Abstracts

Rationale: Rasmussen’s encephalitis is a chronic focal encephalitis of presumed autoimmune etiology. Numerous immunomodulatory therapies have been used, with limited impact on the long term outcome of the disease. Methods: Case Study Results: Herein we describe an 18 year old right handed male with a 3 year history of progressive right arm and right face epilepsia partialis continua and cognitive decline. His condition was initially responsive to methylprednisolone but eventually became resistant to methylprednisolone, intravenous immunoglobulin, tacrolimus and subsequently had a frontal resection of the left hand and face area. MRI of the brain initially revealed bilateral white matter hyperintensities, however subsequent imaging revealed a right insular hyperintensity. Brain biopsy demonstrated chronic inflammatory changes consistent with Rasmussen’s encephalitis. Hemispherectomy was deemed contraindicated due the primary involvement of the dominant hemisphere along with bilateral involvement from the initial presentation. Three years after his initial presentation, ablative cyclophosphamide therapy (daily doses of 50 mg/kg for 4 days) was initiated. Seizure frequency remained stable during suppression of white cell count for a period of 10 days. With recovery of white cells count seizure frequency dramatically worsened with the patient requiring admission to the intensive care unit for management of status epilepticus. The patient died three weeks post-therapy following a change in management to compassionate terminal care. Post-mortem studies revealed dramatic focal bilateral cortical neuronal loss with a striking paucity of active inflammation compared to his initial biopsy two years earlier. Real time RT-PCR studies on brain tissue revealed modest activation of T-cells with elevation of CD3 transcripts but not CD8b, together with increased expression of IL-10 suggesting that an immune reconstitution syndrome is unlikely to be an underlying cause for his rapid decline post-cyclophosphamide treatment. Furthermore, there was significant downregulation of GluR3 and GluR4 expression, perhaps suggestive of a role for glutamate receptor expression in the pathogenesis of Rasmussen’s Encephalitis. Conclusions: Ablative cyclophosphamide is unlikely to be of benefit in the late stages of Rasmussen’s Encephalitis. Future trials of ablative immunotherapy might be more likely to succeed in the earlier phase of the disease course.