PP08.1 – 2529: Cyclophosphamide in treatment resistant tumour negative pediatric NMDAR encephalitis

Abstract

Objective Report 2 children with treatment resistant NMDAR encephalitis. Case reports and results: Case 1: A 4.5 year-old-girl presented with an 8 week history of acute onset agitation, insomnia, abnormal involuntary movements, and mutism. On examination, she had no visual fixation or auditory perception, no communication or understanding, had continuous dyskinetic movements. A diagnosis of anti NMDAR-encephalitis was concluded after the IgG antibodies to NR1 subunit of NMDA receptors was positive in both CSF and serum. She was given methylprednisolone and 4 weeks later IVIG, with no response. Cyclophosphamide pulse therapy (3 doses monthly cycles) was initiated 8 months into the illness with the child still in vegetative state. There was remarkable improvement with cyclophosphamide therapy. At the last follow up, 21 months after onset she has started attending regular school. Case 2: A 8-year-old boy presented with acute onset seizures, impaired speech, lack of sleep, and abnormal behaviour. On examination he was delirious, mute and had abnormal movements. CSF and serum IgG antibodies to NR1 subunit of NMDA receptor were positive. He was treated with pulse methylprednisolone and IVIG. Two weeks later, the child was given Rituximab (4 doses every 4 weeks) with no improvement. Cyclophosphamide pulse therapy (3, monthly cycles) was initiated after 6 months of his disease onset. At last follow up, 12 months after disease onset he continues to be normal and attends regular school. Conclusion Use of cyclophosphamide resulted in near complete recovery in two children with tumor negative NMDAR encephalitis resistant to steroids, IVIG and Rituximab (case 2). This despite the fact that the illness was severe and the symptoms had persisted for more than 6 months. This suggests that cyclophosphamide is an effective immunomodulator in children with Anti NMDAR encephalitis. Its use should be considered in children with incomplete or no response to first line agents.