral nerves by activated T cells and macrophages
Explanation: In GBS, activated T cells and macrophages infiltrate the nerves and mediate demyelination, leading to impaired conduction velocity. This immune response is often triggered by molecular mimicry between microbial antigens (e.g., Campylobacter jejuni lipooligosaccharides) and host nerve components.
CHOICE C: Antibody-mediated destruction of Schwann cells via complement activation
Explanation: While antibodies may play a role in some variants of GBS, the primary mechanism in classic GBS involves T-cell-mediated demyelination rather than direct antibody-mediated destruction of Schwann cells.
CHOICE D: Inhibition of acetylcholine release from motor nerve terminals by a bacterial exotoxin
Explanation: This mechanism describes botulism, caused by Clostridium botulinum toxin, which blocks acetylcholine release at neuromuscular junctions, leading to descending flaccid paralysis.
CHOICE E: Ischemic damage to peripheral nerves due to microvascular inflammation
Explanation: Ischemic damage to peripheral nerves can occur in vasculitic neuropathies associated with systemic vasculitis (e.g., polyarteritis nodosa). These conditions often present with asymmetric neuropathy or mononeuritis multiplex. This patient's symmetric ascending weakness and hyporeflexia are more consistent with GBS than ischemic neuropathy.
FINAL VERDICT…
CORRECT ANSWER: B) Autoimmune demyelination of peripheral nerves by activated T cells and macrophages
Guillain-Barré syndrome is often triggered by an antecedent infection, such as Campylobacter jejuni, which induces an autoimmune response. The immune system mistakenly attacks the myelin sheath of peripheral nerves, leading to demyelination and impaired nerve conduction.
The primary mechanism is autoimmune demyelination mediated by activated T cells and macrophages. This process disrupts nerve conduction, leading to the characteristic ascending weakness, hyporeflexia, and decreased conduction velocity seen on nerve studies.
KEY CONCEPTS:
Guillain-Barré Syndrome (GBS):
Acute inflammatory demyelinating polyneuropathy.
Often triggered by infections (e.g., Campylobacter jejuni, viral illnesses).
Characterized by ascending symmetric weakness, hyporeflexia/areflexia, and sensory symptoms (e.g., paresthesia).
Pathophysiology of GBS:
Molecular mimicry between microbial antigens and host nerve components triggers an autoimmune response.
Activated T cells and macrophages infiltrate peripheral nerves, causing segmental demyelination.
Demyelination slows or blocks nerve conduction, leading to weakness and hyporeflexia.
Nerve Conduction Studies in GBS:
Show decreased conduction velocity or conduction block due to demyelination.
May also show prolonged distal latencies or absent F-waves.
Differential Diagnosis for Weakness:
Descending paralysis: Botulism.
Proximal muscle weakness: Lambert-Eaton myasthenic syndrome or myopathies.
Asymmetric neuropathy: Vasculitic neuropathies or mononeuritis multiplex.
Treatment of GBS:
Supportive care (e.g., respiratory monitoring for impending respiratory failure).
Immunotherapy: Intravenous immunoglobulin (IVIG) or plasmapheresis.
Corticosteroids are generally not effective in GBS.
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