[Non-surgical treatment of refractory epilepsy in children]. / Tratamiento no quirúrgico de la epilepsia refractaria en niños.

Approximately 30% of people with epilepsy will be refractory. This manuscript reviews current evidencebased non-surgical treatment modalities for pediatric refractory epilepsy, including pharmacological and dietary strategies.

Aproximadamente el 30% de las personas con epilepsia será refractaria. Este manuscrito revisa las modalidades actuales y basadas en la evidencia de tratamientos no quirúrgicos para la epilepsia refractaria pediátrica, incluyendo estrategias farmacológicas y dietéticas.

An update on the novel methods for the discovery of antiseizure and antiepileptogenic medications: where are we in 2024?

INTRODUCTION: Despite the availability of around 30 antiseizure medications, 1/3 of patients with epilepsy fail to become seizure-free upon pharmacological treatment. Available medications provide adequate symptomatic control in two-thirds of patients, but disease-modifying drugs are still scarce. Recently, though, new paradigms have been explored. AREAS COVERED: Three areas are reviewed in which a high degree of innovation in the search for novel antiseizure and antiepileptogenic medications has been implemented: development of novel screening approaches, search for novel therapeutic targets, and adoption of new drug discovery paradigms aligned with a systems pharmacology perspective. EXPERT OPINION: In the past, worldwide leaders in epilepsy have reiteratively stated that the lack of progress in the field may be explained by the recurrent use of the same molecular targets and screening procedures to identify novel medications. This landscape has changed recently, as reflected by the new Epilepsy Therapy Screening Program and the introduction of many in vitro and in vivo models that could possibly improve our chances of identifying first-in-class medications that may control drug-resistant epilepsy or modify the course of disease. Other milestones include the study of new molecular targets for disease-modifying drugs and exploration of a systems pharmacology perspective to design new drugs.

[Neuropsychological profile of Mexican paediatric patients with pharmacoresistant focal epilepsy]. / Perfil neuropsicológico de pacientes pediátricos mexicanos con epilepsia focal farmacorresistente.

INTRODUCTION: At least 20% of paediatric patients with epilepsy present resistance to multiple anti-crisis drugs in trials, which has a negative impact on their neuropsychological state, quality of life and prognosis; it is therefore necessary to document their neuropsychological profile in order to improve the clinical approach to them. AIMS: To describe the neuropsychological profile (cognitive, academic, behavioural, emotional, adaptive, sleep disturbances and quality of life) of paediatric patients with drug-resistant focal epilepsy in the frontal, temporal and occipital lobes, and to compare performance between patients with frontal and temporal foci, and to assess the link between the duration of the condition, the frequency of seizures and the amount of anti-crisis drugs and the neuropsychological profile. PATIENTS AND METHODS: The neuropsychological profile of 19 paediatric patients with a diagnosis of pharmacoresistant epilepsy with a mean age of 10.89 years was evaluated. RESULTS: 57.9% of the 19 patients were men. 63.2% presented frontal focus; 26.3% presented temporal focus; and 10.5% presented occipital focus. Deficiencies in attention, comprehension, verbal memory, working memory and processing speed, in addition to adaptive difficulties were observed. When the patients with frontal and temporal focus were compared, the former were found to present greater deficits in planning, while the patients with temporal focus presented more severe symptoms of anxiety. Patients with a longer disease duration were found to present greater impairment to their intelligence quotient and adaptive behavioural skills. CONCLUSIONS: Pharmacoresistant epilepsy in paediatric patients affects intelligence quotient and adaptive skills, as well as attention, memory and executive functions, and neuropsychological intervention programmes must therefore be implemented to improve these patients' quality of life.

TITLE: Perfil neuropsicológico de pacientes pediátricos mexicanos con epilepsia focal farmacorresistente.Introducción. Al menos el 20% de los pacientes pediátricos con epilepsia muestra resistencia a los ensayos de múltiples fármacos anticrisis, que impactan negativamente en su estado neuropsicológico, calidad de vida y pronóstico; por tal motivo, es necesario documentar ampliamente su perfil neuropsicológico para mejorar su abordaje clínico. Objetivos. Describir el perfil neuropsicológico (cognitivo, académico, conductual, emocional, adaptativo, alteraciones del sueño y calidad de vida) de pacientes pediátricos con epilepsia focal farmacorresistente de los lóbulos frontal, temporal y occipital, así como comparar el desempeño entre los pacientes con foco frontal y temporal, y evaluar la asociación entre la duración del padecimiento, la frecuencia de las crisis y la cantidad de fármacos anticrisis con el perfil neuropsicológico. Pacientes y métodos. Se evaluó el perfil neuropsicológico de 19 pacientes pediátricos con diagnóstico de epilepsia farmacorresistente, con una edad promedio de 10,89 años. Resultados. De los 19 pacientes, el 57,9% fueron hombres. El 63,2% presentó foco frontal; el 26,3%, temporal; y el 10,5%, occipital. Se encontraron deficiencias en atención, comprensión, memoria verbal, memoria de trabajo y velocidad de procesamiento, además de dificultades adaptativas. Al comparar a los pacientes con foco frontal y temporal, se encontró que los primeros presentaron mayores deficiencias en planificación, mientras que los pacientes con foco temporal presentaron mayores síntomas de ansiedad. Con respecto a la duración de la enfermedad, se encontró que los pacientes con mayor duración del padecimiento presentaron mayor afectación en el cociente intelectual y en las habilidades en la conducta adaptativa. Conclusiones. La epilepsia farmacorresistente en pacientes pediátricos afecta el cociente intelectual y las habilidades adaptativas, así como a la atención, la memoria y las funciones ejecutivas, por lo que es necesaria la implementación de programas de intervención neuropsicológica para mejorar la calidad de vida de estos pacientes.

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy-A Preliminary Study in a Brazilian Cohort Sample.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series.

OBJECTIVE: Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications. METHODS: This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®. RESULTS: All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported. SIGNIFICANCE: This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.

Memory and language risk assessment with Wada test in patients candidates for epilepsy surgery. / Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.

AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.

TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.

Surgical Anatomy and Technique of Peri-Insular Hemispherotomy in Pediatric Epilepsy.

BACKGROUND AND OBJECTIVES: Hemispherotomy is a highly complex procedure that demands a steep learning curve. An incomplete brain disconnection often results in failure of seizure control. The purpose of this article was to present a step-by-step guide to the surgical anatomy of this procedure. It is composed of a 7-stage approach, enhancing access to and improving visualization of deep structures. METHODS: A retrospective analysis of 39 pediatric patients with refractory epilepsy who underwent this technique was conducted. Engel scores were assessed 1 year postsurgery. Cadaveric dissections were performed to illustrate the procedure. RESULTS: Between 2015 and 2022, 39 patients were surgically treated using the peri-insular technique. The technique involved 7 stages: patient positioning, operative approach, opercular resection, transventricular callosotomy, fronto-orbital disconnection, anterior temporal disconnection, and posterior temporal disconnection. Most of the patients (92.30%) were seizure-free (Engel class I) at 1 year postoperative, 5.13% were nearly seizure-free (Engel II), and 2.56% showed significant improvement (Engel III). Complications occurred in 8% of cases, including 1 infection, 2 cases of aseptic meningitis, and 1 non-shunt-requiring acute hydrocephalus. CONCLUSION: The peri-insular hemispherotomy technique offers excellent seizure control with a low complication rate. Our visual documentation of surgical anatomy, complemented by detailed descriptions of surgical nuances, significantly contributes to a comprehensive understanding of this technique.

Replacement of traditional vagus nerve stimulation with cardiac-based device and seizure reduction: A systematic review and meta-analysis.

