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      • Record: found
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      Is Open Access

      An observational study of alemtuzumab following fingolimod for multiple sclerosis

      research-article
      Author(s): , BSc, MBBCh, MRCP, , MBBCh, MD, FRCP, , MD, PhD, , MD, , MSc, PhD, , MD, FRCP, , BSc, MBChB, MRCP, , MD, PhD, , MD, PhD, , MD, PhD, , PhD, MRCP, , MD, FRCP
      Publication date (Electronic):
      Journal: Neurology® Neuroimmunology & Neuroinflammation
      Publisher: Lippincott Williams & Wilkins

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective:

          To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab.

          Methods:

          Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers.

          Results:

          Nine patients were identified. Median disease duration to alemtuzumab treatment was 94 (39–215) months and follow-up from time of first alemtuzumab cycle 20 (14–21) months. Following first alemtuzumab infusion cycle, 8 patients were identified by at least 1 clinical relapse and radiologic disease activity and 1 by significant radiologic disease activity alone.

          Conclusions:

          We acknowledge the potential for ascertainment bias; however, these cases may illustrate an important cause of reduced efficacy of alemtuzumab in a vulnerable group of patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive lymphocytes following fingolimod withdrawal, allowing these cells to be concealed from the usual biological effect of alemtuzumab. Subsequent lymphocyte egress then provokes disease reactivation. Further animal studies and clinical trials are required to confirm these phenomena and in the meantime careful consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalized treatment regimens.

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          Most cited references7

          • Record: found
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          Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model.

          Mary Roberts, W M Siders, Andy S. Gale … (2009)
          Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on the surface of normal and malignant lymphocytes. It is approved for the treatment of B-cell chronic lymphocytic leukaemia and is undergoing Phase III clinical trials for the treatment of multiple sclerosis. The exact mechanism by which alemtuzumab mediates its biological effects in vivo is not clearly defined and mechanism of action studies have been hampered by the lack of cross-reactivity between human and mouse CD52. To address this issue, a transgenic mouse expressing human CD52 (hCD52) was created. Transgenic mice did not display any phenotypic abnormalities and were able to mount normal immune responses. The tissue distribution of hCD52 and the level of expression by various immune cell populations were comparable to those seen in humans. Treatment with alemtuzumab replicated the transient increase in serum cytokines and depletion of peripheral blood lymphocytes observed in humans. Lymphocyte depletion was not as profound in lymphoid organs, providing a possible explanation for the relatively low incidence of infection in alemtuzumab-treated patients. Interestingly, both lymphocyte depletion and cytokine induction by alemtuzumab were largely independent of complement and appeared to be mediated by neutrophils and natural killer cells because removal of these populations with antibodies to Gr-1 or asialo-GM-1, respectively, strongly inhibited the activity of alemtuzumab whereas removal of complement by treatment with cobra venom factor had no impact. The hCD52 transgenic mouse appears to be a useful model and has provided evidence for the previously uncharacterized involvement of neutrophils in the activity of alemtuzumab.
          Article 0 comments Cited 102 times – based on 0 reviews     Review now
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            Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation.

            C Vaughan Tuohy, Huan Loh, Grant Hill-Cawthorne … (2013)
            The association between lymphopenia and autoimmunity is recognized, but the underlying mechanisms are poorly understood and have not been studied systematically in humans. People with multiple sclerosis treated with the lymphocyte-depleting monoclonal antibody alemtuzumab offer a unique opportunity to study this phenomenon; one in three people develops clinical autoimmunity, and one in three people develops asymptomatic autoantibodies after treatment. Here, we show that T-cell recovery after alemtuzumab is driven by homeostatic proliferation, leading to the generation of chronically activated (CD28(-)CD57(+)), highly proliferative (Ki67(+)), oligoclonal, memory-like CD4 and CD8 T cells (CCR7(-)CD45RA(-) or CCR7(-)CD45RA(+)) capable of producing proinflammatory cytokines. Individuals who develop autoimmunity after treatment are no more lymphopenic than their nonautoimmune counterparts, but they show reduced thymopoiesis and generate a more restricted T-cell repertoire. Taken together, these findings demonstrate that homeostatic proliferation drives lymphopenia-associated autoimmunity in humans.
            Article 0 comments Cited 80 times – based on 0 reviews     Review now
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              Clinical pharmacokinetics of fingolimod.

