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ObjectivesMethodsResultsDiscussionSome anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy.Diet-naïve adults with epilepsy who began MAD were divided into three groups based on ASM use: EIASMs, non-EIASMs, and those on no ASMs. Demographic information, epilepsy-specific clinical history, anthropometrics and lipid values were obtained through retrospective chart review at baseline and after a minimum of 12 months of MAD use.Forty-two adults on MAD had baseline and follow up 12-month lipid outcomes. There was a significant increase in median levels of TC, LDL, non-HDL, and HDL after 12 months of MAD use. There was no change in median levels of TG. When separated according to ASM category, adults on non-EIASMs showed significant elevations in TC, HDL, and LDL after 12 months of MAD use. In contrast, adults on EIASMs only showed a significant increase in HDL after 12 months of MAD use.The increase in atherogenic cholesterol levels observed after 12 months of MAD use was most pronounced in adults with epilepsy on non-EIASMs and not observed in adults with epilepsy on EIASMs despite a higher proportion of abnormal cholesterol levels at baseline in those on EIASMs. [ABSTRACT FROM AUTHOR]

Infantile Epileptic Spasm Syndrome (IESS) is a group of infantile spasm syndromes of various etiologies that typically present in early infancy, predispose to refractory epilepsy, and leave intellectual disability. Ketogenic diet therapy (KDT) is a non-pharmacologic treatment modality for medically refractory IESS. Recent scientific evidence supported the efficacy, safety, and tolerability of KDT for the treatment of IESS. KDT not only reduces the frequency of seizures in infants with IESS, but also improve their cognition and long-term prognosis. Recently, it has also received increasing attention as a potential treatment for neurological disorders. This reviewed the recent research progress of KDTs for the treatment of IESS, and discussed the different types and the mechanisms of KDTs, the expansion of KDT applications, the influencing factors, and future research issues.

Abstract Objective To investigate the effectiveness and tolerability of ketogenic diet therapy (KDT) in patients with developmental and epileptic encephalopathy (DEE) associated with genetic etiology which onset within the first 6 months of life, and to explore the association between response to KDT and genotype/clinical parameters. Methods We retrospectively reviewed data from patients with genetic DEE who started KDT at Beijing Children's Hospital between January 1, 2016, and December 31, 2021. Results A total of 32 patients were included, involving 14 pathogenic or likely pathogenic single genes, and 16 (50.0%) patients had sodium/potassium channel gene variants. The median age at onset of epilepsy was 1.0 (IQR: 0.1, 3.0) months. The median age at initiation of KDT was 10.0 (IQR: 5.3, 13.8) months and the median duration of maintenance was 14.0 (IQR: 7.0, 26.5) months, with a mean blood β‐hydroxybutyrate of 2.49 ± 0.62 mmol/L. During the maintenance period of KDT, 26 (81.3%) patients had a ≥50% reduction of seizure frequency, of which 12 (37.5%) patients achieved seizure freedom. Better responses were observed in patients with STXBP1 variants, with four out of five patients achieving seizure freedom. There were no statistically differences in the age of onset, duration of epilepsy before KDT, blood ketone values, or the presence of ion channel gene variants between the seizure‐free patients and the others. The most common adverse effects were gastrointestinal side effects, which occurred in 21 patients (65.6%), but all were mild and easily corrected. Only one patient discontinued KDT due to nephrolithiasis. Significance KDT is effective in treating early onset genetic DEE, and no statistically significant relationship has been found between genotype and effectiveness in this study. KDT is well tolerated in most young patients, with mild and reversible gastrointestinal side effects being the most common, but usually not the reason to discontinue KDT. Plain Language Summary This study evaluated the response and side effects of ketogenic diet therapy (KDT) in patients who had seizures within the first 6 months of life, and were diagnosed with genetic developmental and epileptic encephalopathy (DEE), a type of severe epilepsy with developmental delay caused by gene variants. Thirty‐two patients involving 14 gene variants who started KDT at Beijing Children's Hospital between were included. KDT was effective in treating early onset genetic DEE in this cohort, and patients with STXBP1 variants responded better; however, no statistically significant relationship was found between gene variant and response. Most young patients tolerated KDT well, with mild and reversible gastrointestinal side effects being the most common.

The quality of a mother's diet is important to ensure child growth and development and keep women healthy. This systematic review aimed to identify the outcomes of a carbohydrate-restricted diet during lactation. PubMed, EMBASE, Scopus, Web of Science, and LILACS were searched for studies published between 2012 and 2023; 16 studies were selected, all of them case reports or care series. The carbohydrate restriction described in the papers mainly was ketogenic, low-carb, low-carbohydrate and high-fat, and modified ketogenic diets. The main goal of women undertaking these diets was weight loss, with therapeutic purposes (monitored and supervised by health professionals) in only 2 cases: (1) ketogenic diet therapy for treatment of seizures in the infant and (2) to reduce symptoms of mother's gastroesophageal reflux. Most articles reported that lactating women were hospitalized, experiencing symptoms such as vomiting, muscle weakness, nausea, abdominal pain, general malaise, and fatigue. However, articles did not mention poor outcomes for the infants. Most of the studies in this review were published in the past 3 years, indicating a possible increase in cases of women practicing carbohydrate restriction during lactation for weight loss caused by body dissatisfaction. In conclusion, carbohydrate restriction during lactation may be harmful to the lactating woman and contribute to the state of lactational ketoacidosis, but infant outcomes are mainly a change in feeding patterns. Thus, education on food and nutrition is necessary for this population. Carbohydrate restriction during lactation may cause problems for both the mother and the child. There has been an increase in the number of cases of lactating women restricting carbohydrates for weight loss purposes because of dissatisfaction with their bodies. This could result in hospitalization. Ketogenic diet therapy, when assisted by specialized professionals and performed for therapeutic purposes, provides evidence for the potential treatment and control of convulsions in infants. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness and tolerability of ketogenic diet therapy (KDT) in patients with developmental and epileptic encephalopathy (DEE) associated with genetic etiology which onset within the first 6 months of life, and to explore the association between response to KDT and genotype/clinical parameters. Methods: We retrospectively reviewed data from patients with genetic DEE who started KDT at Beijing Children's Hospital between January 1, 2016, and December 31, 2021. Results: A total of 32 patients were included, involving 14 pathogenic or likely pathogenic single genes, and 16 (50.0%) patients had sodium/potassium channel gene variants. The median age at onset of epilepsy was 1.0 (IQR: 0.1, 3.0) months. The median age at initiation of KDT was 10.0 (IQR: 5.3, 13.8) months and the median duration of maintenance was 14.0 (IQR: 7.0, 26.5) months, with a mean blood β‐hydroxybutyrate of 2.49 ± 0.62 mmol/L. During the maintenance period of KDT, 26 (81.3%) patients had a ≥50% reduction of seizure frequency, of which 12 (37.5%) patients achieved seizure freedom. Better responses were observed in patients with STXBP1 variants, with four out of five patients achieving seizure freedom. There were no statistically differences in the age of onset, duration of epilepsy before KDT, blood ketone values, or the presence of ion channel gene variants between the seizure‐free patients and the others. The most common adverse effects were gastrointestinal side effects, which occurred in 21 patients (65.6%), but all were mild and easily corrected. Only one patient discontinued KDT due to nephrolithiasis. Significance: KDT is effective in treating early onset genetic DEE, and no statistically significant relationship has been found between genotype and effectiveness in this study. KDT is well tolerated in most young patients, with mild and reversible gastrointestinal side effects being the most common, but usually not the reason to discontinue KDT. Plain Language Summary: This study evaluated the response and side effects of ketogenic diet therapy (KDT) in patients who had seizures within the first 6 months of life, and were diagnosed with genetic developmental and epileptic encephalopathy (DEE), a type of severe epilepsy with developmental delay caused by gene variants. Thirty‐two patients involving 14 gene variants who started KDT at Beijing Children's Hospital between were included. KDT was effective in treating early onset genetic DEE in this cohort, and patients with STXBP1 variants responded better; however, no statistically significant relationship was found between gene variant and response. Most young patients tolerated KDT well, with mild and reversible gastrointestinal side effects being the most common. [ABSTRACT FROM AUTHOR]

Abstract Objective There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug‐resistant epilepsy in whom KDT was used. Methods A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug‐resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival. Results Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow‐up of 1 month were included; 13 had early‐infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable. Significance Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary.

