Overlapping NMOSD-AQP4 and Bickerstaff Encephalitis: an intriguing case report

CASE PRESENTATION

A 50-year-old previously healthy male presented with sudden malaise, blurred vision, imbalance, nausea, and vomiting. During an ENT consultation, ischemic causes were ruled out with CT and MRI. Despite initial treatment with betahistine and cinnarizine, symptoms persisted, evolving to drowsiness, dysphonia, dysphagia, and urinary retention, prompting a neurology evaluation. Patient reported experiencing recurrent sharp pain on the lateral aspect of his right thigh ten days prior to symptom onset. On physical examination, he presented with skew deviation, multidirectional nystagmus, right internuclear ophthalmoplegia, globally increased and symmetric reflexes, right dysmetria, and significant dysbasia. A lumbar puncture revealed significant pleocytosis (50 cells), raising the suspicion of possible rhombencephalitis of infectious or inflammatory etiology. Empirical treatment with intravenous antibiotics was initiated. The patient's symptoms remained refractory, and viral PCRs and cultures were negative. A MRI performed at our facility revealed multiple inflammatory lesions with periventricular and perivenular distribution, associated with perivascular diffusion restriction in the right cerebellar peduncle, corpus callosum, and subcortical regions, with contrast enhancement. A new lumbar puncture showed increased pleocytosis (110 cells), oligoclonal bands of IgG were present, IgG index > 0.5 and positive Anti-GQ1b. Additionally, positive AQP4-IgG was positive in the serum.  Given the Anti-AQP4 positivity and neuroimaging findings, the diagnosis of NMOSD-AQP4 was established. The patient underwent pulse therapy with methylprednisolone, plasmapheresis, and maintenance therapy with rituximab.

DISCUSSION

Anti-GQ1B syndromes are well-documented with specific diagnostic criteria, which typically exclude NMOSD. There is only one other similar reported case in the literature, involving a Miller Fisher Syndrome with AQP4-IGG positivity.

FINAL COMMENTS

This case report demonstrates a clinical and serological overlap between NMOSD-AQP4 and Bickerstaff encephalitis (anti-GQ1B syndromes), which is unique in the literature. This case raises the hypothesis of whether there is an overlap of diseases or if there is a disease spectrum related to AQP4-IGG.