Transition in epilepsy - A pilot study with patients in and outside of academic centers.

RATIONALE: Epilepsy is a complex condition and seizures are only one part of this disease. The move from pediatric to adult healthcare system proves difficult for many adolescents with epilepsy and their families. The challenges increase when patients have epilepsies associated with intellectual and/or developmental disabilities, autism spectrum disorder, and motor disorders. Knowledge and system gaps may exist between the two systems, adding to the challenges. The main goal of this study is to understand the perception of patients with epilepsy and their families who were preparing to move from pediatric to adult healthcare system or had already moved. METHODS: A survey was distributed to patients/caregivers of patients with epilepsy through patient support groups in North America and in-person through the 2019 Epilepsy Awareness Day at Disneyland. Patients were required to be 12 years or older at the time of the survey and were divided into two groups: those between 12 and 17 years and those 18 years or older. Caregivers answered on behalf of patients who were unable to respond (e.g., intellectual disability). Major components of the survey included demographics, epilepsy details, quality and access to care received in pediatric and adult years, and questions regarding transition and readiness. RESULTS: Responses were received from 58 patients/caregivers of patients with epilepsy from Canada and the United States. In group A (patients between 12 and 17 years), none of the 17-year-old patients were spoken to about transition. Patients (caregivers) with epilepsy and intellectual and/or developmental disabilities (IDD) had less time to discuss important things during the transition/transfer phase than patients with normal intelligence. Finally, there was a statistically significant difference observed in access to specialty care reported in the adult years, compared to the years in the pediatric system. In the group B (patients 18 years and older) a) 35 % still visit their family doctor for epilepsy related treatment despite the majority being on 2 or more antiseizure medications (ASMs); b) 27 % of patients in this group were still being followed by their pediatric neurologist; c) one patient received care only through visits to the emergency department; d) only 4 % felt that they received clear instructions during transfer of care such as knowing the name of the adult healthcare practitioner and/or the name of the care institution they were being transferred to. CONCLUSIONS: This study highlights the lack of appropriate transition to adult healthcare system (AHCS) amongst an unselected group of patients with epilepsy in Canada and United States. An overwhelming majority of patients followed in the community and in academy centers were simply "transferred" to an adult health practitioner, or they remained under the care of pediatricians. Finally, most patients lack access to significant social and medical support after moving to the AHCS.

Neurologists' knowledge of and attitudes toward physical exercise for people with epilepsy in Latin America.

INTRODUCTION: Despite the favorable effects of exercise in people with epilepsy (PWE), the lower participation in physical/sports activities may be partly due to inadequate knowledge and attitudes of health professional about their benefits. In this regard, in 2016, the International League Against Epilepsy (ILAE) through its Task Force on Sports and Epilepsy published a consensus paper that provided general guidance concerning participation in exercise/sport activities for PWE. We investigated views and attitudes toward physical exercise practice among neurologists in Latin America. METHODS: A 22-item cross-sectional online questionnaire-based study among neurologists included the following: (1) profile of participating neurologists, (2) doctors' attitudes and perceptions about physical/sport activities for PWE, and (3) neurologist experience concerning patient's report about their involvement in physical/sport activities. RESULTS: In total, 215 of 519 neurologists from 16 different countries returned the questionnaire. Although about one-third of neurologists had no information about the effect of exercise on epilepsy, and 60% of them did not know the published recommendations of the ILAE Task Force on Sports and Epilepsy, the majority (92.5%) advised the practice of exercise, were aware of sport activities for their patients and agreed that exercise can reduce comorbidities associated with epilepsy (X2 = 249.34; p < 0.001). Most of the neurologists did not believe that exercise is a seizure-inducing factor, but more than half would restrict their patients with uncontrolled seizures for exercise practice (X2 = 250.77; p < 0.001). Most barriers considered by PWE in the past, currently are not viewed by neurologists and their patients (X2 = 249.34; p < 0.001). CONCLUSION: While this study reveals that neurologists have some knowledge gaps in attitudes toward physical exercise for PWE, encouraging attitudes were observed by neurologists. Considering that physicians can impact on patient confidence and decision, a better communication between neurologists and their patients concerning the benefits of exercise can increase PWE participation in physical/sports activities. To improve this scenario, more efforts should be made to increase the neurologists' knowledge and perceptions on this issue.

Geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples, and its possible relationship with the prevalence of enamel fluorosis in children in four municipalities of the department of Huila (Colombia).

