Oliver Grauer

CD4+ T Cells Predominate in Cerebrospinal Fluid and Leptomeningeal and Parenchymal Infiltrates in Cerebral Amyloid β–Related Angiitis

BACKGROUNDnIn amyloid (Aβ)-related angiitis (ABRA)of the central nervous system (CNS), cerebral amyloid angiopathy occurs in association with primary vasculitis of small- and medium-sized leptomeningeal and cortical arteries. It has been suggested that ABRA is triggered by vascular deposition of A followed by an Aβ-directed (auto)immune response.nnnOBJECTIVEnTo provide a detailed description of the cellular composition of the inflammatory infiltrates in the cerebrospinal fluid (CSF) and CNS and their response to immunotherapy in a typical case of ABRA.nnnDESIGNnReport of a single case.nnnSETTINGnNeurologic referral center.nnnPATIENTn67-year-old white woman.nnnMAIN OUTCOME MEASURESnNeurologic examination,magnetic resonance imaging, lumbar puncture, flow cytometry,leptomeningeal biopsy, and histopathologic analysis.nnnRESULTSnIn a typical case of ABRA, we demonstrate for the first time the presence of a vast majority of partially activated CD4(+) T cells in CSF and leptomeningeal and parenchymal (peri)vascular infiltrates, which were frequently found in close proximity to major histocompatibility complex (MHC) class II-expressing microglia, epithelioid macrophages, and multinucleated giant cells containing intracellular deposits of Aβ.nnnCONCLUSIONnOur findings support the notion of adaptive Aß-directed autoimmunity as the underlying pathogenic mechanism in ABRA.

Targeting B cells in relapsing–remitting multiple sclerosis: from pathophysiology to optimal clinical management

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that is caused by an autoimmune response against central nervous system (CNS) structures. Traditionally considered a T-cell-mediated disorder, the contribution of B cells to the pathogenesis of MS has long been debated. Based on recent promising clinical results from CD20-depleting strategies by three therapeutic monoclonal antibodies in clinical phase II and III trials (rituximab, ocrelizumab and ofatumumab), targeting B cells in MS is currently attracting growing interest among basic researchers and clinicians. Many questions about the role of B and plasma cells in MS remain still unanswered, ranging from the role of specific B-cell subsets and functions to the optimal treatment regimen of B-cell depletion and monitoring thereafter. Here, we will assess our current knowledge of the mechanisms implicating B cells in multiple steps of disease pathology and examine current and future therapeutic approaches for the treatment of MS.

Benefits of contrast-enhanced SWI in patients with glioblastoma multiforme.

AbstractIntroductionSWI can help to identify high-grade gliomas (HGG). The objective of this study was to analyse SWI and CE-SWI characteristics, i.e. the relationship between contrast-induced phase shifts (CIPS) and intratumoral susceptibility signals (ITSS) and their association with tumour volume in patients with glioblastoma multiforme (GBM).Materials and methodsMRI studies of 29 patients were performed to evaluate distinct susceptibility signals comparing SWI and CE-SWI characteristics. The relationship between these susceptibility signals and CE-T1w tumour volume was analysed by using Spearman’s rank correlation coefficient and Kruskal-Wallis-test. Tumour biopsies of different susceptibility signals were performed in one patient.ResultsComparison of SWI and CE-SWI demonstrated different susceptibility signals. Susceptibility signals visible on SWI images are consistent with ITSS; those only seen on CE-SWI were identified as CIPS. Correlation with CE-T1w tumour volume revealed that CIPS were especially present in small or medium-sized GBM (Spearman’s rho ru2009=u20090.843, Pu2009<u20090.001). Histology identified the area with CIPS as the tumour invasion zone, while the area with ITSS represented micro-haemorrhage, highly pathological vessels and necrosis.ConclusionCE-SWI adds information to the evaluation of GBM before therapy. It might have the potential to non-invasively identify the tumour invasion zone as demonstrated by biopsies in one case.Key Points• MRI is used to help differentiate between low- and high-grade gliomas.n • Contrast-enhanced susceptibility-weighted MRI (CE-SWI) helps to identify patients with glioblastoma multiforme.n • CE-SWI delineates the susceptibility signal (CIPS and ITSS) more than the native SWI.n • CE-SWI might have the potential to non-invasively identify the tumour invasion zone.

Neurocognitive decline in HIV patients is associated with ongoing T-cell activation in the cerebrospinal fluid.

HIV‐associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play a major role in the development of HAND.

The role of ion channels in malignant brain tumors.

Malignant gliomas are the most common primary brain tumors and have poor clinical prognosis, despite multimodal therapeutic strategies. In recent years, ion channels have emerged as major players in tumor pathophysiology regarding all hallmarks of cancer. Since ion channels are easily accessible structures, they may prove to be effective targets for canner therapy, although their broad expression pattern and role in physiological processes should be taken into consideration. This review summarizes the current knowledge on the role of ion channels in the pathophysiology of malignant gliomas, especially glioblastoma, and evaluates their potential role in targeted antiglioma therapy.

Rapidly progressive B-cell dominated inflammatory neuropathy and littoral cell angioma of the spleen associated with plasmablastic B-cell lymphoma

In hematological malignancies a variety of (auto)immune phenomena occur due to systemic dysregulation of cellular and humoral immune responses [1]. Among other tissues the central and peripheral ne...

Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma

BackgroundnThe GLARIUS trial, which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) compared with standard temozolomide in the first-line therapy of O6-methylguanine-DNA methyltransferase (MGMT)-nonmethylated glioblastoma, showed that progression-free survival was significantly prolonged by BEV/IRI, while overall survival was similar in both arms. The present report focuses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease.nnnMethodsnPatients (n = 170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard temozolomide. At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm questionnaires. A generalized estimating equation (GEE) model evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration were analyzed separately.nnnResultsnIn all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions of motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation.nnnConclusionsnGLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM.