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Neurology, multiple sclerosis

Emanuele D'Amico, Francesco Patti, Aurora Zanghì, Mario Zappia
Using the term of progressive multiple sclerosis (PMS), we considered a combined population of persons with secondary progressive MS (SPMS) and primary progressive MS (PPMS). These forms of MS cannot be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile...
October 17, 2016: International Journal of Molecular Sciences
S Kemp, R S Allan, N Patanjali, M H Barnett, B P Jonker
We report a unique case of neurological deficit from late onset multiple sclerosis (MS), in a 65-year-old woman, after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). At 3.5months post-SRS for TN, the patient developed ataxia and left leg paraesthesiae and brain MRI showed altered signal and enhancement in the vicinity of the right trigeminal root entry zone (REZ). The symptoms remitted following treatment with intravenous methylprednisolone, however, 10months post-SRS, the patient developed gait ataxia and left lower limb weakness...
October 17, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Anne Wickström, Maria Fagerström, Lucas Wickström, Gabriel Granåsen, Charlotte Dahle, Magnus Vrethem, Peter Sundström
BACKGROUND: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. OBJECTIVES: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. METHODS: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar...
October 6, 2016: Multiple Sclerosis: Clinical and Laboratory Research
J Pakpoor, D Saylor, I Izbudak, L Liu, E M Mowry, D M Yousem
BACKGROUND AND PURPOSE: The increasing use of the emergency department MR imaging scanner at our institution raises questions about its added value to certain patient groups. We hypothesized that the use of emergency department MR imaging for identifying active demyelination in MS patients presenting with new neurologic symptoms would be of low yield. MATERIALS AND METHODS: Electronic medical records were reviewed for patients with MS who had emergency department MR imaging scans for a suspected MS exacerbation between March 1, 2014, and March 1, 2016...
October 6, 2016: AJNR. American Journal of Neuroradiology
Ke-Wei Tian, Fan Zhang, Hong Jiang, Beibei Wang, Shu Han
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits...
October 19, 2016: Journal of Anatomy
Nabil K El Ayoubi, Samia J Khoury
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system. Only a few biomarkers are available in MS clinical practice, such as cerebrospinal fluid oligoclonal bands and immunoglobulin index, serum anti-aquaporin 4 antibodies, and serum anti-John Cunningham virus antibodies. Thus, there is a significant unmet need for biomarkers to assess prognosis, response to therapy, or potential treatment complications. Here we describe emerging biomarkers that are in development, focusing on those from peripheral blood...
October 18, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Alon Kalron, Uri Givon, Lior Frid, Mark Dolev, Anat Achiron
Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8...
2016: PloS One
Jasna Jančić, Vesna Đurić, Nikola Ivančević, Blažo Nikolić, John N van den Anker, Janko Samardžić
The serine/threonine kinase mechanistic target of rapamycin (mTOR) is an important sensor of the cellular energy condition which, at the same time, represents a kind of master switch between anabolic and catabolic cellular processes. Tuberous sclerosis complex (TSC) is a genetic disease which is considered to be a prototype of a dysregulated mTOR signaling pathway. The dysregulated mTOR pathway in TSC leads to characteristic structural and physiologic abnormalities in multiple organs. In this review we focus on the pharmacological properties of mTOR inhibitors and clinical investigations of mTOR inhibitors for two important neurological TSC manifestations: subependymal giant cell astrocytomas (SEGAs) and epilepsy...
October 12, 2016: Current Medicinal Chemistry
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Chen Gu
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Many believe autoimmune pathogenesis plays a key role in MS, but its target(s) remains elusive. A recent study detected autoantibodies against KIR4.1, an ATP-sensitive, inward rectifier potassium channel, in nearly half of the MS patients examined. KIR4.1 channels are expressed in astrocytes. Together with aquaporin 4 (AQP4) water channels, they regulate astrocytic functions vital for myelination. Autoantibodies against AQP4 have been established as a key biomarker for neuromyelitis optica (NMO) and contributed to diagnostic and treatment strategy adjustments...
2016: Frontiers in Molecular Neuroscience
Ann Cathrine Kroksveen, Astrid Guldbrandsen, Marc Vaudel, Ragnhild Reehorst Lereim, Harald Barsnes, Kjell-Morten Myhr, Øyvind Torkildsen, Frode S Berven
In the current study, we conducted a quantitative in-depth proteome and deglycoproteome analysis of cerebrospinal fluid (CSF) from relapsing-remitting multiple sclerosis (RRMS) and neurological controls using mass spectrometry and pathway analysis. More than 2000 proteins and 1700 deglycopeptides were quantified, with 484 proteins and 180 deglycopeptides significantly changed between pools of RRMS and pools of controls. Approximately 300 of the significantly changed proteins were assigned to various biological processes, including inflammation, extracellular matrix organization, cell adhesion, immune response and neuron development...
October 11, 2016: Journal of Proteome Research
Deepak K Kaushik, Heather Y F Yong, Jennifer N Hahn, Claudia Silva, Steven Casha, R John Hurlbert, Francois H Jacques, Robert Lisak, Omar Khan, Carolina Ionete, Catherine Larochelle, Alex Prat, Amit Bar-Or, V Wee Yong
Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects...
2016: PloS One
Violaine K Harris, Tamara Vyshkina, Saud A Sadiq
BACKGROUND AIMS: There is a critical unmet need to develop regenerative therapies for the demyelinating disease multiple sclerosis (MS). We previously characterized the immunoregulatory and trophic properties of neural progenitors derived from bone marrow mesenchymal stromal cells (MSC-NPs) and established that cells derived from MS and non-MS patients alike were therapeutically viable. In an experimental model of MS, intrathecal MSC-NP injection resulted in disease amelioration with decreased T-cell infiltration, and less severe lesion pathology associated with recruitment of resident progenitors to inflammatory sites...
October 7, 2016: Cytotherapy
Denise S M Medrado da Costa, Joana Hygino, Thais B Ferreira, Taissa M Kasahara, Priscila O Barros, Clarice Monteiro, Aleida Oliveira, Felipe Tavares, Claudia Cristina Vasconcelos, Regina Alvarenga, Cleonice A M Bento
Vitamin D deficiency is an environmental risk factor for MS, a Th17 cell-mediated autoimmune disease that results in demyelination in the CNS. Therefore, we aimed to evaluate the ability of in vitro 1,25(OH)2D in modulating different Th17 cell subsets in MS patients in remission phase. In the present study, the production of Th17-related cytokines (IL-1β, IL-6, IL-17, IL-22), as well as GM-CSF, was significantly higher in cell cultures from MS patients than in healthy subjects (HS). The 1,25(OH)2D reduced all pro-inflammatory cytokines essayed, mainly those released from HS cell cultures...
October 15, 2016: Journal of Neuroimmunology
Sven Briken, Sina Cathérine Rosenkranz, Oliver Keminer, Stefan Patra, Gesche Ketels, Christoph Heesen, Rainer Hellweg, Ole Pless, Karl-Heinz Schulz, Stefan M Gold
BACKGROUND: Clinical studies have suggested beneficial effects of exercise on cognitive function in ageing adults and neurodegenerative diseases such as dementia. Recent work indicates the same for progressive multiple sclerosis (MS), an inflammatory and degenerative disease of the central nervous system (CNS). The biological pathways associated with these effects are however not well understood. OBJECTIVE: In this randomized controlled study, we explored serum levels of the myokine Irisin, the neurotrophin brain-derived neurotrophic factor (BDNF) and Interleukin-6 (IL-6) during acute endurance exercise and over the course of a 9-weeks endurance exercise training period in n=42 patients with progressive MS...
October 15, 2016: Journal of Neuroimmunology
Jueqiong Wang, Congying Zhao, Peng Kong, Guanyun Bian, Zhe Sun, Yafei Sun, Li Guo, Bin Li
Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect of MB on experimental autoimmune encephalomyelitis (EAE), a classical animal model of multiple sclerosis (MS). MB treatment reduced the clinical scores of EAE significantly and attenuated pathological injuries in spinal cords...
October 15, 2016: Journal of Neuroimmunology
Daniel Jons, Maria Kneider, Linda Fogelstrand, Anders Jeppsson, Stefan Jacobsson, Oluf Andersen
Contemporary evidence supports that MS immunopathology starts in the peripheral lymphatic system. However, the site and character of crucial initiating events are unknown. We examined subsets of the first stages of blood cells in the bone marrow of 9 MS patients and 11 neurologically healthy controls using FACS analysis. The proportion of natural killer T cells was lower (P=0.045) in the bone marrow of MS patients, but proportions of hematogenous stem cells, myeloblasts, and B cell precursor subsets in the bone marrow did not differ between MS patients and controls...
October 15, 2016: Journal of Neuroimmunology
Leah H Suttner, Amanda Mejia, Blake Dewey, Pascal Sati, Daniel S Reich, Russell T Shinohara
Diffusion tensor imaging (DTI) has become the predominant modality for studying white matter integrity in multiple sclerosis (MS) and other neurological disorders. Unfortunately, the use of DTI-based biomarkers in large multi-center studies is hindered by systematic biases that confound the study of disease-related changes. Furthermore, the site-to-site variability in multi-center studies is significantly higher for DTI than that for conventional MRI-based markers. In our study, we apply the Quantitative MR Estimation Employing Normalization (QuEEN) model to estimate the four DTI measures: MD, FA, RD, and AD...
2016: NeuroImage: Clinical
Chiara Cordiglieri, Fulvio Baggi, Pia Bernasconi, Dimos Kapetis, Elisa Faggiani, Alessandra Consonni, Francesca Andreetta, Rita Frangiamore, Paolo Confalonieri, Carlo Antozzi, Renato Mantegazza
Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative alterations, ultimately progressing to neurological handicap. Therapies are effective in counteracting inflammation but not neurodegeneration. Biomarkers predicting disease course or treatment response are lacking. We investigated whether altered gene and protein expression profiles were detectable in the peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease-modifying therapies. A discovery/validation study on RR-MS responsive to glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3, CD177, IGJ, IL5RA, MMP8, P2RY12, and S100β...
October 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Ryan B Griggs, Leonid M Yermakov, Keiichiro Susuki
Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria...
October 4, 2016: Neuroscience Research
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