Seronegative Autoimmune Encephalitis: A Case Report and Literature Review

Autoimmune encephalitis is an inflammatory disorder of the central nervous system frequently associated with antibodies directed against neuronal surface or intracellular antigens. However, a substantial subset of patients remains seronegative, posing diagnostic challenges. We report the case of a 65-year-old man who presented to the emergency department with acute confusion, prosopagnosia, psychomotor agitation, and generalized tonic-clonic seizures, followed by coma requiring intubation and intensive care admission. Extensive microbiological findings, including CSF PCR for herpes simplex virus (HSV) and varicella-zoster virus (VZV) and CSF cultures, as well as a comprehensive autoimmune encephalitis panel in serum and CSF (anti-NMDA, anti-AMPA, anti-GABA, anti-LGI1, anti-CASPR2, anti-DPPX), were all negative. Brain magnetic resonance imaging demonstrated faint diffuse cortical hyperintensity on diffusion-weighted imaging, more pronounced in the temporo-parietal regions, without contrast enhancement. Electroencephalography revealed diffuse epileptiform activity. Based on clinical presentation, neuroimaging findings, exclusion of alternative etiologies, and electroencephalographic abnormalities, a diagnosis of probable seronegative autoimmune encephalitis was established. The patient was treated with high-dose intravenous methylprednisolone followed by intravenous immunoglobulins, resulting in rapid neurological improvement and complete recovery (modified Rankin Scale (mRS) score of 1 upon discharge from the hospital). This case highlights the importance of clinical judgment in suspected autoimmune encephalitis, even in the absence of detectable neuronal antibodies, and underscores the potential for favorable outcomes with early immunotherapy.