Keto Clarity: A Comprehensive Systematic Review Exploring the Efficacy, Safety, and Mechanisms of Ketogenic Diet in Pediatric Epilepsy.

Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population. Antiepileptic drugs (AEDs) constitute the primary treatment; however, drug-resistant epilepsy (DRE), especially in children, poses a therapeutic challenge. Alternative interventions, such as surgery, vagus nerve stimulation, and the ketogenic diet (KD), have been explored. This systematic review aims to investigate various types of KDs, their distinctions, their effectiveness, and their safety concerning the reduction of seizure frequency, achieving seizure freedom, and the occurrence of adverse events. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was conducted using databases such as PubMed Central (PMC), MedLine, and Science Direct to identify relevant articles. Eligibility criteria and quality assessment tools were applied to evaluate the potential risk of bias and select 11 articles for inclusion in this review. The selected articles encompassed four randomized controlled trials (RCTs), two systematic reviews, and five narrative reviews. The data collected for this review was completed on October 2, 2023. Challenges, such as palatability, cultural factors, and adherence difficulties, were identified. Family or caregiver involvement plays a pivotal role in treatment success. Despite numerous RCTs and reviews, information gaps persist, hindering conclusive outcomes. Evaluating the risk-benefit ratio is crucial, considering potential side effects. The highly individualized nature of KD therapy, influenced by diverse seizure types and syndromes, necessitates a trial-and-error approach monitored by a multidisciplinary team. Long-term safety and efficacy demand continuous real-life patient data review. In summary, while KD presents a promising alternative for DRE, its success relies on meticulous planning, individualized implementation, and ongoing research to address existing challenges and information gaps.

Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet.

Introduction: Ketogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors. Possible variations in glycemia and ketone bodies blood levels according to the menstrual cycle have not been systematically assessed yet, but this time window deserves special attention because of hormonal and metabolic related changes. Methods: This study aims at searching for subtle changes in KBs blood level during menstrual cycle in female patients undergoing a stable ketogenic diet, by analyzing 3-months daily measurement of ketone bodies blood levels and glucose blood levels throughout the menstrual cycle. Results: We report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet. A significant increase in glucose blood levels during menstruation was found in the entire cohort. As far as the ketone bodies blood levels, an inversely proportional trend compared to glycemia was noted. Conclusion: Exploring whether ketonemia variations might occur according to the menstrual cycle is relevant to determine the feasibility of transient preventive diet adjustments to assure a continuative treatment efficacy and to enhance dietary behavior support. Clinical trial registration: clinicaltrials.gov, identifier NCT05234411.

Classic ketogenic diet in parenteral nutrition in a GLUT1DS patient: Doing more with less in an acute surgical setting.

Ketogenic Dietary Treatments (KDTs) are to date the gold-standard treatment for glucose transporter type 1 (GLUT1) deficiency syndrome. Administration of KDTs is generally per os; however, in some conditions including the acute gastro-enteric post-surgical setting, short-term parenteral (PN) administration might be needed. We report the case of a 14-year-old GLUT1DS patient, following classic KDT for many years, who underwent urgent laparoscopic appendectomy. PN-KDT was required, after 1 day of fasting. No ad hoc PN-KDTs products were available and the patient received infusions of OLIMEL N4 (Baxter). On the sixth day postoperatively enteral nutrition was progressively reintroduced. The outcome was optimal with rapid recovery and no exacerbation of neurological manifestations. Our patient is the first pediatric patient with GLUT1DS in chronic treatment with KDT efficiently treated with exclusive PN for five days. This case reports on real-word management and the ideal recommendations for PN-KDT in an acute surgical setting.

Consuming an All-Meat Ketogenic Diet for the Long-Term Management of Candida Vulvovaginitis and Vaginal Hidradenitis Suppurativa: A 47-Month Follow-Up Case Report.

This case report describes long-term therapeutic management in a 33-year-old diagnosed with Candida vulvovaginitis and vulvar hidradenitis suppurativa 47 months previously. Candida spp. yeasts are part of many women's normal vaginal microflora, and the development of vulvovaginal candidiasis is typically a result of a disturbance in the patient's microbial ecosystem, which manifests itself by intense pruritus, erythema, swelling, and thick white vaginal discharge. Hidradenitis suppurativa is a chronic auto-inflammatory skin condition that causes painful weeping lesions in areas of dense apocrine glands. Although certain mechanisms underlying the pathogenesis of Hidradenitis Suppurativa (e.g., risk factors include smoking, obesity, and family history) have been investigated, a definitive explanation remains elusive. Nutritional intervention in the form of an all-meat ketogenic diet may be considered therapy in the management of both diseases, as successfully seen in this case report. The patient refused standard of care with oral fluconazole for Candida vulvovaginitis and surgical removal for Hidradenitis suppurativa, and instead consumed a zero-carbohydrate all-meat ketogenic diet mostly of beef with strict adherence to the diet for 43 days in which symptoms ceased.

Favorable response to classic ketogenic diet in a child with anti-GAD 65 antibody mediated super refractory status epilepticus.

Autoimmune encephalitis refers to a spectrum of inflammatory brain diseases which can present as drug-resistant seizures in children. Hereby, we report a case of anti-GAD-65 antibody encephalitis in a 7-year-old child who presented with superrefractory status epilepticus (SRSE). The traditional management with multiple anti-seizure medications at appropriate dosage and immunotherapy was tried despite which the child continued to have seizures. Hence the child was initiated on a classic ketogenic diet. He achieved ketosis within 48 h of diet initiation and there was a drastic reduction in the seizure frequency followed by a completed remission. Hence, this non-pharmacological intervention was an effective adjunct in achieving seizure control in our patient. A ketogenic diet has been sparingly used for the management of post-encephalitic epilepsy and autoimmune epilepsy. However, the data onthe effectiveness of the ketogenic diet in the management of autoimmune encephalitis is scarce. Starting KD early in the disease course helped not only in seizure control but also preserved the cognitive and neurological well-being of the child.

Medium-chain Triglyceride Ketogenic Diet as a Treatment Strategy for Adult Super-refractory Status Epilepticus.

How to cite this article: Dutta K, Satishchandra P, Borkotokey M. Medium-chain Triglyceride Ketogenic Diet as a Treatment Strategy for Adult Super-refractory Status Epilepticus. Indian J Crit Care Med 2022;26(1):139-140.

Tratamiento de la epilepsia refractaria. Comparación entre la dieta cetogénica clásica y la de Atkins modificada en cuanto a eficacia, adherencia y efectos indeseables / Treatment of refractory epilepsy. A comparison between classic ketogenic diet and modified Atkins diet in terms of efficacy, adherence, and undesirable effects

Introducción: la dieta cetogénica (CD) es un tratamiento no farmacológico efectivo, ya establecido para la epilepsia refractaria en la infancia. Objetivo: el objetivo de este estudio fue comparar la eficacia, la presencia de efectos indeseables y la adherencia entre la dieta cetogénica clásica (DCC) y la dieta de Atkins modificada (DAM).Materiales y métodos: se realizó una investigación retrospectiva y comparativa, evaluando las historias clínicas de todos los pacientes que iniciaron tratamiento con dieta cetogénica a cargo de un mismo equipo de trabajo entre 2008 y 2018. Se incluyeron 57 pacientes que iniciaron una dieta DAM y 19 pacientes con dieta DCC. Resultados: se observó que tanto la dieta Atkins como la clásica fueron igualmente eficaces (80 %, aproximadamente; p = 0,252). En relación a la adherencia, se registró un porcentaje significativamente mayor de adherencia a la dieta Atkins que a la clásica (p = 0,018). Se observaron menos efectos adversos con la DAM que con la dieta CC (p = 0,012). El 21 % de los pacientes con DAM presentaron efectos desfavorables (12/57), mientras que el 52.63 % de los pacientes en DCC tuvieron complicaciones (10/19). Conclusión: se describe una efectividad equiparable en cuanto al control de crisis entre la DAM y la DCC. Sin embargo, la DAM presenta una adherencia mucho mejor que la observada con la DCC y sus efectos indeseables son más leves y más infrecuentes. Es por eso que, de acuerdo con otros trabajos, la DAM probablemente sea la primera elección para los pacientes con epilepsia refractaria en un gran porcentaje de los casos. (AU)

Background: the ketogenic diet (CD) is an established, effective non-pharmacological treatment for refractory epilepsy in childhood. Aim: the objective of this study was to compare the efficacy, the presence of undesirable effects, and adherence between the classic ketogenic diet (DCC) and the modified Atkins diet (DAM). Materials and methods: a retrospective and comparative investigation was carried out to evaluate the medical records of all the patients who started treatment with a ketogenic diet by the same team between 2008 and 2018. In all, 57 patients were started on a DAM diet and 19 patients were given a DCC diet. Results: it was observed that both the Atkins and the classic diets were equally effective (approximately, 80 %; p = 0.252). Regarding adherence, there was a significantly higher percentage of adherence to the Atkins diet than to the classic diet (p = 0.018). Fewer adverse effects were observed with DAM than with DCC (p = 0.012). In all, 21 % of patients under DAM had unfavorable effects (12/57), while 52.63 % of patients on DCC had complications (10/19). Conclusion: a comparable effectiveness in terms of crisis control was found between DAM and DCC. However, DAM exhibits a much better adherence than DCC, and its undesirable effects are milder, less common. That is why, according to other works, it is likely that DAM should be first-choice for patients with refractory epilepsy in a large percentage of cases. (AU)

Efficacy and safety of ketogenic dietary theraphies in infancy. A single-center experience in 42 infants less than two years of age.

PURPOSE: Ketogenic dietary therapies (KDT) are high-fat and low-carbohydrate diets that may achieve seizure control and improve cognitive state. We describe our KDT experience in infants (children less than two years of age). RESEARCH METHODS & PROCEDURES: We conducted a retrospective, descriptive and observational study of 42 infants treated with KDT between 2000-2018. RESULTS: The types of KDT started were: classic ketogenic diet ratio 3:1 (40), ratio 4:1 (1) and modified ketogenic diet with medium-chain triglycerides (1). Four patients switched to a modified Atkins diet. During follow-up, 79%, 57%, 38% and 17% of infants remained on KDT at 3, 6, 12 and 24 months, respectively. Seizure reduction ≥50% compared to baseline was achieved in 50%, 45%, 38% and 17% at 3, 6, 12 and 24 months, respectively. Seizure control was excellent (reduction >90%) in 33%, 31%, 26% and 12%, and seizure-free infants were 9, 9, 10 and 4, at different follow-up intervals, respectively. Sixty-three percent of infants with West syndrome were responders to KDT. Mean length of KDT was 390 days (16 days-4.9 years). Ineffectiveness was the reason for withdrawal in 50% of patients. Early adverse effects (during first month) occurred in 40% of infants. The most frequent early side effects were asymptomatic hypoglycemia and gastrointestinal disturbances. Late-onset side effects occurred in 55-14% of infants during therapy, and most frequent were hypercalciuria and dyslipidaemia. CONCLUSION: KDT are useful and effective treatments in infancy. Side effects are frequent but mild and easy to manage.

The efficacy comparison of classic ketogenic diet and modified Atkins diet in children with refractory epilepsy: a clinical trial.

Dietary therapy has an important role in the therapeutic process in children suffering refractory epilepsy. There are two kinds of dietary therapy which are the most common in children with refractory epilepsy: The classic ketogenic diet (KD) and the modified Atkins diet (MAD). The purpose of the present study was to compare the efficacy, tolerability, and compliance of these two dietary therapies in the children who have refractory epilepsy during 6 months of treatment. From March 2017 to November 2018, 45 children aged 2-15 years who had refractory epilepsy were randomly allocated in KD or MAD group. The intervention period was 6 months in both groups. The frequencies of seizures were determined from parental reports and were compared between the groups. The patients with upper than 50% reduction in seizure frequency were deemed as responders to the diets. Twenty-four patients were assigned to the KD and 11 patients to the MAD. Overall, 45.8% of children treated with the KD and 45.5% of children treated with MAD had over than 50% response to the diet therapies. The difference was not statistically significant (P = 0.437). The MAD was more advantageous regarding better tolerability and fewer side effects. There is not much difference regarding the efficacy between the MAD and classic KD. The MAD with fewer side effects may be more suitable as the first line of dietary therapy in children with refractory epilepsy.

Ketogenic diet: overview, types, and possible anti-seizure mechanisms.

The ketogenic diet (KD) has been used for a long time as a therapeutic approach for drug-resistant epilepsy. It is a high-fat, low-carbohydrate, and adequate protein diet. There are various types of KD with some differences in their compositions that mainly include classic KD, medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment. The anti-seizure mechanisms of KDs have not yet completely understood but, some possible mechanisms can be theorized. The aim of the present study was to review the various types of KD and explain the probable biochemical mechanisms involved in its anti-seizure property.

Non-pharmacological Interventions for Intractable Epilepsy.

In 30% of epileptic individuals, intractable epilepsy represents a problem for the management of seizures and severely affects the patient's quality of life due to pharmacoresistance with commonly used antiseizure drugs (ASDs). Surgery is not the best option for all resistant patients due to its post-surgical consequences. Therefore, several alternative or complementary therapies have scientifically proven significant therapeutic potential for the management of seizures in intractable epilepsy patients with seizure-free occurrences. Various non-pharmacological interventions include metabolic therapy, brain stimulation therapy, and complementary therapy. Metabolic therapy works out by altering the energy metabolites and include the ketogenic diets (KD) (that is restricted in carbohydrates and mimics the metabolic state of the body as produced during fasting and exerts its antiepileptic effect) and anaplerotic diet (which revives the level of TCA cycle intermediates and this is responsible for its effect). Neuromodulation therapy includes vagus nerve stimulation (VNS), responsive neurostimulation therapy (RNS) and transcranial magnetic stimulation therapy (TMS). Complementary therapies such as biofeedback and music therapy have demonstrated promising results in pharmacoresistant epilepsies. The current emphasis of the review article is to explore the different integrated mechanisms of various treatments for adequate seizure control, and their limitations, and supportive pieces of evidence that show the efficacy and tolerability of these non-pharmacological options.

The ketogenic and atkins diets effect on intractable epilepsy: a comparison.

OBJECTIVE: Intractable epilepsy is a major difficulty in child neurology, because the numbers of drugs that are available for treatment are limited and new treatments such as diets must be tried. Now there are some diets available for treating patients with intractable epilepsy. The oldest diet is the classic ketogenic diet and one of the newest diets is the modified Atkins diet. Patients have a harder time accepting the classic ketogenic diet than the Atkins diet, which is easier to accept because the food tastes better. This study compares the efficacy of the ketogenic diet and the Atkins diet for intractable epilepsy in children. MATERIALS & METHODS: This study is a clinical trial survey with sample size of 40 children with refractory epilepsy who were patients at Mofid hospital in Tehran, Iran. Initially, from Jan 2005-Oct 2007, 20 children were treated with the Atkins diet, and then from Oct 2007-March 2010, the other group was treated with the classic ketogenic diet and the results were compared. RESULTS: In this study, response to treatment was greater than a 50% reduction in seizures and at the end of first, second, and third months for the ketogenic diet were 55%, 30%, and 70% and for the Atkins diet were 50%, 65%, and 70%, respectively. CONCLUSION: The results of this study show that there is no significant difference between the classic Ketogenic diet and the Atkins diet at the end of first, second, and third months and both had similar responses to the treatments.