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Gene microarray has been used to identify prognostic markers and genes of interest for therapeutic targets; a less common use is to show possible histogenetic relationships between rare tumor types and more common neoplasms. Intracranial malignant ectomesenchymoma (MEM) is a pediatric tumor postulated to arise from neural crest cells that contain divergent neuroectodermal and mesenchymal tissues, principally mature ganglion cells and rhabdomyosarcoma (RMS). We investigated a case of MEM by molecular, cytogenetic, and gene array analyses and compared results with our previously unpublished series of 51 pediatric tumors including conventional RMS, Ewing sarcoma (EWS), medulloblastoma (MED), atypical teratoid rhabdoid tumor (ATRT), and malignant peripheral nerve sheath tumor (MPNST); the latter is a sarcoma also with potential for divergent differentiation. Standard cytogenetic analyses and RT-PCR testing for the classic gene rearrangements seen in RMS [t(2;13)-PAX3/FKHR] and EWS ([t(11;22) & t(21;22)-EWS/FLI-1 & EWS/ERG), were used for characterization of the MEM, with gene expression microarray analyses on all tumor types. Gene rearrangement studies were negative in MEM. Gene expression microarray analyses showed tight clustering of the MEM with the MPNST (n = 2), but divergence from other pediatric tumors. MEM and MPNST both showed complex karyotypes, but without diagnostic translocations. Despite the presence of malignant skeletal muscle differentiation in the MEM, gene array testing showed no overlap with RMS, MED, or ATRT, but rather with MPNST. This suggests a common stem cell origin or embryonic gene recapitulation for these tumors and provides novel insights into their underlying biology.

OBJECTIVE Cutaneous stigmata or congenital anomalies often prompt screening for occult spinal dysraphism (OSD) in asymptomatic infants. While a number of studies have examined the results of ultrasonography (US) screening, less is known about the findings when MRI is used as the primary imaging modality. The object of this study was to assess the results of MRI screening for OSD in infants. METHODS The authors undertook a retrospective review of all infants who had undergone MRI of the lumbar spine to screen for OSD over a 6-year period (September 2006–September 2012). All images had been obtained on modern MRI scanners using sequences optimized to detect OSD, which was defined as any fibrolipoma of the filum terminale (FFT), a conus medullaris ending at or below the L2–3 disc space, as well as more complex lesions such as lipomyelomeningocele (LMM). RESULTS Five hundred twenty-two patients with a mean age of 6.2 months at imaging were included in the study. Indications for imaging included isolated dimple in 235 patients (45%), asymmetrically deviated gluteal cleft in 43 (8%), symmetrically deviated (Y-shaped) gluteal cleft in 38 (7%), hemangioma in 28 (5%), other isolated cutaneous stigmata (subcutaneous lipoma, vestigial tail, hairy patch, and dysplastic skin) in 31 (6%), several of the above stigmata in 97 (18%), and congenital anomalies in 50 (10%). Twenty-three percent (122 patients) of the study population had OSD. Lesions in 19% of these 122 patients were complex OSD consisting of LMM, dermal sinus tract extending to the thecal sac, and lipomeningocele. The majority of OSD lesions (99 patients [81%]) were filar abnormalities, a group including FFT and low-lying conus. The rate of OSD ranged from 12% for patients with asymmetrically deviated gluteal crease to 55% for those with other isolated cutaneous stigmata. Isolated midline dimple was the most common indication for imaging. Among this group, 20% (46 of 235) had OSD. There was no difference in the rate of OSD based on dimple location. Those with OSD had a mean dimple position of 15 mm (SD 11.8) above the coccyx. Those without OSD had a mean dimple position of 12.2 mm (SD 19) above the coccyx (p = 0.25). CONCLUSIONS The prevalence of OSD identified with modern high-resolution MRI screening is significantly higher than that reported with US screening, particularly in patients with dimples. The majority of OSD lesions identified are FFT and low conus. The clinical significance of such lesions remains unclear.

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Object The incidence, type, and severity of pediatric cervical spine injuries (CSIs) are related to age and mechanism of injury. In this study, the authors assessed the prevalence of CSIs in infants with head trauma treated in their institution. Methods The authors reviewed the medical records of children younger than 1 year of age who presented to The Children's Hospital with head injuries between January 1993 and December 2007. They excluded infants with head injuries resulting from motor vehicle accidents and known falls from heights greater than 10 ft. For each patient, collected data included age, cause of injury, diagnosis, discharge disposition, and outcome. Relevant imaging data were reviewed, and when appropriate, autopsy reports were also reviewed. Results Nine hundred five infants with head trauma and without a major mechanism/cause were identified. Their mean age was 4.3 months. Of the 905 patients, only 2 cases of CSI were detected, giving a prevalence of 0.2%. The mechanism of injury in these 2 patients was nonaccidental trauma (NAT). Conclusions The study revealed a very low prevalence of CSIs in infants with head trauma (0.2%). Routine cervical spine imaging in these infants, therefore, appears to have low diagnostic yield. The mechanism of head injury was NAT in the 2 patients who sustained an associated CSI. This supports the need for more stringent cervical spine imaging criteria for the infant with suspected NAT.

