The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience

Abstract

Purpose: This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. Methods: We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1–23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. Results: Patients have been treated for 1–18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3–4 months on ketogenic diet. Conclusion: This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9–12 months.

Introduction

The ketogenic diet is an individually calculated and rigidly controlled high-fat, low-protein, low-carbohydrate diet (Freeman et al., 2000). It originally developed in the 1920s to mimic the biochemical changes associated with starvation and used at that time for the treatment of difficult-to-control seizures (Swink et al., 1997). With the development of newer, effective antiepileptic drugs, however, its use decreased significantly. Now, despite advances in both pharmacotherapy and surgery of epilepsy (Magrath et al., 2000), in Europe there is a resurgence in the use of the ketogenic diet, because many children continue to have difficult-to-control seizures. Several uncontrolled, retrospective studies, especially in the US, over the last decades have reported that 60–75% of children with refractory seizures have more than 50% decrease in their seizures on this diet (Kinsman et al., 1992, Freeman et al., 1998, Casey et al., 1999, Vining, 1999, Katyal et al., 2000, Lefevre and Aronson, 2000). Despite this, the diet is considered by many physicians unpalatable, difficult to initiate and maintain, and its effectiveness over time is controversial. The current prospective study was carried out by three Italian centers of Child Neuropsychiatry to evaluate the diet efficacy, considering seizure type, epilepsy form and the age-related effectiveness. The tolerability and practicality of the ketogenic diet in otherwise intractable epilepsy children, adolescents and young patients were also evaluated.