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Mariella G Filbin, Dominik Sturm
Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features...
February 2018: Seminars in Neurology
Elizabeth R Gerstner, Kristian W Pajtler
Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades...
February 2018: Seminars in Neurology
Sarah Löw, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma limited to the brain, spinal cord, leptomeninges, and eyes. The majority of patients are immunocompetent, with a median age of 65 years at diagnosis. Historically, whole-brain radiation therapy (WBRT) was the first and sole treatment for PCNSL. Today, due to the recognized neurotoxicity of WBRT, this modality is usually avoided in the treatment. Most chemotherapy regimens are based on high-dose methotrexate plus the anti-CD20 monoclonal antibody rituximab, leading to high response rates, but 5-year survival is still poor at approximately 30% compared with other extranodal lymphomas...
February 2018: Seminars in Neurology
Michael Platten, David A Reardon
Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined...
February 2018: Seminars in Neurology
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Andreas von Deimling, Takahiro Ono, Mitsuaki Shirahata, David N Louis
Estimating the malignancy level of tumors is key to management, and has been part of oncology practice for the past ∼100 years. A central aspect of assessing malignancy level is based on histological "grading"-a process in which a pathologist evaluates microscopic features of a tumor and interprets those findings in light of large prognostic studies. For the diffuse astrocytic gliomas, there have been many such studies over the past century and these have proven useful in estimating prognosis for patients...
February 2018: Seminars in Neurology
Maria Martinez-Lage, Felix Sahm
The updated 2016 WHO classification of Central Nervous System tumors introduced a novel concept of neuropathology diagnostics. Molecular parameters are now included into the definition of several entities. This evolution from a previously purely histology-based classification to an integrated approach of histology and genetic characteristics has implications in daily diagnostic and clinical practice. Both the spectrum of diagnostic workup demanded from the neuropathologist and the range of relevant markers to be considered by clinicians and clinical investigators have increased...
February 2018: Seminars in Neurology
Antonella Sferra, Fabiana Fattori, Teresa Rizza, Elsabetta Flex, Emanuele Bellacchio, Alessandro Bruselles, Stefania Petrini, Serena Cecchetti, Massimo Teson, Fabrizia Restaldi, Andrea Ciolfi, Filippo M Santorelli, Ginevra Zanni, Sabina Barresi, Claudia Castiglioni, Marco Tartaglia, Enrico Bertini
Microtubules participate in fundamental cellular processes, including chromosomal segregation and cell division, migration, and intracellular trafficking. Their proper function is required for correct central nervous system development and operative preservation, and mutations in genes coding tubulins, the constituting units of microtubules, underlie a family of neurodevelopmental and neurodegenerative diseases, collectively known as "tubulinopathies", characterized by a wide range of neuronal defects resulting from defective proliferation, migration, and function...
March 14, 2018: Human Molecular Genetics
Vassilis E Papadopoulos, Georgia Nikolopoulou, Ivi Antoniadou, Antonia Karachaliou, Giovanna Arianoglou, Evangelia Emmanouilidou, S Pablo Sardi, Leonidas Stefanis, Kostas Vekrellis
Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's Disease (PD) and are associated with decreased Glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system (CNS) suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein, a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes...
March 14, 2018: Human Molecular Genetics
Miriam Fritz, Benjamin Berger, Mathias Schemmerer, Dominique Endres, Jürgen J Wenzel, Oliver Stich, Marcus Panning
There is growing evidence that hepatitis E virus (HEV) infection can present with extrahepatic manifestations including neurological disorders. Among these, neuralgic amyotrophy (NA) has been reported to occur in some industrialized countries. We investigated 35 patients with NA and a control group for markers of HEV infection. Acute HEV infection was found in NA patients only and was associated with an inflammatory response in the central nervous system. Shedding of HEV RNA into the cerebrospinal fluid and intrathecal production of anti-HEV IgM occurred in one patient suggesting that HEV is neurotropic...
March 14, 2018: Journal of Infectious Diseases
Kelsey A Herrmann, Heather T Broihier
Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways...
