Purpose Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%–40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions The combination of PD-1 blockade and localized radiation therapy results in long-term survival in mice with orthotopic brain tumors. These studies provide strong preclinical evidence to support combination trials in patients with GBM.

Carotid web is associated with high recurrent stroke/TIA risk, despite antithrombotic use, and is amenable to carotid stenting.

Object Arachnoid cysts are commonly encountered fluid collections in the central nervous system. Recent advances in neuroimaging have translated into an increased detection of these cysts; that is, diagnoses can be made more frequently at earlier stages. Significant advances have also been made in the surgical management of these lesions. The authors report on a case series that illustrates the diverse forms of presentation and the treatment modalities commonly used for arachnoid cysts. Methods Between January 2002 and December 2006, 20 patients with arachnoid cysts underwent surgery performed by the senior author at The Johns Hopkins Hospital. Seventy percent of the cysts were supratentorial, 5% infratentorial, and 25% spinal. All diagnoses were confirmed on neuroimaging, surgery, and histological examination. Included in the study were 12 male (60%) and eight female (40%) patients, ranging in age from 2 weeks to 39 years (mean age 10.9 years) at the time of surgery. Symptoms at presentation included headache (41%), weakness (23%), seizure (14%), hydrocephalus (9%), scoliosis (4%), cognitive decline (4%), and visual loss (4%). Twenty-five percent of the cysts were sylvian, 20% intraventricular, and 20% suprasellar. Supratentorial cysts were treated endoscopically in 73% of patients and with open resection in the remaining 27%. Complications included spasticity, hemiparesis, cerebrospinal fluid leak, hydrocephalus, and subdural hygroma. On follow-up evaluation, 60% of patients had stable cysts and improved symptoms, 13% complete symptom resolution, and 13% stable symptoms. All patients with spinal cysts underwent laminectomies and fenestration, and one cystosubarachnoid (CS) shunt was placed. Cyst reaccumulation occurred in three patients; two patients required cystoperitoneal (CP) and CS shunts. No deaths occurred. Conclusions Most arachnoid cysts are found incidentally and can be managed conservatively. Symptomatic patients are surgical candidates. Treatments include CP shunt placement, craniotomy, or endoscopic fenestration, and stereotactic aspiration. Recent advances in neurosurgical techniques and neuroendoscopy continue to favor fenestration over shunt insertion as the method of choice for initial cyst decompression.

Subarachnoid hemorrhage (SAH) can lead to devastating neurological outcomes, and there are few pharmacologic treatments available for treating this condition. Both animal and human studies provide evidence of inflammation being a driving force behind the pathology of SAH, leading to both direct brain injury and vasospasm, which in turn leads to ischemic brain injury. Several inflammatory mediators that are elevated after SAH have been studied in detail. While there is promising data indicating that blocking these factors might benefit patients after SAH, there has been little success in clinical trials. One of the key factors that complicates clinical trials of SAH is the variability of the initial injury and subsequent inflammatory response. It is likely that both genetic and environmental factors contribute to the variability of patients' post-SAH inflammatory response and that this confounds trials of anti-inflammatory therapies. Additionally, systemic inflammation from other conditions that affect patients with SAH could contribute to brain injury and vasospasm after SAH. Continuing work on biomarkers of inflammation after SAH may lead to development of patient-specific anti-inflammatory therapies to improve outcome after SAH.