INTRODUCTION: For patients with drug-resistant epilepsy (DRE) who are not suitable for surgical resection, neuromodulation with vagus nerve stimulation (VNS) is an established approach. However, there is limited evidence of seizure reduction when replacing traditional VNS (tVNS) device with a cardiac-based one (cbVNS). This meta-analysis compares the seizure reduction achieved by replacing tVNS with cbVNS in a population with DRE. METHODS: We systematically searched PubMed, Embase, and Cochrane Central following PRISMA guidelines. The main outcomes were number of patients experiencing a ≥ 50 % and ≥80 % reduction in seizures, as defined by the McHugh scale. Additionally, we assessed the number of patients achieving freedom from seizures. RESULTS: We included 178 patients with DRE from 7 studies who were initially treated with tVNS and subsequently had it replaced by cbVNS. The follow-up for cbVNS ranged from 6 to 37.5 months. There was a statistically significant reduction in seizure frequency with the replacement of tVNS by cbVNS, using a ≥ 50 % (OR 1.79; 95 % CI 1.07 to 2.97; I²=0 %; p = 0.03) and a ≥ 80 % (OR 2.06; 95 % CI 1.17 to 3.62; I²=0 %; p = 0.01) reduction threshold. Nineteen (13 %) participants achieved freedom from seizures after switching to cbVNS. There was no difference in the rate of freedom from seizures between groups (OR 1.85; 95 % CI 0.81 to 4.21; I²=0 %; p = 0.14). CONCLUSION: In patients with DRE undergoing battery replacement, cbVNS might be associated with seizure reduction (≥50 % and ≥80 % threshold) after switching from tVNS. Randomised controlled trials are necessary to validate these findings.

ATP1A2-related epileptic encephalopathy and movement disorder: Clinical features of three novel patients.

OBJECTIVE: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. METHODS: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions. RESULTS: Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects. SIGNIFICANCE: This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.

Assessing short-term and long-term security and efficacy of anterior nucleus of the thalamus deep brain stimulation for treating drug-resistant epilepsy: A systematic review and single-arm meta-analysis.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is a persistent debate regarding the short-term and long-term efficacy and safety of ANT-DBS. Thus we conducted a systematic review and meta-analysis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT-DBS. Short-term analysis was considered for studies with a mean follow-up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure-related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short-term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%-79%) of responders and 33% (95% CI 21%-46%) of nonresponders. In addition, 4% (95% CI 0%-9%) of the patients presented increased seizure frequency. In the long-term analysis, we observed 72% (95% CI 66%-78%) responders and 27% (95% CI 21%-34%) nonresponders. Moreover, there was a 2% (95% CI 0%-5%) increase in seizure frequency. No procedure-related mortality was reported at any follow-up. ANT-DBS effectively treats refractory epilepsy, with lasting short-term and long-term benefits. It remains safe and efficient despite complications, showing no procedure-linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.

Dancing epilepsy: A stereo encephalography case report.

Ictal semiology is essential to identify the epileptogenic zone (EZ), especially in drug-resistant focal epilepsy (DRE), as its accurate identification determines the surgical prognosis. Dancing is highly unusual ictal semiology, and its underlying neural networks remain somehow unclear since both temporal and frontal lobe (FL) have been implicated in its generation. We present a 21-year-old male with DRE characterized by dancing seizures. Homemade videos were obtained. Through a non-invasive pre-surgical evaluation, the epileptogenic zone was localized within a gross lesion in the left FL. Using stereo electroencephalography (SEEG), we successfully identified the ictal-onset zone in the mesial middle, inferior, and orbito-frontal cortex, with rapid propagation of ictal activity extending backward and laterally to the precentral regions. Subsequently, a left frontal middle and inferior gyrectomy was performed, resulting in seizure freedom for the patient. Pathology results revealed a mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). Atypical seizure semiology, such as dancing, provides an interesting starting point for the analysis of the areas involved in the EZ. Further intracranial recordings are required to fully comprehend the underlying networks and interactions of cerebral areas during dancing seizures.

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.

Síndrome de apnea del sueño en población colombiana con epilepsia empleando la escala de apnea del sueño del cuestionario de trastornos del sueño / Sleep apnea syndrome in a Colombian population with epilepsy using the Sleep Apnea Scale of the Sleep Disorders Questionnaire

