Marisa Armeno

Ketogenic dietary therapies (KDTs) are increasingly used worldwide as a non‐pharmacological treatment for epilepsy, including among people of childbearing potential. In many cases, KDTs allow for the reduction of antiseizure medications (ASMs) and lower drug exposure during pregnancy. However, limited evidence on maternal tolerability, fetal safety, and lactation outcomes has led to reluctance among healthcare providers to recommend KDTs during pregnancy. To inform evidence‐based counseling, it is crucial to systematically collect data on maternal and offspring outcomes following KDT exposure. Over the past 25 years, international epilepsy pregnancy registries have provided robust data on the teratogenic risks of ASM exposure. Yet, no standardized dataset currently exists for documenting KDT exposure during pregnancy and lactation. The International League Against Epilepsy Ketogenic Dietary Treatments Task Force conducted a structured consensus process to develop the first international core dataset designed to capture maternal KDT exposure within existing pregnancy registries. This dataset provides a standardized, pragmatic framework for recording diet type, exposure duration, maternal‐fetal outcomes, and lactation parameters. By harmonizing data collection across registries, this initiative aims to transform isolated case reports into aggregated, high‐quality multicenter evidence, closing a critical knowledge gap. Incorporating these standardized questions into epilepsy pregnancy registries represents both a scientific necessity and a call to action to ensure safer, evidence‐based care for women with epilepsy and their children. Plain Language Summary: More people are using ketogenic diets as a treatment for epilepsy around the world, including during pregnancy. It is not yet known if these diets are safe for mothers and babies during pregnancy and breastfeeding. Collecting standardized information about pregnancy outcomes in existing registries will inform us about the safety and effectiveness of these diets. The authors, who are either members of the International League Against Epilepsy dietary task force or specifically chosen by them for their expertise, followed a consensus process to suggest the addition of key standardized questions to the existing international pregnancy outcome registries for epilepsy.

Objective: Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare metabolic encephalopathy caused by pathogenic SLC2A1 variants. Ketogenic dietary therapy (KDT) is the mainstay of treatment. In Latin America, Glut1DS remains underdiagnosed due to limited awareness and restricted access to genetic testing. This study describes the clinical and genetic features, management, and response to KDT in an Argentine cohort. Methods: A retrospective multicenter study was conducted including patients with a clinical and/or genetic diagnosis of Glut1DS. Clinical data, seizure types, neurodevelopmental features, treatment response, and KDT characteristics were collected from medical records using a standardized form. Genetic confirmation was obtained by SLC2A1 sequencing. Descriptive and comparative analyses were performed. Results: Thirty‐nine patients with Glut1DS (64% males) were included. Mean age at evaluation was 13.7 years. Median ages at symptom onset and diagnosis were 6 and 55 months, respectively, with a median diagnostic delay of 49 months. Cognitive impairment was present in two‐thirds of patients, and movement disorders in 79%. Epilepsy occurred in 74%. Of 39 patients, all but one received KDT, with MCT oil in 64%. Thirty patients remained on KDT, achieving seizure freedom in 86% and >50% reduction in four others. Improvements were reported in motor coordination (38%), cognition and attention (10%), energy (10%), and behavior (8%). No major adverse effects were reported. Significance: This first national report underscores the clinical diversity of Glut1DS in Argentina and a positive trend toward earlier KDT initiation. Strengthening early diagnosis, systematic follow‐up, and equitable access to therapy remains essential.

