Incidence of anencephalus and spina bifida in Greece

A cross-sectional national survey of 11,048 births in the whole of Greece in April 1984 identified 7 cases of anencephalus and 9 of spina bifida. There was thus an incidence of 1.45 neural tube defects per 1,000 total births. This is the first geographically defined population study from southern Europe. In comparison with hospital-based data from the 2 countries on its borders, the Greek rates are rather similar to those of Yugoslavia but much lower than reports from Turkey.     

Neural crest anomaly syndromes in children with spina bifida.

A hereditary contribution to the etiology of neural tube defects (NTDs) has been suggested by clinical studies and animal models. To evaluate the hypothesis that common genes are important for both neural tube defects and neural crest anomalies, we examined children with developmental abnormalities of the spinal cord for anomalies of neural crest-derived structures. Neural crest anomalies, particularly auditory and pigmentary disorders, were identified and classified according to inheritance and type of anomaly. Of the 515 children screened, 44 (8.5%) had neural crest anomalies, 20 (3.9%) of which were apparently familial. Another 19 (3.7%) families had neural crest anomalies in two or more close relations, but the NTD subject was unaffected. Sixteen (3.1%) children with NTDs had a recognizable syndrome, including nine (1.7%) with a subtype of the Waardenburg syndromes. The coincidence of familial neural crest anomaly syndromes in subjects with spina bifida implies that defects in genes underlying neural crest development may contribute to the etiology of neural tube defects in a fraction of cases. The rate of anomalies and familial syndromes of neural crest-derived structures must be assessed in an adequate control sample to evaluate whether or not these abnormalities constitute risk factors for NTDs.     

Birth ranks of spontaneous abortions in sibships of children affected by anencephaly or spina bifida.

Data on the birth ranks of miscarriages within sibships in which a case of anencephaly or spina bifida (ASB) had occurred were analysed by the Haldane-Smith statistical test. This showed that miscarriages in ASB sibships tend to have a negative birth order effect--that is, they occur in earlier rather than later pregnancies within the sibship. The strongest source of bias in this analysis--the fact that mothers tend to forget early spontaneous abortions--worked against this finding, so the negative birth order effect is probably genuine. Because ASB itself shows a negative birth order effect and because spontaneous abortions in normal sibships do not show such an effect, the additional spontaneous abortions in ASB sibships are probably of fetuses affected by ASB.     

Sleep problems, chronotype, and diurnal preferences in children and adults with spina bifida

Spina bifida meningomyelocele (SBM) is a neural tube defect that involves dysraphism of the spinal cord and extensive reorganization of the brain. The authors assessed the relationship between chronotype, diurnal preferences, and sleep problems in individuals with SBM and healthy controls. Although individuals with SBM showed the characteristic decelerating quadratic relationship between age and chronotype, the curve was displaced, peaking at a younger age in controls compared with SBM (23.4 vs. 29.2 years). Groups did not differ in morningness-eveningness preferences. Individuals with SBM endorsed more sleep problems than controls. Further examination of the relationship between entrainment and sleep in SBM is warranted.     

A mouse model for neural tube defects: the curtailed (Tc) mutation produces spina bifida occulta in Tc/+ animals and spina bifida with meningomyelocele in Tc/t

Curtailed (Tc), a dominant mutation on mouse chromosome 17, causes a tailless phenotype and occasional hindlimb paralysis in heterozygotes. Histologically, Tc/+ embryos show a variety of abnormalities including budding and ventral duplication of the developing spinal cord, duplication and intermittent absence of the notochord, and partial or complete absence of bony vertebrae, all posterior to midliver level. When Tc is heterozygous with t-haplotypes that contain the "tail interaction factor," tct, the phenotype is more severe, and a dorsal blood blister exists in the lumbosacral area. Our microscopic observations reveal that Tc/tw5 mice have a lumbosacral spina bifida with meningomyelocele. This results from the absence of bony vertebrae, extensive thinning of the dermis dorsally, and the rupturing of the previously closed neural tube, probably by increased cerebrospinal fluid (CSF) pressure on the necrotic, attenuated roof plate. Thinning of the roof plate, which facilitates the rupturing of the spinal cord, is not observed in Tc/+, which suggests that this phenomenon is associated with the interaction of Tc with the t-allele. Later in the development of Tc/tw5 embryos, adjacent blood vessels are ruptured, resulting in hemorrhage into the CSF space to give the external appearance of a blood blister. Tc/+ mice also show an absence of bony vertebrae dorsally in the lumbosacral region, but they lack the dorsal blood blister, and the dermal layer overlying the bony defect retains its normal thickness; these observations describe a spina bifida occulta.     

Therapeutic potential of in utero mesenchymal stem cell (MSCs) transplantation in rat foetuses with spina bifida aperta

Neural tube defects (NTDs) are complex congenital malformations resulting from incomplete neurulation in embryo. Despite surgical repair of the defect, most of the patients who survive with NTDs have a multiple system handicap due to neuron deficiency of the defective spinal cord. In this study, we successfully devised a prenatal surgical approach and transplanted mesenchymal stem cells (MSCs) to foetal rat spinal column to treat retinoic acid induced NTDs in rat. Transplanted MSCs survived, grew and expressed markers of neurons, glia and myoblasts in the defective spinal cord. MSCs expressed and perhaps induced the surrounding spinal tissue to express neurotrophic factors. In addition, MSC reduced spinal tissue apoptosis in NTD. Our results suggested that prenatal MSC transplantation could treat spinal neuron deficiency in NTDs by the regeneration of neurons and reduced spinal neuron death in the defective spinal cord.