Fluoride is an element that affects teeth and bone formation in animals and humans. Though the use of systemic fluoride is an evidence-based caries preventive measure, excessive ingestion can impair tooth development, mainly the mineralization of tooth enamel, leading to a condition known as enamel fluorosis. In this study, we investigated the geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples in four endemic enamel fluorosis sentinel municipalities of the department of Huila, Colombia (Pitalito, Altamira, El Agrado and Rivera), and its possible relationship with the prevalence of enamel fluorosis in children. The concentration of fluoride in drinking water, table salt, active sediment, rock, and soil was evaluated by means of an ion selective electrode and the geochemical analyses were performed using X-ray fluorescence. Geochemical analysis revealed fluoride concentrations under 15 mg/kg in active sediment, rock and soil samples, not indicative of a significant delivery to the watersheds studied. The concentration of fluoride in table salt was found to be under the inferior limit (less than 180 µg/g) established by the Colombian regulations. Likewise, exposure doses for fluoride water intake did not exceed the recommended total dose for all ages from 6 months. Although the evidence does not point out at rocks, soils, fluoride-bearing minerals, fluoridated salt and water, the hypothesis of these elements as responsible of the current prevalence of enamel fluorosis cannot be discarded since, aqueducts might have undergone significant changes overtime.

Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics.

Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2 years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.

Models for transition clinics.

Transition is a purposeful, planned process that addresses the medical, psychosocial, educational, and vocational needs of adolescents and young adults with chronic medical conditions, as they advance from a pediatric and family-centered to an adult, individual focused health care provider. This article describes some of the models for transition clinics or services for epilepsy in five countries (Canada, France, Colombia, Germany, and the United Kingdom). These models include joint adult and pediatric clinics, algorithm-driven service, and a check list system in the context of pediatric care. Evaluation of these models is limited, and it is not possible to choose an optimal program. The attitude and motivation of health care providers may be the most important elements.

The international league against epilepsy primary healthcare educational curriculum: Assessment of educational needs.

OBJECTIVE: To assess the need for an epilepsy educational curriculum for primary healthcare providers formulated by the International League Against Epilepsy (ILAE) and the importance attributed to its competencies by epilepsy specialists and primary care providers and across country-income settings. METHODS: The ILAE primary care epilepsy curriculum was translated to five languages. A structured questionnaire assessing the importance of its 26 curricular competencies was posted online and publicized widely to an international community. Respondents included epilepsy specialists, primary care providers, and others from three World Bank country-income categories. Responses from different groups were compared with univariate and ordinal logistic regression analyses. RESULTS: Of 785 respondents, 60% noted that a primary care epilepsy curriculum did not exist or they were unaware of one in their country. Median ranks of importance for all competencies were high (very important to extremely important) in the entire sample and across different groups. Fewer primary care providers than specialists rated the following competencies as extremely important: definition of epilepsy (p = .03), recognition of seizure mimics (p = .02), interpretation of test results for epilepsy care (p = .001), identification of drug-resistant epilepsy (0.005) and management of psychiatric comorbidities (0.05). Likewise, fewer respondents from LMICs in comparison to UMICs rated 15 competencies as extremely important. SIGNIFICANCE: The survey underscores the unmet need for an epilepsy curriculum in primary care and the relevance of its competencies across different vocational and socioeconomic settings. Differences across vocational and country income groups indicate that educational packages should be developed and adapted to needs in different settings.

Segregation of a haplotype encompassing FEB1 with genetic epilepsy with febrile seizures plus in a Colombian family.

Febrile seizures and epilepsy are believed to be linked and some forms of epilepsy are associated with a history of febrile seizures (FS). Linkage analysis to seven known loci for FS and/or genetic epilepsy with febrile seizures plus (GEFS plus) was performed in a small Colombian family. Short tandem repeat (STR) markers were genotyped and two-point linkage analysis and haplotype reconstruction were conducted. A maximum LOD score of 0.75 at marker D8S533 for FEB1 at a recombination fraction (θ) of 0 and a segregating haplotype were identified. FEB1 was the first locus to be associated with FS and this is the second report to describe this association. Two genes in this region, CRH and DEPDC2, are good putative candidate genes that may play a role in FS and/or GEFS plus.

