Expanding Indications for a Ketogenic Diet as an Adjuvant Therapy in Adult Refractory Status Epilepticus: an Exploratory Study Using Moderation Analysis

Abstract

Refractory status epilepticus (RSE) requires multimodal treatment approaches to achieve rapid seizure cessation and neuroprotection. A ketogenic diet (KD) has demonstrated efficacy as a nutritional therapeutic option for adult RSE. However, the group of adult RSE patients who would benefit from adopting a KD needs to be determined to appropriately select the patients indicated for a KD. Therefore, we conducted a nonrandomized retrospective cohort study to explore the therapeutic efficacy of a KD by investigating the moderation effect of a KD on the association between the clinical characteristics of RSE patients and their functional outcomes. This study investigated 140 RSE patients, including 32 patients treated with a KD; among these patients, 28 (81%) achieved seizure cessation. We found that KD moderated the reduction in the modified Rankin scale (mRS) score at discharge among patients who were older, had higher seizure severity scores, were under continuous intravenous anesthetic therapy (CIVAD), and had super-RSE. Age and seizure severity scores, but not CIVAD or super-RSE, were associated with a KD-moderated change in mRS score at 3 months. Thus, we consider that our study provides evidence of a neuroprotective effect of KD in the most severe RSE patients with very few remaining therapeutic options, but future randomized controlled trials in these subgroups of KD patients are necessary.

Keywords: Ketogenic diet; Moderation analysis; Neuroprotection; Nutritional therapy; Refractory status epilepticus.

Fig. 1

A graphical representation of the moderation analysis. Abbreviations: mRS, modified Rankin scale

Fig. 2

mRS score at discharge according to the RSE characteristics. a, b, c Least-squares regression lines of mRS score on age, STESS, and mSTESS score in non-KD and KD cohorts. d, e Distribution of mRS scores at discharge in specific subgroups of IV anesthetic therapy and SRSE. The upper stacked bar plot shows the mRS score at discharge in the non-KD cohort, and the lower stacked bar plot shows the mRS score in the KD cohort. Abbreviations: CIVAD, continuous intravenous anesthetic drugs; KD, ketogenic diet; mRS, modified Rankin Scale; mSTESS, modified Status Epilepticus Severity Score; SRSE, superrefractory status epilepticus; STESS, Status Epilepticus Severity Score