Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

November 2020; 7 (6) ArticleOpen Access

Serum neurofilament light chains in MS

Association with the Timed Up and Go

Gilles Allali, Jens Kuhle, Gautier Breville, David Leppert, Stephane Armand, Patrice H. Lalive
First published September 25, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000895
Gilles Allali
From the Division of Neurology (G.A., G.B., P.H.L.), Department of Clinical Neurosciences, Geneva University Hospitals and Geneva University, Switzerland; Department of Neurology (G.A.), Albert Einstein College of Medicine, Yeshiva University, New York; Neurologic Clinic and Policlinic (J.K., D.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel; Willy Taillard Laboratory of Kinesiology (S.A.), Geneva University Hospitals and University of Geneva; Division of Laboratory Medicine (P.H.L.), Department of Genetic and Laboratory Medicine, Geneva University Hospitals; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jens Kuhle
From the Division of Neurology (G.A., G.B., P.H.L.), Department of Clinical Neurosciences, Geneva University Hospitals and Geneva University, Switzerland; Department of Neurology (G.A.), Albert Einstein College of Medicine, Yeshiva University, New York; Neurologic Clinic and Policlinic (J.K., D.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel; Willy Taillard Laboratory of Kinesiology (S.A.), Geneva University Hospitals and University of Geneva; Division of Laboratory Medicine (P.H.L.), Department of Genetic and Laboratory Medicine, Geneva University Hospitals; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gautier Breville
From the Division of Neurology (G.A., G.B., P.H.L.), Department of Clinical Neurosciences, Geneva University Hospitals and Geneva University, Switzerland; Department of Neurology (G.A.), Albert Einstein College of Medicine, Yeshiva University, New York; Neurologic Clinic and Policlinic (J.K., D.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel; Willy Taillard Laboratory of Kinesiology (S.A.), Geneva University Hospitals and University of Geneva; Division of Laboratory Medicine (P.H.L.), Department of Genetic and Laboratory Medicine, Geneva University Hospitals; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Leppert
From the Division of Neurology (G.A., G.B., P.H.L.), Department of Clinical Neurosciences, Geneva University Hospitals and Geneva University, Switzerland; Department of Neurology (G.A.), Albert Einstein College of Medicine, Yeshiva University, New York; Neurologic Clinic and Policlinic (J.K., D.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel; Willy Taillard Laboratory of Kinesiology (S.A.), Geneva University Hospitals and University of Geneva; Division of Laboratory Medicine (P.H.L.), Department of Genetic and Laboratory Medicine, Geneva University Hospitals; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephane Armand
From the Division of Neurology (G.A., G.B., P.H.L.), Department of Clinical Neurosciences, Geneva University Hospitals and Geneva University, Switzerland; Department of Neurology (G.A.), Albert Einstein College of Medicine, Yeshiva University, New York; Neurologic Clinic and Policlinic (J.K., D.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel; Willy Taillard Laboratory of Kinesiology (S.A.), Geneva University Hospitals and University of Geneva; Division of Laboratory Medicine (P.H.L.), Department of Genetic and Laboratory Medicine, Geneva University Hospitals; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrice H. Lalive
From the Division of Neurology (G.A., G.B., P.H.L.), Department of Clinical Neurosciences, Geneva University Hospitals and Geneva University, Switzerland; Department of Neurology (G.A.), Albert Einstein College of Medicine, Yeshiva University, New York; Neurologic Clinic and Policlinic (J.K., D.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel; Willy Taillard Laboratory of Kinesiology (S.A.), Geneva University Hospitals and University of Geneva; Division of Laboratory Medicine (P.H.L.), Department of Genetic and Laboratory Medicine, Geneva University Hospitals; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Serum neurofilament light chains in MS
Association with the Timed Up and Go
Gilles Allali, Jens Kuhle, Gautier Breville, David Leppert, Stephane Armand, Patrice H. Lalive
Neurol Neuroimmunol Neuroinflamm Nov 2020, 7 (6) e895; DOI: 10.1212/NXI.0000000000000895

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
622

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Objective This cross-sectional study aims to assess the association between neuroaxonal damage assessed by serum neurofilament light chain (sNfL) and the Timed Up and Go (TUG)—a reliable and rapid measure of global neurologic disability—in patients with MS.

