OBJECTIVE:We aimed to compare the efficacy, safety, and tolerability of a modified Atkins diet (MAD) with the classic ketogenic diet (KD) for the treatment of intractable childhood epilepsy.

METHODS:From March 2011 to March 2014, 104 patients aged 1-18 years who had refractory epilepsy were randomly assigned to each diet group (ClinicalTrials.gov, number NCT2100501). A seizure diary record was used to compare seizure frequencies with the baseline prediet seizure frequency at the third and sixth months after diet therapy initiation.

RESULTS:Fifty-one patients were assigned to the KD and 53 patients to the MAD. The KD group had a lower mean percentage of baseline seizures compared with the MAD group at 3 months (38.6% for KD, 47.9% for MAD) and 6 months (33.8% for KD, 44.6% for MAD), but the differences were not statistically significant (95% confidence interval [CI] 24.1-50.8, p = 0.291 for 3 months; 95% CI 17.8-46.1, p = 0.255 for 6 months). Instead, for patients aged 1-2 years, seizure outcomes were consistently much more favorable in patients consuming the KD compared with those consuming the MAD. The rate of seizure freedom at 3 months after diet therapy initiation was significantly higher (53% for KD, 20% for MAD, p = 0.047) in these patients. The MAD had advantages with respect to better tolerability and fewer serious side effects.

SIGNIFICANCE:The MAD might be considered as the primary choice for the treatment of intractable epilepsy in children, but the classic KD is more suitable as the first line of diet therapy in patients<2 years of age.

OBJECTIVE:The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet.

METHODS:We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown.

RESULTS:Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed.

SIGNIFICANCE:The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not.

OBJECTIVE: Kidney stones are an adverse event with the ketogenic diet (KD), occurring in approximately 6% of children who are started on this therapy for intractable epilepsy. Potassium citrate (Polycitra K) is a daily oral supplement that alkalinizes the urine and solubilizes urine calcium, theoretically reducing the risk for kidney stones.

METHODS: Children who started the KD from 2000 to 2008 at Johns Hopkins Hospital, with at least 1 month of follow-up, were evaluated (N = 313). From 2000 to 2005, children were treated with daily Polycitra K at 2 mEq/kg per day only in the setting of identified hypercalciuria, whereas, since 2006, it has been started for all children empirically at KD onset.

RESULTS: Polycitra K was administered to 198 children preventatively overall, 4 (2.0%) of whom developed kidney stones, compared with 11 (10.5%) of 105 who did not receive Polycitra K (P = .003). Two children since 2006 refused Polycitra K, 1 of whom developed a kidney stone. Successful empiric administration of Polycitra K at KD onset resulted in a kidney-stone incidence of 0.9% (1 of 106) compared with administration only because of hypercalciuria, 6.7% (13 of 195; P = .02). Polycitra K resulted in less acidic urine (mean pH: 6.8 vs 6.2; P = .002) but not reduced serum acidosis. No adverse effects of oral citrates were reported.

CONCLUSIONS: Oral potassium citrate is an effective preventive supplement against kidney stones in children who receive the KD, achieving its goal of urine alkalinization. Universal supplementation is warranted.

PURPOSE:To evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies.

METHODS:Data from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as>or = 50% seizure reduction. Treatment effects on EEG, developmental outcome and the "outcome-predictive" value of various clinical factors were also assessed.

RESULTS:50 children (22 boys; mean age 4.5 years+/-3.55) were included. Mean follow-up was 3.93+/-2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly (p=0.014) and a significantly lower rate of epileptic discharges (p=0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress (p=0.038). Favourable treatment outcome was associated with a shorter disease duration (p=0.025) and generalised tonic clonic seizures (p=0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome. Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate (p=0.001) and valproate (p=0.046).

CONCLUSION:Despite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development.

The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated.

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.