Sports-Related Concussion in Helmeted vs. Unhelmeted Athletes: Who Fares Worse?

In the management of sports-related concussion, little is known about the effect of wearing or not wearing a helmet (i. e., helmet status) on the acute outcomes of concussed athletes. We endeavored to assess acute neurocognitive and symptom changes after SRC in helmeted vs. unhelmeted athletes. In a retrospective study, 1 025 athletes from 2 regional databases sustained a SRC. Athletes were matched by age, gender, number of prior concussions, and days to post-concussion test, yielding a final cohort of 138 athletes. For each group of 69, differences in post-concussion neurocognitive and symptom scores were compared using group mean differences as well as reliable change index (RCI) scores set at the 80% confidence interval. With gender, prior concussions, and days to post-concussion test similar in each group, using group mean change scores and RCI methodology, we found no significant differences between the helmeted and unhelmeted groups in 4 neurocognitive tests and one total symptom score. In a cohort of carefully matched athletes from 2 regional concussion centers, helmet status was unrelated to neurocognitive scores and total symptoms in athletes after suffering a SRC. These findings suggest that acute outcomes in helmeted vs. unhelmeted sports are quite similar.

Intracranial paracrine interleukin-2 therapy stimulates prolonged antitumor immunity that extends outside the central nervous system.

To explore the potential efficacy of local cytokine delivery against tumors in the central nervous system (CNS), C57BL6 mice were simultaneously given intracranial injections of tumor challenge and of irradiated B16F10 melanoma cells transduced to secrete interleukin-2 (IL-2). Intracranial IL-2 therapy generated antitumor responses capable of extending the survival of animals that received simultaneous intracranial tumor challenge either locally or at distant sites in the brain. Nontransduced melanoma cells had little effect. Animals that survived intracranial IL-2 therapy and tumor challenge showed prolonged survival compared with controls when challenged with a second tumor dose 70 days after initial treatment. In addition, animals that rejected intracranial tumors were also protected from tumor growth upon rechallenge at sites outside the CNS (i.e., subcutaneous tumor challenge). Conversely, identical or 10-fold larger doses of IL-2-transduced cells administered by subcutaneous injection failed to generate protection against intracranial tumor challenges. Elimination of T-cell and natural killer (NK) subsets using gene knockout mice and antibody-depletion techniques demonstrated that NK cells were most important for the initial antitumor response, whereas CD4+ T-cells were not necessary. These studies demonstrate that local IL-2 therapy in the brain not only generates an immediate local antitumor immune response, but also establishes long-term immunologic memory capable of eliminating subsequent tumor challenges within and outside of the CNS. Furthermore, the antitumor response to paracrine IL-2 in the brain differed significantly from that in the flank, suggesting that the intrinsic CNS cells involved in initiating immunity within the brain have different cytokine requirements from their peripheral counterparts.

Intracranial leiomyosarcoma in a patient with AIDS.

We report an intracranial leiomyosarcoma in the pontine cistern of a 34-year-old woman infected with the human immunodeficiency virus (HIV). The clinical, radiological and pathological data are reviewed. The tumor was Epstein-Barr virus (EBV) positive by in situ hybridization. This case emphasizes that smooth muscle neoplasms arising in the setting of immunocompromise can occur intracranially, and corroborates a hypothesis that EBV coinfection may have a role in development of these tumors.

Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.

The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.

Endothelial cell expression of intercellular adhesion molecule 1 in experimental posthemorrhagic vasospasm.

OBJECTIVE: The exposure of large intracranial arteries to blood after an aneurysmal subarachnoid hemorrhage leads to a cascade of morphological and physiological changes in the vessels, a condition generally described as vasospasm. This response to the periadventitial deposition of blood is mediated in part by the endothelial layer of the vessel. This study was undertaken to examine the role of endothelial cell expression of intercellular adhesion molecule 1 (ICAM-1) in the initiation and regulation of this response. METHODS: The femoral artery model of vasospasm was used in rats (65 animals, 130 arteries). In each rat, one artery was exposed to blood and the contralateral vessel was exposed to saline, so that each animal served as its own control. Animals were perfused and killed at sequential time points, from 1 hour to 20 days after blood exposure. The vessels were examined immunohistochemically and histologically for the presence of ICAM-1 and morphological features of vasospasm, respectively. RESULTS: Endothelial cell ICAM-1 immunoreactivity was extensively increased in only the blood-exposed vessels, beginning 3 hours after clot placement and persisting for 24 hours. ICAM-1 immunoreactivity returned to baseline by 48 hours after blood exposure. The influx of inflammatory cells correlated directly with the time and location of increased ICAM-1 expression. Peak arterial remodeling was observed on the blood-exposed side 8 to 12 days after clot placement, as quantified by measurements of increased wall thickness, decreased lumen size, and increased collagen content. CONCLUSION: Endothelial cell ICAM-1 expression seems to be an early and specific signal used by a vessel in response to the deposition of blood periadventitially. This molecule may be a marker for vessels likely to undergo subsequent morphological remodeling and vasospasm.

Interstitial delivery of dexamethasone in the brain for the reduction of peritumoral edema.

Controlled-release polymers have facilitated the interstitial delivery of drugs within the central nervous system. In the present study, dexamethasone was incorporated into ethylene-vinyl acetate polymers, which were then implanted adjacent to a 9L gliosarcoma in the brain of Fischer 344 rats. The effect of interstitial delivery of dexamethasone on peritumoral edema was assessed and compared to the effect of dexamethasone delivered systemically. Eighty-five rats underwent intracranial implantation of the 9L gliosarcoma. Five days later, the animals were randomly assigned to one of four treatment groups: Group 1 received intracranial implantation of controlled-release polymers containing dexamethasone; Group 2 received intraperitoneal implantation of controlled-release polymers containing dexamethasone; Group 3 received serial intraperitoneal injections of dexamethasone; and Group 4 received sham treatment. The animals were sacrificed 3 days after initiation of therapy and their brains were removed for measurement of the water content (edema) in the tumor-bearing and contralateral hemispheres. Brain and plasma samples were analyzed by reverse-phase high-performance liquid chromatography to determine the tissue and plasma concentrations of dexamethasone. Measurement of the release kinetics of dexamethasone from the ethylene-vinyl acetate polymers in an in vitro system showed that the drug was released in a controlled, tapering fashion. During the first 3 days of controlled release in vitro, 330 micrograms of a total content of 7.5 mg of dexamethasone was released into the medium. Analysis of tissue for drug levels demonstrated, however, that the interstitial delivery of this fractional amount of dexamethasone within the brain resulted in levels 19 times higher than those achieved by administering the full dose of 7.5 mg systemically over a 3-day period. Conversely, the systemic administration of dexamethasone resulted in plasma levels 16 times higher than those measured in the interstitial delivery of dexamethasone in the brain. Brain-water content determinations showed that the interstitial controlled release of the fractional amount of dexamethasone within the brain was as effective in controlling peritumoral edema as systemic administration of the full dose by serial intraperitoneal injections. The study demonstrates the following: 1) controlled-release polymeric carriers deliver biologically active dexamethasone in a sustained fashion; 2) very high concentrations of dexamethasone in brain tissue can be achieved using interstitial polymer-mediated drug delivery while minimizing plasma concentrations of this drug which are sometimes associated with serious systemic side effects; and 3) peritumoral brain edema can be effectively treated by the interstitial delivery of dexamethasone directly within the tumor bed.