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Autoimmune-encephalitis is a condition that often presents with predominant psychiatric symptoms, causing delays in appropriate management, making early diagnosis crucial, as it is treatable. It’s an immune-mediated inflammatory disorder of the central nervous system, characterised by the immune system attacking neural tissue. It presents with psychiatric symptoms, ranging from anxiety and mood disturbances to frank psychosis, including hallucinations, delusions, and catatonia, rapidly progressing over weeks to months. Post herpes simplex virus encephalitis (HSVE) development of anti-NMDAR antibodies leading to autoimmune-encephalitis is a rare complication. Anti-NMDAR encephalitis typically develops within 1-4 weeks following HSVE. In children, it commonly presents with movement disorders such as choreoathetosis and orofacial dyskinesias, whereas in adults, psychiatric manifestations are more prominent.

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We report a case of a 35-year-old female with no psychiatric or significant medical history, who initially presented with acute febrile-illness and altered consciousness, suggestive of a CNS infection. Following recovery she developed psychiatric symptoms over two months, including depression, anxiety, delusions, and cognitive decline. This led to a diagnosis of MDD with psychotic features, and was subsequently treated with antidepressants and anti-psychotics. Despite treatment her condition deteriorated and she experienced a decline in cognitive function, pointing towards an underlying etiology. Further evaluation revealed temporal lobe epileptiform activity on EEG and MRI findings suggesting encephalitis, with serological evidence.

Persistent neuropsychiatric symptoms even after the management of viral encephalitis and imaging findings raised suspicion of autoimmune-encephalitis with psychiatric manifestations and subclinical epilepsy. The patient showed significant improvement following immunotherapy with high-dose corticosteroids, intravenous-immunoglobulin, immunonodulators and neuroprotective agents.

The case highlights the importance of considering a differential of autoimmune-encephalitis in patients presenting with atypical, progressive psychiatric symptoms, especially associated with cognitive deficits and poor response to conventional therapy, following infectious episodes like HSV-1 encephalitis. Early recognition can significantly improve outcomes and prevent long-term morbidity.