Ketogenic Research Articles

533-P: A Ketogenic Diet Reduces Blood Glucose and Restores Exercise Training–Induced Improvements in Aerobic Capacity in Hyperglycemic Mice

Evidence suggests that hyperglycemia can blunt improvements in aerobic capacity (VO2peak) with exercise training. Accordingly, people with diabetes have lower VO2peak than normoglycemic controls, increasing their risk of complications and mortality. We hypothesized that reducing blood glucose levels with a dietary intervention would restore exercise training-induced improvements in VO2peak in hyperglycemic mice. To test this, we induced hyperglycemia in male CD-1 mice with streptozotocin (STZ) , which increased random blood glucose to 220 ± 31 mg/dL on a standard diet (80% carbohydrate, 10% fat & protein) . A subset of STZ mice was fed a ketogenic (KETO) diet consisting of 90% fat and 10% protein, which reduced blood glucose to 177 ± 26 mg/dL. Eight weeks after starting the dietary intervention, STZ and KETO mice underwent voluntary wheel running or remained sedentary for 8 weeks. Exercise training improved VO2peak and time to exhaustion during a graded exercise test in KETO-fed mice while no significant improvement was observed in STZ mice. Trained STZ and KETO mice had similar fat and lean mass, indicating improved VO2peak in trained KETO mice was independent of body composition. Our data demonstrate that reducing blood glucose using a carbohydrate-restricted diet may restore training-induced improvements in exercise capacity that are prevented by hyperglycemia. Disclosure R.C.Nava: None. E.M.Cooney: None. S.J.Lessard: None. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) RDK124258 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32 Postdoctoral Training Fellowship 5T32DK007260-45

Effect of Dietary Intake Through Whole Foods on Cognitive Function: Review of Randomized Controlled Trials.

This review evaluated recent randomized controlled trials (RCTs) examining the chronic intake of whole foods associated with the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Mediterranean-DASH Intervention for Neurogenerative Delay (MIND), and ketogenic (KETO) diets on cognitive function. We identified RCTs related to olive oil (N = 3), nuts (N = 7), fatty fish (N = 1), lean meats (N = 4), fruits and vegetables (N = 9), legumes (N = 1), and low-fat dairy (N = 4), with 26/29 reporting positive results on at least one measure of cognition. We also identified 6 RCTs related to whole food-induced KETO diets, with half reporting positive effects on cognition. Variations in study design (i.e., generally the studies are < 6months and include middle-aged and older, cognitively intact participants) and small sample sizes make it difficult to draw conclusions across studies; however, the current evidence from RCTs generally supports individual component intakes of these dietary patterns as an effective, nonpharmacological approach to improve cognitive health in adults.

Chronic Ketosis Modulates HIF1α-Mediated Inflammatory Response in Rat Brain.

Hypoxia inducible factor alpha (HIF1α) is associated with neuroprotection conferred by diet-induced ketosis but the underlying mechanism remains unclear. In this study we use a ketogenic diet in rodents to induce a metabolic state of chronic ketosis, as measured by elevated blood ketone bodies. Chronic ketosis correlates with neuroprotection in both aged and following focal cerebral ischaemia and reperfusion (via middle cerebral artery occlusion, MCAO) in mouse and rat models. Ketone bodies are known to be used efficiently by the brain and metabolism of ketone bodies is associated with increased cytosolic succinate levels that inhibits prolyl hydroxylases allowing HIF1α to accumulate. Ketosis also regulates inflammatory pathways, and HIF1α is reported to be essential for gene expression of interleukin10 (IL10). Therefore we hypothesised that ketosis-stabilised HIF1α modulates the expression of inflammatory cytokines orchestrating neuroprotection. To test changes in cytokine levels in rodent brain, eight-week-old rats were fed either the standard chow diet (SD) or the ketogenic (KG) diet for 4weeks before ischaemia experiments (MCAO) were performed and the brain tissues were collected. Consistent with our hypothesis, immunoblotting analysis shows IL10 levels were significantly higher in KG diet rat brain compared to SD, whereas the TNFα and IL6 levels were significantly lower in the brains of KG diet fed group.

