Ketogenic diet as a successful early treatment modality for SCN2A mutation

Türkdoğan, Dilşad; Thomas, G.; Demirel, Birsen

doi:10.1016/j.braindev.2018.10.015

Cited by 17 publications

(21 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 However, neither could prove whether the KD was also effective earlier in the course of the disease process. Turkdogan et al described a neonate who achieved seizure control at the age of 39 days after starting a KD, 16 which is similar to our case; however, that child had a different de novo mutation. Early use of KD in cases with SCN2A may lead to better seizure control and may affect the outcome positively.…”

Section: Discussionsupporting

confidence: 84%

A Case of Neonatal Epileptic Encephalopathy due to SCN2A Mutation Responsive to a Ketogenic Diet

et al. 2018

View full text Add to dashboard Cite

Neonatal seizures may have multiple causes including metabolic and genetic etiologies. If a genetic diagnosis is known, it can guide the physician to choose the most appropriate treatment modality. SCN2A mutation is a rare cause of epileptic encephalopathy in the neonatal age group. It has a wide phenotypic variation, ranging from benign familial epilepsy to a malignant form of epilepsy. This mutation has been associated with Ohtahara syndrome, migrating focal seizures of infancy, West syndrome, Lennox–Gastaut syndrome, and generalized epilepsy with febrile seizures plus. We present the case of a newborn girl who presented with multiple types of seizures, starting at the age of 3 days. Our initial investigations were not able to identify the etiology of her intractable seizures. Whole exome sequencing confirmed an SCN2A mutation. Various antiepileptic drugs (AEDs), including phenobarbitone, phenytoin, levetiracetam, topiramate, vigabatrin, carbamazepine, clonazepam, and mexiletine, were tried. However, none provided an optimal response. She ultimately showed a dramatic response to the ketogenic diet (KD). This report highlights the effectiveness of the KD as a treatment modality for SCN2A mutation-related epileptic encephalopathy, particularly when seizures are intractable and unresponsive to conventional AEDs.

show abstract

Section: Discussionsupporting

confidence: 84%

A Case of Neonatal Epileptic Encephalopathy due to SCN2A Mutation Responsive to a Ketogenic Diet

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In our previous research, we assessed the efficacy of the ketogenic diet according to the causative genes in DEE and found that the ketogenic diet is especially effective in patients with SCN1A, KCNQ2, STXBP1, and SCN2A mutations (Ko et al, 2018). There have also been other reports of successful treatment of SCN2A-related DEE with the ketogenic diet (Turkdogan et al, 2019;Su et al, 2018). High-dose steroid, which was tried in patients with Ohtahara syndrome or West syndrome, was also effective (4/5).…”

Section: Discussionmentioning

confidence: 99%

The phenotype and treatment of SCN2A‐related developmental and epileptic encephalopathy

Kim¹,

Yang²,

Kim³

et al. 2020

Epileptic Disorders

View full text Add to dashboard Cite

We aimed to delineate the phenotypic spectrum of SCN2A-related developmental and epileptic encephalopathy (DEE) and determine the effectiveness of various treatment modalities, including sodium channel blockers and the ketogenic diet. Methods. Eleven patients with SCN2A-related DEE were included in the study. The characteristics of SCN2A mutations, electroclinical features, clinical course, and response to treatment modalities were analysed. Results. The 11 patients were aged between 0.4 and 9.7 years. The onset of seizures ranged from neonate (six patients) to infant (four patients), to childhood (one patient). Epilepsy presented as Ohtahara syndrome, West syndrome, epilepsy of infancy with migrating focal seizures (EIMFS), and focal epilepsy in neonatal-to infantile-onset patients. The only childhoodonset patient in our study presented with focal epilepsy with autism. Neonatal-to infantile-onset patients had drug-resistant epilepsy (9/10), however, sodium channel blockers were effective in all treated patients (9/9). The ketogenic diet (6/8) and high-dose steroid treatment (4/5) were also effective. The seizures in the childhood-onset patient worsened during treatment with sodium channel blockers. All mutations in neonatal-to infantile-onset patients were missense mutations, whereas the mutation in the childhood-onset patient was a truncation mutation. Conclusions. These results support earlier observations regarding the epilepsy syndromes and response to antiepileptic drugs in patients with SCN2A-related DEE.

show abstract

“…As KD can be effective in difficult‐to‐treat seizures, including SCN2A associated self‐limited formerly benign neonatal seizures, neonatal infantile seizures and epileptic encephalopathies, 9–13 potential interactions between AEDs and KD have to be considered. KD can result in delayed drug absorption through delayed gastric emptying, enhanced absorption of lipophilic drugs, stimulation of bile secretion and intestinal lymph drug absorption, inhibition of epithelial transporters, alteration of protein‐binding (increased free drug fraction due to changed protein intake, or binding competition with high amounts of free fatty acid 23 ), and gastrointestinal tract irritations resulting in reduced absorption 24–26 .…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacotherapy of SCN2A ‐seizures is often supplemented by KD, which seems potentially effective even in AED unresponsiveness, particularly if started at early age 9–13 . KD has numerous first‐ and second‐line indications with few adverse effects in children/infants and good tolerance 14–16 .…”

Section: Introductionmentioning

confidence: 99%

Drug–drug and drug–food interactions in an infant with early‐onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet

Welzel

Ziesenitz

Weber

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

Sodium channel 2 subunit α (SCN2A) mutations cause difficult‐to‐treat early‐onset epilepsy. Effective treatment includes high‐dose phenytoin or carbamazepine ± ketogenic diet (KD). We describe an infant with early‐onset SCN2A‐epilepsy with subtherapeutic carbamazepine concentration during transition from phenytoin treatment to avoid long‐term neurotoxicity. The transition from high‐dose phenytoin (20 mg kg−1 d−1, concentration: ≥20 mg/L) with KD, to carbamazepine (50–75 mg kg−1 d−1, concentration: 9–12 mg/L) lasted 85 days, which we suspected was due to significant drug–drug and/or drug–food interactions. Model‐based analysis of carbamazepine pharmacokinetics quantified significant time‐ and dose‐dependent phenytoin‐mediated CYP3A4 induction and carbamazepine concentration‐dependent auto‐induction (apparent clearance increased up to 2.5/3‐fold). Lower carbamazepine concentrations under KD were modelled as decreased relative bioavailability (44%), potentially related to decreased fraction absorbed (unexpected for this lipophilic drug), increased intestinal/hepatic metabolism and/or decreased protein‐binding with KD. This suggests importance of carbamazepine‐concentration monitoring during KD‐introduction/removal and necessity of high carbamazepine doses to achieve therapeutic concentrations, especially in infants treated with high‐dose phenytoin.

show abstract

Ketogenic diet as a successful early treatment modality for SCN2A mutation

Cited by 17 publications

References 10 publications

A Case of Neonatal Epileptic Encephalopathy due to SCN2A Mutation Responsive to a Ketogenic Diet

A Case of Neonatal Epileptic Encephalopathy due to SCN2A Mutation Responsive to a Ketogenic Diet

The phenotype and treatment of SCN2A‐related developmental and epileptic encephalopathy

Drug–drug and drug–food interactions in an infant with early‐onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet

Contact Info

Product

Resources

About