Caroline D. Robson

High dose dexmedetomidine as the sole sedative for pediatric MRI

Objective:  This large‐scale retrospective review evaluates the sedation profile of dexmedetomidine.

Mutations in LRP2 , which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes

Donnai-Barrow syndrome is associated with agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. By studying multiplex families, we mapped this disorder to chromosome 2q23.3–31.1 and identified LRP2 mutations in six families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome. LRP2 encodes megalin, a multiligand uptake receptor that regulates levels of diverse circulating compounds. This work implicates a pathway with potential pharmacological therapeutic targets.

The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management

Background: Mutations in the PTEN gene cause two disorders that predispose to cancer, Bannayan–Riley–Ruvalcaba and Cowden syndromes. Some patients with a PTEN mutation have only macrocephaly and autism, but they may still be at risk for neoplasms. Vascular anomalies occur in patients with a PTEN mutation, but they have not been systematically studied or precisely defined. Method: We analysed the clinical and radiological features of the vascular anomalies in 26 patients with PTEN mutations who were either seen or had their medical records reviewed at Children’s Hospital Boston. Results: All 23 patients who had their head circumference measured were macrocephalic, and all 13 male patients who were fully examined had penile freckling. Vascular anomalies were found in 14/26 (54%) of patients: 8/14 (57%) had multiple lesions and 11/13 (85%) who had cross-sectional imaging had intramuscular vascular lesions. Radiographic studies showed that 12/14 (86%) were fast-flow vascular anomalies, and angiography typically showed focal segmental dilatation of draining veins. Excessive ectopic fat in the vascular anomalies was present in 11/12 (92%) of patients on CT or MRI. Intracranial developmental venous anomalies (DVAs) were found in 8/9 (89%) of patients who had brain MRI with contrast. Conclusions: Vascular anomalies in patients with a PTEN mutation are typically multifocal intramuscular combinations of fast-flow channels and ectopic fat. Cerebral DVAs are very common. PTEN mutational analysis should be considered for all macrocephalic patients with fast-flow vascular anomalies or multiple intracranial DVAs.

Lymphadenitis Due to Nontuberculous Mycobacteria in Children: Presentation and Response to Therapy

The most common manifestation of infection due to nontuberculous mycobacteria (NTM) in children is cervical lymphadenitis in an otherwise healthy patient. We identified and reviewed 19 cases of proven or presumptive lymphadenitis due to NTM seen at our hospital over the course of 13 months. Nine patients underwent initial surgical excision of involved lymph nodes. Ten children did not have involved lymph nodes excised initially and were treated with macrolide-containing antibiotic regimens. Of these patients, five required subsequent surgical excision and five were cured with combination chemotherapy. Six patients underwent radiographic imaging of the head and neck that revealed asymmetrical adenopathy with ring-enhancing masses but minimal inflammatory stranding of the subcutaneous fat, a finding that may distinguish adenitis caused by NTM from staphylococcal and streptococcal adenitis. Our data suggest that if surgical excision is not considered feasible, antimicrobial therapy for adenitis due to NTM may be beneficial for some patients.

Volumetric MRI Study of Brain in Children With Intrauterine Exposure to Cocaine, Alcohol, Tobacco, and Marijuana

OBJECTIVE. The objective of this study was to use volumetric MRI to study brain volumes in 10- to 14-year-old children with and without intrauterine exposure to cocaine, alcohol, cigarettes, or marijuana. METHODS. Volumetric MRI was performed on 35 children (mean age: 12.3 years; 14 with intrauterine exposure to cocaine, 21 with no intrauterine exposure to cocaine) to determine the effect of prenatal drug exposure on volumes of cortical gray matter; white matter; subcortical gray matter; cerebrospinal fluid; and total parenchymal volume. Head circumference was also obtained. Analyses of each individual substance were adjusted for demographic characteristics and the remaining 3 prenatal substance exposures. RESULTS. Regression analyses adjusted for demographic characteristics showed that children with intrauterine exposure to cocaine had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than comparison children. After adjustment for other prenatal exposures, these volumes remained smaller but lost statistical significance. Similar analyses conducted for prenatal ethanol exposure adjusted for demographics showed significant reduction in mean cortical gray matter; total parenchymal volumes; and head circumference, which remained smaller but lost statistical significance after adjustment for the remaining 3 exposures. Notably, prenatal cigarette exposure was associated with significant reductions in cortical gray matter and total parenchymal volumes and head circumference after adjustment for demographics that retained marginal significance after adjustment for the other 3 exposures. Finally, as the number of exposures to prenatal substances grew, cortical gray matter and total parenchymal volumes and head circumference declined significantly with smallest measures found among children exposed to all 4. CONCLUSIONS. These data suggest that intrauterine exposures to cocaine, alcohol, and cigarettes are individually related to reduced head circumference; cortical gray matter; and total parenchymal volumes as measured by MRI at school age. Adjustment for other substance exposures precludes determination of statistically significant individual substance effect on brain volume in this small sample; however, these substances may act cumulatively during gestation to exert lasting effects on brain size and volume.

