Methionyl-tRNA Formyltransferase (MTFMT) Deficiency Mimicking Acquired Demyelinating Disease.

Disease-related mutations in the mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene encoding a critical enzyme for mitochondrial translation have been rarely reported and are described in association with Leigh syndrome and combined oxidative phosphorylation deficiency. Symptoms include developmental delay, followed by ataxia and spasticity manifesting at later stages. A man had a clinical picture suggestive of an acquired demyelinating disease. Brain magnetic resonance imaging (MRI) demonstrated extensive involvement of the optic nerves, cerebral white matter, brain stem, and spinal cord. Whole-exome sequencing detected a pathologic homozygous c.626C>T mutation in the MTFMT gene. These findings expand the clinical features and neuroimaging spectrum associated with MTFMT mutations to include a relapsing-remitting phenotype.

Lymphocytic hypophysitis associated with pediatric multiple sclerosis.

BACKGROUND: Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland and infundibulum most often observed in the setting of autoimmune disease with a variety of clinical and endocrine presentations. The association between lymphocytic hypophysitis and multiple sclerosis has not been reported. PATIENT AND RESULTS: We describe an adolescent boy with polyfocal neurological signs including optic neuritis as well as hypopituitarism and diabetes insipidus related to lymphocytic hypophysitis. His imaging met 2010 McDonald criteria for multiple sclerosis. This diagnosis was further supported by cerebrospinal fluid analysis and a negative evaluation for an alternate diagnosis. Imaging features of lymphocytic hypophysitis include an absent posterior pituitary bright spot with an enlarged cystic pituitary gland, stalk thickening, and improvement with corticosteroid therapy. CONCLUSIONS: Lymphocytic hypophysitis and multiple sclerosis share a common autoimmune pathogenesis, perhaps explaining the co-occurrence of the diseases. The presentation of endocrinologic disturbances such as diabetes insipidus with typical features of a multiple sclerosis attack should prompt further investigation of possible comorbid inflammatory disease involving the hypothalamic-pituitary axis.

Pediatric multiple sclerosis: current concepts and consensus definitions.

Multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) commonly diagnosed in adults, is being recognized increasingly in children. An estimated 1.7%-5.6% of all patients with MS have clinical symptoms before reaching the age of 18 years. In comparison with adults, the diagnosis of MS in children can be more difficult, being dismissed or misdiagnosed as other clinical disorders. Although adults and children share basic aspects of the disorder, children have distinctive clinical features, neuroimaging, laboratory, and courses of the disease. The 2010 McDonald criteria have simplified the requirements for establishing the diagnosis of MS and have been proposed to be applicable for the diagnosis of pediatric MS, mainly in children 12 years and older. This paper describes the distinctive features of common pediatric demyelinating disorders, including MS, and summarizes the most recent advances based on the available literature.

Pediatric multiple sclerosis in Venezuela.

OBJECTIVE: To describe the epidemiological and clinical characteristics of Venezuelan pediatric patients with multiple sclerosis (MS). METHODS: Database records from the National Program for MS were searched for patients with an established diagnosis of MS whose first symptoms appeared before age 18. RESULTS: The national database held records of 1.710 patients; 3.8% had onset of the first symptoms before age 18. 46.7% were boys, yielding an F:M ratio of 1.13:1. Many children had a disease onset characterized by motor impairment (30.7%), brainstem/cerebellum and spinal cord affectation (27.6%), headache (26%). Less frequent symptoms were sensory symptoms (8%) and optic neuritis (7%). DISCUSSION: Pediatric MS patients in Venezuela represent a significant proportion of all MS cases. The clinical pattern is characterized by motor symptoms at onset, and predominantly monosymptomatic presentation with a relapsing-remitting pattern. This is the first systematic attempt to estimate the prevalence of pediatric MS in Venezuela.

Pediatric multiple sclerosis in Venezuela / Esclerosis múltiple pediátrica en Venezuela

OBJECTIVE: To describe the epidemiological and clinical characteristics of Venezuelan pediatric patients with multiple sclerosis (MS). METHODS: Database records from the National Program for MS were searched for patients with an established diagnosis of MS whose first symptoms appeared before age 18. RESULTS: The national database held records of 1.710 patients; 3.8% had onset of the first symptoms before age 18. 46.7% were boys, yielding an F:M ratio of 1.13:1. Many children had a disease onset characterized by motor impairment (30.7%), brainstem/cerebellum and spinal cord affectation (27.6%), headache (26%). Less frequent symptoms were sensory symptoms (8%) and optic neuritis (7%). DISCUSSION: Pediatric MS patients in Venezuela represent a significant proportion of all MS cases. The clinical pattern is characterized by motor symptoms at onset, and predominantly monosymptomatic presentation with a relapsing-remitting pattern. This is the first systematic attempt to estimate the prevalence of pediatric MS in Venezuela.