Study of Glycemic Control by Ketogenic Diet Supplemented with Different Oils in Type II Diabetic Rats

In recent years, very low carbohydrate ketogenic diets (VLCKD) have been emphasized. While commonly debated and often opposed, these are clearly successful as a method for treating obesity, hyperlipidemia and diabetes at least in the short to medium term. Therefore, this research was conducted to investigate the impact of ketogenic diet (KD) supplemented with oil of either grape seed or fish and virgin olive on diabetic rats. Forty eight male albino rats weighing 200 to 210 g, were assigned into two main groups. The first group (n=8) was control negative group (-ve), the second main group (n=40) were intraperitoneally injected with a single dose of streptozotocin (STZ) [60 mg/kg b.w.] for induction of diabetes, then these rats were divided into five subgroups. Subgroup one was fed on the basal diet and served as a control positive group, while subgroup 2 was fed on KD only and subgroups from 3 to 5 were fed on KD supplemented with 4% oil of either grape seed or fish and virgin olive, respectively for 8 weeks. The results indicated that, STZ treated rats showed significant reduction (P≤0.05) in serum insulin concentration and increased glucose levels compared to normal rats. KD supplemented with oil of either grape seed or fish and virgin olive improved the biochemical changes due to diabetes. Furthermore, the intervention caused favorable changes in blood lipids and restored liver and kidney functions of the treated rats compared to the control positive group. In conclusion, the ketogenic diet and KD supplemented with oil of either grape seed or fish or virgin olive are potentially promising diets for diabetic patients دراسة التحکم في نسبة جلوکوز الدم بواسطة النظام الغذائي الکيتونى المدعم بالزيوت المختلفة في الفئران المصابة بمرض السکرى من النوع الثاني في السنوات الأخيرة ، کان هناک ترکيز متزايد على النظم الغذائية الکيتونية المنخفضة جدا فى الکربوهيدرات ، في حين يتم مناقشتها بشکل شائع ومعارضتها في کثير من الأحيان ، فمن الواضح أنها ناجحة کوسيلة لعلاج السمنة وفرط الدهون والسکرى على الأقل على المدى القصير إلى المتوسط. لذلک أجريت هذه الدراسة للتحقق من تأثير النظام الغذائي الکيتوني المدعم اما بزيت بذر العنب أوالسمک أوالزيتون البکر على الفئران المصابة بداء السکرى. تم استخدام عدد 48 من ذکور الفئران التي تزن 200 إلى 210 جم ، تم تقسيمهم الى مجموعتين رئيسيتين. تم الاحتفاظ بالمجموعة الرئيسية الأولى (ن = 8) کمجموعة ضابطة سالبة ، المجموعة الرئيسية الثانية تم استخدام عدد 40 من الفئران واستخدمت کمجموعة ضابطة موجبة تم حقنهم بمادة الاستربتوزوتين (60ملجم/کجم من وزن الجسم) لاحداث السکرى، ثم قسمت هذه الفئران إلى خمس مجموعات فرعية .تم تغذية المجموعة الفرعية الأولى على النظام الغذائي الأساسي واستخدمت کمجموعة ضابطة موجبة ، في حين تم تغذية المجموعة الفرعية 2 على النظام الغذائي الکيتوني فقط بينما تم تغذية المجموعات الفرعية من 3 إلى 5 على النظام الغذائي الکيتوني المدعم بنسبة 4% اما بزيت بذر العنب أوالسمک أوالزيتون البکر على التوالي . بعد 8 أسابيع ، تم ذبح الفئران وجمع عينات الدم للحصول على السيرم . اوضحت النتائج أن الفئران المعاملة بـالاستربتوزوتين أظهرت انخفاض معنوي (P≤0.05) في ترکيز الأنسولين في الدم وزيادة مستويات الجلوکوز مقارنة بالفئران الطبيعية. ادى النظام الغذائي الکيتوني المدعم بزيت بذر العنب أوالسمک أوالزيتون البکر في تحسين النتائج البيوکيميائية الناتجة عن مرض السکرى .علاوة على ذلک ، أدى التدخل إلى إحداث تغييرات إيجابية في صورة دهون الدم وتحسين وظائف الکبد والکلى للفئران المعالجة مقارنة بالمجموعة الضابطة الموجبة. الخلاصة إن النظام الغذائي الکيتوني والکيتونى المدعم بزيت بذر العنب أوالسمک أوالزيتون البکر هو نظام غذائي واعد محتمل لمرضى السکرى.

What Diet Therapy Is Best for Drug-Resistant Childhood Epilepsy?