An epilepsy curriculum for primary health care providers: a report from the Education Council of the International League Against Epilepsy

Objective: Primary health care providers are directly responsible for the care of people with epilepsy. However, their education about epilepsy might be inadequate or lacking. Our objective was to develop an evidence-based and consensus-driven educational curriculum for the management of epilepsy within the primary healthcare setting. Methods: The International League Against Epilepsy (ILAE) Education Council commissioned a task force of international experts, who met virtually at monthly intervals in 2020/2021 to develop the curriculum. The task force adopted and added to five domains from the ILAE Epileptology Curriculum after discussions on context, structure and wording of associated competencies and learning objectives. The consensus-approved curriculum was disseminated to the ILAE leadership and constituency in six different languages. An online survey was used to collate structured feedback which further refined the curriculum. Results: Feedback was obtained from 785 voluntary respondents who were inclusive of epilepsy specialists and primary healthcare providers. Nearly two thirds of the respondents approved the use of the curriculum to advance the competency of primary health care providers in epilepsy. The final educational curriculum comprised six domains, 26 competencies and 85 learning objectives. The six domains were: (1) ability to diagnose epilepsy and its broad subtypes; (2) ability to provide counselling to people with epilepsy over a range of issues; (3) ability to introduce treatment and follow-up to people with epilepsy; (4) competency to appropriately refer people to higher centres of care; (5) ability to manage epilepsy emergencies including status epilepticus; and (6) ability to recognize and provide basic care for psychiatric and somatic comorbidities. Conclusions: The curriculum represents an advance in providing inclusive care for epilepsy within the primary health care setting and ideally should be used to facilitate future primary health care epilepsy education packages.

Epilepsy for primary health care: a cost-effective Latin American E-learning initiative.

A lack of neurologists in Latin America forces primary health care providers to manage epilepsy. With the main goal of improving diagnostic and therapeutic management of patients with epilepsy through training of physicians in the primary health care level, the International League Against Epilepsy Education Commission (2013-2017) created a low-cost, regional, virtual course. The course, set-up in Moodle platform, was structured in eight modules, each lasting for a week. Teaching was based on written didactic material, videos, and interactive discussions, both in Spanish and Portuguese. Topics included epidemiology, diagnosis, classification, treatment, prognosis, social issues, and epilepsy policies. Each course was limited to 50 participants and priority was given to general practitioners. Certification was given to those approving the final examination. Since 2015, five courses have been developed, involving 143 participants from 17 countries and 21 tutors. Of the participants, 61% worked in primary health care services. A total of 129 participants (90%) completed the course, and 110 submitted the final examination with an approval rate of 95%. From 85 participants completing the course evaluation, 98% would recommend the course to other colleagues, and 99% showed interest in taking other similar courses. High self-confidence for the management of patients with epilepsy increased from 21% at baseline to 73% after the course. The online course on epilepsy for primary care physicians in Latin America was shown to be a cost-effective course, with good retention and excellent approval rates. Our current challenges include periodic updating, complete self-sustainability, and exploring different strategies to reach our target audience more effectively.

Risk factors for early childhood caries experience expressed by ICDAS criteria in Anapoima, Colombia: a cross-sectional study.

The aim of this study was to assess whether caries risk, nutritional status, access to dental care and socio-behavioral factors are associated to two caries experience outcome variables using the Epidemiologic International Caries Detection and Assessment System (ICDASepi), which includes initial enamel caries lesions: 1- The presence of ICDAS-epi caries experience (dmf-ICDASepi ≥ 1), and 2- Having an ICDAS-epi caries experience (dmft-ICDASepi) higher than national figures for the same age. The sample included 316 eight- to 71-month-old children from the municipality of Anapoima, Colombia. Assessments included: prevalence and mean of caries experience using the ICDASepi system without compressed air-drying of teeth surfaces (dmf-ICDASepi), caries risk and nutritional status. Caregivers completed an elevenitem questionnaire assessing oral health-related social determinants, practices and quality of life (OHRQoL), and children's access to dental care. Data were analysed using the Wilcoxon-rank-sum test, the test, the Fisher-exact test, and bivariate-linear and non-conditioned logistic-multivariate regression models. Prevalence and mean number of teeth with dmft-ICDASepi were 65. 2% and 3. 5±4. 13, respectively. Nutritional status outside the normal status, lower educational level of caregivers and age were significantly associated with dmf-ICDASepi≥ 1. OHRQoL, access barriers to miss and to attend dental care, operative-treatment or emergency being the reason to attend dental care, high caries risk, and age were significantly associated with a higher-than-national dmft-ICDASepi. The significant associations found between early childhood caries experience and other variables represent oral-health inequalities in early childhood in Anapoima, Colombia.

El objetivo de este estudio fue evaluar en la primera infancia la asociación entre el riesgo de caries, el estado nutricional, el acceso a la consulta odontológica y los factores socio-comportamentales y dos variables de desenlace de experiencia de caries usando el Sistema epidemiológico Internacional de Detección y Valoración de Caries (ICDASepi), que incluye lesiones de caries en el esmalte: 1-La presencia de experiencia de caries ICDAS-epi (ceod-ICDASepi ≥ 1) y, 2- Tener una experiencia de caries ICDASepi (ceod-ICDASepi) mayor que los datos nacionales correspondientes para la misma edad. La muestra fue de 316 niños del municipio de Anapoima, Colombia, de 8 a 71 meses de edad. Las valoraciones incluyeron: prevalencia y promedio de experiencia de caries usando el sistema ICDASepi sin secado de las superficies de los dientes con aire comprimido (dmf-ICDASepi); riesgo de caries y estado nutricional. Los cuidadores respondieron un cuestionario de once ítems que valoraba en relación con salud oral, determinantes sociales, prácticas y calidad de vida y, el acceso de los niños a la consulta odontológica. Los datos fueron analizados con la prueba de suma de rangos de Wilcoxon, la prueba de χ2, la prueba exacta de Fisher y, modelos de regresión logística multivariada tipos bivariantelineal y no condicionada. La prevalencia de experiencia de caries (ceod-ICDASepi) fue de 65. 18% y el promedio de dientes con ceod-ICDASepi de 3. 5 ± 4. 13. El estado nutricional por fuera de rangos de normalidad, el bajo nivel educativo de los cuidadores y la edad se asociaron significativamente con ceo-ICDASepi ≥ 1. Se encontró asociación estadísticamente significativa entre tener un ceod-ICDASepi mayor que el promedio nacional y, calidad de vida relacionada con salud oral, barreras de acceso para perder y asistir a consulta odontológica, tratamiento operatorio o urgencia como motivo de consulta odontológica, alto riesgo de caries y edad. Las asociaciones estadísticamente significativas encontradas en este estudio entre la experiencia de caries de infancia temprana y demás variables representan inequidades en salud oral en la primera infancia en Anapoima, Colombia.

Raoultella Planticola: Bacteremia and Sepsis in a Patient with Cirrhosis.

This case report describes a 66-year-old male who presented to the emergency department with sepsis and jaundice. He reported that he had been eating seafood at local restaurants for the past two weeks. The medications that he was taking at the time of admission included esomeprazole (proton pump inhibitor (PPI)), which may have contributed to his infection with Raoultella planticola. In addition, the patient had a prior medical history of alcoholic liver cirrhosis, which may have contributed to the bacteremia based on his immunocompromised status.

Patrón de distribución de severidad de fluorosis: ¿qué nos dice sobre exposición local a fluoruros? / Padrão de distribuição de severidade da fluorose: Que nos diz sobre exposição local ao fluoretos? / Distribution pattern of enamel fluorosis severity: What is it telling us about local fluoride exposure?

Resumen Introducción y objetivo: la severidad de la fluorosis dental refleja exposición a fluoruros durante el desarrollo del esmalte. Recientemente se han reportado asociaciones entre la exposición prenatal y postnatal a fluoruros y efectos negativos en el neurodesarrollo. El objetivo de este estudio fue describir y comparar la severidad y el patrón de distribución de la fluorosis en las denticiones primaria y permanente, como base para discutir la temporalidad de la exposición en niños viviendo en áreas endémicas en el departamento del Huila. Materiales y métodos: odontólogos entrenados diagnosticaron fluorosis en 840 niños (preescolares y escolares) de cuatro municipios usando el índice de Thylstrup & Fejerskov. Para estimar la prevalencia de las diferentes severidades, cada niño se clasifico de acuerdo con la severidad más alta en boca. La distribución de la prevalencia de severidades por grupo etario y tipo de dentición se reportan como tasas de prevalencia (%). Resultados: la prevalencia en preescolares y escolares fue de 97.2% y 99.9%, respectivamente y la fluorosis moderada la más prevalente (75.6% y 63.5%, respectivamente). En ambas denticiones, la fluorosis leve fue más prevalente en los dientes anteriores que en posteriores. Las severidades moderada y severa tuvieron mayor prevalencia en dientes posteriores que en anteriores. Conclusiones: el patrón de distribución de la severidad de la fluorosis sugiere exposición prenatal y postnatal a fluoruros, por encima de los niveles recomendados. Este estudio resalta la importancia de la alidación de la fluorosis del dental como un potencial biomarcador histórico de exposición a luoruros en momentos críticos para el neurodesarrollo.