The Coronavirus disease-2019 pandemic has led to the spread of telemedicine management of ketogenic diet therapy (KDT) in children with drug-resistant epilepsy (DRE). In this study, we evaluated the views and satisfaction of families about telemedicine and KDT management. Families of 25 children who underwent KDT for DRE were included in the 17-item questionnaire. Nearly half of the families had a primary education level. Most children with DRE were in the process of maintaining KDT. 88% of the families were applying KDT with telemedicine due to the pandemic. 60% of families found it difficult to start KDT via telemedicine, but 96% reported that reaching the KDT team via telemedicine was sufficient. The necessity of laboratory analyzes and evaluation of the results of the KDT team was evaluated as good in 72%, and their response when dietary changes or vitamin addition was required was evaluated as good in 68%. All families were satisfied with the management of the KDT team in emergencies. 60% of the family recommended others to follow the KDT with telemedicine at all times and 40% recommended them during the pandemic period. According to the results of our study, in selecting patients who will be started with telemedicine and KDT, it should be noted that the families have sufficient education levels. The use of the telemedicine method may be a good option in the presence of an experienced and trained team in KDT management.

Objective: There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug‐resistant epilepsy in whom KDT was used. Methods: A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug‐resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival. Results: Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow‐up of 1 month were included; 13 had early‐infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable. Significance: Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary. [ABSTRACT FROM AUTHOR]

The Coronavirus disease-2019 pandemic has led to the spread of telemedicine management of ketogenic diet therapy (KDT) in children with drug-resistant epilepsy (DRE). In this study, we evaluated the views and satisfaction of families about telemedicine and KDT management. Families of 25 children who underwent KDT for DRE were included in the 17-item questionnaire. Nearly half of the families had a primary education level. Most children with DRE were in the process of maintaining KDT. 88% of the families were applying KDT with telemedicine due to the pandemic. 60% of families found it difficult to start KDT via telemedicine, but 96% reported that reaching the KDT team via telemedicine was sufficient. The necessity of laboratory analyzes and evaluation of the results of the KDT team was evaluated as good in 72%, and their response when dietary changes or vitamin addition was required was evaluated as good in 68%. All families were satisfied with the management of the KDT team in emergencies. 60% of the family recommended others to follow the KDT with telemedicine at all times and 40% recommended them during the pandemic period. According to the results of our study, in selecting patients who will be started with telemedicine and KDT, it should be noted that the families have sufficient education levels. The use of the telemedicine method may be a good option in the presence of an experienced and trained team in KDT management. [ABSTRACT FROM AUTHOR]

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and effcacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease. [ABSTRACT FROM AUTHOR]

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and efficacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease.

In 1921, the classic ketogenic diet was created at the Mayo Clinic in Rochester, Minnesota to treat epilepsy in children and adults. Over a century later, it is a widely used, standard-of-care therapy for typically treatment-resistant epilepsy worldwide. There are currently five versions of ketogenic diet therapy that can be started either in or out of the hospital setting. It is overall effective in approximately half of children started, usually within a few months. Established indications for ketogenic diet therapy exist, in which this treatment may potentially even be more advantageous than antiseizure medications. Some of these indications include Glut1 deficiency, pyruvate dehydrogenase deficiency, infantile epileptic spasms syndrome, epilepsy with myoclonic-atonic seizures, and formula-fed children. Although most children are also receiving antiseizure medications with ketogenic diet therapy, its use may lead to medication reduction or withdrawal in some cases, and improvement in cognition and quality of life. Supplements are begun when ketogenic diet therapy is initiated in order to prevent common side effects, including constipation, kidney stones, growth disturbance, and dyslipidemia. Typically, after 2 years in most children, ketogenic diet therapy is discontinued gradually., (© 2024 The Author(s). Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

There are many treatment options available for patients with medically refractory epilepsy including antiseizure medications, surgery, devices and ketogenic diet therapy. Ketogenic diet therapy has been shown to be a safe and effective treatment option in adult and pediatric patients. In order to obtain maximal clinical effectiveness and tolerability of any treatment option, adjustments are often necessary. This article outlines the "fine-tuning" options available for antiseizure medications, vagus nerve stimulation and ketogenic diet therapies and demonstrates that ketogenic diet therapies offer a wider array of personalizing and fine-tuning options. • Ketogenic diet therapies are safe and effective treatment options for adults and children with medically refractory epilepsy. • Patients desire treatment options which can be tailored to their individual needs. • KDTs may offer greater opportunity for enhancement and personalization than ASMs or VNS, but require more time and workload [ABSTRACT FROM AUTHOR]

