Primary CNS Lymphoma

Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system is an aggressive malignancy that exhibits unique biological features and characteristic clinical behaviour, with overall long-term survival rates of around 20–40 %. Clinical outcome has improved following the advent of chemoradiation protocols incorporating high-dose methotrexate in the mid-1980s, but disease relapse and adverse neurocognitive sequelae remain major clinical challenges. To address this, investigators have focused on improving drug therapy with novel cytotoxic combinations, monoclonal antibody therapy, and intensive chemotherapy consolidation approaches, in an attempt to improve disease control whilst reducing the requirement for whole-brain radiotherapy. Outcomes for patients that are older, immunocompromised, or have relapsed/refractory disease remain unsatisfactory and there is a paucity of clinical trial data to guide treatment of these groups. This review highlights recent advances in pathobiology, imaging, and clinical management of PCNSL and looks ahead to research priorities for this rare and challenging lymphoid malignancy

The knowledge domain of chain and network science

This editorial paper aims to provide a framework to categorise and evaluate the domain of Chain and Network Science (CNS), and to provide an envelope for the research and management agenda. The authors strongly feel that although considerable progress has been made over the past couple of years in the development of the CNS domain, a number of important and exciting challenges are still waiting to be tackled. This paper provides a definition of the object of study of CNS, its central problem area, the organisation and governance of chain and network co-operation, and the relationships between chain organisation and technology development, market dynamics, and the economy and society at large. It indicates relevant sources of knowledge among the various academic disciplines. It touches upon CNS problem solving by identifying areas for knowledge development and CNS tool construction

Overexpression of Sox11 Promotes Corticospinal Tract Regeneration after Spinal Injury While Interfering with Functional Recovery

Embryonic neurons, peripheral neurons, and CNS neurons in zebrafish respond to axon injury by initiating pro-regenerative transcriptional programs that enable axons to extend, locate appropriate targets, and ultimately contribute to behavioral recovery. In contrast, many long-distance projection neurons in the adult mammalian CNS, notably corticospinal tract (CST) neurons, display a much lower regenerative capacity. To promote CNS repair, a long-standing goal has been to activate pro-regenerative mechanisms that are normally missing from injured CNS neurons. Sox11 is a transcription factor whose expression is common to a many types of regenerating neurons, but it is unknown whether suboptimal Sox11 expression contributes to low regenerative capacity in the adult mammalian CNS. Here we show in adult mice that dorsal root ganglion neurons (DRGs) and CST neurons fail to upregulate Sox11 after spinal axon injury. Furthermore, forced viral expression of Sox11 reduces axonal dieback of DRG axons, and promotes CST sprouting and regenerative axon growth in both acute and chronic injury paradigms. In tests of forelimb dexterity, however, Sox11 overexpression in the cortex caused a modest but consistent behavioral impairment. These data identify Sox11 as a key transcription factor that can confer an elevated innate regenerative capacity to CNS neurons. The results also demonstrate an unexpected dissociation between axon growth and behavioral outcome, highlighting the need for additional strategies to optimize the functional output of stimulated neurons

Complex regulation of neutrophil-derived MMP-9 secretion in central nervous system tuberculosis.

BACKGROUND: Central nervous system tuberculosis (CNS-TB) may be fatal even with treatment. Neutrophils are the key mediators of TB immunopathology, and raised CSF matrix metalloproteinase-9 (MMP-9) which correlates to neutrophil count in CNS-TB is associated with neurological deficit and death. The mechanisms by which neutrophils drive TB-associated CNS matrix destruction are not clearly defined. METHODS: Human brain biopsies with histologically proven CNS-TB were stained for neutrophils, neutrophil elastase, and MMP-9. Neutrophil MMP-9 secretion and gene expression were analyzed using Luminex and real-time PCR. Type IV collagen degradation was evaluated using confocal microscopy and quantitative fluorescent assays. Intracellular signaling pathways were investigated by immunoblotting and chemical inhibitors. RESULTS: MMP-9-expressing neutrophils were present in tuberculous granulomas in CNS-TB and neutrophil-derived MMP-9 secretion was upregulated by Mycobacterium tuberculosis (M.tb). Concurrent direct stimulation by M.tb and activation via monocyte-dependent networks had an additive effect on neutrophil MMP-9 secretion. Destruction of type IV collagen, a key component of the blood-brain barrier, was inhibited by neutralizing neutrophil MMP-9. Monocyte-neutrophil networks driving MMP-9 secretion in TB were regulated by MAP-kinase and Akt-PI3 kinase pathways and the transcription factor NF-kB. TNFα neutralization suppressed MMP-9 secretion to baseline while dexamethasone did not. CONCLUSIONS: Multiple signaling paths regulate neutrophil-derived MMP-9 secretion, which is increased in CNS-TB. These paths may be better targets for host-directed therapies than steroids currently used in CNS-TB

Tertiary lymphoid organs in central nervous system autoimmunity

Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS), which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease; however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines, and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs) were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function, and clinical significance. Mechanistic studies in patients are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE) recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation, and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs

Engaging Nursing Staff in Research: The Clinical Nurse Specialist Role in an Academic-Clinical Partnership

Purpose: The purpose of this article is to describe the processes of exploring and implementing an academic-clinical study, engaging nursing staff in research, and maintaining their enthusiasm within the context of an academic-clinical research partnership. Description: The core competencies of the clinical nurse specialist (CNS) role address evidence-based practice, quality improvement, and research. Studies and exemplars of the CNS role in the literature illustrate expert practitioner and facilitator of evidence-based practice, but less attention is given to methods used by the CNS to engage staff in clinical research. Outcome: The CNS was successful in obtaining staff engagement in the research project from exploration through sustainment. Conclusion: Collaborative research between academic and clinical partners enhances the educational and professional environment for students and clinicians, promotes evidence-based practice, and from this project may promote Veteran and family-centered care. The CNS played a key role in engaging and sustaining staff commitment, which contributed to the success of this study

The Role of the Faith Community Nurse in Fostering Spirituality in those with Alzheimer\u27s Disease

Alzheimer ’s disease (AD) strips individuals of memories and abilities that have defined them as productive adults throughout their life. While the decline in memory is real and results in a ‘loss of self’ this does not equate to a ‘loss of soul.’ AD patients continue to have spiritual needs throughout their life as do the family, and/or caregivers. This article explores the spiritual needs and care of AD patients and families and the unique opportunity faith community nurses have to help the AD patient and their support system. The Reisberg Functional Assessment Staging System is used to explain the expected functional and cognitive decline and guide in specific nursing interventions at each stage of the disease. Music, prayer, singing, reading from the Bible, the Torah or other books significant to the individual are among the interventions introduced to help the individual continue to make the spiritual connection necessary for transition to end-of-life. Resources are suggested to increase caregiver resiliency throughout the illness and after the death of the family member