              R Schmouder, M Kovarik, François David (2012)
              Fingolimod (FTY720), a sphingosine 1-phosphate receptor modulator, is the first in a new class of therapeutic compounds and is the first oral therapy approved for the treatment of relapsing forms of multiple sclerosis (MS). Fingolimod is a structural analogue of endogenous sphingosine and undergoes phosphorylation to produce fingolimod phosphate, the active moiety. Fingolimod targets MS via effects on the immune system, and evidence from animal models indicates that it may also have actions in the central nervous system. In phase III studies in patients with relapsing-remitting MS, fingolimod has demonstrated efficacy superior to that of an approved first-line therapy, intramuscular interferon-β-1a, as well as placebo, with benefits extending across clinical and magnetic resonance imaging measures. The pharmacokinetic profiles of fingolimod and fingolimod phosphate have been extensively investigated in studies in healthy volunteers, renal transplant recipients (the indication for which fingolimod was initially under clinical development, but the development was subsequently discontinued) and MS patients. Results from these studies have demonstrated that fingolimod is efficiently absorbed, with an oral bioavailability of >90%, and its absorption is unaffected by dietary intake, therefore it can be taken without regard to meals. Fingolimod and fingolimod phosphate have a half-life of 6-9 days, and steady-state pharmacokinetics are reached after 1-2 months of daily dosing. The long half-life of fingolimod, together with its slow absorption, means that fingolimod has a flat concentration profile over time with once-daily dosing. Fingolimod and fingolimod phosphate show dose-proportional exposure in single- and multiple-dose studies over a range of 0.125-5 mg; hence, there is a predictable relationship between dose and systemic exposure. Furthermore, fingolimod and fingolimod phosphate exhibit low to moderate intersubject pharmacokinetic variability. Fingolimod is extensively metabolized, with biotransformation occurring via three main pathways: (i) reversible phosphorylation to fingolimod phosphate; (ii) hydroxylation and oxidation to yield a series of inactive carboxylic acid metabolites; and (iii) formation of non-polar ceramides. Fingolimod is largely cleared through metabolism by cytochrome P450 (CYP) 4F2. Since few drugs are metabolized by CYP4F2, fingolimod would be expected to have a relatively low potential for drug-drug interactions. This is supported by data from in vitro studies indicating that fingolimod and fingolimod phosphate have little or no capacity to inhibit and no capacity to induce other major drug-metabolizing CYP enzymes at therapeutically relevant steady-state blood concentrations. Population pharmacokinetic evaluations indicate that CYP3A inhibitors and CYP3A inducers have no effect or only a weak effect on the pharmacokinetics of fingolimod and fingolimod phosphate. However, blood concentrations of fingolimod and fingolimod phosphate are increased moderately when fingolimod is coadministered with ketoconazole, an inhibitor of CYP4F2. The pharmacokinetics of fingolimod are unaffected by renal impairment or mild-to-moderate hepatic impairment. However, exposure to fingolimod is increased in patients with severe hepatic impairment. No clinically relevant effects of age, sex or ethnicity on the pharmacokinetics of fingolimod have been observed. Fingolimod is thus a promising new therapy for eligible patients with MS, with a predictable pharmacokinetic profile that allows effective once-daily oral dosing.
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                Author and article information

                Contributors
                Mark Willis:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. (1) Wellcome Trust Research Training Fellowship

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Owen Pearson:
                Comment :

                Scientific Advisory Boards:

                1. (1)Biogen, Novartis, Roche (2)UK MS register

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Biogen, Roche, Merck Serono, Novartis, Teva, Genzyme Sanofi.

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Zsolt Illes:
                Comment :

                Scientific Advisory Boards:

                1. (1) Biogen Idec (2) Novartis (3) Sanofi-Aventis-Genzyme (4) Teva Pharmaceuticals

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Biogen Idec (2) Novartis (3) Sanofi-Aventis-Genzyme (4) Teva Pharmaceuticals (5) Bayer Healthcare (5) Merck Serono

                Editorial Boards:

                1. Clinical and Experimental Neuroimmunology

                Patents:

                1. Lambertsen K, Clausen B, Nielsen HH, Finsen B, Illes Z. 2015. Fumaric acid derivates for Medical use. No. PCT/DK2015/050344. The use of fumaric acid derivates in acute ischemic stroke.

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. (1) Biogen Idec

                Research Support, Government Entities:

                1. (1)Region of Southern Denmark, primary investigator, 2014

                Research Support, Academic Entities:

                1. (1)Odense University Hospital

                Research Support, Foundations and Societies:

                1. (1)Scleroseforeningen (2) Lundbeckfonden (3) Direktor Ejnar Jonasson, kaldet Johnsen, og Hustru's Mindelegat

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Tobias Sejbaek:
                Comment :

                Scientific Advisory Boards:

                1. Novartis, Biogen, Teva, Merck, Roche

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. Biogen, Teva, Novartis

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Christian Nielsen:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Martin Duddy:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Sanofi Genzyme, speaker honoraria, travel to conference, advisory board (2) Novartis, speaker honoraria, travel to conference, advisory board (3) Biogen, speaker honoraria, travel to conference, advisory board (4) Merck, speaker honoraria (5) Teva, speaker honoraria, travel to conference (6) Roche, honorarium for development of educational programme, advisory board (7) Medscape, development and delivery of online educational programme

                Editorial Boards:

                1. Multiple Sclerosis Journal, Associate Editor, 2013-present

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. (1) Novartis (2) Biogen (3) Roche (4) Sanofi Genzyme

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. (1) MS Trust, London, UK

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Kate Petheram:
                Comment :

                Scientific Advisory Boards:

                1. (1) Roche Product Limited. Scientific advisory board.