OBJETIVO: Describir las características clínicas y epidemiológicas de pacientes pediátricos venezolanos con EM. MÉTODOS: Se revisó la base de datos del Programa Nacional para EM, identificando pacientes con diagnóstico establecido de EM antes de los 18 años de edad. RESULTADOS: La base de datos registró 1.710 pacientes y 3,8% tenía una edad de aparición menor de 18 años. De estes, 46,7% eran varones, dando una relación F:M de 1.13:1. Muchos niños tuvieron una aparición de la enfermedad caracterizada por déficit motor (30,7%), afectación del tronco encefálico-cerebelo y la médula espinal (27,6%), dolor de cabeza (26%). Síntomas menos frecuentes fueron sensoriales (8%) y neuritis óptica (7%). DISCUSIÓN: Los pacientes pediátricos venezolanos con MS representan una proporción significativa de todos los casos de MS. El patrón clínico está caracterizado por síntomas motores y presentación predominantemente monosintomática con patrón brote-remisión. Este es el primer intento sistemático para estimar la prevalencia de MS pediátrica en Venezuela.

[Attention-deficit / hyperactivity disorder in autism spectrum disorders]. / Déficit de atención e hiperactividad en los trastornos del espectro autista.

According to the DSM-IV-TR, symptoms of inattention and hyperactivity are frequent in children with Autism Spectrum Disorders (ASD). This statement is supported by clinical observation and formal assessment. However, ASD diagnosis is still among the exclusion criteria for the Attention-Deficit/Hyperactivity Disorder (ADHD). Such exclusion generates controversy and questions regarding the need and benefits of maintaining or not these separations; so much so, that the proposed criteria for the DSM-V eliminate that exclusion condition. It is necessary a better understanding of the comorbidity between both entities in order to be able to have an appropriate sequence of the intervention goals. For that reason, if inattention and hyperactivity in individuals with ASD are considered as a representation of a comorbid diagnosis of ADHD, treatment plans for this group would be better adjusted and more likely to offer a real benefit in the outcome of their adaptive functioning.

Déficit de atención e hiperactividad en los trastornos del espectro autista / Attention-deficit / hyperactivity disorder in autism spectrum disorders

De acuerdo al DSM-IV-TR los síntomas de falta de atención e hiperactividad son frecuentes entre los individuos con Trastornos del Espectro Autista (TEA). Estas aseveraciones están reflejadas en a observación clínica y la valoración formal. Sin embargo, el diagnóstico de TEA aún continúa dentro de los criterios de exclusión para el Trastorno por Déficit de Atención-Hiperactividad (TDAH). Dicha exclusión ha ocasionado controversia e interrogantes con respecto a la necesidad y el beneficio de mantener o no estas separaciones; tanto así, que los criterios propuestos para el DSM-V eliminan dicho criterio de exclusión. Es necesaria una clara comprensión de la comorbilidad entre ambas entidades para realizar una secuencia óptima y apropiada de los objetivos de la intervención. Es por esto, que si se considera la falta de atención e hiperactividad en individuos con un diagnóstico asociado de TEA como una representación de un diagnóstico comórbido de TDAH, los planes de tratamiento serán más apropiados y con mayor impacto en su funcionamiento adaptativo.

According to the DSM-IV-TR, symptoms of inattention and hyperactivity are frequent in children with Autism Spectrum Disorders (ASD). This statement is supported by clinical observation and formal assessment. However, ASD diagnosis is still among the exclusion criteria for the Attention-Deficit/Hyperactivity Disorder (ADHD). Such exclusion generates controversy and questions regarding the need and benefits of maintening or not these separations; so much so, that the proposed criteria for the DSM-V eliminate that exclusion condition. It is necessary a better understanding of the comorbidity between both entities in order to be able to have an appropriate sequence of the intervention goals. For that reason, if inattention and hyperactivity in individuals with ASD are considered as a representation of a comorbid diagnosis of ADHD, treatment plans for this group would be better adjusted and more likely to offer a real benefit in the outcome of their adaptive functioning.

NMO in pediatric patients: brain involvement and clinical expression.