Introduction: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disorder characterized by respiratory failure, autonomic dysregulation, and endocrine abnormalities. Some of these patients may also develop neuroendocrine tumors (ROHHAD-NET). The aim of this study was to evaluate the clinical features, biochemical findings, treatments, and outcomes in a cohort of pediatric patients with ROHHAD-NET syndrome followed at a single tertiary center. Methods: A retrospective review of 10 medical records of patients with ROHHAD-NET syndrome followed between 2007 and 2024 was conducted. Data analyzed included clinical, biochemical, therapeutic interventions and outcomes. Results: Rapid-onset obesity, observed in all 10 patients, was the first clinical sign with a mean age at onset (MAO) of 5.1 ± 1.8 years. Neurobehavioral disorders were also an early manifestation, occurring in 5 cases with a MAO of 5 ± 1 years. All patients developed respiratory symptoms, with a MAO of 7.4 ± 3 years. Six patients were diagnosed with obstructive sleep apnea syndrome, including 2 with associated alveolar central hypoventilation. Seven patients required ventilatory support. All patients had hypothalamic dysfunction, MAO 6.6 ± 1.3 years. Disorders of water balance were the most frequent manifestation (n = 10), followed by hyperprolactinemia, central hypothyroidism, growth hormone deficiency, adrenal insufficiency, precocious puberty, and hypogonadotropic hypogonadism. Autonomic dysregulation was present in the entire cohort (MAO 6.7 ± 2.3 years), with strabismus as the most common clinical sign (n = 6). Neural crest tumors (ganglioneuromas) were identified in 5 patients, with a MAO of 5.4 ± 1.3 years. Tumor location included the adrenal gland (n = 2) and mediastinum (n = 3). Other clinical findings included thrombocytopenia, celiac disease, enuresis, type 1 and type 2 diabetes, seizures, hypo- and hypertension, and primary hypothyroidism. All patients received symptomatic treatment; 3 also received intravenous immunoglobulin as compassionate therapy, without significant benefit. Three patients died. Conclusion: High clinical suspicion and early recognition are essential for a prompt diagnosis, timely initiation of respiratory support, and reduction of morbidity and mortality. Larger cohorts are needed for better characterization of this syndrome and to further elucidate its etiology.

Objective: Ketogenic diet therapies (KDTs) are increasingly used as a treatment for people with epilepsy of childbearing potential (PWECP) and glucose transporter type 1 deficiency syndrome (Glut1DS). The aim of this study was to collect information on clinical experience with KDT during pregnancy and lactation in these populations. Methods: Between December 2023 and June 2024, an online survey was widely circulated to healthcare professionals (HCPs) working with PWECP and people with Glut1DS of childbearing potential on KDT. The survey explored KDT use during pregnancy and lactation. Only HCPs working with patients who expressed interest in KDT and who were planning to become pregnant or were already pregnant were invited to complete the survey. Results: Thirty‐five HCPs had counseled patients about whether to follow KDT during pregnancy. Sixty percent of HCPs did not recommend KDT during pregnancy. Key concerns included a lack of expertise with KDT use during pregnancy, insufficient data on the safety of KDT use during pregnancy, and uncertainty about the impact on fetal development. Among the HCPs (40%) who recommended KDT during pregnancy, there was no consensus regarding the version of KDT or optimal macronutrient composition. Even fewer HCPs ( n = 5) had provided counseling on diet adaptation during lactation. Low Glycemic Index Treatment and the modified Atkins diet were most recommended. Blood ketone monitoring was unanimously recommended during lactation. Significance: Based on the survey results, HCPs have variable opinions about the safety, management, ideal diet, and levels of ketosis for people with epilepsy (PWE) and Glut1DS on KDT during pregnancy and lactation. There was consensus about monitoring ketosis levels and ensuring micronutrient supplementation. Patient enrollment in pregnancy registries that capture KDT use is crucial to support future research and expand knowledge about the safety of KDT so HCPs and PWE or Glut1DS can make informed decisions about their treatment. Plain Language Summary: Most healthcare providers (HCPs) did not advise ketogenic diet therapy (KDT) for epilepsy during pregnancy, though some noted exceptions for glucose transporter type 1 deficiency syndrome. Their main concerns were not having enough information about safety for the parent and fetus and their own lack of experience using KDT during pregnancy. The 40% of HCPs who supported the use of KDT during pregnancy stressed the need for personalized care and close monitoring to reduce risks. Few HCPs have used KDT during lactation. Experts advised using more flexible versions of KDT during lactation. More research is needed.

