Severe hyponatremia masking cryptococcal meningitis in a fingolimod-treated patient: a case report

Background: Cryptococcal meningitis is a life-threatening fungal infection and diagnostic delays have been associated with increased mortality. In individuals without human immunodeficiency virus infection, immunosuppressive medications are important risk factors for this condition. As it typically affects immunocompromised patients, cryptococcal meningitis may present without classic meningeal signs. In addition, hyponatremia is associated with central nervous system infection and may contribute to encephalopathy, potentially making the diagnosis even more challenging.

Case Description: A 77-year-old man with a history of multiple sclerosis receiving fingolimod for 15 years presented with a four-week history of progressive confusion. On presentation, he was afebrile. Physical examination revealed a lethargic appearance with disorientation to place, without meningeal signs or new focal neurologic deficits. Laboratory evaluation demonstrated severe hyponatremia and lymphopenia. Head computed tomography (CT) was unremarkable. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis and mildly elevated protein levels, with a normal opening pressure. CSF smear demonstrated encapsulated round yeast-like organisms. Cryptococcal polymerase chain reaction of the CSF was positive, and both CSF and blood cultures grew Cryptococcus neoformans, consistent with disseminated cryptococcosis. Dual antifungal therapy with liposomal amphotericin B and flucytosine was initiated. The patient’s systemic symptoms and altered mentation subsequently resolved without sequelae.

Conclusion: In patients receiving fingolimod who present with subacute altered mental status and severe hyponatremia, clinicians should maintain a high index of suspicion for cryptococcal meningitis and consider early cerebrospinal fluid evaluation, even in the absence of fever or meningeal signs.