Efectos del tratamiento con vitamina E en el tubo neural y médula espinal en embriones y fetos de ratones Mus musculus expuestos al uso de ácido valproico / Effects of treatment with vitamin E in the neural tube and spinal cord Mus musculus mouse embryos exposed to the use of valproic acid

El ácido valproico (VPA) es el principal anticonvulsivante utilizado contra la epilepsia durante la gestación. Sin embargo, en etapas iniciales del embarazo actúa como teratógeno y ocasiona malformaciones como fisura labio-palatina, alteraciones en el desarrollo genital y espina bífida, siendo esta última la más frecuente. Esto se produce debido al aumento de especies reactivas de oxígeno, pudiendo contrarrestarse administrando vitamina E. El objetivo fue determinar si la vitamina E disminuye el daño en tubo neural y médula espinal de embriones y fetos de ratonas expuestas a VPA. Se conformaron 8 grupos de animales. A los 8 días post-fecundación se les administró a los grupos 1 y 5 suero fisiológico 0,3 mL; grupos 2 y 6 VPA 600 mg/Kg; grupos 3 y 7 VPA 600 mg/Kg y vitamina E 200 UI/Kg; grupos 4 y 8 vitamina E 200 UI/kg. A los 12 días post-fecundación, se sacrificaron los grupos 1, 2, 3 y 4, y a los 17 días los restantes grupos. Los embriones fueron procesados y teñidos con cresil violeta, observándose cortes histológicos a nivel cervical, torácico y lumbar. Los grupos tratados con vitamina E presentaron menor cantidad de neuroblastos y motoneuronas, pero de tamaño mayor en comparación al grupo tratado con VPA (p<0,05), siendo similares a los grupos controles. Al comparar el tubo neural y médula espinal en los distintos niveles (cervical, torácico y lumbar), no hubo diferencias estadísticamente significativas. La administración prenatal de vitamina E disminuye los defectos en tubo neural y médula espinal de embriones de 12 y 17 días de gestación sometidos a VPA.

Valproic Acid (VPA) is the main anticonvulsant used for epilepsy throughout the gestation period. However, when used at early stages of pregnancy, it acts as a tetarogenic agent, causing congenital malformations such as cleft-lip and/or cleft palate, abnormal genital development and spina bifida, being the latter the most frequent. This is the result of the increase of reactive oxygen species, which can be countered with the supplementation of vitamin E. The aim was determine if vitamin E minimizes the damage to the neural tube and spinal cord of mice embryos and fetuses previously exposed to VPA. Eight groups of mice were constituted. Eight days post fertilization, groups 1 and 5 were administered 0,3 ml of saline solution; groups 2 and 6 600mg/Kg of VPA, groups 3 and 7 600mg/Kg of VPA and 200UI/Kg of Vitamin E; groups 4 and 8 200 UI/Kg of Vitamin E. 12 days after fertilization, groups 1, 2, 3 and 4 were euthanized, whereas in the case of the remaining groups, the same process was performed 17 days after fertilization. The embryos were stained with cresyl violet, thus enabling the observation of histological sections at cervical, thoracic and lumbar levels. Groups supplied with vitamin E presented a lower amount of neuroblasts and motoneurons. However, these elements were bigger in size compared to the group treated with VPA (p<0,05), being these results similar to those obtained with the control groups. When comparing the neural tube and spinal cord at different levels (cervical, thoracic and lumbar), no statistically significant differences were found. It was determined that prenatal administration of vitamin E lessens the damage to the neural tube and spinal cord of mice embryos of 12 and 17 days of gestation previously exposed to VPA.

De la embriogénesis a la prevención de cardiopatías congénitas, defectos del tubo neural y de pared abdominal / From embryogenesis to the prevention of congenital cardiopathies, defects of the neural tube and the abdominal wall

