Severe and progressive neuronal loss in myelomeningocele begins before 16 weeks of pregnancy.

BACKGROUND: Despite undisputable benefits, midtrimester prenatal surgery is not a cure for myelomeningocele (MMC): residual intracranial and motor deficits leading to lifelong handicap question the timing of prenatal surgery. Indeed, the timing and intensity of intrauterine spinal cord injury remains ill defined. OBJECTIVE: We aimed to describe the natural history of neuronal loss in MMC in utero based on postmortem pathology. STUDY DESIGN: Pathology findings were analyzed in 186 cases of myelomeningocele with lesion level between S1 and T1. Using a case-control, cross-sectional design, we investigated the timewise progression and topographic extension of neuronal loss between 13 and 39 weeks. Motor neurons were counted on histology at several spinal levels in 54 isolated MMC meeting quality criteria for cell counting. These were expressed as observed-to-expected ratios, after matching for gestational age and spinal level with 41 controls. RESULTS: Chiari II malformation increased from 30.7% to 91.6% after 16 weeks. The exposed spinal cord displayed early, severe, and progressive neuronal loss: the observed-to-expected count dropped from 17% to ≤2% after 16 weeks. Neuronal loss extended beyond the lesion to the upper levels: in cases <16 weeks, the observed-to-expected motor neuron count was 60% in the adjacent spinal cord, decreasing at a rate of 16% per week. Progressive loss was also found in the upper thoracic cord, but in much smaller proportions. The observed-over-expected ratio of motor neurons was not correlated with the level of myelomeningocele. CONCLUSIONS: Significant neuronal loss is present ≤16 weeks in the exposed cord and progressively extends cranially. Earlier prenatal repair (<16 weeks) could prevent Chiari II malformation in 69.3% of cases, rescue the 17% remaining motor neurons in the exposed cord, and prevent the extension to the upper spinal cord.

17q21.31 microdeletion: brain anomalies leading to prenatal diagnosis.

Ultrasound examination performed on a 36-year-old woman at 33 weeks of gestation showed the presence of isolated and bilateral ventriculomegaly in the fetus. Array-based comparative genomic hybridization (array-CGH) performed on uncultured amniocytes at 35 weeks of gestation revealed a 17q21.31 microdeletion. After genetic counseling, the pregnancy was terminated at 37 weeks of gestation. At autopsy, the fetus displayed facial dysmorphic features and triventricular ventriculomegaly. To our knowledge, this is the first case of a 17q21.31 microdeletion detected prenatally. Our report suggests that array-CGH should be performed when severe ventriculomegaly is observed in prenatal ultrasound examination.