Abstracts

Rationale: Febrile Infection Related Epilepsy Syndrome (FIRES) is a catastrophic epileptic encephalopathy with an unidentified etiology that comprises a small minority of all patients with refractory status epilepticus. This syndrome occurs in previously healthy children with 66-100% of survivors becoming developmentally disabled. The mortality rate is up to 30%. There is a critical need for new therapies to adequately treat this condition. We describe the experience of using Cannabadiol (CBD) in one patient with FIRES at a pediatric tertiary care center. Methods: A 4 year old male patient with FIRES was treated with CBD (Epidiolex®) under an expanded access program through GW Pharmaceuticals. Prior to initiating treatment, FDA IND, Federal DEA, Texas DPS, institutional IRB approvals, and informed consent were obtained. Safety laboratory studies, physical/ neurological exams, 24 hour video/EEG and seizure types and frequencies were assessed at baseline and one month after starting CBD. Treatment was initiated using CBD oral solution 25 mg/ mL at a dose of 10 mg/ kg/ day given in two divided doses, increasing by 5 mg/ kg/ day every 3 days to a final dose of 25 mg/ kg/ day. During the first month of treatment, no changes were made to concomitant AEDs. Results: Prior to initiation of CBD, the patient's super-refractory status epilepticus had been treated with midazolam infusion, pentobarbital infusion, propofol infusion, lidocaine infusion, ketamine, fosphenytoin, methylprednisolone, thiamine, rituximab, cyclophosphamide, and a hypothermia protocol. At the time of initiation of CBD, the patient was being treated with levetiracetam, clobazam, perampanel, phenobarbital, fosphenytoin, and vagus nerve stimulation therapy. Baseline 24 hour EEG showed very frequent mulifocal spikes bilaterally and 203 seizures were recorded. Seizure frequency before CBD, as reported by the parents, averaged 50-70 seizures per day. Over the month after initiation of CBD treatment, the parents reported only a total of 5 seizures. A reduction in seizure frequency was noted almost immediately after beginning CBD. The repeat 24-hour EEG study was significantly improved with a reduced overall burden of epileptiform activity, and no electrographic seizures were recorded. Follow up laboratory tests showed no changes in safety studies or concomitant AED levels. No treatment related adverse affects were observed. Conclusions: CBD treatment was very well tolerated and associated with a dramatic and nearly immediate improvement in clinical and electrographic seizure burden in a child with super-refractory status epilepticus due to FIRES. This open label experience is encouraging and supports the need for randomized, controlled clinical research studies using this novel compound.