Children with drug-resistant epilepsy often benefit from the high-fat, low-carbohydrate ketogenic diet. To assess whether the low-carbohydrate modified

Research progress on adverse reactions of ketogenic diet

Ketogenic diet(KD) has been used for centuries in the treatment of epilepsy, which can restrict calorie and liquid intake, with significant therapeutic effects. In recent years, KD has been proved to have therapeutic effects in other fields, such as obesity, diabetes, hypertension, cancer, Alzheimer′s disease and other chronic diseases. KD has a positive effect on the treatment of many diseases, but the high proportion of fat intake in KD process, as well as too little intake of carbohydrates, proteins and trace elements will lead to a very uneven absorption of nutrients. Therefore, the use of KD to treat disease may cause a variety of adverse reactions, and its long-term results are the subjects of controversy. The purpose of this review is to summarize the literature of KD adverse effects and their prevention and treatment methods, in order to provide guidance and assistance to clinical administration. Key words: Ketogenic diet; Dietotherapy; Side effects

Research progress of ketone bodies in ketogenic diet therapy of epilepsy

Ketogenic dietary therapy (KDT) is a kind of formulated diet with high fat, low carbohydrates, and appropriate protein and other nutrients, which is mainly used for the treatment of intractable epilepsy in children.The main metabolic change in the body during KDT is the production of a large number of ketone bodies which can not only provide energy, but also plays an important role in inhibiting the transmission of abnormal excitatory signals in the brain.However, the anti-epileptic mechanism of ketone bodies in KDT is still not very clear.Some clinical studies have found that the level of blood ketone is inconsistent with the effect of epilepsy control.The latest progress of research on the synthesis, monitoring, effective concentration range and the relationship with efficacy of ketone bodies in ketogenic diet therapy are reviewed in this article, in order to provide reference blood ketone range in clinical ketogenic diet. Key words: Ketone bodies; Ketogenic dietary therapy; Epilepsy

Diagnosis and treatment of 12 cases of febrile infection-related epilepsy syndrome

Objective To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome (FIRES). Methods The clinical data of 12 children with FIRES admitted to Xiangya Hospital of Central South University from 2015 to 2018 were retrospectively analyzed. The basic information, clinical manifestations, electroencephalogram, imaging examination, treatment and prognosis were analyzed. Results Of the 12 patients, 7 were male and 5 were female. The age of onset was (7.0±3.7)years (1.3 year to 13 years). The average hospitalization time (34-86 days, median 52 days). Twelve patients were healthy before the disease, and had fever before convulsion. The interval between fever and seizure was (3.5±1.7)days (1-7 days). The status epilepticus and consciousness deficit were the main clinical manifestations. The electrogram of 8 patients showed status epilepticus when admitted. 12 patients had disturbance of consciousness; the acute episodes were focal seizures (100%, 12/12) and generalized tonic-clonic seizures (41.7%, 5/12). All patients used 3-5 antiepileptic drugs (median 4), all treated with hormones and gamma globulin. 4 patients with ketogenic diet (KD) were treated within 2 weeks of onset, and the average duration from onset to electroencephalogram (EEG) improvement was (19.2±5.0)days. In 8 patients who did not use KD within 2 weeks of onset, the average duration from onset to EEG improvement was (29.9±9.6)days. Conclusions FIRES is more common in normal children with school age. The main manifestation is refractory status epilepticus in the days after acute fever, focal episodes of seizures, anti-epileptic drug resistance. Early initiation of KD produces a favorable prognosis. Key words: Acute febrile encephalopathy; Status epilepticus; Drug resistant epilepsy; Ketogenic diet; Child

Prospective control study of efficacy and safety of ketogenic diet on drug refractory Dravet syndrome

Objective To investigate the efficacy and safety of ketogenic diet (KD) and antiepileptic drugs(AEDs) in the children with drug refractory Dravet syndrome (DS). Methods Thirty-two cases of drug refractory DS were enrolled into the Department of Neurology, Shenzhen Children′s Hospital Affiliated to Shantou University Medical School from July 2016 to December 2017, and they were divided into 2 groups: KD group and AEDs group (16 cases for each group), respectively.KD was added to as an additional therapy for KD group, and oral AEDs were administered only in AEDs group.In KD group, oral AEDs were not adjusted for the first 3 months.AEDs could be adjusted within a limited range in 2 groups after 3 months.The clinical efficacy, improvement of cognitive function, retention rate and side effects were observed and compared after 3, 6, 12 months of treatment.The average monthly seizure frequency within 3 months before enrollment was recorded as the baseline.The clinical efficacy was assessed by comparing the seizure frequency of each observation period with the baseline. Results In KD group, after 3, 6, 12 months′ follow-up, KD the-rapy was maintained in 15, 14, 12 patients.The number of patients whose seizure reduction over 50% was 10, 12, 11 cases, respectively.The number of patients whose seizure reduction over 90% was 7, 9, 10 cases, respectively.The number of patients who were seizure free was 3, 6, 8 cases, respectively.In AEDs group, after 3, 6, 12 months′ therapy, the number of patients whose seizure reduction over 50% was 6, 7, 8 cases, respectively, the number of patients whose seizure reduction over 90% was 3, 3, 4 cases, respectively.The number of patients who were seizure-free was 2, 1, 2 cases, respectively.There was a significant difference in the seizure reduction between 2 groups after 6, 12 months (P 0.05). Conclusions KD can not only reduce seizure frequency and relieve SE, but also improve the cognitive function of drug refractory DS.The adverse reaction ratio of KD does not increase significantly compared to AEDs.Therefore, KD is effective and safe therapy for children with drug-resistant DS. Key words: Ketogenic diet; Antiepileptic drugs; Dravet syndrome; Efficacy; Safety

