Journal ArticleDOI
Multiple Sclerosis: An Immune or Neurodegenerative Disorder?
Bruce D. Trapp,Klaus-Armin Nave +1 more
TLDR
Data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients are reviewed and it is questioned whether inflammatory demyelination is primary or secondary in the disease process.Abstract:
Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable, usually starts with reversible episodes of neurological disability in the third or fourth decade of life, and transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. We review data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients. We question whether inflammatory demyelination is primary or secondary in the disease process and discuss the challenges of elucidating the cause of MS and developing therapies that will delay or prevent the irreversible and progressive neurological decline that most MS patients endure.read more
Citations
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Journal ArticleDOI
Mechanisms underlying inflammation in neurodegeneration.
TL;DR: There is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators in neurodegenerative diseases.
Journal ArticleDOI
Spike timing-dependent plasticity: a Hebbian learning rule
Natalia Caporale,Yang Dan +1 more
TL;DR: This work has examined the functional consequences of STDP directly in an increasing number of neural circuits in vivo, and revealed several layers of complexity in STDP, including its dependence on dendritic location, the nonlinear integration of synaptic modification induced by complex spike trains, and the modulation ofSTDP by inhibitory and neuromodulatory inputs.
Journal ArticleDOI
Remyelination in the CNS: from biology to therapy
TL;DR: The mechanisms of remyelination provide critical clues for regeneration biologists that help them to determine why remYelination fails in MS and in other demyelinating diseases and how it might be enhanced therapeutically.
Journal ArticleDOI
The relation between inflammation and neurodegeneration in multiple sclerosis brains
Josa M. Frischer,Stephan Bramow,Assunta Dal-Bianco,Claudia F. Lucchinetti,Helmut Rauschka,Manfred Schmidbauer,Henning Laursen,Per Soelberg Sørensen,Hans Lassmann +8 more
TL;DR: It is found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease, and the disease processes of multiple sclerosis may die out in aged patients with long-standing disease.
Journal ArticleDOI
Myelination and support of axonal integrity by glia
TL;DR: Cell biology and mouse genetics have provided insight into axon–glia signalling and the molecular architecture of the myelin sheath, and glial cells that myelinate axons were found to have a dual role by also supporting the long-term integrity of those axons.
References
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Journal ArticleDOI
Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis
W. Ian McDonald,A Compston,Gilles Edan,Donald E. Goodkin,Hans-Peter Hartung,Fred D. Lublin,Henry F. McFarland,Donald W. Paty,Chris H. Polman,Stephen C. Reingold,Magnhild Sandberg-Wollheim,William A. Sibley,Alan J. Thompson,Stanley van den Noort,Brian Y. Weinshenker,Jerry S. Wolinsky +15 more
TL;DR: The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including “monosymptomatic” disease suggestive of MS, disease with a typical relapsing‐remitting course, and disease with insidious progression, without clear attacks and remissions.
Journal ArticleDOI
Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".
Chris H. Polman,Stephen C. Reingold,Gilles Edan,Massimo Filippi,Hans-Peter Hartung,Ludwig Kappos,Fred D. Lublin,Luanne M. Metz,Henry F. McFarland,Paul O'Connor,Magnhild Sandberg-Wollheim,Alan J. Thompson,Brian G. Weinshenker,Jerry S. Wolinsky +13 more
TL;DR: New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease.
Journal ArticleDOI
Axonal transection in the lesions of multiple sclerosis.
TL;DR: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
Journal ArticleDOI
Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination.
Claudia F. Lucchinetti,Wolfgang Brück,Joseph E. Parisi,Bernd W. Scheithauer,Moses Rodriguez,Hans Lassmann +5 more
TL;DR: At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.
Journal ArticleDOI
A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis
Chris H. Polman,Eva Havrdova,Michael Hutchinson,Ludwig Kappos,David Miller,J. Theodore Phillips,Fred D. Lublin,Gavin Giovannoni,A Wajgt,Martin Toal,F Lynn,Michael Panzara,Alfred Sandrock +12 more
TL;DR: Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis and hold promise as an effective treatment for relapsed multiple sclerosis.
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Chris H. Polman,Stephen C. Reingold,Brenda Banwell,Michel Clanet,Jeffrey A. Cohen,Massimo Filippi,Kazuo Fujihara,Eva Havrdova,Michael Hutchinson,Ludwig Kappos,Fred D. Lublin,Xavier Montalban,Paul L. O’Connor,Magnhild Sandberg-Wollheim,Alan J. Thompson,Emmanuelle Waubant,Brian G. Weinshenker,Jerry S. Wolinsky +17 more