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Glioblastoma multiforme (GBM) are the most common and among the deadliest brain tumors in adults. Current mainstay treatments are insufficient to treat this tumor, and therefore, more effective therapies are desperately needed. Immunotherapy, which takes advantage of the body's natural defense mechanism, is an exciting emerging field in neuro-oncology. Adoptive cell therapy with chimeric antigen receptor (CAR) T cells provides a treatment strategy based on using patients’ own selected and genetically engineered cells that target tumor-associated antigens. These cells are harvested from patients, modified to target specific proteins expressed by the tumor, and re-introduced into the patient with the goal of destroying tumor cells. Here, we review the history of CAR T-cell therapy, and describe the characteristics of various generations of CAR T therapies, and the challenges inherent to treatment of GBM. Finally, we describe recent and current CAR T clinical trials designed to combat GBM.

Abnormal tumor vasculature is a potent mediator of treatment resistance because it results in heterogeneous perfusion, hypoxia, increased interstitial fluid pressure, and incomplete penetration of cytotoxic chemotherapies. Targeting this abnormal tumor vasculature is a promising therapeutic strategy, but results with antiangiogenic drugs in brain cancer have been mixed. Vasculature's response to treatment is a dynamic physiological process that can change rapidly throughout treatment, so it requires noninvasive techniques to serially monitor these changes in order to improve outcome. We review the role of vascular magnetic resonance imaging to measure tumor response to treatment and highlight opportunities and future avenues for expanding these promising techniques.

To highlight the most recent advances in the imaging of gliomas with a focus on high-grade gliomas. In the last several years, MRI and PET imaging of the brain have moved beyond anatomic imaging and are now capable of probing different aspects of tumor biology and response to treatment. These new techniques are increasingly being incorporated into clinical trials and even into clinical practice. Therefore, it is important to be familiar with the available imaging techniques and their potential uses versus limitations.In 2010, updated response assessment criteria for high-grade gliomas were published. It was the first revision to imaging response criteria for gliomas since 1990 and represents an international effort to standardize criteria for clinical trials. Although this revision represents an important development, there are several promising imaging techniques on the horizon such as vascular permeability measurement, perfusion imaging, diffusion imaging, and new PET tracers that will continue to improve our understanding of tumor biology.Advances in neuroimaging of brain tumors are enabling investigators to noninvasively visualize tumor response to treatment over time. As these tools are validated, they will add substantially to our ability to understand glioma biology and response to therapy.

PURPOSE OF REVIEW This review will summarize new neuroimaging techniques, particularly MRI and PET imaging, that can be used to assess brain tumor growth and angiogenesis. RECENT FINDINGS Glioma tumor vasculature is abnormal, and advances in MRI now permit visualization of the hemodynamic properties of gliomas including cerebral blood volume and blood flow, vascular permeability, and blood vessel diameter. New radiolabeled PET tracers have allowed more specific interrogation of glioma physiology such as hypoxia assessment or tumor proliferation rate. These two techniques are complementary and will likely yield important information on tumor response to therapy, particularly in the setting of antiangiogenic agents, which confound the interpretation of standard contrast-enhanced MRI scans. SUMMARY These techniques may allow development of patient-specific therapy to improve outcome in patients with gliomas.

OBJECTIVE: To present the case of a man with progressive speech loss and other clinical features and diagnostic tests consistent with fronto-temporal dementia but whose postmortem neuropathologic findings revealed Alzheimer disease (AD). BACKGROUND: Progressive apraxia of speech presents without true language abnormalities, usually seen with frontal lesions and not associated with AD pathology. METHOD: We describe the clinico-pathologic case of an 87-year-old man with progressive loss of speech function and present the prospective presentation of his syndrome using structural (magnetic resonance imaging) and metabolic (positron emission tomography) neuro-imaging studies, neuropsychologic testing, and pathology. RESULTS: His syndrome was characterized over the first 6 to 9 years by progressive deterioration of speech production, alteration of mood, and dysphagia but near normal language, memory, and visual-spatial function. At 8 years, fluorodeoxyglucose-positron emission tomography showed largely frontal metabolic abnormality. Over his final 1(1/2) years, he was mute and withdrawn. Neuropathologic findings showed neuritic plaques and neurofibrillary tangles, but no signs of frontotemporal dementias such as Pick bodies or ubiquitinated tau-negative inclusions. CONCLUSIONS: There can be overlap in the presentation of fronto-temporal dementia and AD despite the disparate pathologic bases of the underlying diseases. It has yet to be determined how to differentiate these diseases in such variant presentations and whether such atypical AD syndromes are equally amenable to standard therapies for AD.

Primary CNS lymphoma (PCNSL) is a potentially curable brain tumor or at least one in which durable remission can be achieved. We report follow-up study results from NABTT 96-07, a phase II multicenter trial in which 25 HIV-negative adult patients with newly diagnosed PCNSL were treated with 8 g/m2 of methotrexate IV every 2 weeks until a complete response (CR), as determined by radiographic criteria, was achieved or a maximum of eight induction doses was reached.1 For patients achieving a CR, two consolidation cycles were administered every 14 days followed by 11 maintenance cycles (28 days each). We report updated results of NABTT 96-07 after a minimum of 6.5 years of follow-up. Twelve of the original 25 patients (52%) achieved a CR to methotrexate induction. Five of these 12 patients (40%) who achieved CR have not relapsed after a median follow-up of 6.8 years. Eleven patients died of progressive disease or unknown cause and 3 died from other medical illnesses (2 with cardiac disease, 1 with septic arthritis) for a total of 14 …

True drop attacks are characterized by a sudden fall without loss of consciousness. Cardiac disease and epilepsy are widely accepted causes, but other etiologies have been described, including vestibulopathy, hypothyroidism, third ventricle or posterior fossa cysts, cervical spine disease, and brainstem ischemia.1-3 We present a case of drop attacks caused by an anomalous circle of Willis in the setting of a critical stenosis of the ipsilateral internal carotid artery (ICA). A 73-year-old right-handed man with a history of hypertension and past smoking, on oral anticoagulation for atrial fibrillation, presented to an outside institution with several months of drop attacks. The episodes occurred one to four times per week and he described his legs giving out, seeing the floor “coming up,” and then being on the ground. There were no prodromal symptoms such as lightheadedness, palpitations, or residual weakness after an attack. Witnesses confirmed no alteration …