OBJECTIVE: To analyze the clinical, neuroimaging characteristics and positivity of the acquaporin water channel (NMO-IgG) in pediatric patients with neuromyelitis optica (NMO). This disorder could have a variable clinical expression. To address such variability, the term NMO spectrum has been suggested. METHOD: We evaluated six pediatric patients, with a median age of 11 years at the time of the study, with the diagnosis of NMO by the Wingerchuck criteria. RESULTS: All the cases exhibited bilateral optic neuritis (ON). Four patients had abnormalities on brain MRI from the onset,although only three of them developed symptoms correlated to those lesions during the course of their disorder. NMO-IgG was positive in 80%. CONCLUSION: Optic neuropathy is the most impaired feature in NMO patients. Brain MRI lesions are not compatible with multiple sclerosis and positivity of the NMO-IgG are also present in NMO pediatric patients, confirming the heterogeneity in the expression of this disorder.

NMO in pediatric patients: brain involvement and clinical expression / NMO en pacientes pediátricos: afectación del cerebro y expresión clínica

OBJECTIVE: To analyze the clinical, neuroimaging characteristics and positivity of the acquaporin water channel (NMO-IgG) in pediatric patients with neuromyelitis optica (NMO). This disorder could have a variable clinical expression. To address such variability, the term NMO spectrum has been suggested. METHOD: We evaluated six pediatric patients, with a median age of 11 years at the time of the study, with the diagnosis of NMO by the Wingerchuck criteria. RESULTS: All the cases exhibited bilateral optic neuritis (ON). Four patients had abnormalities on brain MRI from the onset,although only three of them developed symptoms correlated to those lesions during the course of their disorder. NMO-IgG was positive in 80 percent. CONCLUSION: Optic neuropathy is the most impaired feature in NMO patients. Brain MRI lesions are not compatible with multiple sclerosis and positivity of the NMO-IgG are also present in NMO pediatric patients, confirming the heterogeneity in the expression of this disorder.

OBJETIVO: Analizar las características clínicas y de neuroimagen, y la positividad del canal de agua acuaporin (NMO-IgG) en pacientes pediátricos con neuromielitis óptica (NMO). Este trastorno puede tener una expresión clínica variable. El término espectro de NMO ha sido propuesto para poder incluir la variabilidad. METODO: Evaluamos seis pacientes pediátricos, con una mediana de edad de 11 años al momento del estudio, con el diagnóstico de NMO de acuerdo a los criterios de Wingerchuck. RESULTADOS: Todos los casos exhibían neuritis óptica bilateral (ON). Cuatro pacientes tuvieron anormalidades en la RM cerebral desde el inicio, aunque solo tres de ellos desarrollaron síntomas relacionados con las lesiones durante el curso de la enfermedad. NMO-IgG fue positiva en el 80 por ciento. CONCLUSIÓN: Neuropatía óptica es la característica mayormente observada en los pacientes con NMO. Lesiones cerebrales en la RM cerebral no compatibles con esclerosis multiple y positividad de la NMO-IgG están también presentes en los pacientes pediátricos con NMO; lo cual confirma la heterogeneidad en la expresión clínica de este trastorno.

Síndrome de Aicardi: descripción de cuatro casos venezolanos / Aicardi syndrome: a report of four venezuelan patients

El síndrome de Aicardi (SA) se caracteriza por agenesia del cuerpo calloso, espasmos infantiles y lesiones lacunares coriorretinianas. Su espectro evolutivo es variable, con pronóstico habitualmente muy grave en los primeros cinco años de vida. El objetivo de este trabajo es describir el espectro del fenotipo clínico y evolución de este trastorno en cuatro pacientes venezolanos. Todas las pacientes evaluadas cumplieron los criterios diagnósticos mayores, mostraron retraso psicomotor grave y convulsiones de inicio muy temprano. En dos pacientes se observó microftalmía. En tres (75 por ciento) de ellas se observó coloboma del nervio óptico, quistes interhemisféricos y heterotopías periventriculares. La primera paciente, con mayor tiempo de evolución, tiene actualmente 22 años. Todos los casos exhibieron un patrón asimétrico de hipsarritmia alternante en el electroencefalograma. Estos casos ilustran la expresión clínica y gravedad variables del síndrome de Aicardi. Su diagnóstico debe considerarse en niñas con retardo del desarrollo psicomotor y crisis convulsivas recurrentes iniciadas en la infancia temprana.

Aicardi syndrome is characterized by agenesis of the corpus callosum, infantile spasms and chorioretinal lacunae. The evolution of this disorder is variable, with a severe outcome over the first five years of age. The purpose of this report was to demonstrate the spectrum of the clinical phenotype and the course of this disorder in four Venezuelan patients. All patients met the major criteria, had severe psychomotor impairment and early onset seizures. There were microphtalmia in two of the patients. Three patients (75 percent) showed coloboma, interhemispheric cyst and periventricular heterotopias. The first patient, with longer follow-up, is currently aged 22. They all exhibited a typical asymmetric pattern on the electroencephalogram. These cases illustrate the variable clinical expression and severity of the Aicardi syndrome. A diagnosis of this disorder should be considered in girls with developmental delay, particularly, when there are accompanying recurrent seizures occurring in early childhood.