March 13, 2018: Current Opinion in Neurobiology
Brin Freund, James J Gugger, Alexandra Reynolds, William O Tatum, Jan Claassen, Peter W Kaplan
PURPOSE: Periodic discharges (PDs) are EEG patterns denoting brain dysfunction and ictal tendency. Their exact meaning regarding etiology and outcomes is not well known. In particular, bilateral independent PDs (BIPDs) are poorly described. METHODS: We performed a retrospective, multicenter study evaluating neuroimaging, epileptic, clinical, and EEG correlates of BIPDs. RESULTS: Twenty-five patients studied with a mean Glasgow Coma Scale 6...
March 15, 2018: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Kiran T Thakur, Alexandra Boubour, Deanna Saylor, Mitashee Das, David R Bearden, Gretchen L Birbeck
: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral therapy (cART). Importantly, growing evidence shows that the CNS may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Though there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain...
March 15, 2018: AIDS
Yimin Wang, Fang Ye, Chanyan Huang, Faling Xue, Yingyuan Li, Shaowei Gao, Zeting Qiu, Si Li, Qinchang Chen, Huaqiang Zhou, Yiyan Song, Wenqi Huang, Wulin Tan, Zhongxing Wang
BACKGROUND: Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. METHODS: Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected...
March 15, 2018: Clinical Journal of Pain
Tory P Johnson, Avindra Nath
PURPOSE OF REVIEW: The immune system serves a critical role in protecting the host against various pathogens. However, under circumstances, once triggered by the infectious process, it may be detrimental to the host. This may be as a result of nonspecific immune activation or due to a targeted immune response to a specific host antigen. In this opinion piece, we discuss the underlying mechanisms that lead to such an inflammatory or autoimmune syndrome affecting the nervous system. We examine these hypotheses in the context of recent emerging infections to provide mechanistic insight into the clinical manifestations and rationale for immunomodulatory therapy...
March 14, 2018: Current Opinion in Neurology
Jessica H Hill, Claudia Solt, Michelle T Foster
Obesity and associated metabolic co-morbidities are a worldwide public health problem. Negative health outcomes associated with obesity, however, do not arise from excessive adiposity alone. Rather, deleterious outcomes of adipose tissue accumulation are a result of how adipocytes are distributed to individual regions in the body. Due to our increased understanding of the dynamic relationship that exists between specific adipose depots and disease risk, an accurate characterization of total body adiposity as well as location is required to properly evaluate a population's disease risk...
March 16, 2018: Hormone Molecular Biology and Clinical Investigation
Kirti Gupta, Chirag K Ahuja, Awadh K Pandit, Manisha Biswal, M R Shivaprakash
While neurological manifestations in scrub typhus have been well described both in clinical and radiological reports in the literature, neuropathological features are rarely reported. They range from subtle "typhus nodules" to more widespread capillaritis. Familiarity with pathological features is essential for correct interpretation. We describe the clinical, imaging, and histological findings in an autopsy case of scrub typhus, which was pre-terminally superimposed by fungal meningoencephalitis...
March 2018: Neurology India
Levente Molnár, Béla Fülesdi, Norbert Németh, Csilla Molnár
Sepsis is a leading cause of death in medical and surgical intensive care units (ICUs). Disturbance of consciousness of varying severity is an early warning sign of developing sepsis in the majority of cases. Sepsis-associated encephalopathy (SAE) is the most frequent type of encephalopathy in the ICU and is defined as a state of diffuse cerebral dysfunction caused by the inflammatory response of the body to various infections, where the inflammatory process does not affect the central nervous system (CNS) directly and the primary symptom is a disturbed level of consciousness...
March 2018: Neurology India
Ryota Tamura, Ryosuke Tomio, Farrag Mohammad, Masahiro Toda, Kazunari Yoshida
OBJECTIVE The anterior transpetrosal approach (ATPA) was established in 1984 and has been particularly effective for petroclival tumors. Although some complications associated with this approach, such as venous hemorrhage in the temporal lobe and nervous disturbances, have been resolved over the years, the incidence rate of CSF leaks has not greatly improved. In this study, some varieties of air cell tracts that are strongly related to CSF leaks are demonstrated. In addition, other pre- and postoperative risk factors for CSF leakage after ATPA are discussed...
March 16, 2018: Journal of Neurosurgery
Da-Zhi Guo, Lin Xiao, Yi-Jun Liu, Chen Shen, Hui-Fang Lou, Yan Lv, Shu-Yi Pan
This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells...
March 16, 2018: Experimental & Molecular Medicine
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