Glioblastoma (GBM) is the most common primary brain tumor in adults and often has amplification of the Epidermal Growth Factor Receptor (EGFR) gene. The value of EGFR as a prognostic marker in GBMs is unclear; some studies have shown an adverse correlation, while others indicated a neutral or even favorable association with longer survival. Furthermore, EGFR-amplified GBMs are usually regarded as a single subgroup of tumors, though the range of EGFR copy number varies greatly. In this study, 532 glioblastomas were analyzed for EGFR amplification via fluorescence in situ hybridization at the time of initial diagnosis. While there was no difference in survival by EGFR amplification (P = 0.33), stratification by amount of EGFR amplification showed that, surprisingly, median survival was 39% longer in the high-amplifier group (EGFR: chromosome 7 ratio > 20) versus non-amplified GBMs (P = 0.03), and 43% longer versus GBMs with low-to-moderate EGFR amplification (EGFR:chromosome 7 ratio = 2-20, P = 0.0007). Stratifying by postsurgical treatment regimens, this difference was seen only when temozolomide (TMZ) was used; tumors without amplification and high EGFR amplification both responded better to TMZ than those with low-to-moderate amplification (P = 0.01), whereas those without adjuvant therapy or adjuvant therapy without TMZ showed no survival differences (P = 0.63 and 0.91, respectively). These results suggest that glioblastomas with EGFR amplification are a heterogeneous group of tumors, and that behavior might differ according to degree of amplification, but not in a straightforward dose-response manner.

Sports-related concussions (SRCs) are traumatic events that affect up to 3.8 million athletes per year. The initial diagnosis and management is often instituted on the field of play by coaches, athletic trainers, and team physicians. SRCs are usually transient episodes of neurological dysfunction following a traumatic impact, with most symptoms resolving in 7-10 days; however, a small percentage of patients will suffer protracted symptoms for years after the event and may develop chronic neurodegenerative disease. Rarely, SRCs are associated with complications, such as skull fractures, epidural or subdural hematomas, and edema requiring neurosurgical evaluation. Current standards of care are based on a paradigm of rest and gradual return to play, with decisions driven by subjective and objective information gleaned from a detailed history and physical examination. Advanced imaging techniques such as functional MRI, and detailed understanding of the complex pathophysiological process underlying SRCs and how they affect the athletes acutely and long-term, may change the way physicians treat athletes who suffer a concussion. It is hoped that these advances will allow a more accurate assessment of when an athlete is truly safe to return to play, decreasing the risk of secondary impact injuries, and provide avenues for therapeutic strategies targeting the complex biochemical cascade that results from a traumatic injury to the brain.

1p/19q codeletion is a favorable prognostic marker of oligodendrogliomas. While fluorescence in situ hybridization (FISH) and microsatellite-based polymerase chain reaction (PCR) for loss of heterozygosity (LOH) are common methods to test for 1p/19q codeletion, it is unclear which test is better at prognostic stratification. This study analyzed outcomes of 111 oligodendrogliomas with both 1p/19q FISH and LOH done at the time of diagnosis. Overall concordance between the 2 assays was 81.1%. In grade III oligodendrogliomas, LOH was better than FISH at survival stratification (p < 0.0001 for LOH vs. p = 0.02 for FISH), although increasing the stringency of FISH interpretation criteria improved concordance and prognostic power. Oligodendrogliomas that were 1p/19q-codeleted by FISH but also had 10q LOH were negative for 1p/19q codeletion by PCR analysis in over 70% of cases, with very poor survival in the grade III subset. Thus, although PCR-based LOH is a better stratifier of 1p/19q status, FISH still has clinical and prognostic utility, especially if 10q data can be incorporated.

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.

Epidermal growth factor receptor (EGFR) expressionSurprisingly, an inverse phenomenon was found with grade III anaplastic oligodendrogliomas, in which stronger EGFR expression was a favorable marker for survival. Among all gliomas, the likelihood of EGFR amplification, as viewed by fluorescence in situ hybridization, increased with the strength of EGFR expression, and <1% of cases with weak or no EGFR immunostaining showed amplification. These data suggest that EGFR IHC is useful in certain circumstances (ie, it may help supplement 1p/19q prognostic information in oligodendroglial tumors and screen out cases that would not benefit from more costly EGFR fluorescence in situ hybridization analysis).