Clinical features and ion channel gene mutations analysis in 17 cases of early-onset epileptic encephalopathy

Objective To analyze the clinical characteristics and gene mutations of early-onset epileptic encephalopathy(EOEE) caused by ion channel gene mutation, to identify the etiology, to guide the treatment and to provide the basis for genetic counseling. Methods The clinical data from 17 children with EOEE caused by ion channel gene mutation and the peripheral blood of the children and their parents were collected from June 2014 to May 2018 at the Department of Neurology, Tianjin Children′s Hospital.Epilepsy gene sequencing was performed by using disease gene targeting second generation sequencing technology.The mutation of pathogenic ion channel gene was found.The confirmed mutations were verified by Sanger sequencing and the source of the mutation was identified. Results Among 17 case with EOEE, 3 cases had genetic mutation, and 14 cases had denovo mutations.Dravet syndrome was found in 8 cases (47.1%), there were SCN1A gene missense mutation in 5 cases, SCN1A gene nonsense mutation in 3 cases, KCNQ2 gene missense mutation in 1 case (5.9%) and non-specific epileptic encephalopathy in 8 cases (47.1%). SCN2A gene missense mutation, SCN4A gene missense mutation, SCN8A gene missense mutation, KCNQ2 gene missense mutation and KCNH gene missense mutation were found in suspected pathogenic mutations.There were 1 missense mutation out of 5 genes, 1 missense mutation of CACNA1A gene, 1 missense mutation of GRIN2A gene and 1 missense mutation of GRIN3A gene.Seventeen patients were treated with 2 or more antiepileptic drugs, 4 with ketogenic diet and 1 with vitamin B6 supplementation.During 11 to 96 months of follow-up, seizures were completely controlled in 3 cases (17.6%), decreased in 7 cases (41.2%) by more than 50%, and decreased in 7 cases (41.2%) by less than 50%. Conclusions The clinical phenotypes for children with unexplained EOEE are varied, and gene mutations of ion cha-nnel are most common.Some gene sites are denovo mutations which have not been reported such as missense mutation for 3 case SCN1A gene, 1 case SCN2A gene, 1 case CACNA1A gene, 1 case KCNH5 gene, and nonsense mutation for 2 case SCN1A gene, which have enriched the mutation spectrum of EOEE. Key words: Early-onset epileptic encephalopathy; Ion channel; Etiology; Gene mutation

Ketogenic Diet in Patients with GLUT1 Deficiency Syndrome.

Background:The ketogenic diet (KD) is a high fat, low carbohydrate diet considered to be the treatment of choice for GLUT1deficiency syndrome, a metabolic disorder affecting the nervous system. Aim:To present our experience in four patients with GLUT1 deficiency syndrome who were treated with KD. Methods:Retrospective data from case series. Phenotypical features, mainly movement disorder and seizures, are being described for each patient. All four cases are currently following the Modified Atkins Diet. Results:The response to ketogenic diet in our four patients was significant with improvement of movement disorder or seizures control. Conclusion:The ketogenic diet is the treatment of choice for GLUT1deficiency syndrome. Recognition of the disorder is the key for appropriate management among clinicians. Diet compliance is an important issue in school age children.

The clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children

Objective To study the clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children. Methods Cluster sampling method was employed to select children in children's hospital from January 2015 to June 2017, a total of 25 cases were diagnosed refractor epilepsy and adding ketogenic diet. Engel grade was used to evaluate the efficiency, the side effects , electroencephalogram (EEG) changes and intellectual development at 3 months , 3-6 months , and more than 6 months. Results The effective rate of epileptic seizure control was 0, 66.7% and 87.5% at 3 months, 3-6 months and > 6 months respectively. The improvement rate of EEG discharge index was 33.3%, 50% and 81.3% respectively. The improvement of intelligence development was 33.3%, 50% and 68.8% respectively. Gastrointestinal disturbances were the main side effects. Severe side effect occurred in two cases--they had severe food refusal and were stopped the ketogenic diet adding treament. Conclusions The ketogenic diet is effective, safe, few side effects and tolerable in infants and children with refractory epilepsy. The ketogenic diet may improve cognition and behavior in addition to reducing seizure frequency, the interical epileptiform discharges (IED) index and improve the quality of life of epileptic children. However, the acceptance of ketogenic diet therapy for children is not satisfactory. The sample size is small and needs further promotion. While large samples and long-term observations are still desired to better recipes, and to provide possibly effective alternative to other therapies for refractor epilepsy. Key words: Epilepsy/TH; Diet, carbohydrate-restricted; Ketones; Child

Ketogenic diet for febrile infection related epilepsy syndrome: case report and literature review

目的 总结热性感染相关性癫痫综合征(FIRES)的临床特征、病因及生酮饮食(KD)治疗的作用。 方法 分析1例入住四川大学华西第二医院儿科重症监护室的FIRES患儿临床表现、诊断及KD治疗经过，随诊1年观察预后，综合文献资料，总结该病临床特征、病因、诊断标准及KD治疗效果。 结果 患儿为学龄前期儿童，起病急骤，表现为发热、意识障碍及药物难控制的癫痫持续状态。脑电图示背景慢化，额、颞及顶叶尖波发放，头颅磁共振成像示双侧脑室周围白质异常信号。经KD治疗1周后，成功撤停丙泊酚并转入普通病房，出院后继续口服抗癫痫药物及KD治疗，随访1年期间，未再出现癫痫持续状态，认知水平较住院期间改善，但较病前明显落后。相关文献显示该病好发于既往健康的学龄儿童，常伴发热，病因与炎症介导的免疫反应可能有关，早期KD治疗的患者有1/4～1/3发作减少，有利于尽早撤停静脉麻醉剂，随访显示大部分患者认知损害有改善，癫痫发作频率及出现癫痫持续状态减少。 结论 FIRES病因不明，好发于学龄儿童，常伴发热，癫痫发作呈暴发性、药物难治性，早期KD治疗对控制急性期癫痫发作及改善远期预后有益。

Meta-analysis on efficacy and compliance of ketogenic diet treatment for children with refractory epilepsy

Objective To systematically evaluate the efficacy and compliance of domestic ketogenic diet(KD) for children with refractory epilepsy (RE), in order to provide the basis for further improving the curative effect and compliance by finding out the factors influencing efficacy and compliance. Methods The effect of KD on children with RE was investigated by systematically searching China National Knowledge Infrastructure(CNKI), China Science and Technology Journal Database(CSTJ), Wanfang Data Knowledge Service Platform and PubMed database from January 1, 1989 to January 17, 2018.The relevant literature R3.0.2 software was used to combine the retention rate and therapeutic effect in different periods, based on the systematic analysis of the therapeutic efficacy and compliance literature. Results A total of 11 eligible documents were included.(1)The methodological index for non-randomized studies (MINORS) scores of included literature were rated from 10 to 18 points.(2)A secondary analysis of 9 literatures on the description of the subject′s composition showed that the proportion of male to female in children with RE ranged from 1.44︰1.00 to 2.73︰1.00, and that of 9 literatures included a total of 331 samples, there were 212 male and 119 female, the ratio of male to female was 1.78︰1.00.(3)The sources of the included literatures were from Beijing, Shanghai, Changsha, Shenzhen, Nanchang, Zhengzhou, Suzhou, Chongqing, Shenyang and Xi′an.(4)The retention rates of 1 month(5 studies), 3 months(10 studies), 6 months(7 studies) and 12 months (6 studies) were respectively 93% [95% confidence interval (CI): 88%-98%], 80% (95%CI: 71%-98%), 70% (95%CI: 61%-78%) and 54% (95%CI: 37%-71%). (5) According to the Meta-analysis, the effective rate of 1 month(6 studies), 3 months(10 studies), 6 months(7 studies) and 12 months (7 studies) were respectively 57% (95%CI: 34%-79%), 68% (95%CI: 57%-79%), 76% (95%CI: 62%-89%) and 80% (95%CI: 68%- 93%). (6)Through analyzing the adverse reactions and the causes of termination, the literature showed that common adverse reactions involved digestive system (72 cases), infection (23 cases), urinary calculus (4 cases), and the metabolic disorder.The reason of treatment termination was that the children were not cooperative (26 cases) and the parents had poor comp-liance (24 cases). Conclusion KD is one of the effective methods for treating RE in children.Reducing or relieving adverse reactions in KD to improve the treatment compliance of children with RE and their families is a subject worthy of further study and attention. Key words: Refractory epilepsy; Ketogenic diet; Therapy; Compliance; Incidence; Meta analysis; Child