Introducción: La epilepsia es un desorden caracterizado por la predisposición a generar crisis epilépticas, mientras que el síndrome de apnea del sueño (SAOS) ha sido reconocido como un desorden crónico de colapso intermitente de la vía aérea que genera hipoxia recurrente. En este trabajo se aplicó la escala de trastornos del sueño (Sleep Apnea Scale of the Sleep Disorders Questionnaire SA-SDQ), previamente validada en inglés para pacientes con epilepsia, a fin de determinar su capacidad para detectar apnea de sueño en nuestra población. Materiales y métodos: En una primera etapa se realizó la adaptación transcultural de la escala SA-SDQ en castellano, provista por los autores, al español colombiano. Luego se recopiló la información de los pacientes en quienes se realizó polisomnografía entre mayo y agosto del 2022 y se determinó el valor de corte para diagnosticar SAOS con la escala SA-SDQ. Resultados: Cuarenta pacientes pudieron realizarse la polisomnografía, de los cuales 30 (75 %) tuvieron índices de apnea-hipopnea superiores a 5, lo que indica SAOS. El área bajo la curva fue 0,790 y la puntuación SA-SDQ de 21 proporcionó una sensibilidad del 73,3 % (IC 53,83-87,02 %) y una especificidad del 80 % (IC 44,2-96,5 %). La consistencia interna fue aceptable (α = 0,713). Conclusiones: La escala SA-SDQ es un instrumento útil para tamizar SAOS en la población colombiana que padece epilepsia. Nuestros resultados indican que los puntos de corte sugeridos anteriormente (2936 para hombres y 26-32 para mujeres) pueden ser demasiado altos para nuestra población. Sugerimos un punto de corte de 21 para ambos.

Introduction: Epilepsy is a disorder characterized by a predisposition to have epileptic seizures, while sleep apnea syndrome (OSAS) has been recognized as a chronic disorder of intermittent collapse of the airway that generates recurrent hypoxia. In this work, the sleep disorders scale (SA-SDQ) previously validated in English for patients with epilepsy was applied to determine its ability to detect sleep apnea in our population. Materials and methods: In the first stage, the cross-cultural adaptation of the SA-SDQ scale in Spanish provided by the authors was carried out into Colombian Spanish. then the information of the patients in whom polysomnography was performed between May and August 2022 was collected and the cut-off value was determined to diagnose OSAS with the SA-SDQ scale. Results: 40 patients were able to undergo polysomnography, of which 30 (75 %) had apnea-hypopnea indices greater than five, indicating OSAS. The area under the curve was 0.790 and the SA-SDQ score of 21 provided a sensitivity of 73.3 % (CI 53.83-87.02 %) and a specificity of 80 % (CI 44.2-96, 5 %). The internal consistency was acceptable (α = 0.713). Conclusions: The SA-SDQ scale is a useful instrument for screening OSAS in the Colombian population suffering from epilepsy. Our results indicate that the previously suggested cut-off points (29-36 for men and 26-32 for women) may be too high in our population. We suggest a cutoff of 21 for both.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Resting-state fMRI in patients with refractory epilepsy with and without drop attacks: exploring the connectivity of sensorimotor cortex.

OBJECTIVE: Patients with multifocal or generalized epilepsies manifesting with drop attacks have severe refractory seizures and significant cognitive and behavioural abnormalities. It is unclear to what extent these features relate to network abnormalities and how networks in sensorimotor cortex differ from those in patients with refractory focal epilepsies. Thus, in this study we sought to provide preliminary data on connectivity of sensorimotor cortex in patients with epileptic drop attacks, in comparison to patients with focal refractory epilepsies. METHODS: Resting-state fMRI (rs-fMRI) data was available for 5 patients with epileptic drop attacks and 15 with refractory focal epilepsies undergoing presurgical evaluation. Functional connectivity was analyzed with a seed-based protocol, with primary seeds placed at the precentral gyrus, the postcentral gyrus and the premotor cortex. For each seed, the subjects' timeseries were extracted and transformed to Z scores. Between-group analysis was then performed using the 3dttest+ + AFNI program. RESULTS: Two clusters of reduced connectivity in the group with drop attacks (DA group) in relation to those with focal epilepsies were found in the between-group analysis: the precentral seed showed reduced connectivity in the surrounding motor area, and the postcentral seed, reduced connectivity with the ipsilateral posterior cingulate gyrus. In the intra-group analyses, sensorimotor and premotor networks were abnormal in the DA group, whereas patients with focal epilepsies had the usual connectivity maps with each seed. CONCLUSION: This pilot study shows differences in the cerebral connectivity in the sensorimotor cortex of patients with generalized epilepsies and drop attacks which should be further explored to better understand the biological bases of the seizure generation and cognitive changes in these people.

