Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus

Arya, Ravindra; Peariso, Katrina; Gaínza‐Lein, Marina; Harvey, Jessica C.; Bergin, Ann M.; Brenton, J. Nicholas; Burrows, Brian T.; Glauser, Tracy A.; Goodkin, Howard P.; Lai, Yi‐Chen; Mikati, Mohamad A.; Fernández, Iván Sánchez; Tchapyjnikov, Dmitry; Wilfong, Angus A.; Williams, Korwyn; Loddenkemper, Tobias

doi:10.1016/j.eplepsyres.2018.04.012

Cited by 45 publications

(62 citation statements)

References 29 publications

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“…The rates of KD reported in adults were similar to those reported in pediatric SE. Nine retrospective studies specifically looked at the effectiveness of KD in pediatrics for SE . A total of 85 Patients, 36 (42%) were males, were put on the KD for the treatment of RSE and SRSE, and it was effective in 64 (75%).…”

Section: Discussionmentioning

confidence: 99%

“…KD ratio of 4:1 of fats to nonketogenic proteins and carbohydrates was the most commonly reported regimen in adult patients (Tables and ). In contrast, pediatric SE studies have reported other regimens in addition to the 4:1 ratio such as 3:1, 5:1, 6:1, 1:1, 2:1, 2.75:1, 3.2:1, 3.5:1, and 4.5:1. In addition, less restrictive forms of the KD have been used to successfully induce ketone body production, such as the modified Atkins diet (MAD) in Kumada et al and a low‐glycemic index diet (LGIT) in Martikainen et al.…”

Section: Discussionmentioning

confidence: 99%

“…Nine retrospective studies specifically looked at the effectiveness of KD in pediatrics for SE. 5,11,[18][19][20][21][22][23][24] A total of 85 Patients, 36 (42%) were males, were put on the KD for the treatment of RSE and SRSE, and it was effective in 64 (75%).…”

Section: Effectiveness Of Kd In Adults With Sementioning

confidence: 99%

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Systematic review of ketogenic diet use in adult patients with status epilepticus

2019

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Status epilepticus (SE) is a medical emergency that is associated with a significant morbidity and mortality. Recently, there has been significant interest in the use of ketogenic diets (KD) in the management of SE. KD is a high‐fat, low‐carbohydrate, and adequate protein diet that has been shown to be a safe and effective adjuvant to present SE management in patients with refractory epilepsy. Many case reports and case series have demonstrated the potential safety and effectiveness of KD for the acute treatment of SE; however, quality studies remain scarce on this topic. The purpose of this systematic review is to summarize the available evidence for the safety and effectiveness of KD in adults with SE. A literature search was performed in MEDLINE, EMBASE, Cochrane Library, and CINAHL (September 14, 2018). The search was repeated on March 27, 2019, to include any studies published since the original search. Keywords related to KD and SE were used. Studies were selected based on the reported use of the KD in SE. The search resulted in a total of 954 records. After screening and full‐text review, 17 articles were included in this review: four observational studies, 10 case reports, and 3 case series. Based on the observational studies, a total of 38 Patients with SE have been reported. KD was successful in achieving cessation of SE in 31 Patients (82%). The most common adverse effects reported were metabolic acidosis, hyperlipidemia, and hypoglycemia. The current limited evidence suggests that KD might be considered as an option for adult patients with SE. Although promising, the results need to be interpreted with caution due to the inherent bias, confounding and small sample size of the included studies. A randomized controlled trial is recommended to establish role of KD in the management of SE in adults.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Systematic review of ketogenic diet use in adult patients with status epilepticus

2019

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“…Most of these patients received the diet at a 4:1 ratio, reaching ketosis within a median of 2 days and electrographic seizure cessation within 7 days in 71% of patients. Additionally, 79% of patients could be weaned off continuous infusions within 2 weeks of starting a ketogenic diet [76]. In another pediatric case series, ketogenic diet led to resolution of super-RSE in nine of ten patients in a median of 7 days after diet initiation.…”

Section: Ketogenic Dietmentioning

confidence: 99%

Pharmacotherapy for Pediatric Convulsive Status Epilepticus

2019

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Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABA A receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-d-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

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“…Recent studies with 10 or more patients report good outcomes of KDTs regardless of etiology and a low rate of complications in critically ill patients with RSE/SRSE [37][38][39][40]. For instance, more than half of patients achieved more than 50% seizure reduction within a median of 7 days, desired ketosis was reached within a median of 4 days, and most patients successfully weaned off continuous infusion of anesthesia within 2 weeks after initiation of a KDT.…”

Section: The Gut-brain Axis and Kdtsmentioning

confidence: 99%

Advances in Ketogenic Diet Therapies in Pediatric Epilepsy

2019

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Ketogenic diets are high in fat, low in carbohydrates, and contain an adequate amount of protein. In addition to the classic ketogenic diet, three alternative types of ketogenic diet therapies (KDTs) have emerged. In addition to clarifying the indications for early treatment using KDTs, ongoing research over the past decades has led to the recognition of their contraindications and adverse effects. Recent studies focusing on the targeted therapeutic range of KDTs are expected to elucidate the precise mechanisms by which they alleviate certain epilepsy syndromes and other disorders. In this review, we discuss recent advances in KDTs, focusing on six issues: the selection of a specific KDT; the use of KDTs for febrile infection-related epilepsy syndrome and super-refractory status epilepticus; the use of KDTs for infants with refractory epilepsy; links between the gut-brain axis and KDTs; triheptanoin; and the use of KDTs for disorders other than pediatric epilepsy.

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Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus

Cited by 45 publications

References 29 publications

Systematic review of ketogenic diet use in adult patients with status epilepticus

Systematic review of ketogenic diet use in adult patients with status epilepticus

Pharmacotherapy for Pediatric Convulsive Status Epilepticus

Advances in Ketogenic Diet Therapies in Pediatric Epilepsy

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