Resumo Introdução e objetivo: a severidade da fluorose dentária reflete a exposição a fluoretos durante o desenvolvimento do esmalte. Recentemente, associações entre a exposição pré-natal e pós-natal ao fluoretos e efeitos negativos no desenvolvimento neurológico foram relatadas. O objetivo deste estudo é descrever e comparar o padrão de severidade e distribuição da fluorose na dentição decídua e permanente, como intuito para a discussão sobre a temporalidade da exposição em crianças moradoras em áreas endêmicas de fluorose no departamento de Huila, Colômbia. Materiais e métodos: Cirurgiões-dentistas treinados diagnosticaram fluorose em 840 crianças (pré-escolares e escolares) de quatro municípios, utilizando o índice de Thylstrup & Fejerskov. Para estimar a prevalência dos diferentes estágios de severidade, cada criança foi classificada de acordo com o escore mais severo da boca. A distribuição da prevalência de fluorose nos diferentes estágios de severidade por faixa etária e tipo de dentição é apresentada como taxa de prevalência (%). Resultados: a prevalência de fluorose em pré-escolares foi de 97,2% e em escolares de 99,9%. Fluorose moderada foi a mais prevalente (75,6% e 63,5%, respectivamente). Em ambas as dentições, a fluorose leve foi mais prevalente nos dentes anteriores do que nos posteriores. Porém, tanto fluorose moderada como severa foram mais prevalentes nos dentes posteriores do que nos anteriores. Conclusões: o padrão de distribuição da severidade da fluorose sugere uma exposição pré- e pós-natal a fluoretos acima de níveis recomendados. Este estudo salienta a importância da validação da fluorose dentária como um potencial biomarcador histórico da exposição ao fluoretos durante momentos críticos para o neurodesenvolvimento.

Abstract Introduction and objective: dental fluorosis severity reflects fluoride exposure during dental enamel development. Recently, prenatal and postnatal exposure to fluoride has been associated with negative neurodevelopmental outcomes. The aim of this study was to describe and compare the severity and distribution pattern of dental fluorosis in the primary and permanent dentition, as a basis to discuss the timing and extent of fluoride exposure of children living in endemic areas of fluorosis in the department of Huila. Materials and methods: 840 children (preschoolers and schoolchildren) from four municipalities of the Huila Department were examined by trained dentists for dental fluorosis using the Thylstrup & Fejerskov Index. To estimate the prevalence of severities of fluorosis, each child was classified according to the most severe score. The distribution of the prevalence of enamel fluorosis severity by age-group and type of dentition were reported as prevalence rates (%). Results: Prevalence of dental fluorosis in preschoolers was of 97.2% and in schoolers of 99.9%. For both preschoolers and schoolers moderate fluorosis was the most prevalent (75.6% and 63.5%, respectively). For both primary and permanent teeth, mild fluorosis was more prevalent in anterior teeth than in posterior teeth. Moderate and severe fluorosis were more prevalent in posterior teeth than in anterior teeth. Conclusions: the distribution pattern of the severity of dental fluorosis suggests both prenatal and postnatal exposure to fluoride above recommended levels. This study raises the importance of the validation of dental fluorosis as a potential historical biomarker of fluoride exposure at moments that are critical for neurodevelopment.

Variantes genéticas de susceptibilidad en epilepsia genética generalizada en familias colombianas / Susceptibility gene variants in genetic generalized epilepsy in Colombian families

INTRODUCCIÓN: las epilepsias genéticas generalizadas (EGG) siguen patrones de herencia compleja. Este fenotipo es producto de la interacción de diferentes genes con factores ambientales. Los genes/loci más consistentemente asociados con este grupo de epilepsias son ECA1, ECA2-GABRG2, ECA3-CLCN2 (también conocido como JME6-CLCN2), JME1-EFHC1 y JME5-GABRA1. En Colombia poco se sabe sobre la contribución de las variantes genéticas en estos genes a la susceptibilidad para ser afectado por cualquiera de las formas de EGG. Nuestro propósito fue evaluar el papel de los cinco genes/loci más consistentemente asociados en otros estudios en un grupo de familias colombianas con EGG. MÉTODOS: se evaluaron dos marcadores para cada locus/gen. Los genotipos se obtuvieron mediante las técnicas de PCR-RFLP y ARMS-Tetraprimer. Los análisis estadísticos incluyeron pruebas de asociación alélica y haplotípica, además de pruebas de interacción gen-gen. RESULTADOS: se incluyeron 98 familias, de las cuales 51 fueron epilepsia de ausencias, mientras que 47 fueron epilepsia mioclónica juvenil. Se identificó una interacción significativa entre el alelo G del marcador rs4428455 (valor P=0,0008; gen GABRA1) y el alelo G de marcador rs719395 (valor P=0,002; gen EFHC1). CONCLUSIÓN: estos dos marcadores parecen incrementar el riesgo de EGG en población colombiana. Otros genes no analizados aquí podrían estudiarse con una muestra de mayor tamaño

