2026 ECNP Congress

PS04-4083

Post-infectious anti-NMDA receptor encephalitis associated with HSV: a treatment-resistant case

Beyza Gamze Ozkaya — R.S. Ilhan, C. Ustundag, B. Duman, K.C. Can, B. Colak, Y. Kir, S.Z. Tatli, C. Yucesan, S. Erdogan, R. Yilmaz, O.E. Yalap, G. Cinar, M.C. Saka · Ankara University School of Medicine, Department of Psychiatry, Ankara, Türkiye

2026 ECNP Congress

Introduction

Anti–N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an immune-mediated central nervous system disorder caused by autoantibodies against the NR1 subunit of NMDA receptors, leading to synaptic dysfunction and neuropsychiatric symptoms [1][2];.

It is the most common form of autoimmune encephalitis, with acute or subacute onset and a multiphasic course, with early psychiatric symptoms followed by seizures, movement disorders, cognitive impairment, and autonomic dysfunction [1][2][3];.

Initially described as a paraneoplastic syndrome, infections are increasingly recognized as triggers. Proposed mechanisms for post-infectious encephalitis include molecular mimicry and the release of normally immune-privileged antigens following tissue damage, triggering an antigenic response [4];.

Diagnosis is based on clinical findings and detection of anti-NMDAR antibodies in cerebrospinal fluid (CSF). Electroencephalography is frequently abnormal, whereas magnetic resonance imaging is often normal or nonspecific [1][3];.

Case Presentation

A 43-year-old woman presented with sudden onset of severe headache and loss of consciousness. Initial evaluations were unremarkable; however, CSF analysis revealed HSV-1 PCR positivity, confirming the diagnosis of herpes simplex encephalitis. She was subsequently treated with intravenous acyclovir. Although her consciousness partially improved, she remained disoriented with persistent cognitive impairment.

One month after symptom onset, she developed marked agitation, disorganized behavior, inability to recognize familiar individuals, and purposeless motor activity. Brain magnetic resonance imaging (MRI) revealed contrast-enhancing T2/FLAIR hyperintensities in the left medial temporal lobe and hippocampus, extending into the anterior temporal region and insula.

Follow-up CSF analysis showed pleocytosis, elevated IgG index (6.4), and type 2 oligoclonal band (OCB) positivity, while HSV PCR was negative. Due to persistent neuropsychiatric symptoms, autoimmune encephalitis was suspected, and anti-NMDAR antibodies were detected in CSF. The patient was diagnosed with anti-NMDAR encephalitis following HSV encephalitis, a well-recognized trigger in the literature [4];.

The patient was admitted for severe behavioral symptoms and received symptomatic treatment. Pulse intravenous methylprednisolone was initiated, followed by plasmapheresis due to lack of response.

Despite these treatments, the patient showed no clinical improvement. Following transfer to the intensive care unit, she died due to rapidly progressive multiorgan failure.

Discussion

Anti-NMDAR encephalitis can develop following infections or neoplasms and is mediated by autoantibodies targeting NMDA receptors, leading to synaptic dysfunction [1][2];.

The clinical course is typically multiphasic, with early psychiatric symptoms that may delay diagnosis, particularly in post-infectious cases [1][3];. Infections are increasingly recognized as triggers, and peripheral immune activation combined with blood–brain barrier disruption may promote intrathecal antibody production [2][4];.

EEG findings support diagnosis, most commonly demonstrating generalized slowing, although epileptiform activity may also be observed [1][3];.

Treatment aims to achieve immunosuppression alongside the appropriate management of any underlying malignancy. First-line therapies include high-dose corticosteroids, intravenous immunoglobulin, and plasmapheresis; some patients require second-line immunosuppressive treatments such as rituximab due to inadequate response [1][5];.

In this case, lack of response to corticosteroids and plasmapheresis reflects a treatment-resistant course with poorer outcomes, highlighting the importance of early recognition of post-infectious autoimmune encephalitis [5];.

Conclusions

Anti-NMDAR encephalitis may develop after infectious encephalitis and should be considered in patients with post-infectious neuropsychiatric symptoms.

Delayed diagnosis and late initiation of immunotherapy are associated with poorer outcomes. Early recognition of refractory cases and timely use of second-line immunotherapy may improve clinical outcomes.

References

  1. Nguyen, L., & Wang, C. (2023). Anti-NMDA receptor autoimmune encephalitis: Diagnosis and management strategies. International Journal of General Medicine, 16, 7–21. https://doi.org/10.2147/IJGM.S397429
  2. Dalmau, J., & Graus, F. (2025). Anti-NMDA receptor encephalitis: A narrative review. Brain Sciences, 15(5), 518. https://doi.org/10.3390/brainsci15050518
  3. Zhao, X., Teng, Y., Ni, J., Li, T., Shi, J., & Wei, M. (2023). Clinical characteristics of anti-NMDAR encephalitis: A systematic review. Frontiers in Human Neuroscience, 17, 1261638. https://doi.org/10.3389/fnhum.2023.1261638
  4. Alexopoulos, H., Akrivou, S., Mastroyanni, S., Antonopoulou, M., Dinopoulos, A., Giorgi, M., Konstantinou, K., Kouremenos, E., Lariou, M., Naoumis, D., Pavlidou, E., Pavlou, E., Voudris, K., Vlachoyiannopoulos, P., & Dalakas, M. C. (2018). Postherpes simplex encephalitis: A case series of viral-triggered autoimmunity, synaptic autoantibodies and response to therapy. Therapeutic Advances in Neurological Disorders, 11, 1756286418768778. https://doi.org/10.1177/1756286418768778
  5. Nosadini, M., et al. (2025). Immunotherapy in autoimmune encephalitis: Updated meta-analysis and treatment recommendations. Psychiatry Research, 332, 115792.