Methods A total of 41 consecutive patients with MS (38.0 ± 10.4 years; 57% women) with low level of disability (Expanded Disability Status Scale [EDSS] score 0–3) (EDSS score 1.0, interquartile range [IQR] 0.0–2.0) were included in this study. The TUG and sNfL were measured in a 6-month interval, together with a comprehensive neuropsychological and quantitative gait evaluation. The association of sNfL (dependant variable) with TUG, and other gait, cognitive, and behavioral measures (independent variables) were evaluated with multiple linear regressions adjusted for age, sex, and EDSS score.

Results The sNfL concentration was 23.51 pg/mL (IQR 16.51–32.21 pg/mL), and the mean TUG was 9.27 ± 1.70 seconds. Only the TUG was associated with sNfL (β = 0.021; 95% CI 0.003–0.037; p = 0.022) (after adjusting for age, sex, and EDSS score), whereas this was not the case for gait and neuropsychological measures.

Conclusions The TUG—an easy and unexpansive measure of disability—is associated with the degree of neuroaxonal damage, as measured by sNfL, in patients with MS with low level of disability. These findings confirm the validity of the TUG as a reliable bedside measure of global neurologic disability as a result of neuroaxonal damage.

Glossary

EDSS=
Expanded Disability Status Scale;
IQR=
interquartile range;
NfL=
neurofilament light chain;
sNfL=
serum NfL;
TMT=
Trail Making Test;
TUG=
Timed Up and Go

The Timed Up and Go (TUG) is a rapidly operable and widely used test of mobility and risk of falls in neurologic settings and has been recently validated in MS as a measure of functional mobility.1 The TUG is correlated with common measures of functional mobility in MS, such as the timed 25-foot walk or the Multiple Sclerosis Walking Scale-12 score. In comparison to other measures of functional mobility, the TUG captures elements of the everyday life, such as sitting, standing, and turning around,1 and can be quickly performed by clinicians during the neurologic examination even in a limited office space. In a previous study, we have demonstrated that the TUG was correlated with gait parameters, as well as with cognitive performances, and is considered a sensitive marker for quantifying disability in early stage of MS.2 The TUG has been associated with gray and white matter atrophy in patients with MS,3 but the relationship between the TUG and markers of neuroaxonal damage has not been evaluated.

Neurofilament light chain (NfL), a product of the scaffolding proteins of the neuronal cytoskeleton, represents a biomarker of axonal damage.4 Serum NfL (sNfL) has been validated as a reliable marker for present and potentially future disability in MS,5 including clinically isolated syndrome and early MS.6 However, the association between sNfL and a bedside clinical test of disability, such as the TUG, has never been tested in patients with MS with low disability.

This cross-sectional study aims to assess the association between a biological marker of neuroaxonal damage (assessed by sNfL) and disability (measured by the TUG) in patients with MS with low disability. As the TUG represents a good measure of gait and cognitive disability, and sNfL has been associated with fully established disability in MS, we aimed at evaluating whether the TUG will be associated with sNfL in early phases of disability. Establishing the association between sNfL and TUG in patients with MS with low level of disability will provide an important clue for clinicians to quickly evaluate the level of disability associated with axonal damage.

Methods

Participants

Forty-one consecutive outpatients with relapsing-remitting MS (38.0 ± 10.4 years; 57% female) were included in the protocol. Exclusion criteria were acute medical illness in the past month, neurologic and psychiatric diseases except MS, orthopedic or rheumatologic condition affecting walking, Expanded Disability Status Scale (EDSS) score >3, and an interval of >6 months between sNfL measurement and clinical assessment. All patients were stable under the same treatment for at least 3 months before clinical assessment (table 1).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 1

Clinical characteristics of patients with relapsing-remitting MS (n = 41)

Serum sampling and sNfL measurements

Serum samples were centrifuged at 2,000g for 10 minutes at room temperature and stored at −80°C within 2 hours of collection. Serum NfL levels were determined by single molecule array assay as previously described.7

TUG test

The main outcome variable was the mean ± SD of the time (seconds) of the TUG described by Podsiadlo and Richardson. The TUG was performed at self-selected speed in a well-lit environment: the patients were asked to stand up, walk 3 m, turn around, walk back to the chair, and sit down.