INTRODUCTION: Generalized genetic epilepsies (GGE) follow complex inheritance patterns. This phenotype is due to interaction of several genes with environmental factors. The genes/loci most consistently associated with this group of epilepsies are ECA1, ECA2-GABRG2, ECA3-CLCN2 (also known as JME6-CLCN2), JME1-EFHC1 and JME5-GABRA1. In Colombia, little is known about the contribution of gene variants to susceptibility to GGE forms. Our purpose was to evaluate the role of the five most consistently associated genes /loci in other studies, in Colombian families set with GGE. METHODS: Genotypes were obtained by means of PCR-RFLP and ARMS-Tetraprimer. Statistical analyses included both allelic and haplotypic association tests, in addition to gene-gene interaction tests. Two genetic markers were tested for each gene/locus. RESULTS: Ninety-eight families were included, from which 51 had absence epilepsy, and 47 had juvenile myoclonic epilepsy. A significant interaction was identified between allele G at marker rs4428455 (P-value= 0.0008; gene GABRA1) and allele G at marker rs719395 (P-value= 0.002; gene EFHC1). CONCLUSION: Our results suggest that these two markers are associated with GGE in the Colombian population. Other genes not analyzed could be tested using a larger sample size.

Risk factors for early childhood caries experience expressed by ICDAS criteria in Anapoima, Colombia: a cross-sectional study / Factores de riesgo de experiencia de caries temprana expresada con criterios ICDAS en niños de Anapoima, Colombia. Estudio de corte transversal

The aim of this study was to assess whether caries risk, nutritional status, access to dental care and sociobehavioral factors are associated to two caries experience outcome variables using the Epidemiologic International Caries Detection and Assessment System (ICDASepi), which includes initial enamel caries lesions: 1The presence of ICDASepi caries experience (dmfICDASepi ≥ 1), and 2Having an ICDASepi caries experience (dmftICDASepi) higher than national figures for the same age. The sample included 316 eightto 71monthold children from the municipality of Anapoima, Colombia. Assessments included: prevalence and mean of caries experience using the ICDASepi system without compressed airdrying of teeth surfaces (dmfICDASepi), caries risk and nutritional status. Caregivers completed an elevenitem questionnaire assessing oral healthrelated social determinants, practices and quality of life (OHRQoL), and children's access to dental care. Data were analysed using the Wilcoxonranksum test, the test, the Fisherexact test, and bivariatelinear and nonconditioned logisticmultivariate regression models. Prevalence and mean number of teeth with dmftICDASepi were 65.2% and 3.5±4.13, respectively. Nutritional status outside the normal status, lower educational level of caregivers and age were significantly associated with dmfICDASepi≥ 1. OHRQoL, access barriers to miss and to attend dental care, operativetreatment or emergency being the reason to attend dental care, high caries risk, and age were significantly associated with a higherthannational dmftICDASepi. The significant associations found between early childhood caries experience and other variables represent oralhealth inequalities in early childhood in Anapoima, Colombia (AU)

El objetivo de este estudio fue evaluar en la primera infancia la asociación entre el riesgo de caries, el estado nutricional, el acceso a la consulta odontológica y los factores sociocomporta mentales y dos variables de desenlace de experiencia de caries usando el Sistema epidemiológico Internacional de Detección y Valoración de Caries (ICDASepi), que incluye lesiones de caries en el esmalte: 1La presencia de experiencia de caries ICDASepi (ceodICDASepi ≥ 1) y, 2Tener una experiencia de caries ICDASepi (ceodICDASepi) mayor que los datos nacionales correspondientes para la misma edad.La muestra fue de 316 niños del municipio de Anapoima, Colombia, de 8 a 71 meses de edad. Las valoraciones incluyeron: prevalencia y promedio de experiencia de caries usando el sistema ICDASepi sin secado de las superficies de los dientes con aire comprimido (dmfICDASepi) ; riesgo de caries y estado nutricional. Los cuidadores respondieron un cuestionario de once ítems que valoraba en relación con salud oral, determinantes sociales, prácticas y calidad de vida y, el acceso de los niños a la consulta odontológica. Los datos fueron analizados con la prueba de suma de rangos de Wilcoxon, la prueba de χ2, la prueba exacta de Fisher y, modelos de regresión logística multivariada tipos bivariantelineal y no condicionada. La prevalencia de experiencia de caries (ceodICDASepi) fue de 65.18% y el promedio de dientes con ceodICDASepi de 3.5 ± 4.13. El estado nutricional por fuera de rangos de normalidad, el bajo nivel educativo de los cuidadores y la edad se asociaron significativamente con ceoICDASepi ≥ 1. Se encontró asociación estadísticamente significativa entre tener un ceodICDASepi mayor que el promedio nacional y, calidad de vida relacionada con salud oral, barreras de acceso para perder y asistir a consulta odontológica, tratamiento operatorio o urgencia como motivo de consulta odontológica, alto riesgo de caries y edad. Las asociaciones estadísticamente significativas encontradas en este estudio entre la experiencia de caries de infancia temprana y demás variables representan inequidades en salud oral en la primera infancia en Anapoima, Colombia (AU)

