Abstracts

Rationale: Chronic Focal Encephalitis (CFE) is characterized by progressive hemiparesis, cognitive decline and seizures. The only effective treatment to date is a hemispherectomy. Resected tissue demonstrates an inflammatory histopathology. Evidence suggests this condition is immune mediated (antibodies against brain components including GluR3, tissue immunoreactivity for IgG, and involvement of both B and T-lymphocytes). Attempts to modify disease progression with steroids, IVIG, and plasmaphoresis have shown modest, but short-lived improvements. Rituximab (RTX) is a monoclonal antibody directed against the CD20 antigen found on the surface of B cells and is approved for the treatment of CD20+, B-cell non-Hodgkin’s lymphoma. RTX has also demonstrated efficacy in rheumatoid arthritis and anecdotal reports exist for other autoimmune conditions. This pilot study proposed treatment with RTX to attack B-cells thought to be involved in the development of CFE. Methods: This study was a multi-center, open label, uncontrolled trial investigating the safety, tolerability and efficacy of RTX in the treatment of CFE. After screening, obtaining consent, and confirming eligibility, baseline evaluations were performed and the patients then treated with RTX. Safety and efficacy were then assessed serially. During the study the patient’s AEDs and VNS parameters (if implanted) were held constant. RTX was given as an IV infusion weekly for four doses (375 mg/m2). To prevent hypersensitivity reactions, subjects were pretreated with acetaminophen and diphenhydramine. Results: Nine subjects (ages 6-22) have been treated; 5 had one treatment and 4 received two treatments, 6 months apart. 8/9 had a history of treatment with IVIG, steroids and/or plasmaphoresis. One subject due to lack of efficacy underwent a functional hemispherectomy 3 months following treatment and has continued to have seizures. 8/9 had pathologically confirmed CFE having undergone surgeries ranging from biopsies to multi-lobar resections. One subject had undergone a functional hemispherectomy prior to infusion but continued to have seizures and functional decline. The subjects have been followed post treatment for 3-22 months (mean 10.2). All the infusions were well tolerated without clinical or laboratory evidence of serious side effects. 8/9 of the subjects showed some improvement in seizure severity and frequency (50-100% decrease) with 3 becoming seizure free (including 2 with epilepsia partialis continua). All 8 that continued in the trial demonstrated improved global assessments with some showing dramatic improvements in cognitive and/or motor function. None demonstrated further progression of their disease either clinically or radiographically. Conclusions: This pilot study is the first trial treating CFE with RTX. Despite the small number of subjects and limited follow-up, these results show RTX is well tolerated and preliminary evidence suggests it is disease modifying. While further trials are needed, we recommend considering the use of RTX before undergoing a hemispherectomy.