Loss of Consciousness and Altered Mental State as Predictors of Functional Recovery Within 6 Months Following Mild Traumatic Brain Injury.

OBJECTIVE: The authors tested the hypothesis that a combination of loss of consciousness (LOC) and altered mental state (AMS) predicts the highest risk of incomplete functional recovery within 6 months after mild traumatic brain injury (mTBI), compared with either condition alone, and that LOC alone is more strongly associated with incomplete recovery, compared with AMS alone. METHODS: Data were analyzed from 407 patients with mTBI from Head injury Serum Markers for Assessing Response to Trauma (HeadSMART), a prospective cohort study of TBI patients presenting to two urban emergency departments. Four patient subgroups were constructed based on information documented at the time of injury: neither LOC nor AMS, LOC only, AMS only, and both. Logistic regression models assessed LOC and AMS as predictors of functional recovery at 1, 3, and 6 months. RESULTS: A gradient of risk of incomplete functional recovery at 1, 3, and 6 months postinjury was noted, moving from neither LOC nor AMS, to LOC or AMS alone, to both. LOC was associated with incomplete functional recovery at 1 and 3 months (odds ratio=2.17, SE=0.46, p<0.001; and odds ratio=1.80, SE=0.40, p=0.008, respectively). AMS was associated with incomplete functional recovery at 1 month only (odds ratio=1.77, SE=0.37 p=0.007). No association was found between AMS and functional recovery in patients with no LOC. Neither LOC nor AMS was predictive of functional recovery at later times. CONCLUSIONS: These findings highlight the need to include symptom-focused clinical variables that pertain to the injury itself when assessing who might be at highest risk of incomplete functional recovery post-mTBI.

Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.

Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients.

Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors.

We discovered a high-level amplicon involving the chr19q13.41 microRNA (miRNA) cluster (C19MC) in 11/45 ( approximately 25%) primary CNS-PNET, which results in striking overexpression of miR-517c and 520g. Constitutive expression of miR-517c or 520g promotes in vitro and in vivo oncogenicity, modulates cell survival, and robustly enhances growth of untransformed human neural stem cells (hNSCs) in part by upregulating WNT pathway signaling and restricting differentiation of hNSCs. Remarkably, the C19MC amplicon, which is very rare in other brain tumors (1/263), identifies an aggressive subgroup of CNS-PNET with distinct gene-expression profiles, characteristic histology, and dismal survival. Our data implicate miR-517c and 520g as oncogenes and promising biological markers for CNS-PNET and provide important insights into oncogenic properties of the C19MC locus.