Gait and neuropsychological assessment

Patients were asked to walk on a 10-m walkway at their self-selected speed, as previously described.8 Spatiotemporal gait parameters were computed using Matlab 2015b (MathWorks, Natick, MA) based on the trajectories of heel reflective markers (14 mm) recorded at 100 Hz by an optoelectronic system (12 cameras, Vicon Mx3+; Vicon Peak) and reconstructed by Nexus 1.8.5 (Vicon Peak).

The neuropsychological assessment focused on the cognitive domains commonly disturbed in MS: memory (Selective Reminding Test ), executive functions (verbal fluency task, Stroop, Trail Making Test (TMT) B, and divided attention and working memory subtests from Test of Attention Performance), attention (digit span and symbol digit modalities test from the Wechsler Adult Intelligence Scale-III, Stroop dot condition, and TMT A), fear of falling by the 16-item Falls Efficacy Scale–International, anxiety and depression assessed by the Hospital Anxiety and Depression scale, and were assessed by the same neuropsychologist.

Statistics

The participants' characteristics were summarized using mean values and SDs or frequencies and percentages, as appropriate. Multiple linear regressions were performed to examine the association between the sNfL (independent variable) and TUG, and other gait, cognitive, and behavioral parameters (dependent variables) adjusted for age, sex, and EDSS score. All statistics were performed using SPSS (version 22.0; SPSS, Inc., Chicago, IL).

Standard protocol approvals, registrations, and patient consents

The Geneva University Hospitals Committee on Human Research approved the research protocol, and informed consent was obtained from all participants.

Data availability

Anonymized data that are not published in this article will be made available on request from any qualified investigator after the approval by the Institutional Review Board of the Geneva University Hospitals.

Results

Clinical characteristics of the 41 patients with MS are summarized in table 1. The median EDSS score was 1.0 (interquartile range [IQR] 0.0–2.0), with a mean disease duration of less than 3 years (time since diagnosis: 33.2 ± 34.7 months). The sNfL concentration was 23.51 pg/mL (IQR 16.51–32.21 pg/mL), without any difference between male and female (p = 0.229). Gait parameters were normal (gait speed: 1.30 ± 0.18 m/s; stride time variability: 1.75% ± 1.10%). The mean TUG was 9.27 ± 1.70 seconds. Cognitive and behavioral performances are reported in table e-1 (links.lww.com/NXI/A318).

Among spatiotemporal gait parameters, cognitive and behavioral performances, only the TUG was associated with sNfL in the univariable model; this association was sustained after adjusting for age, sex, and EDSS score (β = 0.021; 95% CI 0.003–0.037; p = 0.022) (table 2)—an increase of 1 pg/mL of NfL concentration was associated with a TUG increase of 0.02 seconds.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 2

Association between serum neurofilament light chain levelsa (independent variable) and Timed Up and Go, and other gait, cognitive, and behavioral variables (dependent variables) adjusted for age, sex, and EDSS score (n = 41)

Discussion

We show that sNfL, a promising serum biomarker of neuroaxonal damage in MS, is associated with the TUG. We observed this association in patients with MS with low disability.

Estimating the extent of neuroaxonal damage in very early disease stages represents a challenge. Here, we provide evidence that the duration of the TUG is associated with the severity of neuroaxonal injury quantified by sNfL.4 CSF NFL levels have been associated with attentional control in patients with MS.9 Also, attentional performances are associated with the duration of the TUG in older adults and in patients with MS,2 in addition to its strong association with the EDSS score and gait disability.1 The multimodality of the TUG that integrates several components of both gait and cognitive parameters may explain why the TUG is the only one measure (among spatiotemporal gait parameters and cognitive performances) that was associated with sNfL in our study. Key phases of the TUG, such as the turn-to-walk and turn-to-sit phases, are associated with specific cognitive domains, such as executive function and visuospatial performance.10 The TUG, which can be performed in the doctor office without any expansive equipment other than a stopwatch, provides important insight to the clinician to the extent of axonal damage in their patients with MS.

