Abstracts

Rationale: Super-refractory status epilepticus (SRSE), refractory status epilepticus that continues despite appropriate treatment with first- and second-line anti-seizure drugs followed by 24 hours of general anesthesia to suppress seizures, results in death in approximately 60% of patients. Currently, there are no standardized algorithms for the treatment of SRSE. The purpose of this study was to establish the feasibility, safety, and efficacy of a ketogenic diet (KD) in treating SRSE. Methods: We performed a prospective multicenter study at 5 tertiary medical centers (Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, Mayo Clinic in Rochester, The Queen's Medical Center, and Thomas Jefferson University Hospital) of adults with SRSE treated with a standardized KD treatment algorithm. Data collected included patient demographics, etiology of SRSE, anti-seizure treatments prior to and during KD, electroencephalography data, concentrations of ketone bodies produced (urine acetoacetate and serum ߭hydroxybutyrate), resolution of SRSE, side effects, and disposition. The primary outcome measure was significant ketone body production as a biomarker of feasibility. Secondary measures included resolution of status epilepticus, disposition at discharge, diet-related side effects, and long-term clinical outcomes. Results: Twenty-three adults were screened for participation at 5 medical centers and 15 patients were enrolled and started on a 4:1 ratio KD. Median age was 47 years (interquartile range [IQR] 30), 5 patients (33%) were male, and the median anti-seizure drugs used prior to initiation of KD was 8 (IQR 7). The median duration of SRSE before diet initiation was 10 days (IQR 7). Barriers to treatment included intravenous propofol use, ileus, and initial care received at a non-participating center prior to transfer. All patients achieved ketosis in a median of 2 days (IQR 1) after KD initiation. Fourteen patients completed treatment and of these, SRSE resolved in 11 (79%; 73% of all patients that began the study using an intention-to-treat analysis). The median time to SRSE resolution from KD initiation was 5 days (IQR 2.5). Potentially diet-related side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, and hypokalemia. Five patients (33%) ultimately died, including all patients in whom SRSE did not resolve with KD, and causes were deemed unlikely to be related to KD by an independent Data and Safety Monitoring Board, as needed (withdrawal of care due to poor prognosis (2), cardiac arrest (1), SRSE (1), and ischemic bowel (1)). Conclusions: Achieving ketosis with KD is feasible in adults with SRSE. Randomized placebo-controlled trials are needed to establish the safety and efficacy of KD in comparison to other available treatment options for SRSE. Funding: The study was funded in part by the Johns Hopkins Center for Refractory Status Epilepticus and Neuroinflammation.