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Objectives: The objectives were to investigate the relationship between ketogenic diet therapy and neutropenia in children with epilepsy. Methods: A retrospective chart review of children who initiated ketogenic diet at the Hospital for Sick Children between January 1, 2000, and May 1, 2018 was performed. Factors associated with the development of neutropenia during ketogenic diet therapy were evaluated and the relationship between development of a significant or suspected infection and neutrophil count was analyzed. Results: One hundred two children met inclusion criteria and were followed on the diet for up to 24 months. Thirteen of 102 (13%) children were neutropenic at diet initiation. In the remaining 89 children, 27 developed neutropenia. Developing neutropenia was significantly associated with the ketogenic diet at 6 (13%), 12 (23%), and 24 (25%) months follow-up. Developing neutropenia was associated with higher urinary ketones (OR = 4.26, 95% CI: 1.27, 14.15) and longer duration of ketogenic diet therapy (OR = 3.29, 95% CI: 1.42, 7.96). There was no significant association between development of a clinically significant infection and neutropenia. Conclusion: Ketogenic diet therapy is associated with neutropenia in children with epilepsy, however, it does not have a significant clinical impact. Concern regarding neutropenia should not discourage the use of the ketogenic diet in children. [ABSTRACT FROM AUTHOR]

Objective: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with frequently encountered variants. Methods: A cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. Results: Twenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. Significance: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable. [ABSTRACT FROM AUTHOR]

Objective To assess the change in inpatient and emergency department utilization and health care costs in children on the ketogenic diet for treatment of epilepsy. Methods Data on children with epilepsy initiated on the ketogenic diet (KD) Jan 1, 2000 and Dec 31, 2010 at Ontario pediatric hospitals were linked to province wide inpatient, emergency department (ED) data at the Institute for Clinical Evaluative Sciences. ED and inpatient visits and costs for this cohort were compared for a maximum of 2 years (730 days) prior to diet initiation and for a maximum of 2 years (730 days) following diet initiation. KD patient were compared to matched group of children with epilepsy who did not receive the ketogenic diet (no KD). Results Children on the KD experienced a mean decrease in ED visits of 2.5 visits per person per year [95% CI (1.5–3.4)], and a mean decrease of 0.8 inpatient visits per person per year [95% CI (0.3–1.3)], following diet initiation. They had a mean decrease in ED costs of $630 [95% CI (249–1012)] per person per year and a median decrease in inpatient costs of $1059 [IQR: 7890; p < 0.001] per child per year. Compared with the no KD children, children on the diet experienced a mean reduction of 2.1 ED visits per child per year [95% CI (1.0–3.2)] and a mean decrease of 0.6 [95% CI (0.1–1.1)] inpatient visits per child per year. Patients on the KD experienced a reduction of $442 [95% CI (34.4–850)] per child per year more in ED costs than the matched group. The ketogenic diet group had greater median decrease in inpatient costs per child per year than the matched group [p < 0.001]. Significance Patients initiated on ketogenic diet, experienced decreased ED and inpatient visits as well as costs following diet initiation in Ontario, Canada. [ABSTRACT FROM AUTHOR]

The very-high-fat ketogenic diet can worsen lipid levels in children with pre-existing hyperlipidemia by increasing serum lipoproteins and reducing antiatherogenic high-density lipoproteins. A retrospective chart review of 160 children treated with the ketogenic diet from September 2000 to May 2011 was performed. Twelve children with pre-existing hyperlipidemia were identified. Lipid levels including total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and total cholesterol/high-density lipoprotein were measured pre-diet and at 3, 6, and 12 months of treatment. During treatment, there was a significant reduction in mean total cholesterol, low-density lipoprotein, and total cholesterol/high-density lipoprotein. Total cholesterol and low-density lipoprotein were normalized in 8 and 7 children at 6 months; and 9 and 9 children at 12 months respectively. At 6 and 12 months, tot cholesterol/HDL ratio was normalized in 5 and 7 children respectively. Diet modifications were made to achieve healthy lipid levels. By extrapolating the data, it suggests lipid levels can be controlled in children and adults with ketogenic diet treatment. [ABSTRACT FROM AUTHOR]

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004–2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month–16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9–2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19–0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic diet. [ABSTRACT FROM PUBLISHER]

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research. [ABSTRACT FROM AUTHOR]

Objective: The concept of “rational polypharmacy” has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies. Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy. Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4–24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5–96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness. Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use. [ABSTRACT FROM AUTHOR]

Childhood is a vulnerable time-developmentally, socially, and cognitively. Any disruption may have long-standing effects on the attainment of critical developmental milestones. The impact of ongoing seizures and epilepsy in children is significant and may result in cognitive delay, poorer educational outcomes, and lower employment rates in adulthood. The early recognition, intervention, and treatment of evolving pharmacoresistant epilepsy in children presents a unique opportunities for health care practitioners. Seizure freedom is the ultimate epilepsy treatment goal, given the broad and long-standing effects of seizures in childhood. However, even when we believe the chance of seizure freedom is low, we should not let the perceived unlikelihood of that goal limit the treatments we offer. All children with pharmacoresistant epilepsy should be evaluated at a comprehensive pediatric epilepsy center. Failing to offer state-of-the-art treatments to these children only increases the burden of epilepsy on children and their families. [ABSTRACT FROM AUTHOR]