The Construction of a Predictive Composite Index for Decision-Making of CSF Diversion Surgery in Pediatric Patients following Prenatal Myelomeningocele Repair.

BACKGROUND AND PURPOSE: There is a wide range of clinical and radiographic factors affecting individual surgeons' ultimate decision for CSF diversion for pediatric patients following prenatal myelomeningocele repair. Our aim was to construct a composite index (CSF diversion surgery index) that integrates conventional clinical measures and neuroimaging biomarkers to predict CSF diversion surgery in these pediatric patients. MATERIALS AND METHODS: This was a secondary retrospective analysis of data from 33 patients with prenatal myelomeningocele repair (including 14 who ultimately required CSF diversion surgery). Potential independent variables, including the Management of Myelomeningocele Study Index (a dichotomized variable based on the shunt-placement criteria from the Management of Myelomeningocele Study), postnatal DTI measures (fractional anisotropy and mean diffusivity in the genu of the corpus callosum and the posterior limb of internal capsule), fronto-occipital horn ratio at the time of DTI, gestational ages, and sex, were evaluated using stepwise logistic regression analysis to identify the most important predictors. RESULTS: The CSF diversion surgery index model showed that the Management of Myelomeningocele Study Index and fractional anisotropy in the genu of the corpus callosum were significant predictors (P < .05) of CSF diversion surgery. The predictive value of the CSF diversion surgery index was also affected by fractional anisotropy in the posterior limb of the internal capsule and sex with marginal effect (.05

.10). The overall CSF diversion surgery index model fit the data well with statistical significance (eg, likelihood ratio: P < .001), with the performance (sensitivity = 78.6%; specificity = 86.5%, overall accuracy = 84.8%) superior to all individual indices in sensitivity and overall accuracy, and most of the individual indices in specificity. CONCLUSIONS: The CSF diversion surgery index model outperformed all single predictor models and, with additional validation, may potentially be developed and incorporated into a sensitive and robust clinical tool to assist clinicians in hydrocephalus management.

Spinal Imaging Findings of Open Spinal Dysraphisms on Fetal and Postnatal MRI.

BACKGROUND AND PURPOSE: Fetal MRI has become a valuable tool in the evaluation of open spinal dysraphisms making studies comparing prenatal and postnatal MRI findings increasingly important. Our aim was to determine the accuracy of predicting the level of the spinal dysraphic defect of open spinal dysraphisms on fetal MR imaging and to report additional findings observed when comparing fetal and postnatal MR imaging of the spine in this population. MATERIALS AND METHODS: A single-center retrospective analysis was performed of fetal MRIs with open spinal dysraphisms from 2004 through 2016 with available diagnostic postnatal spine MR imaging. Images were reviewed by 2 board-certified fellowship-trained pediatric neuroradiologists. Corresponding clinical/operative reports were reviewed. RESULTS: One hundred nineteen fetal MRIs of open spinal dysraphisms were included. The level of the osseous defect between fetal and postnatal MR imaging was concordant in 42.9% (51/119) of cases and was 1 level different in 39% (47/119) of cases. On postnatal MR imaging, type II split cord malformation was seen in 8.4% (10/119) of cases, with only 50% (5/10) of these cases identified prospectively on fetal MR imaging. Syrinx was noted in 3% (4/119) of prenatal studies, all cervical, all confirmed on postnatal MR imaging. CONCLUSIONS: Fetal MR imaging is accurate in detecting the level of the spinal dysraphic defect, which has an impact on prenatal counseling, neurologic outcomes, and eligibility for fetal surgery. In addition, fetal MR imaging is limited in its ability to detect split cord malformations in patients with open spinal dysraphisms. Although rare, fetal MR imaging has a high specificity for detection of cervical spinal cord syrinx.

Senescence associated with the over-replication of a mitochondrial retroplasmid in Neurospora crassa.

Mitochondrial DNA rearrangements and deletions are a prevailing feature of filamentous fungal cultures that undergo senescence. In Neurospora spp., strains containing the Mauriceville and Varkud mitochondrial retroplasmids routinely senesce at elevated temperatures, a process that is initiated by the integration of variant forms of the plasmids into the mitochondrial genome. Here, we describe a strain that is phenotypically distinguishable from previously characterized senescent strains and show that senescence can occur in the absence of plasmid integration and associated alterations in mitochondrial DNA. The MS4416 strain contains a unique variant of the Mauriceville retroplasmid, and undergoes senescence at highly predictable frequencies at 37 degrees, 25 degrees and 18 degrees C. Decline in vegetative growth rate correlates with increased levels of the variant plasmid and alterations in the synthesis of mitochondrially encoded proteins, suggesting that plasmid over-replication interferes with mitochondrial translation. We also report the isolation of a mutant strain that escapes senescence yet still maintains high levels of the variant plasmid. Its ability to tolerate a growth-suppressive retroplasmid suggests that there are mechanisms in Neurospora which compensate for the deleterious effects that plasmid over-replication has on mitochondrial function.