[Display omitted] • KDT does not reduce growth velocity in the first year of life. • Prolonged use of KDT into the second year of life appears to slow down growth. • Infants with severe, difficult to control seizures require close nutritional monitoring. • Additional research is necessary. Ketogenic diet therapy (KDT) is well established for the treatment of early epileptic encephalopathies and specific aetiologies; however, the impact on growth in infancy remains controversial. Our aim was to examine the influence of early KDT on growth velocity and height percentiles completing two tasks. First, we systematically reviewed the literature on growth in infants younger than 12 months. Second, we analysed data from our prospective database, including infants <12 months (n = 63) treated with KDT. The literature review (n = 7) remains descriptive and includes growth percentiles and z-scores as growth velocity was not described. Studies up to 2010 used fasting, calorie restrictions, and ratios >3:1. In individual cases, significant growth delays were found; other authors did not find any changes in growth parameters. Study endpoints in our own cohort included z-scores of growth velocity, standard deviation (SD) of height, weight, BMI, deviation from individual height percentile, and daily macronutrient intake. The median z-score of growth velocity was 1.03 (first year of life). After three months, median daily intake of protein and energy was 1.68 g/kg and 85 kcal/kg. Until the age of one year, neither growth velocity nor individual growth percentiles decreased. Infants showed distinct growth improvements at three months, likely due to continuous nutritional monitoring and reduction in seizures. In the second year of life, z-scores of growth velocity decreased in patients still receiving KDT (from 1.03 at 12 months to −1.5 at 24 months). Furthermore, younger age at epilepsy onset and at KDT start correlated with slower growth velocities in the first year of life. With appropriate nutritional intake and monitoring, KDT does not reduce growth in the first year of life. Future directions might be to study the impact of KDT on growth velocity and growth hormones throughout childhood. [ABSTRACT FROM AUTHOR]

Background. Hypomyelinating leukodystrophy-14 (HLD14) is a rarely seen neurodevelopmental disease caused by homozygous pathogenic ubiquitin-fold modifier 1 gene variants. The disease has an autosomal recessive inheritance. All patients with this condition reported to date have drug-resistant epilepsy. The posttranslational modification of proteins with ubiquitin fold modifier 1 is defective in these patients and is thought to be responsible for severe neurodevelopmental problems. There is no previous report on the effectiveness of the ketogenic diet in the treatment of drug-resistant epileptic seizures in this disease. Therefore, we present a pediatric case diagnosed with HLD14 and whose drug-resistant epileptic seizures were controlled by ketogenic diet therapy. Case. The patient was a three-year-old male with drug-resistant epilepsy and developmental delay. His brain magnetic resonance imaging revealed cerebellar atrophy, periventricular white matter hypomyelination, and ventricular enlargement. Whole-exome sequencing analysis identified a homozygous pathogenic variant in the ubiquitin-fold modifier 1 gene on chromosome 13q13. Ketogenic diet therapy was initiated for his drug-resistant seizures and subsequently reduced seizure frequency by more than 75%. The patient is still on ketogenic diet therapy. Conclusions. Ketogenic diet therapy may be beneficial for seizure control in HLD14 patients with drug-resistant seizures. [ABSTRACT FROM AUTHOR]

Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that causes lactic acidosis and neurodevelopmental changes. Five causative genes have been identified: PDHA1 , PDHB , DLAT , DLD , and PDHX. Four neurological phenotypes have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia. Of these, neonatal encephalopathy has the worst mortality and morbidity and there is no effective treatment. We studied two girls who were clinically diagnosed with PDHC deficiency as neonates; they were subsequently found to have PDHA1 mutations. The clinical diagnosis was based on white matter loss and a lateral ventricular septum on fetal MRI, spasticity of the lower extremities, and lactic acidosis worsening after birth. Intravenous ketogenic diets were started within 24 h after birth. The ketogenic ratio was increased until the blood lactate level was controlled, while monitoring for side effects. In both cases, the lactic acidosis improved immediately with no apparent side effects. Both children had better developmental outcomes than previously reported cases; neither exhibited epilepsy. Intravenous ketogenic diet therapy is a treatment option for neonatal-onset PDHC deficiency. Further studies are needed to optimize this therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the retention rate, efficacy, and safety of ketogenic diet therapy for drug-resistant epilepsy in children and compare the results with those of a previous cohort at our institution.Methods: A total of 634 children with drug-resistant epilepsy were included in this retrospective study. Patients were categorized into two groups. The previous cohort was included as a control group and included 317 children assessed between 2004 and 2011, whereas the current group included 317 children assessed between 2015 and 2019. The control group was provided care as usual, and the current group additionally adopted the goal and long-term management strategy. Outcomes were measured with respect to retention rate, seizure reduction, and adverse reaction.Results: Patient demographics were consistent between both cohorts. Compared to the past ten years, the retention rate significantly increased over time (3 months: 62.8% vs. 82.0%, p <0.001; 6 months: 42.0% vs. 60.6%, p <0.001; 12 months: 24.3% vs. 34.1%, p = 0.007), and the response rate was significantly improved (3 months: 35.0% vs. 55.5%, p <0.001; 6 months: 26.2% vs. 43.2%, p <0.001; 12 months: 18.6% vs. 31.5%, p <0.001). Constipation (n = 79, 24.9%) was the most common side effect in the current cohort. Food refusal and hypoproteinaemia reduced to 3.5% and 0.9%, respectively.Conclusion: Goal and long-term management is effective for ketogenic diet therapy, which significantly improved the ketogenic diet retention rate, efficacy, and incidence of adverse reactions. This strategy has promising applicability in ketogenic diet therapy.Clinical Registration: ChiCTR-IIR-16,008,342. [ABSTRACT FROM AUTHOR]

The MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients' quality of life. A 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient's clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient's refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death. The pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered. [ABSTRACT FROM AUTHOR]

The 2023 American Epilepsy Society Annual Course "It's About Time" addressed timing in epilepsy evaluation and treatment with respect to health disparity and vulnerable populations and diagnostic, clinical, and epilepsy surgery evaluation. This comprehensive course included topics on gaps in epilepsy care and optimization of behavioral health for patients with epilepsy. The summary details current knowledge in areas of seizure forecasting and epileptogenesis. Intricacies and controversies over timing were discussed for treatment of nonconvulsive seizures and ictal-interictal patterns, acute symptomatic seizures, neuromodulation versus surgery, and epilepsy surgery in status epilepticus. Timing regarding clinical care in autoimmune-associated epilepsy, developmental and epileptic encephalopathy, and dietary therapy were examined. Additionally, salient topics on using novel biomarkers and collaboration with neuropsychological outcomes were also tackled in this all-encompassing lecture series., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. DC reports funding from Neurelis Pharmaceuticals for consultation. ET reports personal fees from EVER Pharma, Marinus, Arvelle, Angelini, Argenx, Medtronic, Biocodex Bial-Portela & Ca, NewBridge, GL Pharma, GlaxoSmithKline, Boehringer Ingelheim, LivaNova, Eisai, Epilog, UCB, Biogen, Sanofi, Jazz Pharmaceuticals, and Actavis. His institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Osterreichischer Fond zur Wissenschaftsforderung, Bundesministerium fu¨r Wissenschaft und Forschung, and Jubiläumsfond der Österreichischen Nationalbank. CR received speaker fees from Marinus for education content development, consulting fees from Quattro Consulting, and consulting fees from Azurity Pharmaceutical for advisory committee., (© The Author(s) 2024.)

Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) is a disorder resulting from shortage of energy in the brain caused by reduced GLUT1 activity. Its common clinical symptoms include seizures, microcephaly, intellectual disability, abnormal ocular movements, ataxia, and dystonia. We report a case of GLUT1DS with unusual symptoms, including periventricular calcification. The patient is a Japanese girl, whose seizures had always evolved into status epilepticus since she was 4 months old. She also had cataracts and horizontal nystagmus. Neuroimaging studies showed periventricular calcification and brain atrophy. Laboratory data revealed pseudohyperkalemia, reticulocyte increase, and hypoglycorrhachia. A mutation of c1306_1308delATC (p.Ile436- del) was identified in the SLC2A1 gene, and she was thus diagnosed with GLUT1DS. A case with the identical SLC2A1 gene mutation and similar clinical findings was previously reported by Bawazir et al (2012). The leak of monovalent cations through the red cell membrane causes hemolysis in such patients, and a similar phenomenon may occur at the blood-brain barrier and the lens epithelium. After commencing ketogenic diet therapy, the electroencephalogram (EEG) abnormalities improved markedly and the patient's development advanced. Clinicians should be aware of atypical GLUT1DS. [ABSTRACT FROM AUTHOR]

