Imaging of Hypoxic-Ischemic Injury (in the Era of Cooling).

Hypoxic-ischemic injury (HII) is a major worldwide contributor of term neonatal mortality and long-term morbidity. At present, therapeutic hypothermia is the only therapy that has demonstrated efficacy in reducing severe disability or death in infants with moderate to severe encephalopathy. MRI and MRS performed during the first week of life are adequate to assess brain injury and offer prognosis. Patterns of injury will depend on the gestation age of the neonate, as well as the degree of hypotension.

A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study.

BACKGROUND: Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. METHODS: We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses. RESULTS: Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash. CONCLUSIONS: Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.

Parent-reported cognitive function is associated with leukoencephalopathy in children with brain tumors.

PURPOSE: Cognitive dysfunction is a major concern for children with brain tumors. A valid, user-friendly screening tool could facilitate prompt referral for comprehensive neuropsychological assessments and therefore early intervention. Applications of the pediatric perceived cognitive function item bank (pedsPCF) such as computerized adaptive testing can potentially serve as such a tool given its brevity and user-friendly nature. This study aimed to evaluate whether pedsPCF was a valid indicator of cerebral compromise using the criterion of structural brain changes indicated by leukoencephalopathy grades. METHODS: Data from 99 children (mean age = 12.6 years) with brain tumors and their parents were analyzed. Average time since diagnosis was 5.8 years; time since last treatment was 4.3 years. Leukoencephalopathy grade (range 0-4) was based on white matter damage and degree of deep white matter volume loss shown on MRI. Parents of patients completed the pedsPCF. Scores were based on the US general population-based T-score metric (mean = 50; SD = 10). Higher scores reflect better function. RESULTS: Leukoencephalopathy grade distributions were as follows: 36 grade 0, 27 grade 1, 22 grade 2, 13 grade 3, and 1 grade 4. The mean pedsPCF T-score was 48.3 (SD = 8.3; range 30.5-63.7). The pedsPCF scores significantly discriminated patients with different leukoencephalopathy grades, F = 4.14, p = 0.0084. Effect sizes ranged from 0.09 (grade 0 vs. 1) to 1.22 (grade 0 vs. 3/4). CONCLUSION: This study demonstrates that the pedsPCF is a valid indicator of leukoencephalopathy and provides support for its use as a screening tool for more comprehensive neurocognitive testing.

Enlarged subarachnoid spaces and intracranial hemorrhage in children with accidental head trauma.

OBJECTIVE Benign external hydrocephalus (BEH) is an enlargement of the subarachnoid spaces (SASs) that can be seen in young children. It is controversial whether children with BEH are predisposed to developing subdural hemorrhage (SDH) with or without trauma. This issue is clinically relevant as a finding of unexplained SDH raises concerns about child abuse and often prompts child protection and law enforcement investigations. METHODS This retrospective study included children (1-24 months of age) who underwent head CT scanning after an accidental fall of less than 6 feet. Head CT scans were reviewed, cranial findings were documented, and the SAS was measured and qualitatively evaluated. Enlarged SAS was defined as an extraaxial space (EAS) greater than 4 mm on CT scans. Clinical measurements of head circumference (HC) were noted, and the head circumference percentile was calculated. The relationship between enlarged SAS and HC percentile, and enlarged SAS and intracranial hemorrhage (ICH), were investigated using bivariate analysis. RESULTS Of the 110 children included in this sample, 23 had EASs greater than 4 mm. The mean patient age was 6.8 months (median 6.0 months). Thirty-four patients (30.9%) had ICHs, including subarachnoid/subpial (6.2%), subdural (6.2%), epidural (5.0%), and unspecified extraaxial hemorrhage (16.5%). Enlarged SAS was positively associated with subarachnoid/subpial hemorrhage; there was no association between enlarged SASs and either SDH or epidural hemorrhage. A larger SAS was positively associated with larger HC percentile; however, HC percentile was not independently associated with ICH. CONCLUSIONS Enlarged SAS was not associated with SDH, but was associated with other ICHs. The authors' findings do not support the theory that BEH predisposes children to SDH with minor accidental trauma.

Involvement of the neural stem cell compartment by pediatric and adult gliomas: a retrospective review of 377 cases.

To assess frequency of neural stem cell compartment (NSC) involvement in adult and pediatric gliomas [World Health Organization (WHO) grades 1-4], and to assess whether NSC involvement at presentation impacts on survival, recurrence rates, and/or transformation from low grade (WHO grade 1-2) to high grade disease (WHO grades 3-4). Cranial MRIs for 154 pediatric and 223 adult glioma patients treated from 2000 to 2012 were reviewed. NSC involvement was documented. Tumors were stratified by age (adult vs. pediatric), histology, tumor grade, tumor location, and involvement of midline structures. Odds ratios (OR) for death were calculated based on NSC status at presentation. Rates of transformation and recurrence rates (ORR) were compared using Fisher's Exact Test. Time to recurrence (TTR) was calculated using student t test. Among recurrent and transformed tumors, we also assessed the rate of NSC involvement at time of recurrence or transformation. 74.8 % of tumors had NSC involvement. Higher rates of NSC involvement were seen among adult (p = .0001); high grade (p = .0001)); grade 2 versus grade 1 (p = .0001) and other grade 1 histologies (p = .0001) versus JPA (juvenile pilocytic astrocytoma) patients); grade 2-4 tumors (p = .0001); and supratentorial tumors (p < .0001). No transformation was noted among pediatric low grade tumors or adult grade 1 tumors. 22/119 (18.5 %) adult grade 2 tumors transformed. Rates of transformation were not impacted by NSC status (p = .47). ORR was 15.1 %, and was greater for NSC+ tumors at presentation (p = .05). 36/41 recurrences (87.8 %) involved NSC at time of recurrence. OR for death was 2.62 (1.16-5.9), p = .02 for NSC+ tumors at presentation. Adult and pediatric gliomas (all grades) frequently involve NSC at presentation, although rates are lower in pediatric JPA and all infratentorial tumors. NSC involvement at presentation increases OR death and reduces TTR for pediatric gliomas (all grades) and adult low grade gliomas, and shows a strong trend toward increased ORR.

Deriving visual field loss based upon OCT of inner retinal thicknesses of the macula.

Using a multiple linear regression method, a derived visual field (VF) was obtained from retinal ganglion cell and retinal nerve fiber layer (RNFL) thicknesses measured with frequency-domain, optical coherence tomography (OCT) macular scans. 138 eyes from 92 glaucoma patients or suspects and 58 healthy eyes were included. The derived VF was compared to the VF measured with standard automated perimetry (SAP). The median agreement between the derived and observed VFs was 90%. As the derived and observed VFs should be independent, they can be combined to potentially increase the sensitivity/specificity of a test for glaucoma.