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.

Spatial and Ecological Factors Modulate the Incidence of Anti-NMDAR Encephalitis-A Systematic Review.

Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and environmental factors might influence disease risk has not been explored yet. We performed a systematic review and a meta-analysis of all published papers reporting the incidence of anti-NMDAR encephalitis in a definite country or region. We performed several multivariate spatial autocorrelation analyses to analyze the spatial variations in the incidence of anti-NMDA encephalitis depending on its geographical localization and temperature. Finally, we performed seasonal analyses in two original datasets from France and Greece and assessed the impact of temperature using an exposure-lag-response model in the French dataset. The reported incidence of anti-NMDAR encephalitis varied considerably among studies and countries, being higher in Oceania and South America (0.2 and 0.16 per 100,000 persons-year, respectively) compared to Europe and North America (0.06 per 100,000 persons-year) (p < 0.01). Different regression models confirmed a strong negative correlation with latitude (Pearson's R = -0.88, p < 0.00001), with higher incidence in southern hemisphere countries far from the equator. Seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models confirmed a positive correlation between extreme hot temperatures and the incidence of anti-NMDAR encephalitis in France (p = 0.03). Temperature analyses showed a significant association with higher mean temperatures and positive correlation with higher ultraviolet exposure worldwide. This study provides the first evidence that geographic and climatic factors including latitude, mean annual temperature, and ultraviolet exposure, might modify disease risk.

Moebius syndrome: Craniofacial clinical manifestations and their association with prenatal exposure to misoprostol.

BACKGROUND: A growing link between prenatal exposure to misoprostol (PEM) and Moebius syndrome (MS) or sequence has been reported. Our objectives were to describe the craniofacial clinical manifestations associated with MS and to determine the frequency of PEM, comparing cases of exposure and nonexposure. METHODS: A descriptive, cross-sectional study of 140 patients with MS. Clinical evaluations, as well as 140 interviews with mothers residing in 39 cities or districts of Colombia, were carried out between April 2008 and May 2018. Additionally, previous clinical history of each case was reviewed. RESULTS: The average age of the patients with MS was 8.4 years (29 days to 48 years). All of them presented facial nerve involvement and abducens, 112 (80.8%) with bilateral facial paralysis. 98.5% presented craniofacial disorders, and there were no significant differences between those exposed and not exposed to misoprostol. Forty-seven percentage of patients (64 cases) presented PEM, in 98.4% of which abortion had been intended. CONCLUSION: PEM could have an influence in the appearance of new cases of MS by increasing the frequency of bleeding during gestation, without increasing the number of associated craniofacial malformations. We present the biggest series on MS and craniofacial findings in the literature, along with a meaningful reference for its understanding. LEVEL OF EVIDENCE: 3b.

[Biopercular syndrome: report of two cases and literature review]. / Síndrome biopercular: presentación de dos casos y revisión de la literatura.

The anterior opercular or biopercular syndrome is a cortical pseudobulbar palsy due to bilateral lesions of the anterior brain operculum. It is characterized by preservation of reflex function and automatic activity, without mental impairment. Two cases are reported herein and the relevant literature reviewed. The first case was a 73-year-old female with a history of a stroke occurring seven years previously, without sequelae in the interim. She presented with sudden loss of consciousness. The neurological examination showed a right facial central palsy and anarthria, with reflex acts such as smiling, blinking and yawning, not elicited by commands; she also had a right hemiparesis and walking impairment. A brain CT scan showed an old ischemic infarction in the region of the right medial cerebral artery. Because the right motor involvement did not correlate with the findings of the initial CT scan, another CT scan two days later showed an acute brain infarction in the vicinity of the left medial cerebral artery. The second case was an 8-year-old girl with mental retardation and impairment of verbal development, caused by of biopercular pachygyria. Facio-pharyngo-glosso-masticatory diplegia and volitional selective palsy of the oro-facial muscles was seen in both patients. The neuropsychological assessment showed cognitive, emotional and social interaction impairment in both cases -as part of the frontal convexity syndrome in the first case and of mental retardation in the second. The two patients had difficulty in mastication and swallowing. The prognosis for recovery of verbal capacity is poor, although generally most patients recover the ability to swallow.

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.

Generalidades sobre el autismo / Generalities about Autism

Introducción: el autismo, como uno de los trastornos generalizados del desarrollo, se caracteriza por alteraciones en el desarrollo del lenguaje verbal y no verbal, afectación en la socialización y conductas repetitivas. Objetivo: avanzar en la comprensión de los trastornos del espectro autista, que es un gran reto, por su heterogeneidad clínica e impacto y por constituir una forma grave y temprana de neurosicopatología infantil, que al detectarla y manejarla precozmente mejora su pronóstico. Método: desarrollo de las generalidades y de los aspectos clínicos relevantes para el diagnóstico precoz del autismo. Conclusión: los estudios retrospectivos muestran que el diagnóstico de autismo se hace meses o años más tarde de cuando podrían realizarse, basándose en señales de alerta detectadas por los padres.

Introduction: Autism, a pervasive developmental disorder, is characterized by altered verbal and non-verbal language development, social impairment and repetitive behavior. Objective: To advance in our understanding of autism and autistic spectrum disorders, a clinically heterogeneous group that constitute a severe form of childhood psychopathology with improved prognosis if diagnosed and treated early. Method: Outline of general and clinical aspects relevant to the early diagnosis of autism. Conclusions: Retrospective studies show that the diagnosis of autism is made months to years late, mostly based on signs of alert detected by the parents.

Neuroimagen en la enfermedad de Marchiafava Bignami / Neuroimagen in a case of Marchiafava-Bignami disease

La enfermedad de Marchiafava Bignami (EMB) es una entidad de. Muy baja frecuencia de distribución mundial en la que se produce desmielinización tóxica progresiva y necrosis del cuerpo calloso con extensión ocasional a la sustancia blanca subcortical adyacente, asociada principalmente al consumo crónico de bebidas alcohólicas. Según los datos revisados entre 1987-1997 sólo se han publicado 36 casos en la literatura médica mundial; éste constituye el primer caso reportado en Colombia.