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Genzyme Sanofi. Funding for travel and speaker honoraria. (2) Biogen Idec. Funding for travel.

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Caspar van Munster:
                Comment :

                Scientific Advisory Boards:

                1. (1) Commercial, compensation for serving in a scientific advisory board from Merck Serono.

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Commercial, honoraria for lecturing and consulting from Novartis Pharma AG (2) Commercial, honoraria for lecturing and consulting from Biogen-Idec (3) Commercial, honoraria for lecturing and consulting from Merck Serono

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Joep Killestein:
                Comment :

                Scientific Advisory Boards:

                1. Consultancy (advisory boards) Novartis, Merck-Serono, Biogen, Genzyme, TEVA, Roche

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. Speaker honoraria Biogen, Novartis, TEVA, Merck-Serono, Roche

                Editorial Boards:

                1. Editor of the official scientific journal of the Dutch Society of Neurology, the Dutch Society of Neurosurgeons and the Society of Flemish Neurologists (Tijdschrift voor Neurologie en Neurochirurgie). Editorial board MS Journal

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. Consultancy Novartis, Merck-Serono, Biogen Idec, Genzyme, TEVA

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. I have been involved in clinical trials of companies that market drugs for MS (Schering AG, Biogen Idec, Merck-Serono, Teva, Genzyme, Novartis and Roche).

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Clas Malmeström:
                Comment :

                Scientific Advisory Boards:

                1. (1)Biogen-Idec, Merck-Serono, Novartis and Roche

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Biogen-Idec, Merck-Serono, Novartis and Roche

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Emma Tallantyre:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. I received salary from Biogen Idec as part of a fellowship scheme.

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Neil Robertson:
                Comment :

                Scientific Advisory Boards:

                1. Professor Robertson has served on Advisory boards for Genzyme, Roche, Novartis, Biogen

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. Professor Robertson has recieved honoraria for speaking at academic meetings from Biogen and Genzyme

                Editorial Boards:

                1. Professor robertson serves as an editor for the Journal of Neurology since 2012

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. Neuroimmunology Fellowship Genzyme Mortality of MS Novartis

                Research Support, Government Entities:

                1. National institute of Heath Wales, co-applicant 2015-18

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. Multiple Sclerosis society of Great Britain and Northern Ireland Welcome Trust

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

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                Journal
                Journal ID (nlm-ta): Neurol Neuroimmunol Neuroinflamm
                Journal ID (iso-abbrev): Neurol Neuroimmunol Neuroinflamm
                Journal ID (hwp): nnn
                Journal ID (publisher-id): NEURIMMINFL
                Title: Neurology® Neuroimmunology & Neuroinflammation
                Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )
                ISSN (Electronic): 2332-7812
                Publication date (Electronic): 10 January 2017
                Publication date Collection: March 2017
                Publication date PMC-release: 10 January 2017
                Volume: 4
                Issue: 2
                Electronic Location Identifier: e320
                Affiliations
                From the Department of Neurology (M.W., E.T., N.R.), Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales; Department of Neurology (O.P.), Morriston Hospital, Heol Maes Eglwys, Morriston, Swansea, UK; Departments of Neurology (Z.I., T.S.) and Clinical Immunology (C.N.), Odense University Hospital, University of Southern Denmark; Department of Neurology (M.D.), The Royal Victoria Infirmary, Newcastle upon Tyne; Department of Neurology (K.P.), Sunderland Royal Hospital, UK; VU University Medical Center (C.v.M., J.K.), Amsterdam, the Netherlands; and Department of Neurology (C.M.), Sahlgrenska Academy at the University of Gothenburg, Institute of Clinical Neuroscience and Physiology, Gothenburg, Sweden.
                Author notes
                Correspondence to Dr. Robertson: RobertsonNP@ 123456cardiff.ac.uk

                Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by Wellcome Trust Allocation.

                Article
                Publisher ID: NEURIMMINFL2016011098
                DOI: 10.1212/NXI.0000000000000320
                PMC ID: 5226279
                SO-VID: f1d0f019-ca33-407b-85d1-36cb2b0d2d57
                Copyright © Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 05 October 2016
                Date accepted : 05 December 2016
                Categories
                Subject: 41
                Subject: 131
                Subject: 132
                Subject: Article
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                OPEN-ACCESS TRUE

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