WNT pathway in focal cortical dysplasia compared to perilesional nonlesional tissue in refractory epilepsies.

BACKGROUND: Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/ß-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/ß-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II. METHODS: Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway. RESULTS: Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material. CONCLUSION: Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence.

Modified Atkins diet for drug-resistant epilepsy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE). METHODS: In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively. RESULTS: Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM. SIGNIFICANCE: This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.

Riesgo neuropsicológico en epilepsia del lóbulo temporal / Neuropsychological risk in temporal lobe epilepsy

Introducción: Los síntomas neuropsicológicos son una preocupación importante para los pacientes con epilepsia y pueden llegar a ser muy influyentes en la percepción de calidad de vida. En el caso de la epilepsia del lóbulo temporal, existen muchas variables que influyen en el desempeño cognitivo de los pacientes, entre las más importantes se encuentran la etiología, la edad de inicio, la duración de la enfermedad y la frecuencia de crisis; sin embargo, una de las variables más importantes es la lateralidad de la epilepsia. Está claramente demostrado que los síntomas cognitivos de la epilepsia del lóbulo temporal varían en función del hemisferio cerebral afectado. Contenido: La epilepsia del lóbulo temporal es una de las principales epilepsias focales que es susceptible de manejo quirúrgico, y, en este sentido, el tipo de procedimiento también tiene una gran importancia en el desenlace cognitivo de estos pacientes. En este artículo, realizamos una revisión narrativa de la literatura, con el objetivo de describir el riesgo neuropsicológico relacionado no solamente con la epilepsia del lóbulo temporal per se, sino también con las intervenciones quirúrgicas que se realizan en pacientes refractarios a la medicación. Conclusiones: Es importante conocer los conceptos sobre las implicaciones del impacto cognitivo en los pacientes con epilepsia del lóbulo temporal antes de tomar decisiones quirúrgicas en pacientes refractarios, así como entender que el tipo de cirugía también influye en su desempeño cognitivo. Se debe buscar un equilibrio entre la libertad de crisis y las posibles secuelas neuropsicológicas posquirúrgicas.

Introduction: Neuropsychological symptoms are a major concern for patients with epilepsy and can highly influence the perception of quality of life. In the case of temporal lobe epilepsy, there are many variables that impact the cognitive performance of these people, among the most important are the etiology, the age of onset, the duration of the disease and the frequency of seizures, however, one of the most important variables is the lateralization of the seizure. It has been demonstrated that the cognitive symptoms of temporal lobe epilepsy vary depending on the affected cerebral hemisphere. Contents of the review: Temporal lobe epilepsy is one of the main focal epilepsies that is susceptible to surgical management, and the type of surgery also has great importance in the cognitive outcomes of these patients. In this article, we carry out a narrative review of the literature in order to describe the neuropsychological risk related not only to temporal lobe epilepsy per se, but also to surgical interventions performed in drug-resistant patients. Conclusions: It is important to know the concepts about the implications of cognitive impact in patients with temporal lobe epilepsy before making surgical decisions in refractory patients and to understand that the type of surgery also influences the cognitive performance of these patients. A balance must be sought between the freedom of seizures and the possible postoperative neuropsychological sequelae.

ESTUDIO DEL IMPACTO DE LA DIETA CETOGÉNICA EN LA CALIDAD DE VIDA DE PACIENTES PEDIÁTRICOS CON EPILEPSIA Y SUS FAMILIAS / STUDY OF THE IMPACT OF THE KETOGENIC DIET ON THE QUALITY OF LIFE OF PEDIATRIC PATIENTS WITH EPILEPSY AND THEIR FAMILIES

