Nasoethmoidal meningocele in a child presenting bilateral congenital cystic adenomatoid malformation: Evidence for a new entity or consequence of gestational exposures?

BACKGROUND: Nasoethmoidal meningocele is considered an uncommon type of cephalocele, and congenital cystic adenomatoid malformation (CCAM) is a rare lung disorder characterized by overgrowth of the terminal bronchioles. CASE: We report the unusual association between a nasoethmoidal meningocele and CCAM type II in a fetus exposed to valproic acid and misoprostol. The mother was an 18-year-old woman on her first pregnancy. She had a history of absence seizures since she was 5 years old. She took valproic acid from the beginning of the gestation until the end of the third month. At the end of the third month, she attempted interruption of her pregnancy using misoprostol. The fetal nasoethmoidal meningocele and CCAM type II were identified through morphological ultrasound examination and magnetic resonance imaging. A genome-wide study detected one copy number variation classified as rare, entirely contained into the SPATA5 gene. However, it does not seem to be associated to the clinical findings of the patient. CONCLUSION: To our knowledge, there is only one case reported in the literature showing the same association between a nasoethmoidal meningocele and CCAM. Thus, the malformations observed in our patient may be related to the gestational exposures. Also, we cannot rule out that the patient may present the same condition characterized by a cephalocele and CCAM described by some authors, or even an undescribed entity, because some hallmark features, such as laryngeal atresia and limb defects, were not observed in our case. Further reports will be very important to better understand the associations described in our study.

Thalidomide Embryopathy as Possible Cause of Anterior Sacral Meningocele: A Case Report.

A 54-year-old male presented with a sudden burning sensation during urination and left flank pain. Apart from having congenital facial palsy and malformation of the inner right ear that was linked to thalidomide embryopathy, the patient has always been in good health. Urine examination showed the presence of a urinary tract infection. An abdominal ultrasound revealed a large cyst in the lower abdomen, which on MRI corresponded to a large anterior sacral meningocele (ASM) with sacral agenesis at S1/S2. After antibiotic treatment and the spontaneous passage of a kidney stone, the symptoms resolved. This suggests that the patient's acute symptoms were caused by the urolithiasis and not the ASM. Thalidomide is teratogenic between days 17 and 30 after conception. The neural tube closes between days 20 and 36, therefore, thalidomide embryopathy was the possible cause of ASM in this patient. Birth Defects Research 109:1390-1392, 2017.© 2017 Wiley Periodicals, Inc.

Meningocele and ankyloblepharon following in utero exposure to olanzapine.

Although atypical antipsychotics are widely used during pregnancy, their safety is not well established. This case highlights the possible teratogenic effect of olanzapine, in which the baby was born with meningocele and ankyloblepharon. It is suggested that olanzapine may interfere with embryonic development at different stages of pregnancy.

Examination of meningocele induced by the antitumor agent DE-310 in rat fetuses.

The antitumor drug, DE-310, is the slow release form of the camptothecin derivative DX-8951. We investigated a toxicological profile of meningoceles in SD rat fetuses, whose mothers received intravenous DE-310 at several doses, and the time course changes of histology. DE-310 induced a meningocele in the posterior fontanelle of live fetuses by the four-time administration of 0.3 mg/(kgday) or more during the organogenetic period, or by a single administration of 1.0 mg/kg, particularly, between days 7 and 13 of gestation with an incidence of 100%. The meningocele was caused by the principal ingredient DX-8951. The earliest histological change was focal congestion between the skin and cerebrum, followed by the formation of a space covered by thinned epidermis with necrosed basal cells, hemorrhage in the surrounding connective tissues, cerebrum and ventricles, cavitation of the cerebrum, and incomplete formation of the skull bones and subarachnoid space. DE-310 was characterized as preferentially inducing meningocele (meningoencephalocele in severe cases) in rat fetuses.

Alcohol embryo- and fetopathy. Neuropathology of 3 children and 3 fetuses.

Maternal chronic ethanol abuse during pregnancy causes malformations of the offspring. Three children (aged 6 months, 9 months, 4 1/2 years) and 3 fetuses (17th, 18th, and 20th gestational week) showed a wide spectrum of disorders ranging from severe dysraphic state, arhinencephaly, porencephaly, agenesis of corpus callosum, a range from hydranencephaly to microdysplasias (p.e. reduced gyration of dentate nucleus and inferior olives), and a range from gastrochisis or congenital heart defects to craniofacial dysmorphogenesis and palmar crease anomalies. The patterns of the cerebral malformations were not as uniform as the clinical phenotype of the alcohol embryopathy. The observations did not support the assumption that there exists a specific period for alcohol teratogenicity.

Experimentally induced cranial meningocele and cerebral microgyria.

Teratological study on microgyra is rare, and its morphogenesis is still on dispute. Microgyra associated with cranial meningocele and progressive hydrocephalus were induced in rat siblings by administration of 10 mg/kg.bw of n-methyl n-nitrosourea (MNU) to rat dams on day 9 of gestation. Microgyra were closely similar to human cases. They were formed during progressive stage of hydrocephalus, when the expansion of cranial meningocele was proceeding. This stage was in accord with migratory and postmigratory phase of neuroblasts. The results of this study suggest that the formation of microgyra may be related to the cortical laminar destruction during this critical period of differentiating brain.

[Upper and lower neural tube defects: prevalence and association with illnesses and drugs]. / Defectos del tubo neural altos y bajos, prevalencia, y asociación con enfermedades y medicamentos.

OBJECTIVE: To determine the prevalence of upper and lower neural tube defects and identify its association with the exposure to illnesses and drugs during pregnancy. MATERIAL AND METHODS: This is a case-control study of 107 newborns with upper neural tube defects, 59 with lower neural tube defects, and 166 newborns without malformations, in 56,926 consecutive births between 1989 and 1997. The exposure was documented by a direct interview to the mother of those subject of study. The association was measured by the odds ratios, with confidence interval of 95%. RESULTS: The prevalence of upper neural tube defects was of 1.9 for 1,000 newborn (alive or dead) and of lower neural tube defects of 1.0 for 1,000. The exposure to illnesses of less than a month of duration was associated with upper neural tube defects (OR = 3.11; IC = 1.34-7.39) the most important was flu; also the exposure to drugs (OR = 5.85; IC = 2.97-11.62), the most prominent was acetaminophen. These factors of risk were not associated with lower neural tube defects. The mother's occupation, illness of more than a month of duration and X-ray exposure were not associated with of upper and lower neural tube defects. CONCLUSIONS: More studies are needed in the association among illnesses of less than a month of duration and drugs with upper neural tube defects. The different exposure frequencies between upper and lower neural tube defects suggest heterogeneity.

Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.

Lipopolysaccharide (LPS) has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR), neural tube defects (NTDs) and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg) daily from gestational day (GD)8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg) before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft) and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.

Comparative teratogenicity of triamcinolone acetonide and dexamethasone in the rhesus monkey (Macaca mulatta).

Pregnant rhesus macaques were treated with 0.5 or 2.5 mg/kg triamcinolone acetonide (TAC) or 1.0 or 10.0 mg/kg dexamethasone sodium phosphate (DEX) between 20 and 50 gestational days (GD). Treatment with TAC at 2.5 mg/kg resulted in a fetal loss of 71%; 3/5 recovered fetuses displayed an encephalocele or meningocele. All other treatment groups displayed minor cranial skeletal abnormalities consistent with glucocorticoid-mediated teratogenesis. DEX was shown to have a lower teratogenic potential than TAC in this species.

Meningoencephalocele associated with Tripterygium wilfordii treatment.

We treated a male infant with occipital meningoencephalocele associated with the taking of Tripterygium wilfordii. The infant was delivered normally at 38 weeks of gestation with a huge cystic mass protruding from the occiput. He was diagnosed with occipital meningoencephalocele and cerebellar agenesis. His mother had taken T. wilfordii for rheumatoid arthritis early in her pregnancy. T. wilfordii is a herbal medicine used for rheumatoid arthritis and male contraception. Since its toxicity is high and its use during pregnancy is restricted, it is the most likely cause of this infant's anomalies.

Fatal hypernatremia from saltwater used as an emetic.

An adolescent boy returned home from a party and told his parents he may have taken some pills while there. He was given saltwater to drink, in an effort to induce emesis. He vomited numerous times, then seized. Hypernatremia (195 mmol/L) was diagnosed at the community hospital, and he was transferred to a pediatric intensive care facility. He suffered numerous complications and died from cerebral herniation. This case is presented to remind physicians of the dangers of this obsolete therapy.