[Evidence for association and epistasis between the genetic markers SLC6A4 and HTR2A in autism etiology]. / Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en la población antioqueña.

INTRODUCTION: Autism spectrum disorders are severe neurodevelopmental disorders with a strong genetic component. The potential role of the serotoninergic system in the development of autistic disorder has been based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Multiple molecules involved in serotonin metabolism and neurotransmission have been studied; however, replication studies have been inconsistent. This may be partially related to the marked genetic heterogeneity of autism in different populations. OBJECTIVES: The relationship between autism and single nucleotide polymorphisms of SLC6A4, HTR2A and ITGB3 genes was evaluated in an urban population of northwestern Colombia. MATERIALS AND METHODS: In Antioquia, Colombia, 42 families with history of autism were screened for 10 SNPs in SLC6A4, HTR2A and ITGB3 genes and evaluated for associations with the transmission disequilibrium test. The interactions among these genes and autism was assessed with multidimensional reduction methods. RESULTS: A significant main effect was seen among the SLC6A4 gene variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03). No main effect of the ITGB3 or HTR2A variants was found, however, in the interaction effects, the SLC6A4 and HTR2A genes demonstrated significant evidence of association with autism (p<0.001). CONCLUSION: Significant association of markers were discovered within the SLC6A4 gene and the combination of SLC6A4 and HTR2A (S-A) genes to autism. These results were consistent with previous studies conducted in other populations and provide further evidence for the implication of the serotoninergic system in the etiology of autistic disorders.

Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en la población antioqueña / Evidence for association and epistasis between the genetic markers SLC6A4 and HTR2A in autism etiology

Introducción. El espectro autista constituye un grupo de trastornos graves del neurodesarrollo, con un fuerte componente genético. Se ha sugerido un papel importante del sistema serotoninérgico en el desarrollo de este grupo de trastornos, con base en los estudios de respuesta a medicamentos y la hiperserotoninemia, característica común en el autismo. Se han implicado múltiples moléculas en el metabolismo y la neurotransmisión de la serotonina; sin embargo, los resultados de los estudios han tenido poca congruencia entre diferentes poblaciones. Objetivos. Evaluar la relación entre el autismo y el polimorfismo de nucleótido simple (Single Nucleotide Polymorphism, SNP) en los genes SLC6A4, HTR2A e ITGB3, en una muestra de la población antioqueña. Materiales y métodos. Se genotipificaron 42 núcleos familiares con autismo para 10 variantes en los genes SLC6A4, ITGB3 y HTR2A. Se evaluó la asociación utilizando la prueba de desequilibrio en la transmisión. Se exploró el impacto de la interacción entre estos genes y el autismo, utilizando la reducción multidimensional. Resultados. Se encontró asociación de las variantes rs4583306 (OR=2,6, p=0,004) y rs2066713 (OR=2,2 p=0,03), en el gen SLC6A4, y asociación de combinaciones genotípicas entre los genes SLC6A4 y HTR2A y el riesgo de autismo (p=0,0001). Conclusiones. Se encontró asociación significativa con variantes en el gen transportador de serotonina con el autismo, al igual que interacción entre variantes en los genes HTR2A con SLC6A4. Estos resultados concuerdan con los de estudios previos en otras poblaciones y son pruebas a favor del papel del sistema serotoninérgico en la etiología del espectro autista.