Introducción: El tratamiento mediante los distintos tipos de dietas cetogénicas ha demostrado en diversos trabajos efectividad en la reducción de las crisis convulsivas, de manera total o parcial. Sin embargo, se reportan tasas de deserción en la realización a largo plazo. Objetivo: Este trabajo tiene como objetivo identificar beneficios y dificultades que perciben las familias de niños en el tratamiento de Epilepsia resistente a fármacos que lleven a cabo la dieta cetogénica y que podrían influir en la adherencia o deserción. Materiales y métodos: Se realizó un estudio descriptivo transversal retrospectivo, en el Servicio de Neurología Infantil del HIBA, sección Dieta Cetogénica. Para el estudio, se realizó una encuesta para recabar características sociodemográficas de la población bajo estudio y también sobre dificultades y beneficios hallados en la terapia cetogénica. Se analizaron frecuencias, medias y chi cuadrado para establecer diferencias significativas con intervalo de confianza de 95%. Resultados: La muestra estuvo compuesta por 51 participantes, de 0 a 18 años. Al indagar sobre si percibían mejoras tras realizar terapia cetogénica, el 81% respondió que sí, el 11% no percibió mejoras y el 8% no sabía. Acerca de la presencia de dificultades para llevar a cabo el tratamiento, el 71% respondió que se encontraba con dificultades, el 23% no registró dificultades y el 6% manifestó que a veces. Al relacionar la presencia de dificultades con el nivel socioeconómico, se observaron diferencias significativas entre los grupos, siendo de mayor incidencia en familias de ingresos más bajos. Respecto de la variable edad, no se encontraron diferencias significativas en relación con las dificultades percibidas. Conclusiones: Es importante continuar trabajando con las familias en las dificultades que presentan para evitar deserción del tratamiento. Asimismo, resulta indispensable destacar el alto porcentaje de mejorías que perciben sus padres para lograr mayor adherencia

Introduction: Treatment using the different types of ketogenic diets has been shown in various studies to be effective in reducing seizures, which can be total or partial. However, dropout rates are reported in the long-term completion of it. Objetive: The objective of this work is to identify the benefits and difficulties perceived by the families of children undergoing treatment for drug-resistant epilepsy who follow the ketogenic diet and that could influence adherence or desertion. Materials and methods: A retrospective cross-sectional descriptive study was carried out at the HIBA Child Neurology Service, Ketogenic Diet section. For the study, a survey was carried out to collect sociodemographic characteristics of the population under study and also about difficulties and benefits found in ketogenic therapy. Frequencies, measures and chi square were analyzed to establish significant differences with a 95% confidence interval. Results: The sample consisted of 51 participants, from 0 to 18 years old. When asked if they perceived improvements after performing ketogenic therapy, 81% answered yes, 11% did not perceive improvements and 8% did not know. About the presence of difficulties to carry out the treatment, 71% answered that they had difficulties, 23% did not have them and 6% sometimes.When relating the presence of difficulties with the socioeconomic level, significant differences were observed between the groups, with a higher incidence in lower-income families. Regarding the age variable, no significant differences were found in relation to the perceived difficulties. Conclusion: It is important to continue working with families on the difficulties they present to avoid dropping out of treatment. Likewise, it is essential to highlight the high percentage of improvements that their parents perceive to achieve greater adherence

Cenobamate (YKP3089) and Drug-Resistant Epilepsy: A Review of the Literature.

Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug Administration approved Xcopri®, marketed by SK Life Science Inc., (Paramus, NJ, USA) for adult focal seizures. The European Medicines Agency approved Ontozry® by Arvelle Therapeutics Netherlands B.V.(Amsterdam, The Neatherlands) in March 2021. Cenobamate is a medication that could potentially change the perspectives regarding the management and prognosis of refractory epilepsy. In this way, this study aims to review the literature on CNB's pharmacological properties, pharmacokinetics, efficacy, and safety. CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure freedom. This finding is remarkable in the antiseizure medication literature. The mechanism of action of CNB is still poorly understood, but it is associated with transient and persistent sodium currents and GABAergic neurotransmission. In animal studies, CNB showed sustained efficacy and potency in the 6 Hz test regardless of the stimulus intensity. CNB was revealed to be the most cost-effective drug among different third-generation antiseizure medications. Also, CNB could have neuroprotective effects. However, there are still concerns regarding its potential for abuse and suicidality risk, which future studies should clearly assess, after which protocols should be changed. The major drawback of CNB therapy is the slow and complex titration and maintenance phases preventing the wide use of this new agent in clinical practice.