[Epilepsy, cognition and ketogenic diet]. / Epilepsia, cognicion y dieta cetogenica.

INTRODUCTION: Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. AIM: To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. DEVELOPMENT: In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. CONCLUSIONS: Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

TITLE: Epilepsia, cognicion y dieta cetogenica.Introduccion. Aunque generalmente se controlan bien con medicacion, hasta un 20-30% de las epilepsias infantiles son refractarias al tratamiento farmacologico. Los efectos adversos cognitivos de los farmacos antiepilepticos son frecuentes y pueden afectar negativamente la tolerabilidad, el cumplimiento y el mantenimiento a largo plazo del tratamiento antiepileptico. La dieta cetogenica es un tratamiento eficaz y bien tolerado para las epilepsias infantiles refractarias y no muestra efectos adversos negativos sobre cognicion o conducta. Objetivo. Revisar la evidencia actual existente con respecto a los estudios experimentales y clinicos que analizan los efectos neuroprotectores y cognitivos de la dieta cetogenica, tanto en humanos como en animales de experimentacion. Desarrollo. La dieta cetogenica muestra efectos neuroprotectores y estabilizadores del estado de animo en diversos modelos animales, con o sin epilepsia. En los estudios observacionales en epilepsia infantil se refieren mejorias en cognicion y conducta durante el tratamiento con dieta cetogenica, especialmente evidentes en atencion, nivel de alerta y actividad, socializacion y calidad del sueño. En un estudio aleatorizado controlado en pacientes con epilepsia infantil refractaria, la dieta cetogenica mostro una activacion evolutiva evidente sobre la cognicion y el estado de animo. Conclusiones. La dieta cetogenica tiene un impacto positivo sobre el funcionamiento conductual y cognitivo en niños y adolescentes con epilepsia refractaria. Esta mejoria es mas evidente con respecto a estado de animo, atencion sostenida e interaccion social.

Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

Is the ketogenic diet effective in specific epilepsy syndromes?

Is the ketogenic diet (KD) more effective in certain epilepsy syndromes? The KD has been shown to be effective in treating multiple seizure types and epilepsy syndromes. We review the effectiveness of the KD in Dravet syndrome, epilepsy with myoclonic-atonic seizures, mitochondrial disease, tuberous sclerosis, late infantile and juvenile neuronal ceroid lipofuscinosis, and febrile infection-related epilepsy syndrome. In certain epilepsy syndromes, like epilepsy with myoclonic-atonic seizures, the diet should be considered early in the course of treatment.

Low glycemic index treatment for epilepsy in tuberous sclerosis complex.

Retrospective chart review of 15 patients with tuberous sclerosis complex (TSC) who initiated the low glycemic index treatment (LGIT) for epilepsy management at Massachusetts General Hospital over a five-year period. Prior to dietary therapy, this cohort (average age: 8.5 years) had tried an average of 5.8 anti-epileptic drugs with incomplete seizure control. At 6 months on the LGIT, 7/15 (47%) patients experienced >50% reduction in seizure frequency.

Tumor growth in patients with tuberous sclerosis complex on the ketogenic diet.

PURPOSE: New evidence is emerging that the availability of nutrients plays a key role in regulating the mammalian target of rapamycin complex-1 (mTORC1) signaling pathway in human cancers. Tuberous sclerosis complex (TSC) is a genetic disorder which results in the growth of hamartomatous lesions in multiple organs due to insufficient suppression of the mTORC1 pathway. A minority of patients with TSC who develop epilepsy which is intractable to standard anticonvulsant medical and/or surgical treatments are treated with the ketogenic diet. To provide insight into the effects of nutrient manipulation on tumor growth in this condition, we describe our experience in a unique group of patients with known tuberous sclerosis complex who are on the ketogenic diet for seizure control. METHODS: A retrospective chart review was performed of patients with TSC treated with the ketogenic diet between January 2002 and May 2007 at Massachusetts General Hospital. RESULTS: Five patients with definite TSC underwent serial imaging for tumor growth while on the ketogenic diet or had unchanged imaging prior to the onset of the diet and after termination. Three out of five patients, all children, had progression of a known tumor or tumors or the development of a new tumor while on the ketogenic diet. CONCLUSION: In this limited case series of five TSC patients, the ketogenic diet did not induce tumor regression or suppress the growth of TSC-related tumors.

Home-guided use of the ketogenic diet in a patient for more than 20 years.

A 26-year-old man with tuberous sclerosis complex and multifocal seizures presented to the ketogenic diet clinic for management of his epilepsy. He had been started on the ketogenic diet at another institution at age 6 years, and his family had managed all nutritional aspects for the previous 10 years. Despite the lack of ongoing medical care, excellent seizure control and large urinary ketosis had been maintained, and side effects were limited only to poor growth. He remains on the diet to date, now for 21 years of continuous duration.

Tuberous sclerosis complex and the ketogenic diet.

PURPOSE: Tuberous sclerosis complex (TSC) is a condition that is frequently associated with intractable, early-onset epilepsy, and often is first seen as infantile spasms. If medications fail and no clear epileptogenic tuber is identified, nonpharmacologic therapies are often attempted. The use of the ketogenic diet specifically for children with TSC and epilepsy has not been previously described. METHODS: A chart review was performed of patients with TSC treated with the ketogenic diet over a 5-year period at Johns Hopkins Hospital and Massachusetts General Hospital. RESULTS: Twelve children, ages 8 months to 18 years, were identified. Eleven (92%) children had a >50% reduction in their seizures at 6 months on the diet, and 8 (67%) had a >90% response. Five children had at least a 5-month seizure-free response. Diet duration ranged from 2 months to 5 years (mean, 2 years). CONCLUSIONS: In this limited-duration case series of 12 patients, the ketogenic diet was a generally effective therapeutic modality for the intractable epilepsy occasionally seen in children with TSC.