AES (Abst. 3.336), 2017
IS THE KETOGENIC DIET A SAFE AND TOLERABLE TREATMENT FOR REFRACTORY STATUS EPILEPTICUS? A SYSTEMATIC REVIEW
Authors: Neha Kaul, Royal Melbourne Hospital; University of Melbourne; Judy Nation, University of Melbourne; Patrick Kwan, The University of Melbourne, Parkville, 3050, Victoria, Australia and The Royal Melbourne Hospital, Parkville, 3050, Victoria, Australia; and Terence J. O'Brien, The University of Melbourne
The resolution of refractory status epilepticus (RSE) is critical in reducing neurological, cardio-respiratory, metabolic complications and death. The ketogenic diet (KD) is a well-established treatment option for paediatric drug-resistant epilepsy, but its role in RSE treatment is yet to be established. The aim of this review is to evaluate the current available evidence for the use of KD in RSE.
A literature search was conducted including the MEDLINE and EMBASE databases for relevant studies from January 1946 to May 2017. Search terms included “status epilepticus” and “ketogenic diet”, limited to human subjects. Articles such as review papers or published as abstracts only, or in languages other than English were all excluded.The abstract of each study was reviewed and evaluated, studies with a minimum data set including baseline demographics, type of dietary intervention, time to initiation of diet and outcome data were included in the final analysis.
A total of 51 relevant publications were identified, with 17 articles meeting the minimum data set criteria. The 17 publications included a phase I/II prospective trial (n=1), retrospective audits (n=4) and case reports or series (n=12) treating a total of 84 patients. Baseline demographics included median age was 10 years [IQR: 6.0-29.0 years], majority were children (64%), 52% were female (n=44), 26% (n=22) had a history of epilepsy prior to presentation. The predominate clinical presentations for RSE were associated with encephalitis (32%) and febrile infection-related epilepsy syndrome (26%).Prior to commencement of KD, median number of prior treatments was 7 [range: 2-12 treatments]. The median time to diet initiation was 17 days [range: 2 – 101 days] from onset of RSE. RSE resolved in 71 of the 84 cases (85%) while on the KD. Three patients (4%) died of other complications following resolution of RSE. In the remaining 13 cases, RSE continued uncontrolled requiring other treatments and resulted in death in 5 patients (6%). Median time to resolution of RSE following commencement of KD was 5 days [IQR: 3-9 days]. Complications were reported in 35% of cases, predominately hypertriglyceridaemia, constipation, hypoglycaemia and acidosis.
RSE is a difficult to treat condition and is associated with up to 60% mortality. With only Class III and IV evidence available, it is difficult to conclude the effectiveness of KD as a treatment for RSE. Mortality was significantly lower in the reviewed studies than previous reported, which may reflect bias in patient selection. Although traditionally KD is used for outpatients as treatment for chronic drug-resistant epilepsy, consideration should be made for use in the acute setting. Monitoring of the diet is crucial to limit the risk of side-effects. The time to initiation, duration and cessation of the diet require further investigation. A robust randomised-controlled trial is required to evaluate the efficacy of KD for RSE, but the emerging number of publications with lower level evidence provides promising data that KD may be a safe and effective treatment for RSE.
Patients with refractory status epilepticus (RSE) may benefit from the ketogenic diet (KD), according to a recent review. However strong evidence supporting this treatment option is lacking.
For their literature review, the researchers identified 17 studies that examined the efficacy of KD and included a total of 84 patients. The majority of patients were children (median age 10 years) and 26% had a history of epilepsy prior to presentation. In addition, the predominate clinical presentations for RSE were associated with encephalitis (32%) and febrile infection-related epilepsy syndrome (26%).
The researchers found that the KD resolved RSE symptoms among 71 out of 84 patients (85%) with a median time to resolution after initiating the diet of 5 days. Adverse effects were observed in 35% of patients, which included hypertriglyceridemia, constipation, hypoglycemia, and acidosis.
In addition, 3 patients died of other complications after the resolution of RSE. Thirteen patients continued to have uncontrolled RSE that required additional treatment, of whom 5 died.
“Mortality was significantly lower in the reviewed studies than previous reported, which may reflect bias in patient selection. Although traditionally KD is used for outpatients as treatment for chronic drug-resistant epilepsy, consideration should be made for use in the acute setting,” the researchers concluded. “Monitoring of the diet is crucial to limit the risk of side-effects.”
“A robust randomized-controlled trial is required to evaluate the efficacy of KD for RSE, but the emerging number of publications with lower level evidence provides promising data that KD may be a safe and effective treatment for RSE.”