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Summary:Purpose: To evaluate the efficacy, safety and tolerability of a modified Atkins diet in intractable childhood epilepsy.Methods: Fourteen children with epilepsy were treated prospectively with a modified Atkins diet. Outcome measures included seizure frequency, adverse reactions and tolerability to the diet; blood β-hydroxybutyrate and urine ketones were also measured.Results: Six months after diet initiation, seven (50%) remained on the diet, five (36%) had >50% seizure reduction, and three (21%) were seizure free. The diet was well tolerated by 12 (86%) patients. Most complications were transient and were successfully managed by careful follow-up and conservative strategies. A consistently strong ketosis (β-hydroxybutyrate of >3 mmol/L) seemed to be important for maintaining the efficacy of the diet therapy.Conclusions: The modified Atkins diet was well tolerated and sometimes a modified Atkins diet can be substituted for the conventional ketogenic diet. Serious complications were rare, but long-term complications remain to be determined. Key Words: Atkins diet-Intractable childhood epilepsy.The ketogenic diet (KD) has been used worldwide for the treatment of intractable childhood epilepsy (Kossoff and McGrogan, 2005). However, the KD is not yet a convenient therapy, especially in older children and adolescents (Freeman et al., 1998;Kang et al., 2004). The Atkins diet induces a state of ketosis by providing a high fat content and few carbohydrates, suggesting that this diet may control seizures by a mechanism similar to that of the KD (Stafstrom, 2004). Recently, a modified Atkins diet was shown to be effective and well tolerated in children with intractable epilepsy (Kossoff et al., 2006). We also aimed in this study to evaluate the efficacy, safety and tolerability of a modified Atkins diet in 14 children with intractable childhood epilepsy. METHODSThe subject cohort consisted of 14 patients with intractable childhood epilepsy who had been experiencing more than four seizures per month, which could not be controlled by any combination of three or more antiepileptic drugs. They were treated prospectively with a modified Atkins diet and were followed for at least more than 6 months since the diet had been tried at a tertiary care referral epilepsy center. The modified Atkins diet consisted of a nearly balanced diet (60% fat, 30% protein, and 10% carbohydrates by weight), without the restriction of recommended daily calories according to patient age, and substituting the initial stepwise caloric increase of the nonfasting protocol for initial fasting and fluid restriction (Fig. 1). As suggested by Kossoff et al. (2006), for the first month, carbohydrates were restricted to 10 g/day, but were permitted to increase by 5 g/day at intervals of at least 1 month if the child was having difficulty with the restriction of carbohydrates, to a maximum of 10% carbohydrates per day by weight. Following the start of the diet, all patients were advised to remain in the hospital for 3 or 4 days to ensure adequate diet ...

Objective Maternal immune activation (MIA) triggered by infections, has been identified as a cause of autism in the offspring. Considering the involvement of perturbations in innate immunity in epilepsy, we examined whether MIA represents a risk factor for epilepsy as well. The role of specific MIA components– interleukin-6 and interleukin-1β was also addressed. Methods MIA was induced in C57BL/6 mice by polyinosinic–polycytidylic acid (PIC) injected during embryonic days 12–16. Beginning from postnatal day 40, the propensity of the offspring to epilepsy was examined using hippocampal kindling; autism-like behavior was studied using the sociability test. The involvement of interleukin-6 and interleukin-1β in PIC-induced effects was studied by the co-administration of the cytokine antibodies with PIC, and by delivering recombinant cytokines in lieu of PIC. Results The offspring of PIC-exposed mice exhibited increased hippocampal excitability, accelerated kindling rate, prolonged increase of seizure susceptibility after kindling, and diminished sociability. Epileptic impairments were abolished by antibodies to interleukin-6 or interleukin-1β. Neither of the recombinant cytokines alone increased the propensity to seizures; however when combined, they produced effects similar to the ones induced by PIC. PIC- induced behavioral deficits were abolished by interleukin-6 antibodies and were mimicked by recombinant interleukin-6; interleukin-1β was not involved. Interpretation In addition to confirming previously established critical role of interleukin-6 in the development of autism-like behavior following MIA, the present study shows that concurrent involvement of interleukin-6 and interleukin-1β is required for priming the offspring for epilepsy. These data shed light on mechanisms of comorbidity between autism and epilepsy.

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