Introduction. Autism spectrum disorders are severe neurodevelopmental disorders with a strong genetic component. The potential role of the serotoninergic system in the development of autistic disorder has been based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Multiple molecules involved in serotonin metabolism and neurotransmission have been studied; however, replication studies have been inconsistent. This may be partially related to the marked genetic heterogeneity of autism in different populations. Objectives. The relationship between autism and single nucleotide polymorphisms of SLC6A4, HTR2A and ITGB3 genes was evaluated in an urban population of northwestern Colombia. Materials and methods. In Antioquia, Colombia, 42 families with history of autism were screened for 10 SNPs in SLC6A4, HTR2A and ITGB3 genes and evaluated for associations with the transmission disequilibrium test. The interactions among these genes and autism was assessed with multidimensional reduction methods. Results. A significant main effect was seen among the SLC6A4 gene variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03). No main effect of the ITGB3 or HTR2A variants was found, however, in the interaction effects, the SLC6A4 and HTR2A genes demonstrated significant evidence of association with autism (p<0.001). Conclusion. Significant association of markers were discovered within the SLC6A4 gene and the combination of SLC6A4 and HTR2A (S-A) genes to autism. These results were consistent with previous studies conducted in other populations and provide further evidence for the implication of the serotoninergic system in the etiology of autistic disorders.

Prevalencia, incidencia y brecha terapéutica en la epilepsia / Prevalence, incidence and treatment gap in epilepsy

Se revisa la epidemiología de la epilepsia haciendo énfasis en las definiciones y clasificaciones propuestas por la Liga Internacional contra la Epilepsia. Se estudian las cifras de prevalencia e incidencia tanto de países desarrollados como en desarrollo. Se ilustra sobre el concepto de brecha terapéutica y sus causas.

The epidemiology of epilepsy is reviewed, emphasizing on the definitions and classifications proposed by the International League against Epilepsy. The figures of prevalence and incidence in developed and developing countries are analyzed. The concept of treatment gap and its causes are reviewed.

Esquizencefalia: un trastorno de la migración neuronal / Schizencephaly: a disorder of neuronal migration

La esquizencefalia es el trastorno más frecuente de la migración neuronal y ocurre entre el tercero y quinto meses de la gestación. Se describen en este artículo sus posibles causas genéticas (EMX2), vasculares e infecciosas, así como sus manifestaciones clínicas, radiológicas y electroencefalográficas. El tratamiento es sintomático y multidisciplinario.

Schizencephaly is the most frequent neuronal migration disorder and it develops between the third and fifth gestational months. Genetic (EMX2), vascular and infectious etiologies have been described. Its clinical, radiological and electroencephalographic characteristics are described in this article. Treatment should be symptomatic and multidisciplinary.

Evaluación de la incidencia y los factores de riesgo para hemorragia intraventricular (HIV) en la cohorte de recién nacidos prematuros atendidos en la unidad neonatal del Hospital Universitario San Vicente de Paúl, de Medellín, en el período comprendido entre enero de 1999 y diciembre de 2004 / Incidence and risk factors of intraventricular hemorrhage in preterm newborns

La hemorragia intraventricular (HIV) es la principal complicación neurológica de los recién nacidos prematuros, cuyas frecuencia y gravedad aumentan con el menor peso al nacer y la menor edad gestacional. Se han encontrado otros factores asociados con el aumento o disminución de su frecuencia.Objetivo: determinar la incidencia de HIV en prematuros atendidos en el Hospital Universitario San Vicente de Paúl (HUSVP), de Medellín, Colombia, entre 1999 y 2004 y establecer su asociación con condiciones de la madre y del recién nacido.Metodología: estudio retrospectivo de los prematuros menores de 32 semanas y por debajo de 1.500 gramos, atendidos en el HUSVP entre 1999 y 2004. Se calculó una muestra de 330 historias clínicas, seleccionadas en forma aleatoria, con un nivel de confianza de 95 por ciento, error del 3 por ciento y poder del 80 por ciento,con base en una incidencia del 15 por ciento de HIV en la población general.Resultados: la incidencia encontrada de HIV fue 29,8 por ciento. Como factores protectores se encontraron los siguientes: parto por cesárea, parto en un centro de tercer nivel y maduración pulmonar. Como factores que aumentaron el riesgo de HIV se encontraron: parto vaginal, edad gestacional menor de 28 semanas, uso de surfactante, ventilación mecánica, cateterismo umbilical, acidosis e hipercapnia.Conclusiones: se debe insistir en la importancia de que haya programas adecuados de control prenatal para tratar de disminuir la frecuencia de parto prematuro, procurar la remisión oportuna de las gestantes de alto riesgo a centros de referencia, estimular el uso antenatal de esteroides y el control cuidadoso de los parámetros ventilatorios en los pacientes que requieran este soporte, buscando mantener un adecuado equilibrio ácido-base en los recién nacidos.