Human milk and breastfeeding during ketogenic diet therapy in infants with epilepsy: Clinical practice guideline.

Ketogenic diet therapy (KDT) is a safe and effective treatment for epilepsy and glucose transporter type 1 (GLUT1) deficiency syndrome in infancy. Complete weaning from breastfeeding is not required to implement KDT; however, breastfeeding remains uncommon. Barriers include feasibility concerns and lack of referrals to expert centres. Therefore, practical strategies are needed to help mothers and professionals overcome these barriers and facilitate the inclusion of breastfeeding and human milk during KDT. A multidisciplinary expert panel met online to address clinical concerns, systematically reviewed the literature, and conducted two international surveys to develop an expert consensus of practical recommendations for including human milk and breastfeeding in KDT. The need to educate about the nutritional benefits of human milk and to increase breastfeeding rates is emphasized. Prospective real-world registries could help to collect data on the implementation of breastfeeding and the use of human milk in KDT, while systematically including non-seizure-related outcomes, such as quality of life, and social and emotional well-being, which could improve outcomes for infants and mothers.

Ultrasound attenuation imaging: a reproducible alternative for the noninvasive quantitative assessment of hepatic steatosis in children.

BACKGROUND: Pediatric hepatic steatosis is a global public health concern, as an increasing number of children are affected by this condition. Liver biopsy is the gold standard diagnostic method; however, this procedure is invasive. Magnetic resonance imaging (MRI)-derived proton density fat fraction has been accepted as an alternative to biopsy. However, this method is limited by cost and availability. Ultrasound (US) attenuation imaging is an upcoming tool for noninvasive quantitative assessment of hepatic steatosis in children. A limited number of publications have focused on US attenuation imaging and the stages of hepatic steatosis in children. OBJECTIVE: To analyze the usefulness of ultrasound attenuation imaging for the diagnosis and quantification of hepatic steatosis in children. MATERIAL AND METHODS: Between July and November 2021, 174 patients were included and divided into two groups: group 1, patients with risk factors for steatosis (n = 147), and group 2, patients without risk factors for steatosis (n = 27). In all cases, age, sex, weight, body mass index (BMI), and BMI percentile were determined. B-mode US (two observers) and US attenuation imaging with attenuation coefficient acquisition (two independent sessions, two different observers) were performed in both groups. Steatosis was classified into four grades (0: absent, 1: mild, 2: moderate and 3: severe) using B-mode US. Attenuation coefficient acquisition was correlated with steatosis score according to Spearman's correlation. Attenuation coefficient acquisition measurements' interobserver agreement was assessed using intraclass correlation coefficients (ICC). RESULTS: All attenuation coefficient acquisition measurements were satisfactory without technical failures. The median values for group 1 for the first session were 0.64 (0.57-0.69) dB/cm/MHz and 0.64 (0.60-0.70) dB/cm/MHz for the second session. The median values for group 2 for the first session were 0.54 (0.51-0.56) dB/cm/MHz and 0.54 (0.51-0.56) dB/cm/MHz for the second. The average attenuation coefficient acquisition was 0.65 (0.59-0.69) dB/cm/MHz for group 1 and 0.54 (0.52-0.56) dB/cm/MHz for group 2. There was excellent interobserver agreement at 0.94 (95% CI 0.92-0.96). There was substantial agreement between both observers (κ = 0.77, with a P < 0.001). There was a positive correlation between ultrasound attenuation imaging and B-mode scores for both observers (r = 0.87, P < 0.001 for observer 1; r = 0.86, P < 0.001 for observer 2). Attenuation coefficient acquisition median values were significantly different for each steatosis grade (P < 0.001). In the assessment of steatosis by B-mode US, the agreement between the two observers was moderate (κ = 0.49 and κ = 0.55, respectively, with a P < 0.001 in both cases). CONCLUSION: US attenuation imaging is a promising tool for the diagnosis and follow-up of pediatric steatosis, which provides a more repeatable form of classification, especially at low levels of steatosis detectable in B-mode US.

Increase in the frequency of scurvy in children with food selectivity: A case series. / Aumento de la frecuencia de escorbuto en niños con selectividad alimentaria: serie de casos.