Background The treatment of long-chain mitochondrial β-oxidation disorders (LC-FOD) with a low fat-high carbohydrate diet, a diet rich in medium-even-chain triglycerides (MCT), or a combination of both has been associated with high morbidity and mortality for decades. The pathological tableau appears to be caused by energy deficiency resulting from reduced availability of citric acid cycle (CAC) intermediates required for optimal oxidation of acetyl-CoA. This hypothesis was investigated by diet therapy with carnitine and anaplerotic triheptanoin (TH). Methods Fifty-two documented LC-FOD patients were studied in this investigation (age range: birth to 51 years). Safety monitoring included serial quantitative measurements of routine blood chemistries, blood levels of carnitine and acylcarnitines, and urinary organic acids. Results The average frequency of serious clinical complications were reduced from ~ 60% with conventional diet therapy to 10% with TH and carnitine treatment and mortality decreased from ~ 65% with conventional diet therapy to 3.8%. Carnitine supplementation was uncomplicated. Conclusion The energy deficiency in LC-FOD patients was corrected safely and more effectively with the triheptanoin diet and carnitine supplement than with conventional diet therapy. Safe intervention in neonates and infants will permit earlier intervention following pre-natal diagnosis or diagnosis by expanded newborn screening. [ABSTRACT FROM AUTHOR]

Ketogenic diet therapy (KDT) is a nonpharmacological treatment that has been demonstrated to be effective in reducing seizures in patients with drug-resistant epilepsy. As the majority of patients on KDT are also receiving anti-seizure medications (ASMs), questions about their combination often arise. KDT is typically implemented as an add-on, and not a substitute for ASMs. Drug monitoring and specific laboratory studies may be helpful in specific cases of cotherapy. Valproate, topiramate, zonisamide, and lamotrigine may be potentially problematic with KDT, but the evidence for this is not conclusive. ASM reduction is usually attempted after 1 month of KDT if a child is showing seizure reduction (but weaning ASMs does not require seizure freedom). Failure to wean an ASM does not mean KDT has failed and adding a new ASM may be beneficial in those cases after several months of KDT fine-tuning. The purpose of this review was to discuss the evidence for possible negative (or positive) pharmacodynamic interactions between KDT and ASMs. In addition, practical suggestions for the weaning or adding of ASMs in patients on KDT are provided., (© 2023 The Authors. Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective and importance: Although ketogenic diet therapy is effective in refractory seizures in childhood, its effect on adult encephalitis with similar refractory seizures and prolonged encephalopathy has not been well reported. Clinical presentation: We report here a case of a 22-year-old man with acute encephalitis with refractory repetitive partial seizures (AERRPS). Intervention: Partial seizures of the face developed to repeated generalized convulsions, which were refractory against anti-epileptic drugs and a high dose of propofol. After struggling for 9 months, he dramatically recovered after ketogenic diet therapy. Conclusion: Ketogenic diet therapy may be an important tool to help cure AERRPS. [ABSTRACT FROM AUTHOR]

• Improvement of the sleep quality was detected in 50% of the children with epilepsy. • Improvements in sleep scores were not statistically significant in both groups. • A significant decrease in sleep anxiety was reported in children on the third month. • Low socioeconomic status of the family may adversely affect sleep quality of children. • Careful selection of patients during KDT may lead to better sleep quality. Sleep disorders are common in drug-resistant children with epilepsy and their mothers. Ketogenic diet therapy (KDT) may have positive effects on sleep quality. The aim of this study was to evaluate the sleep quality of children with epilepsy and their mothers after starting KDT. Using a prospective cross-sectional model, pre- and post-KDT questionnaires were given to the study subjects. A children's sleep habits questionnaire was administered to children with epilepsy, and the Pittsburgh sleep questionnaire was administered to their mothers. Sociodemographic and some clinical categorical variables of the patient group were evaluated using descriptive statistics. Evaluation of the data was conducted using the Wilcoxon and paired t-tests as parametric and non-parametric tests. Of 24 patients scheduled to begin KDT between January 2019 and January 2020, 14 were included in the study. Regarding sleep quality, improvement was reported in 7 (50%) of 14 patients, deterioration in 5 (35.7%) patients, and no change was seen in 2 (14.3%) patients. Sleep quality was reported to improve in all working mothers. Seven (50%) patients reported no seizures and 6 (42.9%) patients reported more than 50% seizure reduction. Although there were improvements in sleep scores in both groups, these improvements were not statistically significant. A significant decrease in sleep anxiety was reported in children after the third month of the KDT (p = 0.09). The results of this study determined that three months of KDT offered significant improvement on the sleep anxiety of children with epilepsy. It was thought that paying attention to patient selection may lead to better sleep quality by increasing compliance to KDT. However, a larger scale study and longer term follow-up should be done. [ABSTRACT FROM AUTHOR]

