Ketogenic diet treatment for pediatric super-refractory status epilepticus

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F.; Jarrar, Randa

doi:10.1016/j.seizure.2016.07.006

Cited by 83 publications

(90 citation statements)

References 11 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%

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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%

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

2019

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“…Notably, KD represents an adjunctive therapeutic option for refractory SE in pediatric and adult populations, although the resolution of SE in responsive patients occurs several days after treatment initiation. 17,18 The synergism between MAGL inhibition and KD therefore has clinical significance, representing a potential improvement over the current therapies. In summary, we provide novel evidence showing that MAGL is a promising therapeutic target to achieve a rapid termination of refractory SE and to reduce neuropathologic and neurologic downstream consequences.…”

Section: -38mentioning

confidence: 99%

Inhibition of monoacylglycerol lipase terminates diazepam‐resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet

et al. 2017

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SummaryObjective: Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Inhibiting of monoacylglycerol lipase modulates synaptic activity and neuroinflammation, 2 mediators of excessive neuronal activation underlying seizures. We studied the effect of a potent and selective irreversible MAGL inhibitor, CPD-4645, on SE that was refractory to diazepam, its neuropathologic sequelae, and the mechanism underlying the drug's effects. Methods: Diazepam-resistant SE was induced in adult mice fed with standard or ketogenic diet or in cannabinoid receptor type 1 (CB1) receptor knock-out mice.CPD-4645 (10 mg/kg, subcutaneously) or vehicle was dosed 1 and 7 h after status epilepticus onset in video-electroencephalography (EEG) recorded mice. At the end of SE, mice were examined in the novel object recognition test followed by neuronal cellloss analysis. Results: CPD-4645 maximal plasma and brain concentrations were attained 0.5 h postinjection (half-life = 3.7 h) and elevated brain 2-AG levels by approximately 4-fold. CPD-4645 administered to standard diet-fed mice progressively reduced spike frequency during 3 h postinjection, thereby shortening SE duration by 47%. The drug immediately abrogated SE in ketogenic diet-fed mice. CPD-4645 rescued neuronal cell loss and cognitive deficit and reduced interleukin (IL)-1b and cyclooxygenase 2 (COX-2) brain expression resulting from SE. The CPD-4645 effect on SE was similar in mice lacking CB1 receptors.Gaetano Terrone, Alberto Pauletti, and Alessia Salamone share first authorship. Gaetano Terrone is on leave

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“…The ketogenic diet was effective in the FIRES case with subsequent weaning off the anesthetic medications and resolution of the refractory status but this continued to have daily seizures after discharge from the hospital despite further treatment with anti-seizure medications. The patient with NORSE did not respond to the diet and died in hospice [18].…”

Section: Discussionmentioning

confidence: 99%

Successful surgical management of New Onset Refractory Status Epilepticus (NORSE) presenting with gelastic seizures in a 3 year old girl

Marashly

Lew

Koop

2017

Epilepsy & Behavior Case Reports

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Gelastic seizures (GS) are typically associated with hypothalamic hamartomas and present during childhood. However it is now known that GS can be found in focal epilepsies arising from other regions in the brain, including mesial and neocortical frontal, temporal and parietal regions.GS have rarely been described as the presenting manifestation of New Onset Refractory Status Epilepticus (NORSE). In this article we describe a previously healthy 3-year-old who presented with an explosive onset of GS that were refractory to multiple anti-seizure medications. These seizures arose from the right frontal region. An extensive metabolic and immunological evaluation was negative. Her brain magnetic resonance imaging (MRI) was negative, however the Positron Emission Tomography (PET) scan showed a hypermetabolic region in the right frontal inferior gyrus.She underwent a depth electrode evaluation that revealed a widespread irritative zone involving the PET “lesion” as well as mesial and neocortical regions in the right frontal lobe. The seizure onset zone was widespread and non-localizable. However the GS were associated with a clear ictal epileptiform discharge on invasive EEG arising from the depth of the superior frontal gyrus, which was not overlapping with the PET hypermetabolic region. She underwent a right frontal lobectomy sparing the primary motor region in the pre-central gyrus. She has remained seizure free for 15 months since. The pathological analysis showed focal cortical dysplasia type II in the region of the PET scan hypermetabolism. This case expands the clinical spectrum of GS to include cases of NORSE. Additionally the case highlights the role of resective surgery in GS presenting as NORSE and the potentially excellent outcome that can be achieved by early intervention.

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Ketogenic diet treatment for pediatric super-refractory status epilepticus

Abstract: Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus.

Cited by 83 publications

References 11 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

Inhibition of monoacylglycerol lipase terminates diazepam‐resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet

Successful surgical management of New Onset Refractory Status Epilepticus (NORSE) presenting with gelastic seizures in a 3 year old girl

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