SUMMARYPurpose: To report the efficacy, safety, and tolerability of the low glycemic index treatment (LGIT) in pediatric epilepsy. Methods: A retrospective chart review was performed on patients initiating the LGIT at the Massachusetts General Hospital between January 2002 and June 2008. Demographic and clinical information including seizure type, baseline seizure frequency, medications, blood chemistries, side effects, and anthropometrics were collected. Initiation of the LGIT was done in an outpatient setting. Patients were educated by a dietitian to restrict foods with high glycemic index and to limit total daily carbohydrates to 40-60 g. Change in seizure frequency was assessed at 1-, 3-, 6-, 9-, and 12-month follow-up intervals. Results: Seventy-six children were included in the study. Eighty-nine percent had intractable epilepsy ( ‡3 antiepileptic drugs). A greater than 50% reduction from baseline seizure frequency was observed in 42%, 50%, 54%, 64%, and 66% of the population with follow-up available at 1, 3, 6, 9, and 12 months, respectively. Increased efficacy was correlated with lower serum glucose levels at some time points, but not with b-hydroxybutyrate (BOHB) changes or ketosis status at any time point. Only three patients reported side effects (transient lethargy). Blood urea nitrogen (BUN) was elevated in approximately one-third of follow-up laboratory studies. No significant changes were seen in body mass index (BMI) or BMI z-score at any followup interval. The most cited reason for treatment discontinuation was the restrictiveness of the diet, in 18 patients (24%). Conclusion: The LGIT was associated with reduced seizure frequency in a large fraction of patients, with limited side effects.

SUMMARYDespite the substantial efficacy of the ketogenic diet (KD) in treating refractory epilepsy, use of the KD remains limited because of difficulties in implementation and tolerability. An effective alternative dietary approach is a low glycemic index treatment (LGIT), which liberalizes the extreme carbohydrate restriction of the KD but restricts the type of carbohydrate-containing foods to those that produce relatively small changes in blood glucose. Foods with a "glycemic index" of less than 50 produce less than half the area-under-the-curve elevation of blood glucose compared to a reference food. The LGIT approach produces comparable efficacy to the classic KD, but tolerability is improved and implementation is much simpler. The LGIT appears to be a viable first-line dietary therapy for epilepsy. KEY WORDS: Glycemic index, Low glycemic index treatment, Refractory epilepsy, Dietary therapy.Developed in the 1920s, the classic ketogenic diet (KD) is arguably the most effective treatment available for medically refractory epilepsy. Over the past 80 years, numerous case series of the classic KD, performed largely in children, have shown that up to one-third of patients who initiate the KD experience a dramatic decrease in seizure frequency (Bailey et al., 2005). However, there are several limitations to the availability, implementation, and maintenance of the KD.Traditional implementation of the KD required an initial fast of 24-48 h followed by gradual introduction of the KD over several days during an inpatient hospitalization. Ideally, calculation of the KD is performed by a skilled KD dietitian who educates the child and family in how to implement and maintain the KD, and who also prepares numerous individualized meal plans to meet the child's protein, fat, and carbohydrate goals to 0.1 g precision. Due to several factors, including a relatively limited number of experienced dietitians, difficulty with reimbursement, and the intensity of labor in initiating and maintaining patients on a classic KD, access to this diet remains limited. Even when the KD is available, its restrictiveness often makes it difficult for a child and family to adhere to, and being on

Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a classification of tuber types along a spectrum of severity, using magnetic resonance imaging (MRI) characteristics in 35 patients with TSC and history of epilepsy, and to investigate the relationship between tuber types and genetics, as well as clinical manifestations. Three types of tubers were identified based on the MRI signal intensity of their subcortical white matter component. (1) Tubers Type A are isointense on volumetric T1 images and subtly hyperintense on T2 weighted and fluid-attenuated inversion recovery (FLAIR); (2) Type B are hypointense on volumetric T1 images and homogeneously hyperintense on T2 weighted and FLAIR; (3) Type C are hypointense on volumetric T1 images, hyperintense on T2 weighted, and heterogeneous on FLAIR characterized by a hypointense central region surrounded by a hyperintense rim. Based on the dominant tuber type present, three distinct patient groups were also identified: Patients with Type A tuber dominance have a milder phenotype. Patients with Type C tuber dominance have more MRI abnormalities such as subependymal giant cell tumors, and were more likely to have an autism spectrum disorder, a history of infantile spasms, and a higher frequency of epileptic seizures, compared to patients who have a dominance in Type B tubers, and especially to those with a Type A dominance.

SummaryChildren with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N = 93) were classified into groups according to KD +/− CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD + ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD + TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population.

Summary:Purpose: To evaluate safety and tolerability of ketogenic diet (KGD) and valproate (VPA) cotherapy in the treatment of intractable seizures.Methods: The patient records of children who underwent KGD initiation at the Massachusetts General Hospital for Children from February 2002 to September 2004 were retrospectively assessed. Efficacy was measured by comparing reported seizure frequency at baseline and at 3-month intervals thereafter. Adverse events and reasons for terminating the diet were tabulated.Results: Of 71 patients who underwent KGD initiation, 24 were concomitantly using VPA at the time of initiation. The most serious adverse events were two cases of acute pancreatitis (2.8%), both of which occurred in patients not taking VPA. The most common complications in both groups were acidosis (39.4%), nausea and vomiting (23.9%), hypertriglyceridemia (21.1%), lethargy (18.3%), and behavioral changes and irritability (15.5%). No significant difference in adverse-event profiles was found between the VPA group and the non-VPA group. At 1 year, 32 patients remained on the diet, including 11 in the VPA group. Efficacy was nearly identical in these two groups.Conclusions: KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy. Adverse-event profiles of patients on KGD and VPA cotherapy are similar to those of patients on the KGD without VPA. In considering possible treatment options for intractable seizures, cotherapy with these two modalities should not be excluded for safety or tolerability concerns. In some patients, this combination may provide optimal seizure control.

The frequency of SUIDs during the neonatal period warrants ongoing attention to all circumstances contributing to this category of deaths. The development of a standardized definition of sudden unexpected postnatal collapse and a national registry of these events is recommended. Ongoing research on the effects of early neonatal practices on postneonatal SUID should also be encouraged.

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Clinical manifestations were retrospectively assessed in 5 families with tuberous sclerosis complex, including 1 pair of monozygotic twins. Interfamilial variation in tuber count was significantly larger than intrafamilial variation. Severity of epilepsy and cognitive profiles varied both between and within families, particularly between the monozygotic twins, and IQ was inversely related to tuber count. Cutaneous, renal, and cardiac findings did not appear to cluster within families. Although the monozygotic twins displayed similar physical manifestations of tuberous sclerosis complex (renal and cardiac hamartomas), they differed markedly in neurocognitive profiles. Phenotypic variation within these families may be explained largely as a function of the randomness of second-hit events that cause hamartomas in tuberous sclerosis complex or by as-yet-unidentified genetic modifiers. Familial variation in tuberous sclerosis complex phenotype has important implications for genetic counseling.