P2.254: When Myasthenia Gravis and Miller Fisher Syndrome Collide: Diagnostic and Treatment Complexities

Introduction: Myasthenia gravis (MG) is a rare autoimmune disorder of the neuromuscular junction, affecting an estimated 1–5 children per 1,000,000 annually. It presents with fatigable muscle weakness, most commonly ocular in the pediatric population, and can pose diagnostic challenges, especially when features overlap with other neurological conditions. On occasion, MG coexists with other autoimmune disorders, further complicating diagnosis. Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome (GBS), is another autoimmune condition affecting peripheral nerves. It is caused by anti-GQ1b antibodies and classically presents with ophthalmoplegia, ataxia, and areflexia.

Case Description: A previously healthy 5-year-old female presented to urgent care with eye swelling. Examination revealed bilateral ptosis, left cranial nerve III and VI palsies, and areflexia. Given her recent viral illness and clinical features of ophthalmoplegia and areflexia, initial suspicion was highest for MFS. Other considerations included multiple sclerosis, ocular MG, and acute disseminated encephalomyelitis. Brain MRI, lumbar puncture and anti-GQ1b antibody testing were unremarkable. She received two days of IVIG with slight improvement in her cranial neuropathies but was discharged with persistent bilateral ptosis. Although initial myasthenia antibody testing was negative, repeat testing later detected antibodies suggestive of MG. However, given prior IVIG administration, there was concern for a false-positive result. She was started on pyridostigmine, but within weeks developed dysphonia, and dysphagia, eventually presenting in respiratory distress requiring intubation. This raised concern for cholinergic toxicity versus myasthenic crisis, further complicating her diagnosis. Electromyography ultimately confirmed MG and she was successfully treated with steroids, pyridostigmine and monthly IVIG.

Discussion: The patient’s initial symmetric areflexia suggested MFS, but negative anti-GQ1b antibody testing—while less sensitive in pediatric cases—left room for uncertainty. Her incomplete recovery and persistent cranial neuropathies prompted reevaluation for MG. It remains unclear whether she had coexisting MG and MFS or was misdiagnosed initially. While rare, cases of overlapping MG and MFS have been reported, primarily in adults. Delayed follow-up, language barriers, and challenges with treatment concordance further complicated disease management with concern for cholinergic toxicity, underscoring the impact of health disparities on the diagnosis and treatment of rare diseases.

Conclusion: This case highlights the diagnostic complexity of pediatric MG, particularly when overlapping features with MFS are present. Careful interpretation of clinical findings, neuroimaging, and electrophysiologic studies is crucial. Understanding the barriers posed by unmet social needs is important for ensuring accurate diagnosis and safe, effective treatment planning.