Our study has some limitations. We only include patients with MS with low disability (EDSS score ≤3), preventing the generalization of the study findings to the entire MS population. Although the association between sNfL and TUG has been adjusted on age, sex, and EDSS score, the small number of participants prevents to adjust our association on other variables, such as falls or fear of falling. Future studies should verify whether this association between sNfL and TUG remains significant for patients with MS with increased levels of disability (EDSS score >3).

In conclusion, we demonstrated an association between a biological marker of neuroaxonal damage—measured by sNfL—and the TUG in patients with MS with low disability. These findings may help the clinicians to estimate and monitor the progression of the disease.

Study funding

This study was supported by a grant from the Geneva University Hospitals (PRD 18-2016-II), the Swiss Multiple Sclerosis Society, Swiss National Science Foundation (310030_176078), and the Fondation privée des HUG.

Disclosure

The authors report no disclosures. Go to Neurology.org/NN for full disclosures.

Acknowledgment

The authors are grateful to the patients for their participations to the study.

Appendix Authors

Table

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the Swiss National Science Foundation.

  • Received June 8, 2020.
  • Accepted in final form August 31, 2020.
  • Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

References

  1. 1.↵
    1. Sebastiao E,
    2. Sandroff BM,
    3. Learmonth YC,
    4. Motl RW
    . Validity of the timed up and go test as a measure of functional mobility in persons with multiple sclerosis. Arch Phys Med Rehabil 2016;97:1072–1077.
    OpenUrl
  2. 2.↵
    1. Allali G,
    2. Laidet M,
    3. Assal F, et al
    . Adapted timed up and go: a rapid clinical test to assess gait and cognition in multiple sclerosis. Eur Neurol 2012;67:116–120.
    OpenUrlPubMed
  3. 3.↵
    1. Lorefice L,
    2. Coghe G,
    3. Fenu G, et al
    . “Timed up and go” and brain atrophy: a preliminary MRI study to assess functional mobility performance in multiple sclerosis. J Neurol 2017;264:2201–2204.
    OpenUrl
  4. 4.↵
    1. Teunissen CE,
    2. Khalil M
    . Neurofilaments as biomarkers in multiple sclerosis. Mult Scler 2012;18:552–556.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Barro C,
    2. Benkert P,
    3. Disanto G, et al
    . Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain 2018;141:2382–2391.
    OpenUrl
  6. 6.↵
    1. Kuhle J,
    2. Nourbakhsh B,
    3. Grant D, et al
    . Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology 2017;88:826–831.
    OpenUrl
  7. 7.↵
    1. Disanto G,
    2. Adiutori R,
    3. Dobson R, et al
    . Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome. J Neurol Neurosurg Psychiatry 2016;87:126–129.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Allali G,
    2. Laidet M,
    3. Herrmann FR, et al
    . Gait variability in multiple sclerosis: a better falls predictor than EDSS in patients with low disability. J Neural Transm (Vienna) 2016;123:447–450.
    OpenUrl
  9. 9.↵
    1. Tortorella C,
    2. Direnzo V,
    3. Taurisano P, et al
    . Cerebrospinal fluid neurofilament tracks fMRI correlates of attention at the first attack of multiple sclerosis. Mult Scler 2015;21:396–401.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Ansai JH,
    2. Andrade LP,
    3. Nakagawa TH, et al
    . Cognitive correlates of timed up and go subtasks in older people with preserved cognition, mild cognitive impairment, and Alzheimer's disease. Am J Phys Med Rehabil 2017;96:700–705.
    OpenUrl

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Preferences and User Experiences of Wearable Devices in Epilepsy A Systematic Review and Mixed-Methods Synthesis

Dr. Daniel Friedman and Dr. Sharon Chiang

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Multiple sclerosis
  • Motor Control
  • Disability

Alert Me

  • Alert me when eletters are published
Neurology - Neuroimmunology Neuroinflammation: 10 (2)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise