Use of ketogenic dietary therapy for drug-resistant epilepsy in early infancy.

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.

Long-term effectiveness and adverse effects of ketogenic diet therapy in infants with drug-resistant epilepsy treated at a single center in Argentina.

INTRODUCTION: Ketogenic diet therapy (KDT) is a metabolic treatment with proven effectiveness for the treatment of drug-resistant epilepsy in children. Although previously not used in infants under 2 years of age, recent studies have shown KDT to be highly effective and well tolerated in infants with epilepsy, especially those with epileptic encephalopathies. Here, we describe the effectiveness and tolerability of the diet in infants up to 2 years of age. MATERIAL AND METHODS: A prospective study was conducted in a cohort of infants younger than 2 years of age with drug-resistant epilepsy who received the classic ketogenic diet using a specific protocol at a single center in Argentina. RESULTS: 56 infants with treatment-refractory epilepsy were evaluated. The etiology was genetic in 21.4%, structural in 28.6%, unknown in 44.7%, and metabolic in 5.4%. At 3 months, a > 50% decrease in seizure frequency was observed in 35 patients (62.4%), of whom 11 (19.6%) became seizure free. At 6 months, 34 patients (60.7%) had a decrease in seizure frequency of > 50%, of whom 10 (17.8%) were seizure free. At the one-year follow-up, 27 patients (48.2%) had a > 50% decrease in seizure frequency, of whom six (10.7%) were seizure free. At two years, 14 patients (25%) had a > 50% seizure control, of whom four (7.1%) were seizure free. The most common early adverse effects were hypoglycemia and vomiting, while after 1 month and beyond metabolic acidosis, vomiting, and constipation more commonly found. A trend towards a higher rate of acute adverse events in infants younger than 1 year was observed. CONCLUSIONS: CKD showed to be a useful option in infants with treatment-resistant epilepsy. Adverse effects were common, but not a reason to discontinue the diet. Further studies are necessary to evaluate in which epilepsy syndromes and etiologies KDT is most effective.

The ketogenic diet in patients with myoclonic status in non-progressive encephalopathy.

Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by the recurrence of long-lasting atypical status epilepticus associated with attention impairment and continuous polymorphous jerks, mixed with other complex abnormal movements, in infants suffering from a non-progressive encephalopathy. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. PURPOSE: In this study we assess the efficacy and tolerability of the KD in patients with MSNPE. METHODS: Between March 1, 1980 and August 31, 2013, 99 patients who met the diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins protocol and followed for a minimum period of 24 months. RESULTS: Twelve months after initiating the diet, three patients had a 75%-99% decrease in seizures, two had a 50%-74% decrease in seizures, and the remaining child had a less than 50% seizure reduction. In five patients with a seizure reduction of more than 50%, the myoclonic status epilepticus disappeared within 6 months after starting the diet. All patients had very good tolerability and no adverse events were identified. In most of the patients AEDs were reduced. CONCLUSION: The KD is a promising therapy for MSNPE, with most of our patients showing a more than 50% seizure reduction. In patients that responded well to the diet cognitive performance and quality of life also improved.

[National consensus on the modified Atkins diet]. / Consenso nacional de dieta Atkins modificada.

INTRODUCTION: Epilepsy is a chronic disease that affects 0.5-1% of the population. One third of the patients become refractory to antiepileptic drugs. Among the non-pharmacological treatments available, the modified Atkins diet is an effective treatment used since 2003 as another alternative for children and adults with refractory epilepsy. DEVELOPMENT: The Ketogenic Diet National Committee, which depends on the Argentine Society of Pediatric Neurology, elaborated this consensus on the modified Atkins diet, basing itself on a review of the literature and on their clinical experience. This consensus in Spanish explains the different aspects to be taken into account regarding the modified Atkins diet, patient selection, implementation, different controls and adverse effects. Unlike the classic ketogenic diet, the modified Atkins diet is initiated without fasting or hospital stay, nor does it require protein, calorie or fluid restriction, thus improving patient palatability and consequently patient tolerability. CONCLUSIONS: The modified Atkins diet is a useful treatment for patients with intractable epilepsy. The publication of this consensus offers the possibility for new centers to get oriented regarding this diet implementation.

TITLE: Consenso nacional de dieta Atkins modificada.Introduccion. La epilepsia es una enfermedad cronica que afecta al 0,5-1% de la poblacion, y un tercio de los pacientes evoluciona hacia una forma refractaria a los farmacos antiepilepticos. Dentro de los tratamientos no farmacologicos disponibles, la dieta cetogenica Atkins modificada es un tratamiento efectivo utilizado desde 2003 como otra alternativa en niños y adultos con epilepsia refractaria. Desarrollo. El Comite Nacional de Dieta Cetogenica, dependiente de la Sociedad Argentina de Neurologia Infantil, elaboro este consenso sobre dieta Atkins modificada basandose en una revision de la bibliografia y en su experiencia clinica. Este consenso explica los distintos aspectos que hay que tener en cuenta sobre la dieta Atkins modificada, eleccion de pacientes, forma de implementacion, diversos controles y efectos adversos. A diferencia de la dieta cetogenica clasica, se inicia sin ayuno ni hospitalizacion, y no hay restriccion proteica, calorica o hidrica, por lo que mejora la palatabilidad y, consecuentemente, la tolerabilidad. Conclusiones. La dieta Atkins modificada es un tratamiento util para pacientes con epilepsia intratable. La publicacion de este consenso ofrece la posibilidad de orientar a nuevos centros en su implementacion.

Recommendations for the clinical management of children with refractory epilepsy receiving the ketogenic diet.

The ketogenic diet, a non-drug treatment with proven effectiveness, has been the most commonly used therapy in the past decade for the management of refractory epilepsy in the pediatric population. Compared to adding a new drug to a pre-existing treatment, the ketogenic diet is highly effective and reduces the number of seizures by 50-90% in approximately 45-60% of children after six months of treatment. For this reason, the Argentine Society of Pediatric Neurology established the Ketogenic Diet Working Group. It is integrated by pediatric dietitians, pediatricians, pediatric neurologists and B.S. in Nutrition, who developed recommendations for the optimal management of patients receiving the classical ketogenic diet based on expert consensus and scientific publications in this field.

La dieta cetogénica constituye el tratamiento no farmacológico de eficacia probada más utilizado en la última década para el manejo de la epilepsia refractaria en la población pediátrica. En comparación con el agregado de un nuevo fármaco a un tratamiento preexistente, esta terapia es altamente efectiva, con una reducción de las crisis de entre un 50% y un 90% en aproximadamente 45%-60% de los niños tras 6 meses de tratamiento. Es por ello por lo que la Sociedad Argentina de Neurología Infantil creó el Grupo de Trabajo de Dieta Cetogénica. Este está conformado por médicos nutricionistas infantiles, pediatras, neurólogos infantiles y licenciados en Nutrición, quienes elaboraron estas recomendaciones para un manejo óptimo de los pacientes que reciben la dieta cetogénica clásica, basándose en el consenso de los expertos y la bibliografía publicada en el tema.

The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

AIM: We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. METHODS: Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. RESULTS: One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. CONCLUSION: The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

Ketogenic diet in patients with epileptic encephalopathy with electrical status epilepticus during slow sleep.

UNLABELLED: Epileptic encephalopathy with electrical status epilepticus during slow sleep (ESES) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. PURPOSE: In this retrospective study we assess the efficacy and tolerability of the KD in patients with ESES syndrome. METHODS: Between March 1, 1990 and April 1, 2013, 65 patients who met diagnostic criteria of ESES syndrome were seen at our department. Twelve of them were placed on the KD and followed for a minimum of 18 months. RESULTS: The children had previously received a mean of 5.5 different AEDs and were on a mean of 3 AEDs when the diet was started. Eighteen months after initiating the diet, seven of the initial patients (58%) remained on the diet; one patient (8.3%) had become seizure free, one (8.3%) had a 75-99% decrease in seizures, two (16.6%) had a 50-74% decrease in seizures, and the remaining three children (24.9%) had a <50% decrease in seizures. In the patient who had become seizure free and in the one who had a 75-99% seizure decrease AEDs were reduced. CONCLUSION: The KD is a well-tolerated treatment option for patients with ESES syndrome, not only for structural cases but also for those with an unknown etiology. The diet should be considered in the management of this syndrome.

Ketogenic diet in pediatric patients with refractory focal status epilepticus.

UNLABELLED: The ketogenic diet (KD) has been used as an alternative treatment for patients with refractory status epilepticus (SE). PURPOSE: In this retrospective study we assess the efficacy and tolerability of the KD in patients with refractory SE. METHODS: Between March 1, 2010 and January 1, 2014, 10 patients who met the diagnostic criteria of refractory SE seen at our department were placed on the KD and followed for a minimum of 6 months. RESULTS: Ketonuria was reached within 2-4 days (mean 3 days) for all patients. Seizures stopped in two patients and five patients had a 50-75% seizure reduction within 2-5 days (mean 2.5 days) following the onset of ketonuria and within 5-7 days (mean 5 days) following the onset of the diet. Three patients had a <50% seizure reduction and all of them had severe adverse events so the diet was discontinued. Seven patients remained on the diet for 6 months to 3 years (mean 1.5 years). In all seven patients within 4 months the seizures recurred, but their quality of life did not worsen. The frequency of the seizures consisted of weekly seizures in two, monthly seizures in two, occasional seizures in two, and isolated seizures in one. All of them kept a good tolerability of the diet. CONCLUSION: The KD is an effective and well-tolerated treatment option for patients with refractory SE. In patients with focal SE secondary to inflammatory or probably inflammatory diseases, the KD should be considered earlier in the course of the treatment.

[National consensus on the ketogenic diet]. / Consenso nacional sobre dieta cetogénica.

INTRODUCTION: Epilepsy is a chronic disease with onset in infancy affecting 0.5-1% of the population. One third of the patients is refractory to antiepileptic drugs and they pose a challenge for the health care team. The ketogenic diet is an effective, non-pharmacological, alternative treatment for the management of refractory epilepsy. AIMS: There is a need to establish guidelines for the adequate and increased use of the ketogenic diet in Spanish-speaking countries. The National Committee on the Ketogenic Diet, consisting of paediatric neurologists, clinical nutritionists, and dietitians, of the Argentine Society of Child Neurology has developed this consensus statement to standardize the use of the ketogenic diet based on the literature and clinical experience. DEVELOPMENT: Patient selection, pre-treatment family counseling, drug interactions, micronutrient supplementation, adverse effects, and discontinuation of the diet are discussed. CONCLUSIONS: The ketogenic diet is an effective treatment for children with refractory epilepsy. Education and collaboration of the patient and their family is essential. The patient should be managed by an experienced multidisciplinary team using a protocol. The formation of a national multidisciplinary team and the publication of this document provide possibilities for new centers to integrate the ketogenic diet into their treatment options.

TITLE: Consenso nacional sobre dieta cetogenica.Introduccion. La epilepsia es una enfermedad cronica que afecta al 0,5-1% de la poblacion, mayormente de inicio durante la infancia. Un tercio de los pacientes evoluciona hacia una forma refractaria al tratamiento con farmacos antiepilepticos, lo que plantea al equipo de salud un desafio terapeutico. La dieta cetogenica (DC) es un tratamiento no farmacologico efectivo utilizado como un metodo alternativo para el tratamiento de la epilepsia refractaria. Objetivos. Es necesario establecer directrices para utilizar la DC adecuadamente y asi expandir su conocimiento y utilizacion en paises hispanoparlantes. El Comite Nacional de Dieta Cetogenica, dependiente de la Sociedad Argentina de Neurologia Infantil, elaboro este consenso para estandarizar el uso de la DC basandose en la bibliografia publicada y la experiencia clinica. El grupo esta formado por neuropediatras, medicos nutricionistas y licenciadas en nutricion de cinco provincias de Argentina pertenecientes a 10 centros que aplican la DC como tratamiento de la epilepsia refractaria. Desarrollo. Se exponen temas tales como la seleccion del paciente, el asesoramiento a la familia antes del tratamiento, las interacciones de la DC con la medicacion anticonvulsionante, los suplementos, el control de efectos adversos y la retirada de dicha dieta. Conclusiones. La DC es un tratamiento util para los pacientes pediatricos con epilepsia intratable. Es fundamental la educacion y colaboracion del paciente y la familia. El tratamiento debe llevarlo a cabo un equipo interdisciplinar experimentado, siguiendo un protocolo. La formacion de un grupo nacional interdisciplinar, y la publicacion de este consenso, ofrece la posibilidad de orientar a nuevos centros en su implantacion.

Ketogenic diet in patients with Lennox-Gastaut syndrome.

PURPOSE: The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epilepsy. Lennox-Gastaut syndrome (LGS) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. In this prospective study we assess the efficacy and tolerability of the KD in patients with LGS. METHODS: Between March 1, 1990 and April 1, 2013, 61 patients who met diagnostic criteria of LGS were seen at our department. Twenty of them were placed on the KD and followed for a minimum of 16 months. RESULTS: The children had previously received a mean of 6.5 different AEDs and were on a mean of 2.5 AEDs when the diet was started. Eighteen months after initiating the diet, fifteen of the initial patients (75%) remained on the diet; three patients (15%) were seizure free, three (15%) had a 75-99% decrease in seizures, two (10%) had a 50-74% decrease in seizures, and the remaining seven children (35%) had a <50% decrease in seizures. Three seizure-free patients were tapered off the diet after remaining seizure free. In the three patients who had a 75-99% decrease in seizures AEDs were reduced. CONCLUSION: The KD is an effective and well-tolerated treatment option for patients with LGS, not only for those with cryptogenic, but also for those with structural LGS. The diet should be considered early in the course of this syndrome.

Long-term follow-up of the ketogenic diet for refractory epilepsy: multicenter Argentinean experience in 216 pediatric patients.

PURPOSE: In this Argentinean retrospective, collaborative, multicenter study, we examine the efficacy and tolerability of the ketogenic diet (KD) for different epilepsy syndromes. MATERIALS AND METHODS: we evaluated the clinical records of 216 patients started on the KD between March 1, 1990 and December 31, 2010. RESULTS: One hundred forty of the initial patients (65%) remained on the diet at the end of the study period. Twenty-nine patients (20.5%) became seizure free and 50 children (36%) had a 75-99% decrease in seizures. Thus, 56.5% of the patients had a seizure control of more than 75%. The best results were found in patients with epilepsy with myoclonic-astatic seizures, Lennox-Gastaut syndrome, and West syndrome. Good results were also found in patients with Dravet syndrome, in those with symptomatic focal epilepsy secondary to malformations of cortical development, and in patients with tuberous sclerosis. Seizures were significantly reduced in four patients with fever-induced refractory epileptic encephalopathy in school-age children and in two patients with epileptic encephalopathy with continuous spikes and waves during slow sleep. The median period of follow-up after discontinuation of the diet was 6 years. Twenty patients who had become seizure free discontinued the diet, but seizures recurred in five (25%). Of 40 patients with a seizure reduction of more than 50% who discontinued the diet, 10 presented with recurrent seizures. CONCLUSION: The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.

Ketogenic diet in patients with myoclonic-astatic epilepsy.

For more than 80 years, the ketogenic diet has been used as an alternative to antiepileptic drugs for patients with refractory epilepsy. Myoclonic-astatic epilepsy in early childhood is one of the malignant epilepsy syndromes that often proves refractory to antiepileptic drugs treatment. Objective. In this prospective study we assess the efficacy and tolerability of the ketogenic diet in patients with myoclonic-astatic epilepsy. Material and methods. Between March 1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic-astatic epilepsy were seen at our department. Eleven of them were placed on the ketogenic diet using the Hopkins protocol and were followed for a minimum of 18 months. Results. The children had previously received a mean of 5.2 different antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet was started. Eighteen months after initiating the diet, six of the patients (54.5%) remained on the diet. Two patients (18%) were seizure-free, two (18%) had a 75-99% decrease in seizures, and the remaining two children (18%) had a 50% to 74% decrease in seizures. The first two patients were tapered off the diet after remaining seizure-free, without antiepileptic drugs for several years. In the two patients who had sporadic seizures, antiepileptic drugs were reduced to one, and in the last two the seizure frequency was significantly reduced. No differences in seizure control were found when compared for age, sex, or seizure type. Five of our patients discontinued the ketogenic diet in less than 3 months (four because of lack of effectiveness and one because of persistent vomiting). Conclusion. The ketogenic diet is a promising therapy for patients with myoclonic-astatic epilepsy, with over half the children showing a > 50% reduction in seizures, and seizure-freedom in 18%. In drug resistant cases of myoclonic-astatic epilepsy, the diet should be considered early in the course of this syndrome and not as a last resort.

Ketogenic diet in patients with Dravet syndrome.

PURPOSE: The ketogenic diet (KD) has been used as a therapeutic alternative to antiepileptic drugs (AEDs) for refractory epilepsy. Severe myoclonic epilepsy in infants or Dravet syndrome (DS) is one of the most malignant epileptic syndromes. In this retrospective study, we evaluated the efficacy and tolerability of the KD in patients with diagnostic criteria of DS. METHODS: Between March 1, 1990, and August 31, 2004, 52 patients who met diagnostic criteria for DS were enrolled in a study at our department. Twenty of them were placed on the KD with the Hopkins protocol and followed up for a minimum of 1 year. RESULTS: Three of the 20 original children stayed on the diet for 12 months, four children for 2 years, four children for 3 years, and two children for 4 years. One year after initiating the diet, 13 (65%) of the initial patients remained on the diet. Two (15%) patients were seizure free, eight (61.7%) children had a 75-99% decrease in seizures, and the remaining three (23%) children had a 50-74% decrease in seizures. Thus 1 year after starting the diet, 10 (77%) children had achieved a >75% decrease in their seizures. Four patients have been off the diet for >2 years; one of them is seizure free, two have sporadic seizures, and one, who abandoned the diet after 2 years of adhering to it, relapsed. No differences in seizure control when compared with age, sex, or seizure type were found. CONCLUSIONS: Considering the severity and intractability of seizures in patients with DS, the fact that 10 of the 13 children who remained on the diet had a significant reduction in number of seizures shows that the KD is at present an interesting therapeutic alternative. Even in patients in whom seizure reduction was not dramatic, quality of life improved, and in all of them, the number of AEDs was reduced to one or two. We consider that children with DS should be offered the KD immediately after three adequate trials of AEDs have failed.