Scurvy is a disease caused by vitamin C deficiency. Although rare, in recent years, the number of scurvy cases in children with eating disorders has increased. Its manifestations are varied because vitamin C is a cofactor in numerous processes, such as collagen synthesis. The typical skin manifestations include petechiae, bruising, and hyperkeratosis. Mucosal involvement manifests as gingivitis with hypertrophy, bleeding, and loss of teeth. The diagnosis is based on clinical findings and may be confirmed by measuring plasma vitamin C levels. The objective of this study was to describe a cohort of patients diagnosed with scurvy in recent years, its clinical manifestations, and findings in relation to their eating behavior and neurodevelopmental disorders.

El escorbuto es una enfermedad producida por déficit de vitamina C. Aunque es poco frecuente, en los últimos años observamos un incremento de casos en niños con trastornos de la conducta alimentaria. Sus manifestaciones son variadas, ya que esta vitamina actúa como cofactor en numerosos procesos, como la síntesis de colágeno. Las manifestaciones cutáneas características son las petequias, equimosis e hiperqueratosis. El compromiso mucoso se manifiesta como gingivitis con hipertrofia, hemorragias y pérdida de piezas dentarias. El diagnóstico es clínico y puede confirmarse mediante la determinación de la vitamina C plasmática. El objetivo de este trabajo es describir una cohorte de pacientes diagnosticados en los últimos años, manifestaciones clínicas y hallazgos en relación con su conducta alimentaria y trastornos del neurodesarrollo.

Use of ketogenic dietary therapy for drug-resistant epilepsy in early infancy.

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.

Let food be thy medicine. The interaction between ketogenic diet therapy and anti-seizure medications: A systematic review.

Ketogenic diet therapy (KDT) is a nonpharmacological treatment that has been demonstrated to be effective in reducing seizures in patients with drug-resistant epilepsy. As the majority of patients on KDT are also receiving anti-seizure medications (ASMs), questions about their combination often arise. KDT is typically implemented as an add-on, and not a substitute for ASMs. Drug monitoring and specific laboratory studies may be helpful in specific cases of cotherapy. Valproate, topiramate, zonisamide, and lamotrigine may be potentially problematic with KDT, but the evidence for this is not conclusive. ASM reduction is usually attempted after 1 month of KDT if a child is showing seizure reduction (but weaning ASMs does not require seizure freedom). Failure to wean an ASM does not mean KDT has failed and adding a new ASM may be beneficial in those cases after several months of KDT fine-tuning. The purpose of this review was to discuss the evidence for possible negative (or positive) pharmacodynamic interactions between KDT and ASMs. In addition, practical suggestions for the weaning or adding of ASMs in patients on KDT are provided.

Causes of possible excessive weight gain in exclusively breastfed infants in the first six months of life.

BACKGROUND: The aim of this study was to describe factors related to the infant, mother, and breastmilk composition that may be associated with excessive weight gain in a cohort of exclusively breastfed infants younger than 6 months of life with excessive weight gain, and to compare these findings with data from a group of normal-weight exclusively breastfed infants. METHODS: Thirty-six exclusively breastfed infants younger than 6 months of life seen at two health-care centers between July 2016 and 2017 were enrolled in the study. The clinical features of the infants, their mothers, and the macronutrient composition of the breast milk were evaluated. We classified infants according to weight gain velocity between birth and 6 months of life into an excessive weight gain (EWG) and an adequate weight gain (AWG) group. RESULTS: Mean age at protocol entry was 3.8 months. Thirteen patients were classified as EWG and 23 patients as AWG. Co-sleeping was more often observed in EWG than in AWG infants. Mothers in the EWG group were younger and more often had gained more than 18 kg during pregnancy than those in the AWG group. No significant differences were found in the macronutrient content of the breast milk between both groups. CONCLUSIONS: Greater weight gain in infants under 6 months of age may be related to greater weight gain of the mother during pregnancy, younger age of the mother, and co-sleeping of the mother and child.

Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment. / Deficiencia del transportador de glucosa tipo 1: aspectos clínicos, diagnóstico y terapéutica.

Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid,and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.

El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.

Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet.

Introduction: Ketogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors. Possible variations in glycemia and ketone bodies blood levels according to the menstrual cycle have not been systematically assessed yet, but this time window deserves special attention because of hormonal and metabolic related changes. Methods: This study aims at searching for subtle changes in KBs blood level during menstrual cycle in female patients undergoing a stable ketogenic diet, by analyzing 3-months daily measurement of ketone bodies blood levels and glucose blood levels throughout the menstrual cycle. Results: We report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet. A significant increase in glucose blood levels during menstruation was found in the entire cohort. As far as the ketone bodies blood levels, an inversely proportional trend compared to glycemia was noted. Conclusion: Exploring whether ketonemia variations might occur according to the menstrual cycle is relevant to determine the feasibility of transient preventive diet adjustments to assure a continuative treatment efficacy and to enhance dietary behavior support. Clinical trial registration: clinicaltrials.gov, identifier NCT05234411.

Evaluation of two dietary treatments in obese hyperinsulinemic adolescents.

UNLABELLED: Hyperinsulinemia increases the risk of cardiovascular disease in obese children. Only a few treatments are available to decrease insulin resistance. The reduction of hyperinsulinemia by dietary means would be a simple, physiologic and economic way to reduce the risk of metabolic disease. OBJECTIVE: To compare the effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic adolescents. MATERIALS AND METHODS: Eighty-six randomly assigned insulin-resistant obese adolescents completed a 16 week calorie-restricted diet. The experimental diet had a reduced glycemic index designed to evoke a low insulin response (LIR), with carbohydrates and proteins ingested in separate meals. The control diet was a conventional (CD) with similar proportions (60%, 20% and 20%). Variables studied were blood glucose and insulin concentrations after an oral glucose load, body mass index, waist circumference, and insulin resistance (homeostasis model assessment, HOMA). RESULTS: Mean weight [+/- Standard Deviation (SD)] was significantly reduced after the LIR (-0.53 +/- 0.5) and the CD (-0.54 +/- 0.4), but a greater decrease of waist circumference (cm) was observed after the LIR (-9.1 +/- 4.8 vs. -6.6 +/- 4.6, p = 0.02). Fasting insulin concentrations (-17.9 +/- 27.9 vs. -9.4 +/- 14.8, p = 0.01) and HOMA dropped significantly more after the LIR than after the CD (-3.5 +/- 4.9SD vs. -2.4 +/- 1SD, p < 0.0001). CONCLUSIONS: The LIR diet reduces serum insulin concentrations and waist circumference more than conventional treatment and appears to be a promising alternative to a conventional diet in insulin-resistant obese adolescents. Long-term follow-up is needed to evaluate the maintenance of weight loss and metabolic parameters.

Long-term effectiveness and adverse effects of ketogenic diet therapy in infants with drug-resistant epilepsy treated at a single center in Argentina.

INTRODUCTION: Ketogenic diet therapy (KDT) is a metabolic treatment with proven effectiveness for the treatment of drug-resistant epilepsy in children. Although previously not used in infants under 2 years of age, recent studies have shown KDT to be highly effective and well tolerated in infants with epilepsy, especially those with epileptic encephalopathies. Here, we describe the effectiveness and tolerability of the diet in infants up to 2 years of age. MATERIAL AND METHODS: A prospective study was conducted in a cohort of infants younger than 2 years of age with drug-resistant epilepsy who received the classic ketogenic diet using a specific protocol at a single center in Argentina. RESULTS: 56 infants with treatment-refractory epilepsy were evaluated. The etiology was genetic in 21.4%, structural in 28.6%, unknown in 44.7%, and metabolic in 5.4%. At 3 months, a > 50% decrease in seizure frequency was observed in 35 patients (62.4%), of whom 11 (19.6%) became seizure free. At 6 months, 34 patients (60.7%) had a decrease in seizure frequency of > 50%, of whom 10 (17.8%) were seizure free. At the one-year follow-up, 27 patients (48.2%) had a > 50% decrease in seizure frequency, of whom six (10.7%) were seizure free. At two years, 14 patients (25%) had a > 50% seizure control, of whom four (7.1%) were seizure free. The most common early adverse effects were hypoglycemia and vomiting, while after 1 month and beyond metabolic acidosis, vomiting, and constipation more commonly found. A trend towards a higher rate of acute adverse events in infants younger than 1 year was observed. CONCLUSIONS: CKD showed to be a useful option in infants with treatment-resistant epilepsy. Adverse effects were common, but not a reason to discontinue the diet. Further studies are necessary to evaluate in which epilepsy syndromes and etiologies KDT is most effective.

The evolving indications of KD therapy.

Despite the rapid increase of clinical and basic-science knowledge on ketogenic diet therapies over the past years, it has not always been easy to determine the adequate indications of this treatment. Over the nearly 100 years of use, from being a last resource in the therapeutic algorithm, the diet has become one of the four main treatments for patients with difficult-to-control epilepsy together with antiepileptic drugs, surgery, and vagus nerve stimulation. The use of the diet has also changed. The current paper will briefly discuss the history of the diet together with a review of the literature regarding its most important indications and how they have evolved. The concept of the importance of defining the type of seizure, type of syndrome, and etiology in the selection of patients and timing of diet initiation has been gaining importance. This paper explores how the indications of the diet changed together with the shifting focus of epilepsy teams towards its use in different types of epilepsy and epilepsy syndromes and according to etiologies and as an alternative option in refractory and superrefractory status epilepticus.

Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group.

Glut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed a consensus statement utilizing their collective professional experience, responses to a standardized questionnaire, and serial discussions of wide-ranging issues related to Glut1DS. Key clinical features signaling the onset of Glut1DS are eye-head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. Diagnosis is confirmed by the presence of these clinical signs, hypoglycorrhachia documented by lumbar puncture, and genetic analysis showing pathogenic SLC2A1 variants. KDT represent standard choices with Glut1DS-specific recommendations regarding duration, composition, and management. Ongoing research has identified future interventions to restore Glut1 protein content and function. Clinical manifestations are influenced by patient age, genetic complexity, and novel therapeutic interventions. All clinical phenotypes will benefit from a better understanding of Glut1DS natural history throughout the life cycle and from improved guidelines facilitating early diagnosis and prompt treatment. Often, the presenting seizures are treated initially with antiseizure drugs before the cause of the epilepsy is ascertained and appropriate KDT are initiated. Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long-term disease burden. Impaired development of the brain microvasculature is one such complication of delayed Glut1DS treatment in the postnatal period. This international consensus statement should facilitate prompt diagnosis and guide best standard of care for Glut1DS throughout the life cycle.

Ketogenic parenteral nutrition in three paediatric patients with epilepsy with migrating focal seizures.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare epilepsy syndrome, characterized by an onset of multifocal seizures before the age of six months and a rather typical ictal EEG pattern. The ketogenic diet (KD) has been shown to be a treatment option in these patients with variable results. The KD is generally given by enteral formula or solid food, however, patients on the KD often have coexisting medical disorders that may impair the gastrointestinal tract and, in these cases, parenteral nutrition support may be needed. We present our experience with three patients who had been on the KD because of EIMFS, who were acutely unable to absorb nutrients through the intestinal tract. For these patients, we were unable to reach ketogenic ratios higher than 1.5:1 because of the limited fat intake via the parenteral route. This ratio, nevertheless, was adequate for maintenance of seizure control while allowing short-term bowel rest. Even though our report is limited as it provides no controlled evidence, ketogenic parenteral nutrition should be considered in children on the KD when enteral nutrition is not feasible. Special care should be taken to maintain ketosis and avoid undesired carbohydrates. Patients may respond well to ketogenic parenteral nutrition in spite of a lower ketogenic ratio.

[Serious neurological compromise due to vitamin B12 deficiency in infants of vegan and vegetarian mothers]. / Compromiso neurológico grave por déficit de vitamina B12 en lactantes hijos de madres veganas y vegetarianas.

Vitamin B12 deficiency is one of the most serious complications of vegetarianism and its variants. Infants born to vegan mothers are at greater risk of serious deficiency, being more vulnerable to their effects. B12 deficiency is not usually suspected by the pediatrician in healthy infants with neurological symptoms. The manifestations are nonspecific: apathy, rejection of food and loss of maturational patterns. A nutritional history of the mother, mainly if she is vegetarian, to estimate her reserves is fundamental to detect risk of deficiency of this vitamin in the small child. The objective of this work is to describe a group of infants, children of vegan mothers, with B12 deficiency and serious neurological compromise: central apneas, seizures, hypotonia, loss of connection with the environment and maturational patterns. Our purpose is to alert about the importance of supplying vegan mothers with B12 before conception until the end of breastfeeding.

La deficiencia de vitamina B12 es una de las complicaciones más graves del vegetarianismo. Los lactantes hijos de madres veganas tienen mayor riesgo de deficiencia grave y son más lábiles ante sus efectos. La deficiencia de B12 no es, por lo general, sospechada por el pediatra en lactantes previamente sanos con síntomas neurológicos, ya que las manifestaciones iniciales son inespecíficas: apatía, rechazo del alimento y pérdida de pautas madurativas. La anamnesis nutricional es fundamental para detectar riesgo de déficit de esta vitamina en lactantes. El objetivo de este trabajo es describir a un grupo de lactantes, hijos de madres veganas, con déficit de B12 y compromiso neurológico grave: apneas centrales, convulsiones, hipotonía, pérdida de conexión con el medio y de pautas madurativas. Nuestro propósito es alertar sobre la importancia de suplir B12 a las madres veganas desde antes de la concepción hasta el fin de la lactancia.

A Prospective Study on Changes in Nutritional Status and Growth Following Two Years of Ketogenic Diet (KD) Therapy in Children with Refractory Epilepsy.

INTRODUCTION: Epilepsy is a neurological disorder characterized by an increased susceptibility to seizures. The ketogenic diet (KD) is currently the most important alternative non-pharmacological treatment. Despite its long history of clinical use, it is not clear how this diet affects longitudinal growth in children. METHODS: A prospective study was designed to evaluate growth and nutritional status in 45 children on KD. Growth was assessed by measuring weight, height, and body mass index (BMI). Standard deviation scores (SDS) were calculated for all measurement parameters at KD initiation and at a two-year follow-up. RESULTS: Overall, 45 patients who completed 24 months on KD were enrolled. Median age was 6.6 years (0.8 to 17.3), with a male predominance (n = 23); 74% of the 45 patients were responders on seizure reduction at three months; 26% of patients were non-responders. In our study, using -1 SDS as a cut-off point, growth deceleration was observed in 9% (n: 4) of the patients; however, the nutritional status was maintained or even improved. No correlation with age, sex, or ambulatory status was found. CONCLUSIONS: The nutritional follow-up of these patients was helpful to improve overweight and thinness but could not avoid growth deceleration in some of them. These findings confirm that children with refractory epilepsy on KD treatment require careful growth monitoring.

Deficiencia del transportador de glucosa tipo 1: aspectos clínicos, diagnóstico y terapéutica / Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment

El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.

Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid, and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.

Ketogenic diet use in children with intractable epilepsy secondary to malformations of cortical development: A two- centre experience.

PURPOSE: To evaluate the efficacy and tolerability of the ketogenic diet (KD) as a treatment for drug-resistant epilepsy secondary to malformations of cortical development. METHODS: A two-centre retrospective analysis of 45 paediatric patients with refractory epilepsy due to malformation of cortical development was carried out. Patients were divided into three groups based on malformation type: abnormal neural proliferation (Group 1); abnormal neural migration (Group 2) and abnormal post-migrational development (Group 3). The efficacy of the KD was assessed in terms of seizure frequency reduction. We identified the proportion of patients achieving > 50% seizure frequency reduction overall and in the three subgroups. RESULTS: The adherence to KD was variable. KD was pursued from a minimum of 4 months to a maximum of 96 months. 20 patients (44%) obtained a seizure reduction of > 50% and 2 patients became seizure free. >50% seizure reduction was most commonly achieved by patients in group 3 (64.7%) than in groups 2 (31.8%) and 1 (33.3%). CONCLUSIONS: The best response was observed in patients with malformations of post migrational development. Considering its tolerability, the use of KD should be considered in patients with drug-resistant epilepsy secondary to malformations of cortical development when surgery is not a viable option.

Excessive weight gain in exclusively breast-fed infants.

BACKGROUND: Breastfeeding is recommended as the best source of nutrition in the first months of life and observational studies have associated exclusive breastfeeding with decreased weight gain and a protective effect against obesity in childhood. The objective of this study was to describe the characteristics of a cohort of exclusively breastfed obese infants to determine factors that may lead to this unusual weight gain. METHODS: Infants seen between 2003 and 2015 who were exclusively breastfed and showed excessive weight gain in the first year of life were followed with a focus on features of the mother, the child, feeding patterns and the presence of concomitant factors that influence nutritional status. Additionally, in a subset of the sample, macronutrients of the maternal breast milk were analyzed. A descriptive, prospective cross-sectional study was conducted. RESULTS: Of 73 patients, 63% were girls. At 3 months of life, 64% had a weight-for-height standard deviation score (SDS) >2. At 6 and at 12 months, 100% of the patients had a weight-for-height >2 SDS. The mean age at semisolid-food introduction was 7 months. The mean age at weaning was 15.8 months. The babies were fed on demand and no hunger-satiety pattern was observed. In the breast milk samples analyzed, a significantly lower fat content was found. CONCLUSIONS: The results of our study lead to the assumption that inter-individual variations in mother's milk composition may affect the growth patterns of children.