[Aicardi syndrome: a report of four Venezuelan patients]. / Síndrome de Aicardi. Descripción de cuatro casos venezolanos.

Aicardi syndrome is characterized by agenesis of the corpus callosum, infantile spasms and chorioretinal lacunae. The evolution of this disorder is variable, with a severe outcome over the first five years of age. The purpose of this report was to demonstrate the spectrum of the clinical phenotype and the course of this disorder in four Venezuelan patients. All patients met the major criteria, had severe psychomotor impairment and early onset seizures. There were microphtalmia in two of the patients. Three patients (75%) showed coloboma, interhemispheric cyst and periventricular heterotopias. The first patient, with longer follow-up, is currently aged 22. They all exhibited a typical asymmetric pattern on the electroencephalogram. These cases illustrate the variable clinical expression and severity of the Aicardi syndrome. A diagnosis of this disorder should be considered in girls with developmental delay, particularly, when there are accompanying recurrent seizures occurring in early childhood.

Epidemiological findings of pervasive developmental disorders in a Venezuelan study.

The study aims to determine the prevalence of autism spectrum disorders (ASDs) for children receiving services in Maracaibo County, Venezuela. Children aged 3-9 with diagnosis of any ASD were recruited. We ascertained area, referral process, and definitions of ASD for each patient. A total of 430 children were identified, and 76.5 percent were boys. Prevalences were 1.7 per 1000 for all ASD, 1.1 per 1000 for autism, and 0.6 per 1000 for PDD-NOS and Asperger syndrome combined. These prevalences are lower than current reports in the literature. Differences in case-finding methods, diagnostic criteria, and lack of awareness in the general population may have influenced the number of cases identified. An ASD prevalence of 1.7 per 1000 should alert the health and education authorities to the need to reassess the services available for children with these disorders and their families.

Prevalence rates of attention deficit/hyperactivity disorder in a school sample of Venezuelan children.

A total of 1,535 4-12 year-old children were screened with the Conners' rating scales, followed by diagnostic confirmation by the diagnostic interview schedule for children-IV-parent version. The prevalence of ADHD was estimated to be 10.03%, and only 3.9% of children had received medication for the treatment of ADHD symptoms. Prevalence rates and demographic profile of Venezuelan children with ADHD are very similar to those found in samples from other countries. Authorities need to develop public health policies to correctly identify and treat affected subjects. Furthermore, clinicians must actively search for children with ADHD in order to provide the best-available treatment.

Datos normativos del cuestionario sobre el comportamiento de niños-versión para padres (CBCL) y versión para padres (CBCL) y versión para profesores (TRF) en una muestra de niños venezolanos / Normative data of the child behavior checklist (CBCL) and teacher´s report from in a sample of Venezuelan children

El objetivo de este estudio estuvo dirigiso a obtener datos normativos par una muetar representativa de niños venezolanos, para el Cuestionario sobre el Comportamiento de niños, en sus versiones para padres (CBCL) y en su versión para profesores (TRF). La muestra estuvo constituida por 1.141 niños de ambos sexos, con edades comprendidas entre 5 y 12 años ()Media= 8,79, DT=1,85, de los cuales el 49% pertenecían al sexo femenino, el 51% al masculino. El nivel socioeconómico fue significativo de forma tal que los padres del nivel bajo puntuaron a sus hijos con mayor número de problemas. El sexo tuvo un efecto en las puntuaciones de forma tal que los varones son percibidos con mayor cantidad de problemas que las mujeres tanto por sus padres como por sus profesores. Padre y profesores no mostraron acuerdo en sus valoraciones de las conductas de los niños. Los resultados de este estudio sugieren que los síndromes y dimensiones clínicas medidas por ambas versiones del instrumento poseen validez universal para niños de edades escolares

The aim of the study was to obtain normative data for a representative sAmple Of Venezuelan children for the Child Behaviour Checklist (CBCL) and Teacher´s Report form. The sample was constituted by 1.141 children, boys and girls aged 5 to 12 (Mean= 8.79, SD=1.85), 49% female and 51% male. Socioeconomic status was significant ina way that low SES parents scored their children as havig more problems. Gender has an effect or the scores, males were perceived with more behavir problems tha girls for both parents and teachers. Parents and teachers did not show agreement in the assessment of the children´s behavior. Findings of this study suggest that the syndromes and dimensions assessed by the two versions of the checklist have universal validity for school-age children

[Clinical presentation of attention deficit/hyperactivity disorder as a function of the gender]. / Presentación clínica del trastorno por déficit de atención-hiperactividad como función del género.

