Type 1 diabetes and epilepsy: efficacy and safety of the ketogenic diet.

Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.

Effects of the ketogenic diet on platelet counts and global coagulation tests in childhood epilepsy.

PURPOSE: Several antiseizure drugs (ASD), especially Valproic acid (VPA), influence platelet counts and coagulation parameters. The ketogenic diet (KD), established in drug-resistant epilepsy, is combined with ASDs. Bruising and prolonged bleeding times during KD have been described, but whether hemostatic changes result from the KD or from concomitant ASDs, remains unclear. Aim of the present study was to evaluate bleeding, platelet counts and global coagulation tests prior to and during KD in childhood epilepsy. METHOD: Consecutive children treated with KD were systematically observed for bleeding. Serial measurements of platelet counts and global coagulation tests (APTT, PT and fibrinogen) were obtained at baseline and during KD (at 1, 3, 6 and 12 months). Children with KD monotherapy, concomitant VPA, or other ASDs were compared. RESULTS: Among 162 children receiving KD, we observed neither bleeding in daily life nor perioperative bleeding in those undergoing surgery (n = 25). Most children had normal platelet counts and coagulation parameters. Only a few had transient mild thrombocytopenia and mildly prolonged APTT values, not indicative of a bleeding risk. Even KD combined with VPA did not cause relevant coagulopathy. Unexpectedly, we found mild thrombocytosis in 24 % of patients prior to KD, which was most pronounced in yet untreated epilepsy. Thrombocytosis steadily resolved during KD. CONCLUSIONS: During KD treatment of childhood epilepsy, we observed neither bleeding symptoms nor laboratory results indicating a bleeding risk. Unexpectedly, mild thrombocytosis was present in 24 % at baseline, normalising during KD. Thrombocytosis may reflect the underlying inflammatory process of untreated epilepsy and requires further study.

Efficacy and tolerability of the ketogenic diet in Dravet syndrome - Comparison with various standard antiepileptic drug regimen.

UNLABELLED: There is strong evidence for the use of the ketogenic diet (KD) in Dravet syndrome (DS). The purpose of this study was to evaluate both effectiveness and tolerability in comparison with various antiepileptic drugs (AEDs). METHODS: 32 children (19 males) with genetically confirmed DS treated at our center since 1999 were analyzed retrospectively. Data collected from patients' files included type of mutation, age at treatment initiation and treatment lag, overall seizure frequency and frequency of different seizure types, especially prolonged seizures and status epilepticus (SE). Efficacy and safety of the KD were evaluated. In addition, the effect on seizure count was compared with that of various AED regimen and the vagus nerve stimulation (VNS). RESULTS: Overall response to the KD was 70% at 3 months and 60% at 12 months. No SE occurred while patients were on the diet, and the frequencies of prolonged generalized and myoclonic seizures were reduced. No severe side effects requiring withdrawal of the KD were observed. Although the effect of the KD was independent of age at initiation, it had to be withdrawn due to noncompliance more frequently in solid fed older children compared with infants treated with the liquid ketogenic formula. The KD was not significantly inferior to the current gold standard AED triple combination of Stiripentol+Valproate+Clobazam (89%), Bromides (78%), Valproate alone (48%), Topiramate (35%) and VNS (37%) and significantly more effective than Levetiracetam (30%; p=0.037, Pearson's Chi-square). SIGNIFICANCE: These data suggest that the KD ranks among currently used AEDs as an effective treatment for seizures in DS. According to our results (good effect on SE and prolonged seizures, good tolerability, less compliance problems due to formula treatment) the KD should be considered as an early treatment option in infants with DS.

The ketogenic diet in infants--Advantages of early use.

OBJECTIVE: To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (< 1.5 years of age) compared with older children. METHODS: Patients with complete follow-up data of ≥ 3 months after initiation of the KD were analyzed retrospectively. Infants < 1.5 years at initiation of the KD (Group A) were compared with children > 1.5 years (Group B). RESULTS: 127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000). Looking at infants < 9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001). No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.). SIGNIFICANCE: According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy.

Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy--the Austrian experience.

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 outcome of childhood obesity management depends highly upon patient compliance.

UNLABELLED: Over the last 20 years, obesity in childhood and adolescence has become a major public health concern due to dramatically increasing prevalence rates. We evaluated the outcome of 294 children (135 girls, 159 boys) aged 6-16 years (median 10.9 years) enrolled in a single centre outpatient obesity intervention programme consisting of periodical visits to the outpatient unit with regular medical and dietetic counselling aiming at a modification of dietary and activity patterns of patients and parents. The average number of visits to the outpatient unit was 3.6 (SD 2.7) with a mean visit interval of 62.1 days. A mean drop-out rate of 27.5% between each scheduled appointment occurred. In a stepwise regression model, neither reduction of the standard deviation score of patients' body mass index (BMI-SDS) nor dietary counselling contributed to the total number of visits. The only significant contributor was the patients' initial BMI-SDS explaining 4.6% of the variance of attended visits adjusted for age and sex. Segregation of the patients into an "obesity" (initial BMI-SDS >/=90th percentile, at least three visits attended, n=59) and an "excessive obesity" (initial BMI-SDS >/=99th percentile, at least four visits attended, n=75) subgroup showed a mean reduction of BMI-SDS in the "obesity" group at visit three of 0.14 (SD 0.21, P<0.0001), and in the "excessive obese" group at visit four of 0.17 (SD 0.22, P<0.001). In a stepwise regression model, the mean interval between visits and regular dietary counselling explained 11.7% of the variance of BMI-SDS reduction at visit three in both subgroups. CONCLUSION: there is an urgent need for efficient strategies to improve adherence of outpatients to obesity treatment since, in terms of reduction in body mass index standard deviation score, a beneficial outcome can be achieved for compliant obese children and adolescents.