The efficacy of low glycemic index diet on seizure frequency in pediatric patients with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Despite extensive research examining the effect of a low glycemic index (LGI) diet on the frequency of seizures in patients with epilepsy, the findings are inconclusive. Hence, we performed a systematic review and meta-analysis in order to clarify the potential effect of a low glycemic index (LGI) diet on the frequency of seizures in children. METHODS: A systematic review and meta-analysis written in accordance with the PRISMA checklist was realized using a comprehensive systematic search in four electronic databases until October 2023 without time or language restrictions. A random effects model was employed to combine the data. The main outcomes were analyzed using weight mean difference (WMD) and 95 % confidence interval (95 % CI). In total, 13 studies met the eligible criteria and were included. RESULTS: The publications included in this study were published between 2005 and 2021. The duration of the interventions in the studies included in this analysis ranged from 6 to 58 weeks. Our findings indicated that the pooled efficacy rate for < 50 %, ≥ 50 %, > 90 % seizure reduction in patients with epilepsy receiving a low glycemic index diet was 39 % (95 % CI: 26, 52), 34 % (95 % CI: 23, 45), and 19 % (95 % CI: 13, 25), respectively. It seems that the efficacy of this ketogenic diet in reducing seizures is greater during a shorter intervention period than 12 weeks. CONCLUSION: This systematic review and meta-analysis suggests that the low glycemia index diet can be beneficial as a treatment for epilepsy in pediatric patients.

Effect of a Ketogenic Diet on Oxidative Posttranslational Protein Modifications and Brain Homogenate Denaturation in the Kindling Model of Epilepsy in Mice.

This study focused on the ketogenic diet (KD) effects on oxidative posttranslational protein modification (PPM) as presumptive factors implicated in epileptogenesis. A 28-day of KD treatment was performed. The corneal kindling model of epileptogenesis was used. Four groups of adult male ICR mice (25-30 g) were randomized in standard rodent chow (SRC) group, KD-treatment group; SRC + kindling group; KD + kindling group (n = 10 each). Advanced oxidation protein products (AOPP) and protein carbonyl contents of brain homogenates together with differential scanning calorimetry (DSC) were evaluated. Two exothermic transitions (Exo1 and Exo2) were explored after deconvolution of the thermograms. Factor analysis was applied. The protective effect of KD in the kindling model was demonstrated with both decreased seizure score and increased seizure latency. KD significantly decreased glucose and increased ketone bodies (KB) in blood. Despite its antiseizure effect, the KD increased the AOPP level and the brain proteome's exothermic transitions, suggestive for qualitative modifications. The ratio of the two exothermic peaks (Exo2/Exo1) of the thermograms from the KD vs. SRC treated group differed more than twice (3.7 vs. 1.6). Kindling introduced the opposite effect, changing this ratio to 2.7 for the KD + kindling group. Kindling significantly increased glucose and KB in the blood whereas decreased the BW under the SRC treatment. Kindling decreased carbonyl proteins in the brain irrespectively of the diet. Further evaluations are needed to assess the nature of correspondence of calorimetric images of the brain homogenates with PPM.

Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases.

BACKGROUND: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. METHODS: An observational descriptive study was conducted to describe 18 children (January 2009-August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. RESULTS: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. CONCLUSIONS: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.

The ketogenic diet raises brain oxygen levels, attenuates postictal hypoxia, and protects against learning impairments.

OBJECTIVES: A prolonged vasoconstriction/hypoperfusion/hypoxic event follows self-terminating focal seizures. The ketogenic diet (KD) has demonstrated efficacy as a metabolic treatment for intractable epilepsy and other disorders but its effect on local brain oxygen levels is completely unknown. This study investigated the effects of the KD on tissue oxygenation in the hippocampus before and after electrically elicited (kindled) seizures and whether it could protect against a seizure-induced learning impairment. We also examined the effects of the ketone ß-hydroxybutyrate (BHB) as a potential underlying mechanism. METHODS: Male and female rats were given access to one of three diet protocols 2 weeks prior to the initiation of seizures: KD, caloric restricted standard chow, and ad libitum standard chow. Dorsal hippocampal oxygen levels were measured prior to initiation of diets as well as before and after a 10-day kindling paradigm. Male rats were then tested on a novel object recognition task to assess postictal learning impairments. In a separate cohort, BHB was administered 30 min prior to seizure elicitation to determine whether it influenced oxygen dynamics. RESULTS: The KD increased dorsal hippocampal oxygen levels, ameliorated postictal hypoxia, and prevented postictal learning impairments. Acute BHB administration did not alter oxygen levels before or after seizures. INTERPRETATION: The ketogenic diet raised brain oxygen levels and attenuated severe postictal hypoxia likely through a mechanism independent of ketosis and shows promise as a non-pharmacological treatment to prevent the postictal state.

The role of ketogenic diet in controlling epileptic seizures.

OBJECTIVES: To study the role of the ketogenic diet (KD) in controlling seizures in children with medically resistant epilepsy in Saudi Arabia. METHODS: This retrospective study was conducted in the Pediatric Neurology Clinic at a tertiary care epilepsy center. Thirty-one patients with medically resistant epilepsy were enrolled from 2013 to 2018. The seizure reduction variables were evaluated at 6, 12, 18 and 24 months after enrollment. RESULTS: Of the 31 patients, 14 (45.2%) were males and 17 (54.8%) were females. The most common types of seizures were myoclonic seizures and mixed seizures, both of which occurred in 9 (29%) of the participants. Of the participants, 15 (48.4%) had seizures one to 5 times per day. Six months after starting a KD, 2 (6.45%) of participants were seizure-free; 6 (19.35%) were seizure-free after 12 months of treatment. CONCLUSION: The present study highlighted the effectiveness of KD in medically resistant epilepsy children to local population. A larger cohort is warrant to confirm these findings.

Optimizing data collection in dietary therapy clinics for epilepsy: A recommendation for standardized data collection forms.

OBJECTIVE: The objectives of this study were to 1) examine medical records from one medium-sized dietary clinic as an example of data being collected clinically, 2) identify data limitations, and then 3) create standardized data collection forms with the long-term goals of improving clinical care and facilitating multicenter data analysis. METHODS: A retrospective chart review was conducted at the Dietary Therapies for Epilepsy Clinic at Children's National Medical Center (CNMC) in Washington, D.C. Patients who initiated dietary therapy between 2015 and 2018 were assessed. Categorical variables were examined via Chi Square or Fisher's Exact tests and continuous variables were assessed via an independent t-test or Mann-Whitney U test, depending on normality. RESULTS: Forty-two patients underwent dietary therapy initiation during this time period, but only 26 had follow-up visit data. Of these patients, 54% reported non-seizure symptom improvement(s), and only 16 had quantitative seizure frequency information available, with 63% being clinical responders. No significant associations were observed between patient or diet characteristics and seizure or non-seizure improvement. Some variables, such as seizure duration, seizure severity, beta-hydroxybutyrate, and dietary compliance were not typically included in the records and therefore could not be evaluated statistically. Variations in seizure type(s), etiology, and clinical diagnoses/syndromes also made it unfeasible to evaluate differences in improvement based on these variables. Standardized data collection forms were created to address these limitations and are included as appendices. SIGNIFICANCE: The results suggest limitations with the clinical data currently being collected. Medium-sized clinics may not see enough patients to study specific epilepsy populations. Standardized patient forms could target these issues, thereby improving clinical care and expanding research opportunities. Future research can test these forms for clinical use and as a collection tool for larger scale research across clinics.

Families' Perception of Classic Ketogenic Diet Management in Acute Medical Conditions: A Web-Based Survey.

Objective: To describe families' experiences in managing epileptic patients undergoing ketogenic dietary therapies (KDTs) in acute medical settings. Methods: We conducted a short online survey addressed to the families of patients undergoing a classic ketogenic diet (cKD) for at least three months. The survey was composed of 18 questions exploring the following issues: demographic characteristics, epilepsy diagnosis, ketogenic-diet treatment history, the reason for emergency-ward admission and patient management, surgery-procedure management, and outcomes. Results: A sample of 50 families agreed to participate. Out of 50 patients, 33 (66%) had been undergoing a cKD for more than two years. Fifteen (30%) patients had been admitted at least once to the Emergency Room (ER), and 8.2% had undergone surgical procedures during cKD treatment. The causes of ER admission were the following: seizures, infection, trauma, and gastrointestinal or respiratory problems. In 75% of cases, blood ketonemia was not monitored during ER admission, and according to 46% of responders, the medical staff intervening did not have a basic knowledge of KDTs. Conclusions: According to both our experience and caregivers' reports, it might be useful to search for standardized specific approaches to patients undergoing KDTs in the emergency setting.

Ketogenic diet, neuroprotection, and antiepileptogenesis.

High fat, low carbohydrate ketogenic diets (KD) have been in use for the treatment of epilepsy for almost a hundred years. Remarkably, seizures that are resistant to conventional anti-seizure drugs can in many cases be controlled by the KD therapy, and it has been shown that many patients with epilepsy become seizure free even after discontinuation of the diet. These findings suggest that KD combine anti-seizure effects with disease modifying effects. In addition to the treatment of epilepsy, KDs are now widely used for the treatment of a wide range of conditions including weight reduction, diabetes, and cancer. The reason for the success of metabolic therapies is based on the synergism of at least a dozen different mechanisms through which KDs provide beneficial activities. Among the newest findings are epigenetic mechanisms (DNA methylation and histone acetylation) through which KD exerts long-lasting disease modifying effects. Here we review mechanisms through which KD can affect neuroprotection in the brain, and how a combination of those mechanisms with epigenetic alterations can attenuate and possibly reverse the development of epilepsy.

Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: a non-blinded, prospective clinical trial.

BACKGROUND: Despite appropriate antiseizure drug (ASD) treatment, around two-thirds of dogs with idiopathic epilepsy (IE) have seizures long-term and 20-30per cent of affected dogs remain poorly controlled. METHODS: The current study aim is to test in a field trial the efficacy and tolerability of a commercially available diet enriched with 6.5per cent medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizures, in 10 veterinary practices across Europe. Each dog's quality of life (QoL), ataxia, sedation and frequency and severity of seizures were recorded by owners throughout the study. RESULTS: The mean seizure frequency per month, averaged over the entire 84-day study, significantly (P=0.04) decreased 32per cent compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined (P<0.001) by 42per cent. QoL was reported as very good to excellent (>8.5/10) in 20 of the 21 dogs before starting the diet and this remained unchanged during the trial. CONCLUSIONS: This study demonstrates the use of a diet enriched with MCTs as an adjunct to ASD treatment may have some antiseizure properties for dogs diagnosed with IE, as demonstrated in previous studies.

A multicenter randomized controlled trial of medium-chain triglyceride dietary supplementation on epilepsy in dogs.

BACKGROUND: Medium-chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). OBJECTIVE: To evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. ANIMALS: Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. METHODS: A 6-month multicenter, prospective, randomized, double-blinded, placebo-controlled crossover trial was completed, comparing an MCT-DS with a control-DS. A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study. RESULTS: Seizure frequency (median 2.51/month [0-6.67] versus 2.67/month [0-10.45]; P = .02) and seizure-day frequency were significantly (1.68/month [0-5.60] versus 1.99/month [0-7.42], P = .01) lower when dogs were fed MCT-DS in comparison with the control-DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency. CONCLUSIONS AND CLINICAL IMPORTANCE: These data show antiseizure properties of an MCT-DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug-resistant dogs with epilepsy.

Magnesium Supplementation did not affect the Antiseizure Property of Ketogenic Diet but Reduced Lipid Dysmetabolism.

BACKGROUND: Ketogenic diets (KD) have been used globally in epilepsy management. Similarly, supplementation of diets with magnesium has been associated with disease prevention and improvement. However, the effect of magnesium (Mg) supplementation in conjunction with KD on epilepsy has not yet been investigated. We hypothesized that magnesium supplementation in KD would improve the effectiveness of the diet. METHODS: Forty-eight male Wistar rats were used for the study. The animals were fed on 4 diet types: I-normal rat chow (ND), II-ND with Mg supplement (ND+Mg), III-medium chain ketogenic diet (KD) and IV-KD with Mg supplement (KD+Mg). Animals in each group were divided into 3: experimental, control and observatory. The experimental drug was intraperitoneal Pentylenetetrazole (PTZ) administered at 25 mg/kg. The rats were observed for 2 hours after the drug administration and induced seizures noted. The levels of serum electrolytes and plasma lipid levels were determined using standard methods. RESULTS: The seizure latency was significantly prolonged 60.8±0.5mins in group III compared with 8.7±2.1mins in group I (p<0.05). The seizure duration was 42.5±2.5mins in group III and 142.3±4.7 in group I (p<0.05). With Mg supplementation, seizure latency was 62.6±1.5mins in group IV and 7.9±0.7mins in group I (p<0.05). The seizure duration was 45.5±4.5min in group IV and 139.3±3.9mins in group II (p< 0.05). The KD-fed rats showed a tendency to develop dyslipidemia as evidenced by elevated Total Cholesterol /HDL and LDL/HDL (2.32±0.32 and 1.19±0.08) in group III, which was reversed in the KD+Mg fed group IV (1.96±0.32 and 1.08±0.09) with p<0.05. CONCLUSION: Mg supplementation of KD did not affect its antiseizure property and does not confer antiseizure effect on ND. Mg supplement showed a tendency to reduce derangement in lipid metabolism associated with KD.

Cardiometabolic risk and effectiveness of the modified Atkins Ketogenic Diet for adult patients with pharmacoresistant epilepsies in a middle-income country.

A ketogenic diet may be a therapeutic option for approximately one third of patients with epilepsy. These patients continue to have seizures despite suitable pharmacological treatment. Regardless of the diet's therapeutic potential regarding seizure control, adverse events may coexist. This requires constant monitoring of the patient as comorbidities may emerge. A prospective, nonrandomized and uncontrolled study was conducted to evaluate the effect of a ketogenic diet on cardiometabolic parameters (lipid profile, glycemic profile and body composition variables) and seizure control in adult patients with pharmacoresistant epilepsies. Patients followed the Modified Atkin's Diet (MAD), with a restriction of 20 g of carbohydrates per day, adequate protein amounts and fats ad libitum for 24 weeks. Fourteen eligible patients were enrolled in the study, however, only eight completed the treatment (four women with an average age of 33.5 ± 9.9 years and four men with an average age of 27.5 ± 9.0 years; p = 0.386). The median of focal impaired awareness seizures decreased from 9.0 (interquartile range [IQR] 4.0-28.0) seizures per month pre-diet to 4.0 (IQR 0.5-11.2) seizures per month in 12 weeks (p = 0.028), i.e. a 55.5% reduction. Total cholesterol (19,711 ± 1373 mg/dL to 28,427 ± 2545 mg/dL; p = 0.016), LDL (131.47 ± 1319 mg/dL to 194.85 ± 20.41 mg/dL; p = 0.037), and non-HDL (140.20 ± 13.04 mg/dL to 219.75 ± 28.53 mg/dL; p = 0.028) levels increased progressively over the intervention period, being significant at 24 weeks (n = 6). A significant reduction in blood glucose (89.70 ± 2.20 mg/dL to 82.62 ± 1.45 mg/dL at week 24, p < 0.001, n = 6), insulin (11.02 ± 1.78 µUI/mL to 6.20 ± 0.71 µUI/mL at week 12, p < 0.001, n = 6) and HOMA-IR index was observed (1.46 ± 0.29 to 0.91 ± 0.23 at week 24, p < 0.001, n = 5). The estimated cardiovascular risk after treatment was low for all patients (less than 10 %). A significant reduction in body weight (76.28 ± 6.62 kg to 69.14 ± 5.63 kg; p < 0.001), body mass index (26.41 ± 1.79 kg/m² to 24.05 ± 1.58 kg/m²; p = 0.001), and waist (87.40 ± 4.98 cm to 78.61 ± 3.94 cm; p < 0.001) and arm circumferences (32.12 ± 1.97 cm to 28.98 ± 1.30 cm; p < 0.001) was observed (n = 8), as well as reduction in fat mass (26.85 ± 3.15 g to 21.54 ± 2.64 g; p < 0.001) and fat free mass (48.01 ± 2.75 g to 46.60 ± 2.29 g; p < 0.001), n = 7. Adverse events were generally mild and treatable, with the following being the most common: headache (50 %), weakness (50 %), and gastrointestinal symptoms (37.5 %). Potentially atherogenic lipid profile changes were observed; however, improved glycemic control and reduced body weight and waist circumference demonstrated an improvement in cardiometabolic parameters. Framingham score and the QRISK3 showed lower cardiovascular disease risk for some of the patients. Our data suggests MAD could be an appropriate therapeutic choice for adults with pharmacoresistant epilepsies.

History of dietary treatment from Wilder's hypothesis to the first open studies in the 1920s.

In the ketogenic diet (KD) history, Wilder is often mentioned as the first author to report on the use of KD for patients with epilepsy. Our article aimed to understand how Wilder formulated the hypothesis of the KD effectiveness for patients with epilepsy, and how the KD was used and spread in the 1920s. In 1921, Wilder published two articles on the effects of ketonemia on epilepsy. He first reported on the interest of fasting for patients with epilepsy, suggesting that the benefits of fasting on seizures might be dependent on ketonemia. He then hypothesized that equally good results could be obtained with a KD, very rich in fat and very low in carbohydrate, which would provoke ketogenesis, and observed the effects of this diet on three patients for the first time. Following the publication of Wilder articles, 9 papers on KD were published during the 1920s, involving more than 400 patients with epilepsy. Ketogenic diet therapies (KDT) are now evidence-based treatments of epilepsy. Available experimental data do not confirm the role of ketosis as the unique mechanism of the KD. The KD is still explored to understand all the underlying mechanisms.

Ketogenic parenteral nutrition in three paediatric patients with epilepsy with migrating focal seizures.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare epilepsy syndrome, characterized by an onset of multifocal seizures before the age of six months and a rather typical ictal EEG pattern. The ketogenic diet (KD) has been shown to be a treatment option in these patients with variable results. The KD is generally given by enteral formula or solid food, however, patients on the KD often have coexisting medical disorders that may impair the gastrointestinal tract and, in these cases, parenteral nutrition support may be needed. We present our experience with three patients who had been on the KD because of EIMFS, who were acutely unable to absorb nutrients through the intestinal tract. For these patients, we were unable to reach ketogenic ratios higher than 1.5:1 because of the limited fat intake via the parenteral route. This ratio, nevertheless, was adequate for maintenance of seizure control while allowing short-term bowel rest. Even though our report is limited as it provides no controlled evidence, ketogenic parenteral nutrition should be considered in children on the KD when enteral nutrition is not feasible. Special care should be taken to maintain ketosis and avoid undesired carbohydrates. Patients may respond well to ketogenic parenteral nutrition in spite of a lower ketogenic ratio.

The addition of a lipid-rich dietary supplement eliminates seizure-like activity and paralysis in the drosophila bang sensitive mutants.

OBJECTIVE: To investigate the effect that a diet supplemented with KetoCal 4:1, a commercially available dietary formula consisting of a 4:1 ratio of fats to carbohydrates plus proteins, had on the seizure-like activity (SLA) and paralysis normally exhibited by the Drosophila Bang-sensitive (BS) paralytic mutants following mechanical shock. METHODS: Given that dietary changes are known to reduce seizures in humans and animal models, three BS mutants, easily-shocked (eas), bang-senseless (parabss), and technical knockout (tko), were fed a standard cornmeal/yeast/sugar diet supplemented with 10% KetoCal 4:1 (KetoCal-sup diet). Newly eclosed BS flies were fed this diet for 3-7 days and the effect this had on SLA, paralysis, locomotor activity, triglyceride levels, and glucose levels was examined. RESULTS: All three genotypes displayed significant reductions in SLA and BS sensitivity following mechanical shock. After only 3 days on the diet, 95% of tko flies no longer exhibited SLA or paralysis, and near complete suppression of the BS phenotype was seen by day 7. In the case of eas, there was a 78% reduction of SLA after 3 days on the diet and SLA was completely suppressed by day 7. The parabss flies showed a similar but less robust reduction of SLA on the diet as there was only a 68% reduction of SLA and paralysis following 7 days on the diet. The diet did not suppress activity globally as tko flies had increased basal locomotor activity on the diet while the parabss and eas flies showed no significant change in basal activity. The KetoCal-sup diet did not significantly alter the triglyceride levels or the total glucose levels in the BS mutants. In addition, the SLA and BS suppression was maintained even when the BS mutants were transitioned back to a standard fly diet. CONCLUSIONS: The SLA and paralysis associated with the Drosophila BS phenotype can be effectively suppressed by transient exposure to a KetoCal-sup diet. This suppression was not dependent upon long term maintenance of the diet and it was not associated with alterations in total glucose or triglyceride levels in these flies.

Optimized mid-long term management of ketogenic diet in children with refractory epilepsy.

This study aims to explore the mid-long term management of ketogenic diet (KD) for the treatment of refractory epilepsy in children, and carry out an efficacy assessment. The data of epileptic children who received KD in our hospital from January 2011 to August 2012 (basic management plan group, n=57) were retrospectively analyzed. On this basis, epileptic children who received KD from September 2012 to April 2014 (optimized management plan group, n=52) were managed according to the mid-long term management plan. The effective rate of KD at the first, third, sixth and ninth month was 90.4%, 73.1%, 65.4% and 38.5%, respectively, in the optimized management plan group, and 63.2%, 45.6%, 38.6% and 21.1%, respectively, in the basic management plan group, and the differences were statistically significant. The compliance rate of KD at the third, sixth and ninth month was 94.2%, 78.8% and 63.5%, respectively, in the optimized management plan group, and 82.5%, 47.4% and 28.1%, respectively, in the basic management plan group, and the differences were statistically significant. Optimized mid-long term management of KD in children can improve the control rate of epileptic seizures, and the compliance of patients.

Functional Nutrients for Epilepsy.

Epilepsy is a common neurological disorder of which seizures are a core symptom. Approximately one third of epileptic patients are resistant to antiepileptic drugs and therefore require alternative therapeutic options. Dietary and nutritional supplements can in some cases replace drugs, but with the exception of ketogenic diets, there are no officially recommended dietary considerations for patients with epilepsy. In this review we summarize a selection of nutritional suggestions that have proved beneficial in treating different types of epilepsy. We describe the types of seizures and epilepsy and follow this with an introduction to basic molecular mechanisms. We then examine several functional nutrients for which there is clinical evidence of therapeutic efficacy in reducing seizures or epilepsy-associated sudden death. We also discuss experimental results that demonstrate possible molecular mechanisms elicited by the administration of various nutrients. The availability of multiple dietary and nutritional candidates that show favorable outcomes in animals implies that assessing the clinical potential of these substances will improve translational medicine, ultimately benefitting epilepsy patients.

Outcome of Nonketotic Hyperglycinemia in Lebanon: 14-Year Retrospective Review.

Nonketotic hyperglycinemia is a rare inborn error of glycine metabolism characterized by a severe metabolic encephalopathy with drug-resistant seizures. Here, we report the outcome of nonketotic hyperglycinemia in a cohort of patients diagnosed and followed-up at a tertiary care reference center in Lebanon, between 2000 and 2014.Eight out of 12 patients with nonketotic hyperglycinemia were retrospectively reviewed. The remainders were excluded for incomplete data. The majority of cases presented with seizures and hypsarrhythmia or burst suppression patterns. Half of the patients died. Survival varied between 7 days and 18 years. Seizures remained unresponsive with poor outcome, despite standard supportive care and antiepileptic therapy; however, two patients were responsive to ketogenic diet and one of them became seizure-free.Scarce data on the outcome of nonketotic hyperglycinemia patients from the Middle East and North Africa region are available. The ketogenic diet, in combination with standard therapies, appears to be effective in controlling the seizures in this devastating disorder. Larger multicenter studies are still needed to establish the role of the ketogenic diet in nonketotic hyperglycinemia.

Vitamin E modifies high-fat diet-induced reduction of seizure threshold in rats: Role of oxidative stress.

There is increasing evidence that oxidative stress is a causal factor in different neurodegenerative disorders such as Alzheimer's disease and epilepsy. High-fat diet (HFD) has been shown to induce oxidative stress and neuronal damage that may increase susceptibility to seizures. The present study was undertaken to investigate the relationships between vitamin E, a potent antioxidant, HFD, and chemically induced seizures, using the PTZ seizure model in rats. Animals were randomly assigned into four groups: control, HFD, vitamin E (Vit E), and high-fat diet with vitamin E (HFD + Vit E) group. Vitamin E and/or HFD were administered to animals for 6 weeks. Thereafter, PTZ seizure threshold was measured in control and treated rats, and different brain regions were analyzed for levels of oxidative stress biomarkers. Current results revealed a significant reduction in PTZ seizure threshold in rats consuming HFD, which could be prevented by vitamin E supplement. Alongside, vitamin E supplement prevented HFD induced changes in oxidative stress biomarkers and capacity enzymes. Therefore, current results suggest that prolonged consumption of HFD increases susceptibility to PTZ induced seizures, which may be related to HFD induced oxidative stress. This increase in the PTZ susceptibility could be prevented by the administration of vitamin E, probably through its antioxidant effect, particularly at the brain hippocampal region.