USMLE® Step 1 Question of the Day: Blurry vision

USMLE® Step 1 Question of the Day: Blurry vision

Prepare for the USMLE Step 1 exam with this detailed question about a 39-year-old woman experiencing progressive visual changes and muscle weakness. Linked to an anterior mediastinal mass, can you correctly identify the structure affected at the neuromuscular junction? Test your knowledge and deepen your understanding of complex neuromuscular conditions.

A 39-year-old woman comes to her primary care physician for evaluation of visual changes. She reports having blurry vision that is more pronounced at the end of the day. The symptom started gradually around 3 months ago and has been progressing over time. The patient was recently diagnosed with an anterior mediastinal mass via chest CT. She consumes a diet rich in fresh vegetables and meats. Her temperature is 37.0°C (98.6°F), pulse is 67/min and blood pressure is 118/75 mmHg. Physical examination reveals weakness in the extraocular muscles. When the patient is asked to look upwards toward the ceiling for 60 seconds, she notes double vision after 40 seconds, which resolves after several minutes of rest. Visual acuity and pupillary reflexes are normal. The remainder of the physical examination is unremarkable. 

motor nerve structure

Which of the following structures at the neuromuscular junction is most likely affected in this patient’s condition? 

A. Structure A

B. Structure B

C. Structure C

D. Structure D

E. Structure E

Scroll down for the correct answer!

The correct answer to today’s USMLE® Step 1 Question is…

C. Structure C

Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

A. Structure A

Incorrect: This patient with ptosis, diplopia and extraocular muscle weakness most likely has MG, which occurs due to the formation of auto-antibodies against postsynaptic ACh receptors. In contrast, structure A is a presynaptic mitochondria, which plays no role in the pathogenesis of MG. 

 B. Structure B

Incorrect: Structure B is a presynaptic vesicle containing ACh. Botulinum toxin works by inhibiting extravasation of these vesicles into the synaptic cavity, thereby inhibiting the release of ACh. Clinically, it can manifest as diplopia, dysarthria, dysphagia, and dyspnea. It is unlikely in this patient without any risk factors (e.g. ingestion of expired canned foods).

D. Structure D 

Incorrect: Structure D is a presynaptic calcium channel. Patients with Lambert Eaton myasthenic syndrome develop auto-antibodies against this structure. The condition manifests with muscle weakness that temporarily improves with activity. However, this patient has ptosis that is elicited by prolonged upwards gaze, which suggests that her muscle weakness is worsened with activity. This finding is more consistent with MG. 

E. Structure E

Incorrect: Structure E is a vesicle that has fused with the cellular membrane and is releasing ACh into the neuromuscular junction. As mentioned before, botulinum toxin impairs this process and can manifest with flaccid muscle paralysis, diplopia, dysarthria, and/or dysphagia.

Main Explanation

The patient has extraocular muscle weakness that worsens with repeated activity and improves with rest. These findings are concerning for myasthenia gravis (MG). MG is often associated with thymic abnormalities (e.g., thymic hyperplasia or thymoma), as seen in this patient with recent diagnosis of mediastinal mass on CT scan. 

MG is a type II hypersensitivity reaction that develops when B-cells begin producing antibodies against nicotinic acetylcholine (ACh) receptors on muscle cells. Myasthenia gravis causes muscle weakness via two mechanisms. First, the antibodies block the binding of ACh to its receptors. Second, the antibodies can activate the classical complement pathway, resulting in destruction of ACh receptors.  

Due to the reduced number of available ACh receptors, ACh released at the nerve terminal is unable to generate the postsynaptic potential needed to induce muscle contraction, resulting in muscle weakness. The weakness is more pronounced with the repeated use of a muscle group, since it causes depletion of the ACh store in the neuromuscular junction. 

A minority of people with MG produce another type of antibody against muscle-specific tyrosine kinase (MuSK). This antibody attacks proteins within myocytes and also results in impaired muscle cell activity.

Major Takeaway

MG is a type II hypersensitivity reaction that is most commonly caused by the production of auto-antibodies against nicotinic ACh receptors. The antibodies prevent the binding of ACh to its receptors and cause complement-mediated receptor destruction. A minority of cases are caused by the production of auto-antibodies against MuSK.  

References

  • Melzer, N., Ruck, T., et al. (2016) Clinical features, pathogenesis, and treatment of myasthenia gravis: A supplement to the Guidelines of the German Neurological Society. Journal of Neurology. 263, 1473-1494. Doi: 10.1007/s00415-016-8045-z. 
  • Pasnoor, M., Dimachkie, M.M., Farmakidis, C., Barohn, R.J. (2018) Diagnosis of myasthenia gravis. Neurologic Clinics. 36(2), 261-274. Doi: 10.1016/j.ncl.2018.01.010. 
  • Trouth, A.J., Dabi, A., et al. (2012) Myasthenia gravis: A review. Autoimmune Diseases. 874680. Doi: 10.1155/2012/874680. 

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The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB. 


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