Objective: Identifying factors influencing cannabidiol (CBD) exposure can optimize treatment efficacy and safety. We aimed to describe the population pharmacokinetics of CBD in children with drug‐resistant developmental and epileptic encephalopathies (DEEs) and assess the influence of environmental, pharmacological, and clinical characteristics on CBD systemic exposure.Methods: Data from two pharmacokinetic studies of patients aged 2–18 years with DEEs were included (N = 48 patients). Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6 h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast. CBD plasma concentrations were also available following administration of a CBD‐enriched formulation. Samples were quantified using a validated liquid chromatography/tandem mass spectrometry assay. A CBD population pharmacokinetic model was developed using nonlinear mixed‐effects modeling. The effects of formulation, concomitant food intake, and demographic, clinical, and pharmacological factors on CBD pharmacokinetics were evaluated. Simulated maximum plasma concentration (C_max) and area under the concentration–time curve between 0 and 12 h (AUC_0‐12) were calculated.Results: A one‐compartment model with transit compartments and first‐order elimination best described CBD pharmacokinetics. Mean values for CBD apparent clearance (CL/F) and volume of distribution (V/F) were 143.5 L/h and 1892.4 L, respectively. Weight was allometrically scaled for V/F and CL/F, sex was associated with V/F, and both formulation and food condition were associated with F (relative bioavailability). CBD C_max increased by 41% and AUC_0‐12 by 45% when CBD was administered with food compared to fasting. Dose‐normalized AUC_0‐12 was approximately 50% lower with CBD‐enriched oil compared to purified CBD.Significance: In the present study, we described the effects of food and formulation on CBD exposure in children with DEEs. Increased CBD exposure with food intake and significant changes in drug exposure when switching between CBD formulations should be considered in patient management.

Craniopharyngioma-related hypothalamic involvement may cause disturbed satiety control and the development of severe hypothalamic obesity, for which there are limited therapeutic options. The glucagon-like peptide-1 analogue liraglutide has shown to lead to long-term weight loss and improved eating behavior. Here we report the effectiveness of liraglutide in the multidisciplinary management of an adolescent girl with severe hypothalamic obesity and panhypopituitarism following craniopharyngioma surgery. After one year on liraglutide at 2.4 mg/day, the patient achieved a decrease of 37% of weight/height, 6.8 units of BMI, 16.9 kg of weight, and 11.5 cm waist circumference. Liraglutide is a promising option to decrease body weight and to improve metabolic alterations in patients with hypothalamic obesity due to craniopharyngioma. The safety and efficacy of liraglutide children and adolescents with craniopharyngioma-related hypothalamic obesity should be further evaluated.

Objective: Despite growing recognition of the efficacy of ketogenic diet therapies (KDT) in reducing seizure frequency and improving the quality of life for individuals with epilepsy, several factors hinder their widespread adoption across Latin America. Specific challenges in the region have been discussed but not formally studied. Currently, no data exist on the availability and operation of KDT teams in the region. To address this gap, we conducted a survey of KDT centers across Latin American countries in the framework of the biannual International Ketogenic Diet Conference in September 2023.Methods: A seven‐question survey was distributed via email to neurologists, dietitians, or through indexed publications.Results: Of the 16 centers approached, 14 (87.5%) responded, identifying 98 KDT centers. Nearly half (49%) are public institutions, primarily in Brazil, Chile, and Mexico; 44 are private; and 5 are mixed. Core teams in all centers included a neurologist and dietitian, with some teams in Argentina, Chile, and Paraguay also involving a medical nutritionist. None of the centers reported a protocol for transitioning to adult care, and consistent data on Glut1 patients and protocols were lacking.Significance: Over the past two decades, the KDT landscape in Latin America has improved, with established centers expanding and new ones emerging. However, continued efforts are needed to promote KDT adoption in countries where it is not yet practiced and in regions with limited resources and expertise.

Objective: There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug‐resistant epilepsy in whom KDT was used.Methods: A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug‐resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival.Results: Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow‐up of 1 month were included; 13 had early‐infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable.Significance: Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary.