Cannabidiol in children with treatment-resistant epilepsy with myoclonic-atonic seizures.

PURPOSE: This multicenter study aimed to evaluate the efficacy and tolerability of add-on cannabidiol (CBD) in treatment-resistant patients with epilepsy with myoclonic-atonic seizures (EMAtS) (n = 22) and Sturge Weber syndrome (SWS) with myoclonic-atonic seizures (n = 4). METHODS: Patients who met the diagnostic criteria of treatment-resistant EMAtS or SWS with myoclonic-atonic seizures were included. Cannabidiol was added in doses ranging from 8 to 40 mg/kg/day. Efficacy was assessed by comparing seizure frequency before and after initiating CBD therapy. Neurologic examinations, brain magnetic resonance imaging, repeated prolonged electroencephalography (EEG) and/or video-EEG recordings, and neurometabolic studies were performed in all patients, and genetic investigations in 15. RESULTS: After a mean follow-up of 19 months, 15/26 patients (57.7%) who received add-on CBD had a >50% seizure decrease; three (11.5%) became seizure-free. The remaining 11 patients (42.3%) had a 25-50% seizure reduction. Drop attacks, including myoclonic-atonic seizures and generalized tonic-clonic seizures, as well as atypical absences and nonconvulsive status epilepticus responded well to CBD. In SWS patients, focal motor seizures without consciousness impairment and focal non-motor seizures with consciousness impairment were recognized in two each; in three a 30% reduction of focal seizures was observed. Side effects were mild and did not lead to CBD discontinuation. CONCLUSION: This study evaluating the use of add-on CBD in children with EMAtS or SWS with myoclonic-atonic seizures found that 15/26 (57.7%) had a >50% seizure reduction with good tolerability; three (11.5%) became seizure-free.

Use of sulthiame as add-on therapy in children with myoclonic atonic epilepsy: A study of 35 patients.

PURPOSE: The aim of this retrospective study was to evaluate efficacy and tolerability of sulthiame (STM) as add-on treatment in 35 patients with myoclonic atonic epilepsy (MAE) resistant to other antiseizure medications (ASMs) and/or non-pharmacological treatment. METHODS: Patients were selected according to the diagnostic definition of MAE and were resistant to at least four previous to ASM, alone or in combination. Neurologic examinations, brain magnetic resonance imaging, and repeated prolonged electroencephalography (EEG) or video-EEG studies as well as neurometabolic studies were performed in all cases. Genetic studies were performed in 15 patients. Data on school achievements and/or neuropsychological evaluations were obtained over a mean follow-up of 30 months. Sulthiame was added in doses ranging from 10 to 30 mg/kg/day. Efficacy was assessed by comparing seizure frequency before and after initiating STM therapy. RESULTS: Twenty-one of 35 patients (60%) who received STM as add-on therapy had a greater than 50% seizure decrease after a mean follow-up of 30 months. Complete seizure freedom was achieved in two patients (5.8%). The remaining 14 patients (40%) had a 25-50% seizure reduction. Adverse effects, consisting of hyperpnea and dyspnea, decreased appetite, nausea, drowsiness, headache, and irritability, were observed in 11 (31.4%). The adverse effects were mild and transient in all cases. Discontinuation of STM was not necessary. CONCLUSION: Add-on STM led to a more than 50% seizure reduction in 21 of 35 patients with MAE with only mild or moderate adverse effects.

Vigabatrin-associated brain abnormalities on MRI and other neurological symptoms in patients with West syndrome.

OBJECTIVES: Report a series of children with West syndrome (WS) treated with vigabatrin (VGB) who developed characteristic MRI alterations. In the majority, these adverse events were asymptomatic; however, some of the patients developed movement disorders and acute encephalopathy. METHODS: This is a retrospective analysis of our epilepsy clinical and EEG database of 288 patients with WS seen between 2014 and 2020. All patients who received VGB alone or with concomitant therapies, such as adrenocorticotropic hormone (ACTH), high-dose oral corticosteroids, ketogenic diet, valproate, levetiracetam, or topiramate, were evaluated. RESULTS: In 44 of 288 patients with WS receiving VGB, MRI findings compatible with VGB-associated brain abnormalities were identified; median age at diagnosis was 6.29 months (range, 2 weeks to 11 months). The etiology of WS with vigabatrin-associated brain abnormalities on MRI (VABAM) was unknown in 22 (52.27%), genetic in seven (15.9%), genetic-structural in three (6.8%), structural malformative in three others (6.8%), and structural acquired in eight patients (18.2%). Vigabatrin-associated brain abnormalities on MRI was asymptomatic in 25 of 44 patients. Ten of 44 (22.7%) infants were reported to have had a movement disorder (choreoathetosis, dystonic posturing). Nine of 42 infants exhibited progressive psychomotor deterioration associated with signs and symptoms of encephalopathy. CONCLUSION: MRI abnormalities were observed in infants treated with VGB and they appeared to be dose dependent. In our study common locations for MRI abnormalities included globi pallidi and brainstem, followed by thalami and dentate nuclei. Risk factors for the development of VABAM may include age younger than 11 months and higher VGB dose of VGB (>165 mg/kg/day). Vigabatrin-associated brain abnormalities on MRI usually resolved following VGB discontinuation, probably after a period of 3 months.

An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy.

BACKGROUND: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients. METHODS: Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma. RESULTS: The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates. CONCLUSIONS: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.

West syndrome: A study of 26 patients receiving short-term therapy.

OBJECTIVE: We describe the electroclinical characteristics of a series of 26 patients with idiopathic West syndrome (WS), who had an excellent response to treatment with vigabatrin (VGB) and corticosteroids alone or in combination. METHODS: Evaluating the records of 178 patients with WS studied at Garrahan Hospital, Niño Jesús Hospital, and Clínica San Lucas between January 2005 and June 2017, we selected 26 patients that met the inclusion criteria of idiopathic WS. The inclusion criteria for idiopathic WS were (1) no personal history of disease, (2) normal neurological examination and neurodevelopment, (3) symmetric spasms in clusters not preceded by any other type of seizure, (d) symmetric hypsarrhythmia, (e) normal electroencephalogram (EEG) background, e.g., normal sleep EEG pattern, (f) normal magnetic resonance imaging (MRI) recording, (g) normal neurometabolic and genetic studies, and (h) at least 2 years of follow-up. RESULTS: Fifteen boys and 11 girls met the inclusion criteria of idiopathic WS. The current age of the children ranges between 2 years 10 months and 12 years 10 months. Age at first epileptic spasms (ES) ranged from 4 to 11 months, with a mean age of 7 and a median of 7.5 months, respectively; ES were in clusters, bilateral and symmetrical in all cases. Spasms were flexor in nine (34.7%), mixed flexor-extensor in 15 (57.7%), and extensor in three (7.6%). In all patients the EEG showed typical pattern of hypsarrhythmia. CONCLUSION: These patients with idiopathic WS who have an excellent response to initial treatment should be treated for a short period of time with adrenocorticotropic hormone (ACTH) and VGB alone or in combination.

Genotypes and phenotypes of resistance in Ecuadorian Plasmodium falciparum.

BACKGROUND: Malaria continues to be endemic in the coast and Amazon regions of Ecuador. Clarifying current Plasmodium falciparum resistance in the country will support malaria elimination efforts. In this study, Ecuadorian P. falciparum parasites were analysed to determine their drug resistance genotypes and phenotypes. METHODS: Molecular analyses were performed to search for mutations in known resistance markers (Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, k13). Pfmdr1 copy number was determined by qPCR. PFMDR1 transporter activity was characterized in live parasites using live cell imaging in combination with the Fluo-4 transport assay. Chloroquine, quinine, lumefantrine, mefloquine, dihydroartemisinin, and artemether sensitivities were measured by in vitro assays. RESULTS: The majority of samples from this study presented the CVMNT genotype for Pfcrt (72-26), NEDF SDFD mutations in Pfmdr1 and wild type genotypes for Pfdhfr, Pfdhps and k13. The Ecuadorian P. falciparum strain ESM-2013 showed in vitro resistance to chloroquine, but sensitivity to quinine, lumefantrine, mefloquine, dihydroartemisinin and artemether. In addition, transport of the fluorochrome Fluo-4 from the cytosol into the digestive vacuole (DV) of the ESM-2013 strain was minimally detected in the DV. All analysed samples revealed one copy of Pfmdr1. CONCLUSION: This study indicates that Ecuadorian parasites presented the genotype and phenotype for chloroquine resistance and were found to be sensitive to SP, artemether-lumefantrine, quinine, mefloquine, and dihydroartemisinin. The results suggest that the current malaria treatment employed in the country remains effective. This study clarifies the status of anti-malarial resistance in Ecuador and informs the P. falciparum elimination campaigns in the country.

Malaria epidemiology in low-endemicity areas of the northern coast of Ecuador: high prevalence of asymptomatic infections.

BACKGROUND: The recent scale-up in malaria control measures in Latin America has resulted in a significant decrease in the number of reported cases in several countries including Ecuador, where it presented a low malaria incidence in recent years (558 reported cases in 2015) with occasional outbreaks of both Plasmodium falciparum and Plasmodium vivax in the coastal and Amazonian regions. This success in malaria control in recent years has led Ecuador to transition its malaria policy from control to elimination. RESULTS: This study evaluated the general knowledge, attitude and practices (KAP) about malaria, as well as its prevalence in four communities of an endemic area in northwest Ecuador. A total of 258 interviews to assess KAP in the community indicated that most people in the study area have a basic knowledge about the disease but did not use to contribute to its control. Six hundred and forty-eight blood samples were collected and analysed by thick blood smear and real-time PCR. In addition, the distribution of the infections was mapped in the study communities. Although, no parasites were found by microscopy, by PCR the total malaria prevalence was 7.5% (6.9% P. vivax and 0.6% P. falciparum), much higher than expected and comparable to that reported in endemic areas of neighbouring countries with higher malaria transmission. Serology using ELISA and immunofluorescence indicated 27% respondents for P. vivax and 22% respondents for P. falciparum. CONCLUSIONS: Results suggest that despite a great malaria reduction in Ecuador, transition from control to elimination would demand further improvement in malaria diagnostics, including active case detection to identify and treat parasite asymptomatic carriers, as well as community participation in its elimination.

Assessment oxidative stress biomarkers and metal bioaccumulation in macroalgae from coastal areas with mining activities in Chile.

The aim of this study was to evaluate the effect on seaweeds Scytosiphon lomentaria and Ulva rigida of coastal waters of sites with mining activity, using oxidative stress biomarkers and heavy metal determination both in water and in tissue. The greatest bioaccumulation factors in S. lomentaria and U. rigida were founded for iron and arsenic in Quintay. Bioaccumulation factor in S. lomentaria in descending order was Fe> Cu> Zn> Cd> Cr> As> Mo and in U. rigida, in descending order, was Fe> Cu> Cd> Zn> Cr> Mo> As. Both species had higher antioxidant activity levels in areas with high mining activities. The concentration of metals in waters such as copper and arsenic in S. lomentaria, and iron, arsenic, and cadmium in U. rigida were related with oxidative stress biomarkers measured in both species. The use of both species is proposed to monitor the bioavailability and oxidative damage in coastal areas with mining activity. This work will generate a significant knowledge about the impact of mining wastes on macroalgal community in the area of north-central Chile.

Clonal population expansion in an outbreak of Plasmodium falciparum on the northwest coast of Ecuador.

BACKGROUND: Determining the source of malaria outbreaks in Ecuador and identifying remaining transmission foci will help in malaria elimination efforts. In this study, the genetic signatures of Plasmodium falciparum isolates, obtained from an outbreak that occurred in northwest Ecuador from 2012 to 2013, were characterized. METHODS: Molecular investigation of the outbreak was performed using neutral microsatellites, drug resistance markers and pfhrp2 and pfhrp3 genotyping. RESULTS: A majority of parasite isolates (31/32) from this outbreak were of a single clonal type that matched a clonal lineage previously described on the northern coast of Peru and a historical isolate from Ecuador. All but one isolate carried a chloroquine-resistant pfcrt genotype and sulfadoxine- and pyrimethamine-sensitive pfdhps and pfdhfr genotypes. Pfmdr1 mutations were identified in codons 184 and 1042. In addition, most samples (97 %) showed presence of pfhrp2 gene. CONCLUSIONS: This study indicates that parasites from a single clonal lineage largely contributed to this outbreak and this lineage was found to be genetically related to a lineage previously reported in the Peruvian coast and historical Ecuadorian parasites.

Purified cannabidiol as add-on therapy in children with treatment-resistant infantile epileptic spasms syndrome.

OBJECTIVE: The aim of this study was to assess efficacy, safety, and tolerability of highly purified cannabidiol oil (CBD) as add-on therapy for the treatment of a series of patients with infantile epileptic spasms syndrome (IESS) who were resistant to antiseizure medications and ketogenic dietary therapy. MATERIAL AND METHODS: We conducted a retrospective analysis of the medical records of 28 infants with treatment-resistant IESS aged 6 to 21 months who received highly purified CBD between July 2021 and June 2023. Data were collected on neurological examinations, EEG, Video-EEG and polygraphic recordings, imaging studies, laboratory testing, and seizure frequency, type, and duration, and adverse effects. As the primary outcome, a reduction of frequency of epileptic spasms (ES) was assessed. ES freedom was considered after a minimal time of 1 month without ES. RESULTS: Sixteen male and 12 female patients, aged 6-21 months, who received CBD for treatment-resistant IESS were included. The etiology was structural in 10, Down syndrome in seven, genetic in nine, and unknown in two. Initial CBD dose was 2 mg/kg/day, which was uptitrated to a median dose of 25 mg/kg/day (range, 2-50). Prior to CBD initiation, patients had a median of 69 ES in clusters per day (range, 41-75) and of 10 focal seizures per week (range, 7-13). After a mean and median follow-up of 15 and 12.5 months (range, 6-26 months), seven patients were ES free and 12 had a >50 % ES reduction. Five of seven patients (71 %) with Down syndrome and 3/5 (60 %) with cerebral palsy responded well. Adverse effects were mild. EEG improvements correlated with ES reductions. CONCLUSION: In this study evaluating the use of CBD in children with IESS, 19/28 (67.8 %) had a more than 50 % ES reduction with good tolerability.

[Self-limited focal epilepsies of childhood]. / Epilepsias focales autolimitadas de la infancia.

Self-limited Focal Epilepsies of Childhood (SELFEs) are the most prevalent electroclinical syndromes in pediatric age, whose typical evolution, with age-dependent onset and remission, has allowed the ILAE Nosology and Definitions Working Group (2022) to define them as "Selflimited Focal Epilepsies of Childhood", thus establishing alert and exclusion criteria to standardize their diagnosis. These syndromes include: Self-limited Epilepsy with Centrotemporal Spikes (previously Rolandic Epilepsy), Self-limited Epilepsy with Autonomic Seizures (previously Panayiotopoulos Syndrome), Childhood Occipital Visual Epilepsy, (previously Gastaut Syndrome), and Photosensitive Occipital Lobe Epilepsy. Using the term "benign" to refer to them is no longer recommended, as this would ignore the comorbidities some individuals suffer. Also, the term "idiopathic" is now only used to refer to the syndromes classified as Idiopathic Generalized Epilepsies.

Las Epilepsias Focales Autolimitadas de la Infancia (SELFEs - siglas en inglés) son los síndromes electroclínicos más prevalentes en edad pediátrica, cuya evolución típica, con inicio y remisión dependientes de la edad, ha permitido que el Grupo de Trabajo de Nosología y Definiciones de la ILAE (2022) las defina como "Epilepsias focales autolimitadas de la infancia", estableciendo así, criterios de alerta y exclusión para estandarizar su diagnóstico. Dentro de estos síndromes se incluyen: la Epilepsia Autolimitada con Espigas Centrotemporales (previamente Epilepsia Rolándica), Epilepsia Autolimitada con Crisis Autonómicas. (previamente Síndrome de Panayiotopoulos), Epilepsia Visual Occipital Infantil (previamente Síndrome de Gastaut), y Epilepsia Fotosensible del Lóbulo occipital. Ya no se recomienda utilizar el término "benignas" para referirse a ellas, ya que esto haría caso omiso de las comorbilidades que padecen algunos individuos. Asimismo, el término "idiopático" sólo se utiliza ahora para denominar a los síndromes clasificados como Epilepsias Generalizadas Idiopáticas.

CDKL5-associated developmental and epileptic encephalopathy: A long-term, longitudinal electroclinical study of 22 cases.

OBJECTIVE: The study was conducted to analyze the possible diagnostic value of the electroclinical semiology of the epileptic seizures. METHODS: We evaluated the medical records of 17 females and 5 males with CDKL5 deficiency disorder (CDD) considering the long-term evolution, including the polygraphic video-EEG recordings. RESULTS: We recognized three disease phases. We found that the seizure semiology was already recognizable in the first phase of the syndrome. In the short-term evolution, all patients had focal motor and 12/21 hypermotor seizures. Both epileptic spasms and myoclonic seizures were already present in more than half of the cases in the first 2 months after onset. In the second phase, the intermediate period, the polymorphic pattern was maintained, but in eight patients the electroclinical pattern of epileptic encephalopathy with hypsarrhythmia appeared. In the long-term period, the seizure polymorphism continued but myoclonic and epileptic spasms diminished. Tonic seizures appeared in the last 2 phases. Progressively, with the aggravation of seizures and paroxysmal EEG abnormalities impairment of the neurocognitive status was observed. Severe behavioral disturbances were seen in eight and autistic-like features in 14. CONCLUSION: CDD is a true developmental and epileptic encephalopathy with a specific etiology characterized by the early appearance of epileptic seizures that quickly become polymorphic and drug resistant in infants that are most often female and already have neurological impairment. Polygraphic video-EEG recordings are important to recognize ictal events of the association of hypermotor seizures, epileptic spasms in clusters, and massive myoclonic jerks, already present at onset.

Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies.

The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5-366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (ß = 0.74 ± 0.1649, p < 0.001), 56.8% with food (ß = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (ß = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.

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.

Cannabidiol-enriched medical cannabis as add-on therapy in children with treatment-resistant West syndrome: A study of eight patients.

OBJECTIVE: Here we present a series of patients with WS that were refractory to antiseizure medications and the ketogenic diet and who were treated with cannabidiol-enriched cannabis oil (CBD) as add-on therapy analyzing efficacy, safety, and tolerability. MATERIAL AND METHODS: Medical records of eight patients with WS treated with CBD at a ratio of cannabidiol:Δ-9-tetrahydrocannabinol (CBD:THC) of 25:1 seen between May 2020 and March 2021 were retrospectively analyzed. In all patients CBD was started as add-on therapy. RESULTS: Eight patients (six female and two male) who received CBD for treatment-resistant WS were evaluated. Ages ranged from 16 to 22 months. The etiology was unknown in five and structural in three. Initial CBD dose was 2 mg/kg/day which was uptitrated to a median dose of 12 mg/kg/day (range, 2-25). Prior to CBD initiation, patients had a mean of 63 seizures per day (range, 31-79). After a follow-up of between 6 and 13 months, a 75-99% decrease in seizure frequency was observed in two patients, a 50-74% decrease in two, a less than 50% decrease in three, and no changes in seizure frequency were seen in the remaining patient. The index of EEG abnormalities improved between 20 and 80% in seven patients concurrently with the reduction in seizures. Adverse effects were mild and transient. Somnolence was observed in one patient, nausea and vomiting in one, and behavior disturbances and irritability in another patient. CONCLUSION: This study evaluating the use of cannabidiol-enriched cannabis oil in children with WS showed that four (50%) of eight had a more than 50% seizure reduction with good tolerability.

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.

Electroclinical pattern in the transition from West to Lennox-Gastaut syndrome.

AIM: The aim of this study was to analyze electroclinical features of a group of patients with West syndrome (WS) who subsequently developed Lennox-Gastaut syndrome (LGS) during the transition between both syndromes. METHODS: A retrospective and descriptive study was conducted of a series of patients diagnosed with WS who developed LGS seen at Hospital de Pediatría Prof. Dr. JP Garrahan between January 2012 and January 2019. The medical charts of 170 patients with WS were analyzed. In 63 (37 %) of the children WS evolved to LGS. RESULTS: During the transition from WS to LGS four well-defined electroclinical patterns were recognized. The first corresponded to a group of patients with multiple seizure types, including epileptic spasms associated with multifocal paroxysms; the electroclinical pattern in second group showed mainly focal seizures associated with focal discharges in the EEG; the third group showed predominance of epileptic spasms and myoclonic seizures associated with diffuse spike-and-wave and polyspike-and-wave paroxysms; and the remaining group was characterized by a mixed electroclinical pattern including features of the other three groups. All patients had a neuropsychological deficit. Worsening of cognition and behavior was observed during the transition period in 11, 8, and 5 patients of groups 1, 3, and 4, respectively. CONCLUSION: Our study of the transition period from WS to LGS allowed us to recognize four well-defined electroclinical patterns. The early recognition of the different patterns could, in the future, support a more precocious prognostic evaluation.

Rasmussen syndrome: absence seizures may be induced by oxcarbazepine.

A female patient with electroclinical and neuroradiological features compatible with Rasmussen syndrome developed a particular clinical and EEG pattern. As the seizures were refractory to valproate at 750 mg/kg/day, oxcarbazepine (OXC) at 30 mg/kg/day was added. Seizures became more frequent and on neurological examination, no hemiparesis was detected. The interictal EEG showed focal spikes and diffuse paroxysms in the right fronto-temporal regions. Brain MRI revealed right hemiatrophy, mainly at the Sylvian fissure. After initiating OXC daily, brief absence seizures, lasting less than 20 seconds and associated with bilateral and synchronous 2.5-3-Hz spike-and-waves compatible with typical absences, were observed. OXC was discontinued and the typical absences disappeared. Treatment with intravenous gammaglobulin was started. At the last control visit, at nine years of age, no absence seizures were observed either by the parents or on the EEG recording. Our patient who met the diagnostic criteria for Rasmussen syndrome presented with absence seizures that may have been induced by OXC. The absence seizures disappeared after OXC was discontinued.

Epilepsias focales autolimitadas de la infancia / Self-limited Focal Epilepsies of Childhood

Resumen Las Epilepsias Focales Autolimitadas de la Infancia (SELFEs - siglas en inglés) son los síndromes electroclíni cos más prevalentes en edad pediátrica, cuya evolución típica, con inicio y remisión dependientes de la edad, ha permitido que el Grupo de Trabajo de Nosología y Definiciones de la ILAE (2022) las defina como "Epilep sias focales autolimitadas de la infancia", estableciendo así, criterios de alerta y exclusión para estandarizar su diagnóstico. Dentro de estos síndromes se incluyen: la Epilepsia Autolimitada con Espigas Centrotemporales (previamente Epilepsia Rolándica), Epilepsia Autolimi tada con Crisis Autonómicas. (previamente Síndrome de Panayiotopoulos), Epilepsia Visual Occipital Infantil (previamente Síndrome de Gastaut), y Epilepsia Fotosen sible del Lóbulo occipital. Ya no se recomienda utilizar el término "benignas" para referirse a ellas, ya que esto haría caso omiso de las comorbilidades que padecen algunos individuos. Asimismo, el término "idiopático" sólo se utiliza ahora para denominar a los síndromes clasificados como Epilepsias Generalizadas Idiopáticas.

Abstract Self-limited Focal Epilepsies of Childhood (SELFEs) are the most prevalent electroclinical syndromes in pe diatric age, whose typical evolution, with age-dependent onset and remission, has allowed the ILAE Nosology and Definitions Working Group (2022) to define them as "Self-limited Focal Epilepsies of Childhood", thus establishing alert and exclusion criteria to standardize their diagno sis. These syndromes include: Self-limited Epilepsy with Centrotemporal Spikes (previously Rolandic Epilepsy), Self-limited Epilepsy with Autonomic Seizures (previ ously Panayiotopoulos Syndrome), Childhood Occipital Visual Epilepsy, (previously Gastaut Syndrome), and Photosensitive Occipital Lobe Epilepsy. Using the term "benign" to refer to them is no longer recommended, as this would ignore the comorbidities some individuals suffer. Also, the term "idiopathic" is now only used to refer to the syndromes classified as Idiopathic General ized Epilepsies.

Benign rolandic epilepsy and generalized paroxysms: A study of 13 patients.

PURPOSE: To present a retrospective study of 13 children with benign epilepsy with centrotemporal spikes (BECTS), also known as benign rolandic epilepsy (BRE), associated with generalized spikes and waves as the only EEG manifestation at onset. METHOD: Charts of children with typical clinical criteria of BRE electroclinically followed-up between February 2000 and February 2015 were reviewed. RESULTS: Among 309 patients who met the electroclinical criteria of BRE, we identified 13 children who presented with the typical clinical manifestations but who, on the EEG, only had generalized paroxysms at onset that continued along the course of the syndrome. Generalized spike-and-wave discharges were observed in all patients when awake and during sleep (100%). During the evolution no particular electroclinical pattern was observed. The patients responded well to antiepileptic drugs, such as valproic acid and levetiracetam. Outcome was good in all patients. CONCLUSIONS: We found evidence that patients with BRE may have generalized EEG discharges at onset as the sole manifestation lasting throughout the course of the syndrome. In some, focal paroxysms developed later. The course was benign. In our group of patients, clinical features and evolution were similar to those of typical cases of BRE. Response to valproic acid and levetiracetam was found to be particularly good.