We present a rare manifestation of neuromyelitis optica spectrum disorder (NMOSD), highlighting the diagnostic challenges and therapeutic strategies involved.

NMOSD is an autoimmune astrocytopathy mediated by aquaporin-4 antibodies. Hypothalamic involvement is increasingly recognized and may cause neuroendocrine disturbances. Hyponatremia in NMOSD is usually due to syndrome of inappropriate antidiuresis (SIADH) or, rarely, central diabetes insipidus. Cerebral salt wasting (CSW), a well-recognized entity following subarachnoid hemorrhage or neurosurgery has not previously been described in NMOSD.

A 23-year-old woman with aquaporin-4-positive NMOSD with previous history of three relapses, presented one week after her third rituximab infusion with polyuria, and rapidly progressive encephalopathy leading to intubation and intensive care. Investigations revealed severe hypotonic hyponatremia (serum sodium 104 mmol/L and osmolality 245 mOsm/kg), high urine sodium (107 mmol/L), elevated urine osmolality (164 mOsm/kg), and blood urea 145 mg/dL with polyuria (11L in day 1) and hypovolemia. Cerebrospinal fluid showed isolated elevated proteins (75 mg/dL). MRI brain demonstrated new T2/FLAIR hyperintense lesions in the left hypothalamus, right medial thalamus, left medial temporal lobe, and right periventricular white matter, indicating demyelinating activity compatible with a hypothalamic–thalamic relapse of NMOSD. Her hyponatremia was corrected slowly with hypertonic saline and fludrocortisone, and active disease was managed with intravenous methylprednisolone followed by five plasma-exchange cycles. Her clinical response was excellent. She was started on tapering oral steroids and mycophenolate mofetil. As this represented her fourth relapse despite rituximab therapy despite an adequate B-cell depletion (CD19 lymphocytes 0.7%), treatment was transitioned to tocilizumab for relapse prevention.

This case represents the first reported CSW in an NMOSD relapse, broadening the recognized phenotypic spectrum of the disease. It underscores the critical need to distinguish CSW from SIADH, as management approaches are fundamentally opposite. Prompt recognition and treatment of both hyponatremia and active inflammatory disease are essential for better outcomes.