Introducción: Los defectos congénitos constituyen una causa importante de mortalidad infantil y discapacidad. Las cardiopatías y los defectos del tubo neural y de la pared abdominal son de los más frecuentes. Objetivo: sistematizar los referentes teóricos sobre la embriogénesis y la epidemiología de estas anomalías del desarrollo, que contribuyan a la capacitación de médicos y estudiantes como promotores de salud. Materiales y Métodos: se realizó la revisión de 32 artículos científicos, búsqueda en la Biblioteca Virtual de Salud de Infomed, en las bases de datos Medline Complete, Pubmed Central, Clinical Key, Scielo regional y Scielo Cuba. La búsqueda se realizó entre los meses de octubre de 2014 y febrero de 2015, y quedó limitada a los últimos 8 años. Resultados: los defectos cardiacos se producen por fallas en la embriogénesis, entre la quinta y décima semanas de embarazo; los del tubo neural en la tercera y cuarta semana de embarazo y los de pared anterior entre la cuarta y la duodécima semana de embarazo. La etiología obedece a factores genéticos, ambientales y multifactoriales, y el riesgo de recurrencia depende de la causa. Existen tres niveles de prevención: preconcepcional, prenatal y postnatal. Conclusiones: el más importante es el preconcepcional, pues es el más eficaz, humano y económico(AU)

Background: congenital defects are an important cause of infantile mortality and disability. Cardiopathies and defects of the neural tube and the abdominal wall are among the most frequent ones. Aim: systematizing theoretical referents on embryogenesis and epidemiology of these developmental anomalies, to contribute to physicians and students´ training as health promoters. Materials and methods: 32 scientific articles were reviewed, searching in the Health Virtual Library of Infomed, in the databases Medline Complete, Pubmed Central, Clinical Key, regional Scielo and Scielo Cuba. The search was made from October 2014 to February 2015, and was restricted to the last 8 years.Outcomes: heart defects are produced by failures in embryogenesis, between the fifth and the seventh weeks of pregnancy; the neural tube ones, between the third and fourth weeks of pregnancy, and the ones of the front wall, between the fourth and the twelfth weeks of pregnancy. Etiology is due to genetic, environmental and multifactorable reasons; the recurrence risk depends on the cause. There are three prevention levels: pre-conceptional, prenatal and postnatal. Conclusions: the most important level is the pre-conceptional one, because it is the most efficacious, human and economic(AU)

Estudios genéticos sobre espina Bífida en Chile: por dónde comenzar?: [revisión] / Genetic studies of spina bifida in Chile: where do we start?: [review]

Neural tube defects (NTDs) are a group of congenital anomalies that affect the central nervious system. Spina Bifida (SB) is the most frecuent NTD in live births andi t is usually associated to disease, disability; and mortality. NTDs are considered as a multifactorial disease. Women who use folic acid periconceptionally are at a 50-70% reduced risk for NTD-affected pregnancies. More than 80 candidates genes to SB are been studied, someones related to folic acid metabolic pathway. MTHFR gene is the gene more studied in NTDs. Its allele 677T is asóciate to higher risk to NTD. It is important to study polymorphisms in MTHFR gene in Chile because Chilean population has dfferent ethnic origen from others previous studied populations.

Prevalência de defeitos de fechamento de tubo neural no Vale do Paraíba, São Paulo / Prevalence of neural tube defects in Vale do Paraíba, São Paulo, Brazil

OBJETIVO: Estimar a prevalência de defeitos de fechamento do tubo neural no Vale do Paraíba paulista e identificar possíveis fatores maternos e neonatais associados a tais defeitos. MÉTODOS: Realizou-se um estudo transversal com dados secundários obtidos na Secretaria Estadual da Saúde referentes aos nascimentos ocorridos em 2004 no Vale do Paraíba paulista, que compreende 35 municípios e conta com população de 2 milhões de habitantes. Anencefalia, encefalocele e espina bífida (mielocele e mielomeningocele) foram considerados defeitos de fechamento do tubo neural. As variáveis maternas foram: idade, escolaridade, cor da pele, número de consultas no pré-natal, número de filhos vivos e relato de óbito fetal prévio. As variáveis relativas ao recém-nascido foram: peso, idade gestacional e escore de Apgar. Realizou-se comparação das médias por meio do teste t de Student e obtiveram-se os valores das razões de chance com intervalos de confiança de 95%. RESULTADOS: Foram analisados 33.653 nascidos vivos. Trinta e oito recém-nascidos com o defeito foram encontrados (1,13/1.000 nascidos vivos), sendo 23 casos de espina bífida. Houve associação com baixo peso ao nascimento, prematuridade e menores escores de Apgar de cinco minutos. CONCLUSÕES: A prevalência desta anomalia foi inferior à de outros estudos nacionais e sua presença esteve associada ao baixo peso, à prematuridade e à baixa vitalidade ao nascer.

