Differential Diagnosis for Ocular Diplopia, Ptosis, Generalized Weakness, and Fluctuating Symptoms

• Single Most Likely Diagnosis

  • Myasthenia Gravis: The patient's symptoms of ocular diplopia, ptosis, generalized weakness, and fluctuating symptoms, along with a positive family history and specific electrophysiological findings (reduced CMAP worsened with Edrophonium test and decremental response on RNS at 2 Hz), are highly suggestive of Myasthenia Gravis. The Edrophonium test, in particular, is a diagnostic tool often used to confirm the diagnosis of Myasthenia Gravis due to its ability to temporarily improve muscle strength in these patients.

• Other Likely Diagnoses

  • Lambert-Eaton Myasthenic Syndrome (LEMS): Although LEMS can present with similar symptoms, it typically involves more proximal muscle weakness and autonomic dysfunction. The response to repetitive nerve stimulation (RNS) in LEMS usually shows an incremental response, not decremental, which makes it less likely in this scenario.
  • Congenital Myasthenic Syndromes (CMS): Given the positive family history, CMS could be considered. However, CMS typically presents at birth or in early childhood, and the specific pattern of inheritance and symptomatology can vary widely among the different types of CMS.

• Do Not Miss Diagnoses

  • Botulism: Although rare, botulism can present with similar symptoms, including diplopia, ptosis, and generalized weakness. It is crucial to consider this diagnosis due to its potential for severe outcomes and the need for prompt treatment.
  • Tick-Borne Illnesses (e.g., Tick Paralysis): In endemic areas, tick paralysis can cause ascending paralysis and should be considered, especially if there's a history of tick exposure.

• Rare Diagnoses

  • Slow Channel CMS: This is a rare form of congenital myasthenic syndrome characterized by a prolonged opening of the acetylcholine receptor channel, leading to desensitization and a myasthenic syndrome. It is less likely given the late presentation and specific electrophysiological findings.
  • End Plate Acetylcholinesterase (AChE) Deficiency: Another rare congenital myasthenic syndrome, characterized by a deficiency of acetylcholinesterase at the neuromuscular junction, leading to prolonged neuromuscular transmission and muscle weakness. The presentation and diagnostic findings would need to closely align with this specific disorder for it to be considered a likely diagnosis.