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      • Record: found
      • Abstract: found
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      Is Open Access

      Monitoring disease activity in multiple sclerosis using serum neurofilament light protein

      research-article
      Author(s): , MD , , MD, PhD, , MD, PhD, , MD, PhD, , PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD
      Publication date PMC-release:
      Journal: Neurology
      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 examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).

          Methods:

          NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.

          Results:

          In MS, the correlation between serum and CSF NFL was r = 0.62 ( p < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p < 0.001 and p < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6–32.7) ng/L to 15.7 (IQR 9.6–22.7) ng/L ( p < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission ( p < 0.001) or those without new lesions on MRI ( p < 0.001).

          Conclusions:

          Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.

          Related collections

          Most cited references10

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          • Article: not found

          Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

          R H S R Roxburgh, S. R. Seaman, T Masterman … (2005)
          There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.
          Article 0 comments Cited 250 times – based on 0 reviews     Review now
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            Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis

            M Martínez, Bob Olsson, Laura Bau … (2015)
            Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.
            Article 0 comments Cited 64 times – based on 0 reviews     Review now
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              Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis.

              Charlotte E Teunissen, Til Menge, Ayse Altintas … (2013)
              The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.
              Article 0 comments Cited 58 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Lenka Novakova:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) funding of travel, Biogen (2) speaker honoraria, 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. (1) Neuro Sweden (2) Edit Jacobson Foundation (3) Research Foundation of the Multiple Sclerosis Society of Gothenburg (4) Helena Ahlins Foundation

                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

                Henrik Zetterberg:
                Comment :

                Scientific Advisory Boards:

                1. HZ has served at advisory boards for Roche Diagnostics, Eli Lilly and Pharmasum Therapeutics.

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. Journal of Alzheimer's Disease, Associate Editor Alzheimer's & Dementia, Associate Editor DADM, Associate Senior Editor

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other activities:

                1. HZ is co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg.

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (1) The Swedish Research Council (2013-2546); (2) Swedish State Support for Clinical Research (ALFGBG-144341); (3) VINNOVA; (4) the Knut and Alice Wallenberg Foundation; (5) the European Research Council; and (6) Frimurarestiftelsen

                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

                Peter Sundström:
                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

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Markus Axelsson:
                Comment :

                Scientific Advisory Boards:

                1. (1)Sanofi, Biogen, Genzyme,

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. (1) Biogen, 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. Stiftelsen Edit Jacobsson Stiftelsen Bj?rnsson

                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

                Mohsen Khademi:
                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

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Martin Gunnarsson:
                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

                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

                Anders Svenningsson:
                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. Swedish Medical Research Council, Grant Dnr 2016-00398

                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

                Tomas Olsson:
                Comment :

                Scientific Advisory Boards:

                1. Advisory boards BiogenIdec 2006- 2016 and Genzyme/SanofiAventis 2006- 2017, Merck 2016-2017. Novartis 2009-2017. With all of them advice with regard to therapy in multiple sclerosis

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. For lectures on Multiple sclerosis, Novartis 2008 and BiogenIdec 2006, 2007, 2008, 2009, 2010 , 2011, 2012 and 2016. Genzyme 2012 and 2013.

                Editorial Boards:

                1. Co-editor 2006 in Current opinion in Immunology

                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)Merck, 2)BiogenIdec, 3)SanofiAventis, 4) Novartis

                Research Support, Government Entities:

                1. Tomas Olsson (TO) has received grant support from The Swedish Research council (07488), EU fp7, Euratrans Neurinox 2012-2016 and combiMS, 2013-2014, Swedish Brain foundation,the AFA foundation, Knut and Alice Wallenberg foundation.

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. The Knut and Allice Wallenberg foundation, The Swedish Brain foundation, the AFA foundation, EU FP 7 Neurinox . TO has also received unrestricted research grants from Bayer Schering, Genzyme/Sanofi-AventisBiogen Idec and AstraZeneca.

                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

                Fredrik Piehl:
                Comment :

                Scientific Advisory Boards:

                1. data safety monitoring committee Parexel/Chugai, outside of this study

                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. 1. Biogen - unrestricted academic research projects outside of this study 2. Novartis - unrestricted academic research projects outside of this study 3. Genzyme - unrestricted academic research projects outside of this study

                Research Support, Government Entities:

                1. Swedish Medical Research Council (grant 2014-3077) PI, 2013- ongoing. Pcori, Washington DC (grant MS-1511-33196) PI, 2017- ongoing

                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

                Kaj Blennow:
                Comment :

                Scientific Advisory Boards:

                1. Dr Blennow has served at advisory boards or as a consultant for Alzheon, Eli Lilly, IBL International, Pfizer and Roche Diagnostics.

                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. Fujirebio Europe

                Speakers' Bureaus:

                1. NONE

                Other activities:

                1. Co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. The Research Council, Sweden (project # 14002) and LUA/ALF project, V?stra G?talandsregionen, Sweden (project # ALFGBG-11019)

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. The Torsten S?derberg Foundation at the Royal Swedish Academy of Sciences, the Alzheimer Foundation, Sweden, the Stiftelsen f?r Gamla Tj?narinnor, Stockholm, Sweden and Hj?rnfonden, Sweden.

                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

                Jan Lycke:
                Comment :

                Scientific Advisory Boards:

                1. has served on scientific advisory boards for 1) Almirall, 2) Teva, 3) Biogen, 4) Novartis, 5) Genzyme/SanofiAventis, and Merck

                Gifts:

                1. NONE

                Funding for travel or speaker honoraria:

                1. travel support and/or lecture honoraria from 1) Biogen, 2) Novartis, 3) Teva, and 4) Genzyme/SanofiAventis

                Editorial Boards:

                1. serves on the editorial board of the 1) Acta Neurologica Scandinavica

                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

                Journal
                Journal ID (nlm-ta): Neurology
                Journal ID (iso-abbrev): Neurology
                Journal ID (hwp): neurology
                Journal ID (publisher-id): neur
                Journal ID (pmc): neurology
                Journal ID (publisher-id): NEUROLOGY
                Title: Neurology
                Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )
                ISSN (Print): 0028-3878
                ISSN (Electronic): 1526-632X
                Publication date (Print): 28 November 2017
                Publication date PMC-release: 28 November 2017
                Volume: 89
                Issue: 22
                Pages: 2230-2237
                Affiliations
                From the Department of Clinical Neuroscience (L.N., M.A., C.M., J.L.) and Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, London, UK; Department of Pharmacology and Clinical Neuroscience (P.S.), Umeå University; University Department of Clinical Neuroscience (M.K., T.O., F.P.), Neuroimmunology Unit, and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm; and Department of Neurology (M.G.), Faculty of Medicine and Health, Örebro University, Sweden.
                Author notes
                Correspondence to Dr. Novakova: lenka.novakova@ 123456vgregion.se

                Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by Swedish Research Council.

                Article
                Publisher ID: NEUROLOGY2016792580
                DOI: 10.1212/WNL.0000000000004683
                PMC ID: 5705244
                PubMed ID: 29079686
                SO-VID: 60e6304f-dc21-4993-9b96-9985c78178e7
                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 : 08 January 2017
                Date accepted : 07 September 2017
                Categories
                Subject: 41
                Subject: 319
                Subject: Article
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