OBJECTIVE: To estimate the prevalence of neural tube defects in Vale do Paraíba, São Paulo, Brazil, and to identify possible maternal and neonatal variables associated with these defects. METHODS: This cross-sectional study used secondary records of the Health Department of São Paulo State related live births during 2004 in Vale do Paraíba, São Paulo, Brazil. This region has 35 cities and 2 million inhabitants. Anencephaly, encephalocele and spina bifida (myelocele and myelomeningocele) were considered as neural tube defects. The following maternal variables were analyzed: age, educational level, race, number of born alive and stillborn infants and prenatal visits. Neonatal variables were: birth weight, gestational age and Apgar score. Numerical variables were compared by Student t test, and Odds Ratio values were obtained with the 95%confidence interval. RESULTS: The analysis was performed based on 33,653 records of born alive infants. Twenty-three infants with spina bifida were identified, with an estimated prevalence of 1.13 cases for each 1,000 live births. The presence of neural tube defects was associated to low birth weight, prematurity and low Apgar score. CONCLUSIONS: The estimated prevalence of neural tube defects in this region of São Paulo was lower than others reported in previous Brazilian studies. These defects were associated with low birth weight, prematurity and respiratory depression at birth.

Brain tissue aspiration neural tube defect.

The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP). There were 15 (68.2%) females and 7 (31.8%) males. Age ranged from 18 to 40 weeks of gestation (mean = 31.8). Ten (45.5%) were stillborn, the same newborn, and 2 (9.1%) were abortuses. Diagnosis were: craniorachischisis (9 cases, 40.9%), anencephaly (8 cases, 36,4%), ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each), and early amniotic band disruption sequence (1 case, 4.5%). Only one case (4.5%) exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.

Brain tissue aspiration neural tube defect

O objetivo do estudo foi identificar qual a freqüência de aspiração de tecido cerebral e a existência de heterotopia nos pulmões de casos humanos de defeito de fechamento do tubo neural através da reação imuno-histoquímica para proteína fibrilar glial ácida (GFAP) em cortes histológicos de todos os lobos de ambos os pulmões de 22 casos de fetos e neonatos com defeito de fechamento do tubo neural. Havia 15 casos femininos (68,2%) e 7 masculinos (31,8%), com idade gestacional variando de 18 a 40 semanas (média= 31,8), sendo natimortos e neomortos 10 (45,5%) cada e 2 (9,1%) abortos. Os diagnósticos foram: Craniorraquisquise (9 casos, 40,9%), anencefalia (8 casos, 36,4%), encefalocele occipital rota e raquisquise (2 casos, 9,1%) e 1 (4,5%)caso de seqüência de disruptura amniótica precoce. Somente 1 caso (4,5%) apresentou células positivas dentro de bronquíolos e alvéolos em meio a células epiteliais amnióticas. Não se observou heterotopia no interstício pulmonar. Concluímos que a aspiração de tecido encefálico do líquido amniótico pode ocorrer em casos de defeito do fechamento do tubo neural, mas são infreqüentes e heterotopia não foi observada.

Chromosomal abnormalities in fetuses with open neural tube defects: prenatal identification with ultrasound.