Nasal glioma and encephalocele: diagnosis and management.

Objective To review the biology of nasal glioma and encephalocele and to present an algorithm for preoperative evaluation and surgical management.

Level of In Utero Cocaine Exposure and Neonatal Ultrasound Findings

Objective.  To assess whether there is an association between the level of in utero cocaine exposure and findings on neonatal cranial ultrasound, controlling for potentially confounding variables. Study Design. In a prospective longitudinal study, three cocaine exposure groups were defined by maternal report and infant meconium assay: unexposed, heavier cocaine exposure (>75th percentile self-reported days of use or of meconium benzoylecogonine concentration) or lighter cocaine exposure (all others). Neonatal ultrasounds from 241 well, term infants were read by a single radiologist who was masked to the exposure group. Results. Infants with lighter cocaine exposure did not differ from the unexposed infants on any ultrasound findings. After controlling for infant gender, gestational age, and birth weightz scores and for maternal parity, blood pressure in labor, ethnicity, and use of cigarettes, alcohol, and marijuana during pregnancy, the more heavily cocaine-exposed infants were more likely than the unexposed infants to show subependymal hemorrhage in the caudothalamic groove (covariate adjusted odds ratio: 3.88; 95% confidence interval: 1.45, 10.35). Conclusions. This is the first study to demonstrate that ultrasound findings suggestive of vascular injury to the neonatal central nervous system are related to the level of prenatal cocaine exposure. Inconsistency in previous research in identifying an association between prenatal cocaine exposure and neonatal cranial ultrasound findings may reflect failure to consider dose effects.

How Accurately Does Current Fetal Imaging Identify Posterior Fossa Anomalies

OBJECTIVE The first objective of our study was to describe the prevalence and spectrum of posterior fossa anomalies over 5 years in a major fetal care center where the referral diagnosis (by fetal sonography) was investigated by fetal MRI and, if confirmed, by postnatal MRI if possible. The second objective was to assess the accuracy with which fetal MRI predicts postnatal MRI findings in this population. MATERIALS AND METHODS We retrospectively identified all cases of suspected fetal posterior fossa anomalies referred to our center from 2002 through 2006. We reviewed maternal, fetal, neonatal, and follow-up records of all cases and fetal and early postnatal imaging studies. RESULTS Of the 90 cases of suspected fetal posterior fossa anomalies (by fetal sonography) referred over the study period, 60 (67%) were confirmed by fetal MRI. Of 42 live-born infants, 39 (93%) underwent postnatal MRI. There was complete agreement in fetal and postnatal MRI diagnoses in 23 infants (59%). In 16 cases (41%), fetal and postnatal MRI diagnoses disagreed; postnatal MRI excluded fetal MRI diagnoses in six cases (15%) and revealed additional anomalies in 10 cases (26%). CONCLUSION Although a valuable adjunct to fetal sonography in cases of suspected posterior fossa anomaly, current fetal MRI, particularly in early gestation, has limitations in accurately predicting postnatal MRI abnormalities. Advancing the accuracy of MRI for the diagnosis of posterior fossa anomalies will require greater understanding of normal brain development and improved tissue resolution of fetal MRI. During the interim, our findings strongly support the need for postnatal MRI follow-up in cases with suspected posterior fossa anomalies by fetal MRI.

Transnasal endoscopic excision of midline nasal dermoid from the anterior cranial base.

We recommend that every patient with a midline nasal dermoid be evaluated preoperatively by fine-cut CT scan, in the axial and coronal planes, using both bone and soft-tissue algorithms. Because of CT limitations for assessing soft tissue at the cranial base, a complementary thin-section, high-resolution, multiplanar MRI scan should be considered. Transnasal endoscopic excision of midline nasal dermoid should be used if the dermoid is located within the nasal cavity, and there is minimal or no cutaneous involvement. This approach can be combined with a short vertical midline lenticular excision of a cutaneous punctum. Vertical cutaneous excision should be limited; the best location is the nasal tip. Vertical nasal scars over the bony pyramid invariably widen no matter what intradermal suture is used. Endoscopic removal should be considered even if preoperative radiologic studies show extension to the anterior cranial fossa. Endoscopic excision could also be used to resect a dermoid extending between the dural leaves of anterior fossa. However, a combined intra-extracranial approach is necessary if the dermoid is in the falx cerebri. We agree with other authors that frozen sectioning the superior margin of the specimen should be done to ensure that there is no intracranial extension. Valsalva maneuver during endoscopic visualization of the cranial base is a valuable means of ruling out a cerebral spinal fluid leak.

Neurodevelopmental outcome of fetuses referred for ventriculomegaly

To characterize the delivery and postnatal neurodevelopmental outcomes of fetuses referred for ventriculomegaly (VM).