PP13.2 – 3042: Infantile spasms in an infant with anti-NMDA receptor encephalitis secondary to HSV-1 encephalitis

Abstract

Objective The recent identification of NMDAR antibodies causing choreoatethosis post-herpes simplex encephalitis (HSE) has provided a proof of principle that relapsing symptoms post-HSE are immune mediated. We report the first patient with anti-NMDAR encephalitis post-HSE and infantile spasms. Methods Review of patient's clinical information. Immunological studies as previously reported. Results An 11-month-old boy was admitted to our Pediatric Intensive Care Unit for status epilepticus and fever. The CSF showed 25 WBC/uL and the PCR was positive for HSV1. Intravenous acyclovir was started and over the next days 3 days he developed simple partial seizures that were initially well controlled with valproate (VPA). On day 19th after HSE onset he was readmitted for irritability, impaired interaction, involuntary movements (head shaking and facial twitching), and spasms with EEG hypsarrhythmia. The CSF revealed mild pleocytosis, negative HSV-1 PCR and high titers of NMDAR antibodies. Repeated MRI showed progression of T2/FLAIR abnormalities and intense contrast enhancement that was not present in previous studies. He was treated with midazolam, VPA, vigabatrin and immunotherapy (iv methylprednisolone, IVIg, rituximab, cyclophosphamide) without symptom improvement. Spasms and EEG paroxysmal activity progressively worsened and evolved towards a super-refractory status epilepticus, which was eventually controlled with barbiturate coma, lacosamide and ketogenic diet (KD). Seventy days after HSE onset he underwent plasma exchange for persisting coma and generalized choreoathetosis with partial clinical improvement of symptoms. KD was discontinued after 3 months of seizure control and EEG activity improvement. Conclusion Early onset infantile spasms post-HSE can be caused by anti-NMDAR encephalitis. Recent advances in the genetics of West syndrome (GRIN2B mutations – encoding the NR2B subunit of the NMDA receptor) and the animal model for West syndrome (induced by NMDA) support this hypothesis. Plasma exchange and KD were the most effective treatments in our patient.