Ketogenic diet therapy (KDT), particularly modified Atkins diet (MAD), is increasingly recognized as a treatment for adults with epilepsy. Women with epilepsy (WWE) comprise 50% of people with epilepsy and approximately one in three have catamenial epilepsy. The purpose of this study was to determine whether adding a medium chain triglyceride emulsion to MAD to target catamenial seizures was feasible and well-tolerated. This was a prospective two-center study of pre-menopausal WWE with a catamenial seizure pattern on MAD. After a 1-month baseline interval with no changes in treatment, participants consumed betaquik® (Vitaflo International Ltd.) for 10 days each menstrual cycle starting 2 days prior to and encompassing the primary catamenial seizure pattern for five cycles. Participants recorded seizures, ketones, and menses, and completed surveys measuring tolerability. Sixteen women aged 20–50 years (mean 32) were enrolled and 13 (81.2%) completed the study. There was 100% adherence for consuming betaquik® in the women who completed the study and overall intervention adherence rate including the participants that dropped out was 81.2%. The most common side effects attributed to MAD alone prior to starting betaquik® were constipation and nausea, whereas abdominal pain, diarrhea, and nausea were reported after adding betaquik®. The high adherence rate and acceptable tolerability of betaquik® shows feasibility for future studies evaluating KDT-based treatments for catamenial seizures. [ABSTRACT FROM AUTHOR]

Ketogenic diet therapies (KDTs) are widely used treatments for epilepsy, but the factors influencing their responsiveness remain unknown. This study aimed to explore the predictors or associated factors for KDTs effectiveness by evaluating the subtle changes in brain functional connectivity (FC) before and after KDTs. Segments of interictal sleep electroencephalography (EEG) were acquired before and after six months of KDTs. Analyses of FC were based on network-based statistics and graph theory, with a focus on different frequency bands. Seventeen responders and 14 non-responders were enrolled. After six months of KDTs, the responders exhibited a significant functional connectivity strength decrease compared with the non-responders; reductions in global efficiency, clustering coefficient, and nodal strength in the beta frequency band for a consecutive range of weighted proportional thresholds were observed in the responders. The alteration of betweenness centrality was significantly and positively correlated with seizure reduction rate in alpha, beta, and theta frequency bands in weighted adjacency matrices with densities of 90%. We conclude that KDTs tended to modify minor-to-moderate-intensity brain connections; the reduction of global connectivity and the increment of betweenness centrality after six months of KDTs were associated with better KD effectiveness. [ABSTRACT FROM AUTHOR]

• The effect of ketogenic diet therapy on intractable epilepsy in infantile Alexander disease has not well characterized. • In all the cases, ketogenic diet therapy controlled well the drug-resistant seizures and suppressed the epileptic activities on EEG. • In all the cases, the brain MRI findings deteriorated, even after the epilepsies were controlled. • The concentrations of astroglial chemokines and proinflammatory cytokines in the CSF of the patients decreased but remained still high. • Our results support previous reports arguing neuroinflammation involvement in the pathophysiology of infantile Alexander disease. In infantile Alexander disease (iAxD), one of the serious symptoms is intractable epilepsy, and some reports have suggested that neuroinflammation may be involved in the pathophysiology of the disease. Drug-resistant seizures adversely affect not only the quality of life of the caregivers and patients, but also patients' lifespan. Thus, controlling epilepsy is clinically important. For intractable childhood epilepsy, ketogenic diet therapy (KDT) is well-established, but its effects on iAxD have not been characterized. Here, we describe the use of KDT in three iAxD patients experiencing drug-resistant seizures. In all three cases, the formerly intractable epilepsies were well controlled by KDT. However, the brain magnetic resonance imaging findings deteriorated even after the epilepsy was controlled. In addition, the concentrations of monocyte chemotactic protein-1 and proinflammatory cytokines in the cerebrospinal fluid of the patients remained still high. KDT is effective in controlling epilepsy in iAxD. Our results clinically support previous reports arguing the involvement of neuroinflammation in the pathophysiology of iAxD. Although KDT cannot prevent disease progression, earlier initiation might contribute to a better prognosis. [ABSTRACT FROM AUTHOR]