The ketogenic diet in patients with myoclonic status in non-progressive encephalopathy.

Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by the recurrence of long-lasting atypical status epilepticus associated with attention impairment and continuous polymorphous jerks, mixed with other complex abnormal movements, in infants suffering from a non-progressive encephalopathy. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. PURPOSE: In this study we assess the efficacy and tolerability of the KD in patients with MSNPE. METHODS: Between March 1, 1980 and August 31, 2013, 99 patients who met the diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins protocol and followed for a minimum period of 24 months. RESULTS: Twelve months after initiating the diet, three patients had a 75%-99% decrease in seizures, two had a 50%-74% decrease in seizures, and the remaining child had a less than 50% seizure reduction. In five patients with a seizure reduction of more than 50%, the myoclonic status epilepticus disappeared within 6 months after starting the diet. All patients had very good tolerability and no adverse events were identified. In most of the patients AEDs were reduced. CONCLUSION: The KD is a promising therapy for MSNPE, with most of our patients showing a more than 50% seizure reduction. In patients that responded well to the diet cognitive performance and quality of life also improved.

Déficit de vitamina B12 en grupos vulnerables con alimentación omnívora / Vitamin B12 deficiency in vulnerable groups with omnivorous diet

Introducción: la vitamina B12 cumple un rol esencial en el crecimiento y el neurodesarrollo. El déficit de vitamina B12 (B12) es un problema de salud pública en Argentina, con una alta prevalencia en población de riesgo, como las embarazas y niños en situación social vulnerable, aunque mantengan una dieta omnívora. Objetivos: actualizar la información disponible sobre la deficiencia de B12 en la población vulnerable con el fin de resaltar y actualizar la importancia del tema para realizar un diagnóstico temprano, un tratamiento oportuno y prevenir las complicaciones irreversibles. Resultados: es importante que el pediatra conozca las diferentes formas de presentación del déficit de B12 y principalmente que se considere como diagnóstico diferencial ante niños con alteraciones neurológicas, aún en ausencia de anemia, para lograr intervenciones tempranas que disminuyan el impacto de la enfermedad. Varios investigadores concluyeron que un marcador aislado puede conducir a diagnósticos erróneos, por lo cual actualmente lo más recomendado es usar al menos dos. De los tratamientos evaluados, la mayoría acuerda en realizar entre siete a 10 días de tratamiento, con 1 mg de B12, ya sea intramuscular o vía oral, seguido de tres a 11 semanas de tratamiento semanal. Conclusiones: es de vital importancia relevar datos actualizados de prevalencia de déficit en el país, como así también implementar intervenciones terapéuticas y de políticas públicas preventivas

Introduction: vitamin B12 plays an essential role in growth and neurodevelopment. Vitamin B12 deficiency is a public health problem in Argentina, with a high prevalence in a highrisk population, such as pregnant women and children with a vulnerable social situation, although their omnivorous diet. Objectives: to update the information available on vitamin B12 deficiency in vulnerable populations, in order to highlight the importance of the subject, to achieve an early diagnosis and timely treatment and thus prevent irreversible complications. Results: it is important that the pediatrician knows the different types of vitamin B12 deficiency presentation and to consider it as a differential diagnosis in children with neurological symptoms, even in the absence of anemia, to achieve early interventions and diminish the burden of disease. Many researchers have concluded that an isolated marker can lead to misdiagnoses, so it is currently recommended to use at least two. Most of the treatments evaluated, agree on the administration of 1 mg of B12, for 7 to 10 days, either intramuscular or orally, followed by 3 to 11 weeks of a weekly dose. Conclusions: it is important to update data on the prevalence of B12 deficiency in our country, as well as the implementation of therapeutic interventions and preventive public policies