OBJECT Thirty-day mortality is increasingly a reference metric regarding surgical outcomes. Recent data estimate a 30-day mortality rate of 1.4−2.7% after craniotomy for tumors in children. No detailed analysis of short-term mortality following a diagnostic neurosurgical procedure (e.g., resection or tissue biopsy) for tumor in the US pediatric population has been conducted. METHODS The Surveillance, Epidemiology and End Results (SEER) data sets identified patients ≤ 21 years who underwent a diagnostic neurosurgical procedure for primary intracranial tumor from 2004 to 2011. One- and two-month mortality was estimated. Standard statistical methods estimated associations between independent variables and mortality. RESULTS A total of 5533 patients met criteria for inclusion. Death occurred within the calendar month of surgery in 64 patients (1.16%) and by the conclusion of the calendar month following surgery in 95 patients (1.72%). Within the first calendar month, patients < 1 year of age (n = 318) had a risk of death of 5.66%, while those from 1 to 21 years (n = 5215) had a risk of 0.88% (p < 0.0001). By the end of the calendar month following surgery, patients < 1 year (n = 318) had a risk of death of 7.23%, while those from 1 to 21 years (n = 5215) had a risk of 1.38% (p < 0.0001). Children < 1 year at diagnosis were more likely to harbor a high-grade lesion than older children (OR 1.9, 95% CI 1.5–2.4). CONCLUSIONS In the SEER data sets, the risk of death within 30 days of a diagnostic neurosurgical procedure for a primary pediatric brain tumor is between 1.16% and 1.72%, consistent with contemporary data from European populations. The risk of mortality in infants is considerably higher, between 5.66% and 7.23%, and they harbor more aggressive lesions.

BACKGROUND Pediatric cervical spine injuries (CSI) are rare but potentially devastating sequelae of blunt trauma. Existing protocols to evaluate children at risk for CSI frequently incorporate computed topography (CT) and magnetic resonance imaging (MRI); however, the clinical value of performing both remains unclear. METHODS Single-center retrospective review of pediatric trauma patients who underwent both CT and MRI of the cervical spine between 2001 and 2015. Based on radiographic findings, CT and MRI results were grouped into one of three categories: no injury, stable injury, or unstable injury. Radiographic instability was defined by disruption of two or more contiguous spinal columns while radiographic stability was defined by any other acute cervical spine abnormality on imaging. Clinical instability was defined by the need for surgical intervention (halo or spinal fusion), with the remaining patients, including children discharged in a cervical collar, considered clinically stable. RESULTS In total, 221 children met inclusion criteria, with a median age of 9 (interquartile range, 3–14). The Glasgow Coma Scale (GCS) score of the cohort was 9 (interquartile range, 4–15). Thirty-three (14.9%) children had clinically unstable injuries, requiring surgical intervention. Among the 160 (72.4%) children with no injury on CT, MRI identified no injury in 84 (52.5%) cases, a stable injury in 76 (47.5%) cases, and an unstable injury in none. Among the 21 children with stable injuries on CT, MRI findings were concordant in 17 (81.0%) cases. In four (19.0%) cases, a spinal column injury was identified on CT and appeared to be stable, but later deemed unstable on MRI. Forty (18.1%) patients had an unstable injury on CT with 100% MRI concordance. CONCLUSION In pediatric trauma patients suspected of having a CSI, a normal cervical spine CT is sufficient to rule out a clinically significant CSI as no child with a normal cervical CT was found to be radiographically or clinically unstable. LEVEL OF EVIDENCE Diagnostic Test, level III.

Objective To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥1 year in children with arterial ischemic stroke (AIS). Study design Sixty-one patients with childhood-onset (i.e., >28 days of life) AIS were enrolled in a single-institution cohort study at Children’s Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. Results Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute, sub-acute, and chronic periods post-event in 40%, 43%, and 28% of children. When not receiving anticoagulation, patients were routinely treated with aspirin 2–5 mg/kg once-daily for a minimum of one year. Death, major bleeding (including intracranial hemorrhage [ICH]), and recurrent AIS were infrequent. Pediatric Stroke Outcome Measure at one year demonstrated poor outcome in 54%. Acute cerebral arteriopathy and elevated D-dimer were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR=19.0, 95%CI=1.6–229.8; P=0.02). Conclusions Arteriopathy and coagulation activation are highly prevalent acutely in childhood AIS. Although recurrent AIS and ICH were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at one year, the risk for which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward prognostic stratification in childhood-onset AIS.