Putting More Efforts on Cancer Ketogenic Therapy Research

Putting More Efforts on Cancer Ketogenic Therapy Research

An mHealth Application for Educating and Monitoring Patients Treated with a Ketogenic Diet Regimen.

Ketogenic Diet (KD) is a high-fat diet used to treat refractory epilepsy in patients, also including children. Because of the inherent differences with a balanced diet, patients starting KD face an abrupt switch of dietary habits. Moreover, KD is associated with several side effects that should be closely monitored. In this paper, we propose an mHealth application for training and empowering patients in managing KD. The application also acts as a bridge connecting patients with the health care staff for coaching and monitoring purposes.

Advance of mechanism of ketogenic diet in refractory childhood epilepsy

Ketogenic diet(KD)has an auxiliary treatment for refractory epilepsy.It is recently demonstrated by clinical practice and researches that KD is effective in some children with refractory epilepsy.Despite much progress has been made on the anticonvulsant mechanisms of KD, no biological target related to clinical efficacy has been found so far.The biochemical characteristics of KD and its metabolic changes are discussed(including the roles of neuronal γ-aminobutyric acid, glutamate, ATP sensitive potassium channels and purine metabolism, and so on). The mechanism and recent progress of KD in the treatment of refractory childhood epilepsy are reviewed. Key words: Ketogenic diet; Metabolism; Epilepsy; Child

Dietary therapy in children with autism spectrum disorder

Autism spectrum disorder(ASD)is a severe neurodevelopmental disorder of children that leads to disability which lacks of effective treatment.The specific pathogenesis of ASD remains unclear, which may involve in multiple factors.In recent years, many studies have shown that children with ASD have gastrointestinal(GI)abnormalities and some special diet therapies can effectively ameliorate the symptoms of ASD.These diets include gluten free diet, sensitive or harmful food removing therapy and ketogenic diet.The patients with ASD have GI inflammation or allergy, energy metabolism disorder, oxidative stress injury, neurotransmitter disturbance and dysbiosis of intestinal flora.Diet therapy may improve ASD symptoms by correcting disorders above.This article reviews the application and the related mechanism of diet therapy in ASD children and the effect of diet therapy on the growth and the development of children. Key words: Diet therapy; Autism Spectrum Disorder; Children

The current precision medicine approaches in genetic epilepsies

The increasing identification of genetic causes for epilepsy over the recent years improves the understanding of the underlying epileptog enic process, and allows for the possibility of directed therapeutic approaches. An ideal antiepileptic therapy consists of a drug which is able to influence the functional changes caused by a specific pathogenic variant. In this review, we describe the current precise medicine approaches in genetic epilepsies. Currently established or investigated precise medicine treatments include the ketogenic diet in patients with glucose transporter type1 (GLUT1) deficiency, sodium channel blockers in patients with KCNQ2 mutations, and mechanistic target of rapamycin (mTOR)-inhibitors in patients with SCN2A and SCN8A mutations. These predominantly represent already available treatments that were repurposed for use in epilepsy. The development of new therapeutic agents aiming at targets identified in genetic epilepsies will advance epilepsy treatment considerably. Key words: Epilepsy/DT/GE; Review

Treatment strategies of intractable epilepsy in children

Epilepsy is a common chronic disease of the nervous system in children. Antiepileptic drugs are the first choice for the treatment of epilepsy. However, about 20%-40% of children with epilepsy will develop intractable epilepsy, which can affect children's mental development and bring heavy burden to families and the society. In addition to antiepileptic drugs, epilepsy surgery, neuromodulation and ketogenic diet can also be used as alternative treatments of intractable epilepsy. In order to give a reasonable advice, neurologists must be familiar with the indications and the advantages and disadvantages of the antiepileptic drugs and the various alternative treatments mentioned above. Only in this way can we reduce seizure frequency, even achieve the goal of curing epilepsy. Key words: Epilepsy/TH; Child; Review