Space-brain: The negative effects of space exposure on the central nervous system.

Journey to Mars will be a large milestone for all humankind. Throughout history, we have learned lessons about the health dangers associated with exploratory voyages to expand our frontiers. Travelling through deep space, the final frontier, is planned for the 2030s by NASA. The lessons learned from the adverse health effects of space exposure have been encountered from previous, less-lengthy missions. Prolonged multiyear deep space travel to Mars could be encumbered by significant adverse health effects, which could critically affect the safety of the mission and its voyagers. In this review, we discuss the health effects of the central nervous system by space exposure. The negative effects from space radiation and microgravity have been detailed. Future aims and recommendations for the safety of the voyagers have been discussed. With proper planning and anticipation, the mission to Mars can be done safely and securely.

Operative and Therapeutic Advancements in Breast Cancer Metastases to the Brain.

Patients with breast cancer are surviving longer as the state of the art for care advances. Because patients are surviving longer with primary breast cancer, the incidence of secondary metastatic disease has risen. Metastatic breast cancer to the brain was once thought to be universally fatal. While it is still quite lethal, its treatment after diagnosis is increasingly safe and effective. Critical progress has been made in understanding the interaction between breast metastases and the neural niche, neuroimaging of functional anatomy, minimally invasive image-guided brain surgery, characterizing subtypes of breast cancer based on molecular and genetic profiles, and individualized pharmaceuticals and immunotherapies. In this review, we discuss recent advances that have brought us to state-of-the-art management of metastatic breast cancer to the brain.

Immediate post-operative brachytherapy prior to irradiation and temozolomide for newly diagnosed glioblastoma.

To determine whether immediate post-operative brachytherapy can be safely applied to newly diagnosed glioblastomas to retard tumor progression prior to initiation of external beam radiation therapy (EBRT) and temozolomide. Between 1996 and 2011, eleven patients underwent implantation of GliaSite (n = 9) or MammoSite (n = 2) at the time of surgical resection. Brachytherapy was carried out on post-operative day 2-3, with 45-60 Gy delivered to a 1 cm margin. All patients underwent subsequent standard radiation/temozolomide treatment 4-5 weeks post-irradiation. There were no wound related complications. Toxicity was observed in two patients (2/11 or 18 %), including one post-operative seizure and one case of cerebral edema that resolved after a course of steroid treatment. Immediate post-operative and pre-irradiation/temozolomide magnetic resonance imaging assessment was available for 9 of the 11 patients. Two of these nine patients (22 %) developed new regions of contrast enhancement prior to irradiation/temozolomide. This compares favorably to historical data where 53 % of patient suffer such tumor progression. While there was a trend toward improved 6 month progression free survival in the brachytherapy/temozolomide/radiation treated patients, the overall survival of these patients were comparable to historical controls. This case series demonstrates the safety of immediate post-operative brachytherapy when applied prior to EBRT and temozolomide in the treatment of newly diagnosed glioblastomas.

Diagnostic yield of stereotactic needle-biopsies of sub-cubic centimeter intracranial lesions.

BACKGROUND: Stereotactic brain biopsies are widely used for establishing the diagnosis of intracranial lesions. Here we examine whether stereotactic biopsy of smaller brain lesions, defined for this study as being less than 1 cubic centimeter (1 cc) in volume, are associated with lowered diagnostic yield. METHODS: We conducted a retrospective analysis of 267 consecutive patients who underwent stereotactic brain biopsy between 2007 and 2011. Lesion volumes were calculated and were stratified by <1 or >1 cc. RESULTS: A total of 13 of 246 (5.2%) biopsies for lesions >1 cc resulted in nondiagnostic tissue or an incorrect diagnosis. In contrast, 5 of 21 (23.8%) biopsies for <1 cc lesions yielded nondiagnostic or incorrect diagnosis. Posthoc review of tissue from the <1 cc lesions suggests the neuropathologist's expertise in the handling and analysis of limited specimen as a critical parameter of successful diagnosis. The operative morbidities were low for both the <1 and >1 cc biopsies (0% and 1%, respectively). CONCLUSION: This study demonstrates that stereotactic cerebral biopsy of lesions less than a cubic centimeter in volume results in a lower diagnostic yield versus larger lesions (76.2% versus 94.8%). While auxiliary measures may be taken to improve diagnostic yield, these patients may be best managed in a specialized center with experienced stereotactic neurosurgeons and neuropathologists.

CT322, a VEGFR-2 antagonist, demonstrates anti-glioma efficacy in orthotopic brain tumor model as a single agent or in combination with temozolomide and radiation therapy.

Glioblastomas are among the most aggressive human cancers, and prognosis remains poor despite presently available therapies. Angiogenesis is a hallmark of glioblastoma, and the resultant vascularity is associated with poor prognosis. The proteins that mediate angiogenesis, including vascular endothelial growth factor (VEGF) signaling proteins, have emerged as attractive targets for therapeutic development. Since VEGF receptor-2 (VEGFR-2) is thought to be the primary receptor mediating angiogenesis, direct inhibition of this receptor may produce an ideal therapeutic effect. In this context, we tested the therapeutic effect of CT322, a selective inhibitor of VEGFR-2. Using an intracranial murine xenograft model (U87-EGFRvIII-luciferase), we demonstrate that CT322 inhibited glioblastoma growth in vivo and prolonged survival. Of note, the anti-neoplastic effect of CT322 is augmented by the incorporation of temozolomide or temozolomide with radiation therapy. Immunohistochemical analysis of CT322 treated tumors revealed decreased CD31 staining, suggesting that the tumoricidal effect is mediated by inhibition of angiogenesis. These pre-clinical results provide the foundation to further understand long term response and tumor escape mechanisms to anti-angiogenic treatments on EGFR over-expressing glioblastomas.

Malignancies of the spinal cord.

The management of intramedullary spinal cord tumors (IMSCT) is primarily concerned with the preservation of existing neurologic function. To this end, clinical scientists are continually seeking tools and techniques to improve the safety and efficacy of tumor resection and control. Further advances in safety and efficacy can be proposed at each phase of management, from pre-operative screening to post-treatment monitoring. Innovations within the areas of molecular biology and genetics, intraoperative imaging and stereotactic radiosurgery offer exciting new options to explore in the management of IMSCT. This section will review the pathophysiology and epidemiology of IMSCT and the state-of-the-art management before delving into the promising new tools and techniques for each phase of management.

Balamuthia mandrillaris meningoencephalitis in an immunocompromised patient. Case report.

Balamuthia mandrillaris is a rare but increasingly recognized cause of amebic encephalitis, yet it remains poorly understood. The condition is almost universally fatal, and due to diagnostic difficulty, most cases are identified postmortem. The authors report a case of Balamuthia amebic encephalitis in a patient with combined variable immunodeficiency in which a rare antemortem diagnosis was made via brain biopsy. Despite broad-spectrum antimicrobial therapy, the outcome was fatal. Such presentations are challenging, and definitive diagnosis may require biopsy in consultation with a skilled neuropathologist.