OBJECTIVES: To determine the prevalence of chromosomal abnormalities in fetuses with open neural tube defects (NTD) undergoing prenatal chromosome analysis. The role of prenatal ultrasound in detecting those with an underlying chromosomal abnormality was also investigated. METHODS: Over a 6-year period, 144 fetuses with open NTD underwent prenatal chromosome analysis between 12 and 37 weeks of gestation, as part of a prospective, multicenter prenatal diagnosis and counseling program in Chile. This population included 66 fetuses with spina bifida, 46 with acrania/anencephaly, 21 with cephalocele and 11 with iniencephaly. A confident prenatal diagnosis was made in 143 fetuses (99%) and confirmed postnatally in all cases. RESULTS: An underlying chromosomal abnormality was diagnosed in 10 fetuses (7%), six with spina bifida, three with cephalocele and one with craniorachischisis. The prevalence of chromosomal abnormality varied according to the defect present in the fetus, with a 14% (3/21) prevalence among those with cephalocele, 9% (6/66) among those with spina bifida and 2% (1/57) among those with lethal defects such as acrania, anencephaly or iniencephaly. Karyotype results revealed trisomy 18 in seven cases, trisomy 13 in two and mosaicism for a marker chromosome in one. Prenatal ultrasound before the procedure showed that all chromosomally abnormal fetuses had additional findings. The prevalence of chromosomal abnormality in fetuses with spina bifida and cephalocele was higher when chromosome analysis was performed at or before 24 weeks of gestation in comparison to those performed after 24 weeks (5/31 (16%) vs. 4/56 (7%), respectively). However, this difference did not reach statistical significance, probably due to the small number of cases. CONCLUSIONS: A significant number of fetuses with open NTD are chromosomally abnormal. Although prenatal chromosome analysis should be considered in all cases, prenatal ultrasound seems effective in identifying those fetuses with an underlying chromosomal abnormality.

Sirenomelia asociada a defectos del tubo neural: reporte de un caso clínico y revisión de la literatura / Sirenomelia rarely associated to neural tube: a case clinic report and review literature

Se presenta el caso de una paciente primigesta de 20 años de edad y sin antecedentes pertinentes, controlada por el Servicio de Prenatal de nuestro centro. Es hospitalizada con los diagnósticos de: embarazo de 20 semanas y malformaciones fetales múltiples. Expulsa feto masculino con sirenomelia asociada extrañamente a anencefalia, cráneo-raquisquisis y esbozos auriculares. Se realiza el examen anatomopatológico correspondiente y se verifican otros hallazgos

Ácido fólico na prevenção dos defeitos de fechamento de tubo neural / Folic acid in the prevention of neural tube closing defects

O autor revê as causas dos defeitos de fechamento e a embriologia do tubo neural, recapitulando aspectos do metabolismo do ácido fólico e seu papel na prevençäo daquelas malformaçöes

Afecciones originadas en defectos disraficos lumbosacros congénitos: dermal sinus, meningioma, teratoma sacrocoxígeo / Affections caused in lumbosacral dysraphic defects congenital: dermal sinus, meningocele, sacrococcygeal teratoma

Se presenta la patología originada en defectos disráficos lumbosacros. Se relatan 6 observaciones correspondientes a un período de 20 años: 2 dermal sinus, 3 teratomas sacrocxígeos y 1 meningocele. Se insiste sobre la necesidad de conocer esta patología y del tratamiento quirúrgico precoz, con el fin de evitar las graves complicaciones que origina. En los casos de dermal sinus con conducto fistuloso, cuando no existen síntomas neurológicos ni secreción por orificio cutáneo, es aconsejable efectuar la operación despues de los 18 meses de edad

Afecciones originadas en defectos disraficos lumbosacros congénitos: dermal sinus, meningioma, teratoma sacrocoxígeo / Affections caused in lumbosacral dysraphic defects congenital: dermal sinus, meningocele, sacrococcygeal teratoma

Se presenta la patología originada en defectos disráficos lumbosacros. Se relatan 6 observaciones correspondientes a un período de 20 años: 2 dermal sinus, 3 teratomas sacrocxígeos y 1 meningocele. Se insiste sobre la necesidad de conocer esta patología y del tratamiento quirúrgico precoz, con el fin de evitar las graves complicaciones que origina. En los casos de dermal sinus con conducto fistuloso, cuando no existen síntomas neurológicos ni secreción por orificio cutáneo, es aconsejable efectuar la operación despues de los 18 meses de edad (AU)

Possible mesodermal origin for axial dysraphic disorders.

We report four patients who provide clinical evidence supporting the hypothesis that axial dysraphic states may result from a primary disturbance in the chordoaxial mesoderm. One infant had complete craniorachischisis, an omphalocele, and ambiguous genitalia. A second infant had anencephaly and an omphalocele. The third had iniencephaly. The fourth had cervical vertebral fusion defects, an occipital menigocele, and a laterality malformation sequence. Alteration in the development of structures derived from the chordoaxial mesoderm could explain all of the structure defects observed in the four patients. This hypothesis accounts for the nature of the defects seen in association with dysraphic disorders and for the genetic relationship observed between neural tube defects and vertebral anomalies.