A 62-year-old man with fatigable weakness and ptosis with positive acetylcholine receptor antibodies and a thymoma on CT most likely has which diagnosis?

• A. Amyotrophic lateral sclerosis
• B. Lambert-Eaton syndrome
• C. Multiple sclerosis
• D. Myasthenia gravis

Answer: (A)

The main idea here is autoimmune disruption of neuromuscular transmission at the motor endplate. Myasthenia gravis arises when antibodies target the postsynaptic acetylcholine receptors, reducing the number and function of receptors. This leads to fatigable weakness that worsens with activity and commonly involves the ocular muscles, causing ptosis and diplopia. The strong association of MG with thymic pathology, including thymoma, explains why a thymoma on CT supports this diagnosis and why acetylcholine receptor antibodies are typically positive.

Why other conditions fit poorly: amyotrophic lateral sclerosis causes progressive motor neuron loss with weakness that is not characteristically fatigable in the same way and lacks acetylcholine receptor antibodies or thymic association. multiple sclerosis presents with central nervous system demyelination signs (optic neuritis, sensory or gait disturbances) and does not involve ACh receptor antibodies or thymoma. Lambert-Eaton syndrome features a presynaptic defect with antibodies to voltage-gated calcium channels, often showing strength improvement with repeated use and usually linked to an underlying small cell lung cancer, not thymoma or ACh receptor antibodies.

So the combination of fatigable weakness with ptosis, positive acetylcholine receptor antibodies, and a thymoma strongly points to myasthenia gravis.