Misleading detection of herpes simplex virus type 1 in a patient with paraneoplastic encephalitis

Encephalitis is a potentially life-threatening condition with infectious or autoimmune aetiologies. Autoimmune encephalitis includes paraneoplastic variants associated with specific onconeural antibodies such as anti-Hu, frequently linked to malignancies. Herpes simplex virus type 1 (HSV-1) is the leading infectious cause in adults. Differentiating between these aetiologies can be challenging. We report the case of an 88-year-old woman admitted with confusion following a fall. Initial evaluation showed clinical signs consistent with encephalitis. During hospitalisation, a seizure was witnessed. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis, but no infectious agent was detected, and brain imaging revealed no significant abnormalities. After initial improvement under antiepileptic therapy, the patient experienced worsening cognitive dysfunction. Repeat CSF testing 4 weeks after initial symptom onset showed even milder pleocytosis but was positive for HSV-1 and magnetic resonance imaging showed bilateral hippocampal hyperintensities. Analysis of the first CSF sample retrospectively revealed high-titer anti-Hu antibodies. Positron emission tomography-computed tomography scan identified a hypermetabolic lung lesion and para-aortic lymph node, with biopsy confirming the diagnosis of small cell lung cancer. Immunosuppressive and oncologic treatment led to transient improvement, followed by progressive neurological deterioration. Supportive care was ultimately prioritized. This case underscores the diagnostic challenges of encephalitis, especially when autoimmune and infectious features overlap, and diagnostic findings are misleading. Detection of HSV-1 should not delay the investigation of alternative causes of encephalitis in the absence of typical HSV-related features. Early recognition of paraneoplastic encephalitis is critical, as neurologic symptoms may precede the diagnosis of underlying malignancy.