Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis

Wang, Yanqiu; Fang, Zhixu; Zhang, Yi-Wei; Xie, Lingling; Jiang, Li

doi:10.1016/j.seizure.2020.07.011

Cited by 27 publications

(24 citation statements)

References 37 publications

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“…A meta-analyis examining the efficacy of ketogenic diet in DS by Wang YQ et al displayed a combined efficacy rate for ≥50 % seizure reduction was 63 % at 3, 6 and 12 month checkpoints in 167 combined DS children [55]. Another study of 20 children also reported ≥50 % seizure reduction in 80 % of them [56].…”

Section: Treatmentmentioning

confidence: 99%

A systematic review of adults with Dravet syndrome

Selvarajah

Ali

Marques

et al. 2021

Seizure

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Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on January 18 th , 2021, examining the number of clinical DS studies. We show that there are 208 studies on children exclusively, 28 studies on adults exclusively, and 116 studies involving adults and children combined. This 7:1 ratio of children to adult studies exclusively shows the dearth of research that addresses long-term natural history of DS into adulthood.Through this systematic review, we examine the most up-to-date information in DS adults as it pertains to seizures, electroencephalogram, imaging, treatment, motor abnormalities, cognitive and social behavior outcomes, cardiac abnormalities, sleep disturbances, diagnosis in adults, and mortality.Overall, the frequency of seizures increases in the first decade of life and then myoclonic, atypical absences and focal seizures with impaired awareness tend to decrease in frequency or even disappear in adulthood. Adults tend to have a notable reduction in status epilepticus, especially after 30 years of age. Parkinsonian features were seen in patients as young as 19 years old and are more severe in older patients, suggesting a progression of the parkinsonian symptoms. In adulthood, patients continue to present with behavior problems, associated with a lower health-related quality of life. The leading reported cause of death in DS adults is Sudden Unexpected Death in Epilepsy (SUDEP).Further studies in older adults are needed to understand the long-term outcomes of patients with DS.

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Section: Treatmentmentioning

confidence: 99%

A systematic review of adults with Dravet syndrome

Selvarajah

Ali

Marques

et al. 2021

Seizure

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“…Although KD is an established first‐line therapeutic concept for GLUT1 deficiency syndrome, the list of possible indications comprises different genetic epilepsy syndromes including the Dravet syndrome, which is characterized by a severe clinical phenotype and a poor pharmacoresponsiveness 12 . For Dravet syndrome a recent meta‐analysis has suggested an improvement of seizure control and behavioral symptoms in response to the KD 13 . This finding supports the recommendation of KD for Dravet patients with failure to respond to three or four different antiseizure drugs 14 .…”

Section: Introductionmentioning

confidence: 99%

Metabolomic signature of the Dravet syndrome: A genetic mouse model study

et al. 2021

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Objective Alterations in metabolic homeostasis can contribute to neuronal hyperexcitability and seizure susceptibility. Although the pivotal role of impaired bioenergetics is obvious in metabolic epilepsies, there is a gap of knowledge regarding secondary changes in metabolite patterns as a result of genetic Scn1a deficiency and ketogenic diet in the Dravet syndrome. Methods A comprehensive untargeted metabolomics analysis, along with assessment of epileptiform activity and behavioral tests, was completed in a Dravet mouse model. Data sets were compared between animals on a control and a ketogenic diet, and metabolic alterations associated with Dravet mice phenotype and ketogenic diet were identified. Results Hippocampal metabolomic data revealed complex alterations in energy metabolism with an effect of the genotype on concentrations of glucose and several glycolysis and tricarboxylic acid (TCA) cycle intermediates. Although low glucose, lactate, malate, and citrate concentrations became evident, the increase of several intermediates suggested a genotype‐associated activation of catabolic processes with enhanced glycogenolysis and glycolysis. Moreover, we observed an impact on the glutamate/γ‐aminobutyric acid (GABA)‐glutamine cycle with reduced levels of all components along with a shift toward an increased GABA‐to‐glutamate ratio. Further alterations comprised a reduction in hippocampal levels of noradrenaline, corticosterone, and of two bile acids. Significance Considering that energy depletion can predominantly compromise the function of GABAergic interneurons, the changes in energy metabolism may contribute to seizure susceptibility and ictogenesis. They may also explain the therapeutic potential of the ketogenic diet, which aims to shift energy metabolism toward a more fat‐based energy supply. Conversely, the increased GABA‐to‐glutamate ratio might serve as an endogenous compensatory mechanism, which can be further supported by GABAergic drugs, representing the mainstay of therapeutic management of Dravet syndrome. In view of a possible neuroprotective function of bile acids, it might be of interest to explore a possible therapeutic potential of bile acid–mediated therapies, already in discussion for neurodegenerative disorders.

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“…In addition to epilepsy control, cognitive function improved in 22 patients, language progression in 14 patients, and motor function improved in 13 patients ( 69 ). A recent meta-analysis also concluded that 63, 60, and 47% of DS patients had a ≥50% reduction in seizures at 3, 6, and 12 months after KD, and the seizure control rates at 6 and 12 months were 78 and 49%, respectively ( 37 ). The KD not only effectively controlled seizures, but also improved cognitive, motor and other behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…The KD not only effectively controlled seizures, but also improved cognitive, motor and other behaviors. Even in patients with unreduced seizures, the quality of life was improved, and the number of AEDs reduced to one or two on the ketogenic diet ( 37 , 42 ). Caraballo et al ( 42 ) believed that KD treatment should be considered immediately after three failed AEDs.…”

Section: Discussionmentioning

confidence: 99%

Up to What Extent Does Dravet Syndrome Benefit From Neurostimulation Techniques?

Ding

Wang

et al. 2022

Front. Neurol.

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BackgroundDravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown.MethodsWe searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively.ResultsThe Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs.ConclusionMore than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.

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Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis

Cited by 27 publications

References 37 publications

A systematic review of adults with Dravet syndrome

A systematic review of adults with Dravet syndrome

Metabolomic signature of the Dravet syndrome: A genetic mouse model study

Up to What Extent Does Dravet Syndrome Benefit From Neurostimulation Techniques?

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