Results from studies comparing boys and girls diagnosed as having Attention Deficit-Hyperactivity Disorder (ADHD) have been non conclusive. In general, the results of such studies report boys as being more hyperactive and presenting more conduct problems, and girls as having more cognitive and learning problems. The aim of this study was to collect information about the characterization of the disorder depending on the gender. 169 children (123 males, 46 females), between 4 and 13 years of age with ADHD were studied. The assessment battery included Conners' rating scales-Revised for parents and teachers, short forms of the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) and Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), academic achievement measures, developmental history and the Diagnostic Interview Schedule for Children-IV Version-Parents (DISC-IV). The results indicated the lack of significant differences between genders for the studied variables, ADHD boys and girls scored alike in the various behavioral and cognitive measures. The results presented describe homogeneity in the symptoms, demographic characteristics and neuropsychological functioning for children of both genders; suggesting a syndrome with the same criteria and independent of the gender.

Clima familiar en el trastorno por déficit de atención-hiperactividad / Family environment in Attention Deficit-Hyperactivity Disorder

El efecto del clima familiar en el desarrollo del trastorno por déficit de atención-hiperactividad (TDAH) no se conoce. En este estudio se busca caracterizar a las familias con niños con TDAH para tener un mejor entendimiento de las contribuciones del clima familiar en el desarrollo del trastorno. Se recolectan datos demográficos, escalas de puntuación de padres y profesores, cociente intelectual y la escala de clima familiar (ECF) de 53 niños 8edades 4 a 13 años); 29 con diagnóstico de TDAH y 24 no casos. Análisis estadístico arroja un perfil de clima familiar dentro del rango promedio para ambas muestras. Se encontraron diferencias significativas entre casos y controles para las subescalas de cohesión, orientación, hacia actividades intelectuales y orientación hacia actividades recreativas. Una mayor gravedad en síntomas de TDAH estuvo relacionada con menor cohesión y mayor conflicto familiar. Los hallazgos sugieren falta de asociación entre la calidad de clima familiar y el diagnóstico del TDAH

The effect of family environment on the development of Attention Deficit-Hyperactivity Disorder (ADHD) is not known. We sought to characterize families with children with ADHD in order to better understand the contributions of family environment to the development of ADHD. We collected demographic data, parents´ and teachers´ rating scales, intellectual quotient, and the family environment scale (FES) for 53 children (aged 4-13), 29 with ADHD diagnosis and 24 controls. Statistical analysis indicated a family environment profile within the average range for both samples. There were significant differences between ADHD and controls for the measures of cohesion, intellectual activity orientation, and recreational activities orientation. Greater severity of the TDAH symptoms was related to less cohesion and more conflict. There seems to be no association between the quality of the family environment and the diagnosis of ADHD

Displasias corticales y epilepsia / Cortical displasias and epilepsy

Las displasias corticales comprenden un espectro amplio de malformaciones de la corteza cerebral que se originan durante el desarrollo y se asocian con epilepsia y retardo mental. Con el progreso de las nuevas técnicas de neuroimagen se ha facilitado el diagnóstico in vivo de estos trastornos y la definición de síndromes clínicos específicos. Este artículo revisa los aspectos etiológicos de estos trastornos, discute los hallazgos clínicos y de neuroimagen, así como el pronóstico de la epilepsia secundaria a estas malformaciones

Migraña oftalmoplejica en niños: estudio 3 casos / Ophthalmoplegic migraine in children: study of 3 cases

La parálisis aislada unilateral del nervio motor ocular común es poco frecuente en edad pediátrica y usualmente aparece como un fenomeno congénito o secundario a trauma, tumor o intección. Una forma poco conocida, especialmente en niños, ocurre como complicación de las cefaleas vasculares llamadas Migraña Oftalmoplejica. Describimos 3 casos. Se enfatizan las características clínicas, el diagnóstico diferencial y su evolución

Osteogenesis imperfeta: estudio de 2 casos / Osteogenesis imperfecta: study of 2 cases

Se describen 2 casos, una hembra y un varón, con osteogénesis imperfecta quiénes presentaron fragilidad ósea, deformidad, cortedad de miembros y limitaciones de las extremidades afectadas. Los autores discuten las características clínicas y radiológicas que permiten hacer el diagnóstico desde etapas tempranas de la vida y la necesidad de seguimiento de estos pacientes