Skip to main content
Advertisement

Main menu

  • Home
  • Content
    • Current Issue
    • Accepted Manuscripts
    • Article Preview
    • Past Issue Archive
    • Video Articles
    • AJNR Case Collection
    • Case of the Week Archive
    • Case of the Month Archive
    • Classic Case Archive
  • Special Collections
    • AJNR Awards
    • Low-Field MRI
    • Alzheimer Disease
    • ASNR Foundation Special Collection
    • Photon-Counting CT
    • View All
  • Multimedia
    • AJNR Podcasts
    • AJNR SCANtastic
    • Trainee Corner
    • MRI Safety Corner
    • Imaging Protocols
  • For Authors
    • Submit a Manuscript
    • Submit a Video Article
    • Submit an eLetter to the Editor/Response
    • Manuscript Submission Guidelines
    • Statistical Tips
    • Fast Publishing of Accepted Manuscripts
    • Graphical Abstract Preparation
    • Imaging Protocol Submission
    • Author Policies
  • About Us
    • About AJNR
    • Editorial Board
    • Editorial Board Alumni
  • More
    • Become a Reviewer/Academy of Reviewers
    • Subscribers
    • Permissions
    • Alerts
    • Feedback
    • Advertisers
    • ASNR Home

User menu

  • Alerts
  • Log in

Search

  • Advanced search
American Journal of Neuroradiology
American Journal of Neuroradiology

American Journal of Neuroradiology

ASHNR American Society of Functional Neuroradiology ASHNR American Society of Pediatric Neuroradiology ASSR
  • Alerts
  • Log in

Advanced Search

  • Home
  • Content
    • Current Issue
    • Accepted Manuscripts
    • Article Preview
    • Past Issue Archive
    • Video Articles
    • AJNR Case Collection
    • Case of the Week Archive
    • Case of the Month Archive
    • Classic Case Archive
  • Special Collections
    • AJNR Awards
    • Low-Field MRI
    • Alzheimer Disease
    • ASNR Foundation Special Collection
    • Photon-Counting CT
    • View All
  • Multimedia
    • AJNR Podcasts
    • AJNR SCANtastic
    • Trainee Corner
    • MRI Safety Corner
    • Imaging Protocols
  • For Authors
    • Submit a Manuscript
    • Submit a Video Article
    • Submit an eLetter to the Editor/Response
    • Manuscript Submission Guidelines
    • Statistical Tips
    • Fast Publishing of Accepted Manuscripts
    • Graphical Abstract Preparation
    • Imaging Protocol Submission
    • Author Policies
  • About Us
    • About AJNR
    • Editorial Board
    • Editorial Board Alumni
  • More
    • Become a Reviewer/Academy of Reviewers
    • Subscribers
    • Permissions
    • Alerts
    • Feedback
    • Advertisers
    • ASNR Home
  • Follow AJNR on Twitter
  • Visit AJNR on Facebook
  • Follow AJNR on Instagram
  • Join AJNR on LinkedIn
  • RSS Feeds

AJNR Awards, New Junior Editors, and more. Read the latest AJNR updates

Research ArticleAdult Brain

White Matter Diffusion Changes during the First Year of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis

O.T. Wiebenga, M.M. Schoonheim, H.E. Hulst, G.J.A. Nagtegaal, E.M.M. Strijbis, M.D. Steenwijk, C.H. Polman, P.J.W. Pouwels, F. Barkhof and J.J.G. Geurts
American Journal of Neuroradiology June 2016, 37 (6) 1030-1037; DOI: https://doi.org/10.3174/ajnr.A4690
O.T. Wiebenga
aFrom the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N.†, M.D.S., F.B.)
bAnatomy and Neurosciences (O.T.W., M.M.S., H.E.H., G.J.A.N.†, J.J.G.G.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for O.T. Wiebenga
M.M. Schoonheim
bAnatomy and Neurosciences (O.T.W., M.M.S., H.E.H., G.J.A.N.†, J.J.G.G.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for M.M. Schoonheim
H.E. Hulst
bAnatomy and Neurosciences (O.T.W., M.M.S., H.E.H., G.J.A.N.†, J.J.G.G.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for H.E. Hulst
G.J.A. Nagtegaal
aFrom the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N.†, M.D.S., F.B.)
bAnatomy and Neurosciences (O.T.W., M.M.S., H.E.H., G.J.A.N.†, J.J.G.G.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E.M.M. Strijbis
cNeurology (E.M.M.S., C.H.P.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for E.M.M. Strijbis
M.D. Steenwijk
aFrom the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N.†, M.D.S., F.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for M.D. Steenwijk
C.H. Polman
cNeurology (E.M.M.S., C.H.P.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for C.H. Polman
P.J.W. Pouwels
dPhysics and Medical Technology (P.J.W.P.), Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for P.J.W. Pouwels
F. Barkhof
aFrom the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N.†, M.D.S., F.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for F. Barkhof
J.J.G. Geurts
bAnatomy and Neurosciences (O.T.W., M.M.S., H.E.H., G.J.A.N.†, J.J.G.G.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for J.J.G. Geurts
  • Article
  • Figures & Data
  • Supplemental
  • Info & Metrics
  • Responses
  • References
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Fig 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig 1.

    Spatial extent of lowered FA (in blue) of white matter voxels in the TBSS skeleton (green) (X = 77, Y = 109, Z = 77) of patients treated with natalizumab (upper 2 rows) and those treated with IFNb/GA (lower 2 rows). Patients starting natalizumab had reduced FA in 56.8% (P < .05) of the WM skeleton at baseline and improved to 47.2% at month 12. Patients continuing IFNb/GA had reduced FA in 41.4% of the WM skeleton at baseline and 39.1% at month 12.

  • Fig 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig 2.

    Spatial extent of increased MD (in red) in white matter voxels in the TBSS skeleton (green) (X = 101, Y = 109, Z = 77) of patients treated with natalizumab (upper 2 rows) and those treated with IFNb/GA (lower 2 rows). Patients starting natalizumab had increased MD in 54.3% (P < .05) of the WM skeleton at baseline and 55.7% at month 12. Patients continuing IFNb/GA had increased MD in 33.7% of the WM skeleton at baseline and 36.1% at month 12.

Tables

  • Figures
    • View popup
    Table 1:

    Baseline variables of patients with MS and controls (mean)a

    Patients with Natalizumab (n = 22)Patients with IFNb/GA (n = 17)Healthy Controls (n = 12)P Value
    MS therapyStarting natalizumab at baselineContinuing IFNb/GA at baselineNA
    Descriptives
        Age (yr)37.2 ± 8.838.2 ± 5.035.1 ± 5.3.492
        Sex (male/female)b9:138:93:9.322
        Educationc (mean) (range)6.0 (4–7)6.0 (5–7)7.0 (5–7).016e
        HADS-Ac (mean) (range)6.0 (1–13)6.6 (1–14)4.8 (1–12).369
        HADS-Dc (mean) (range)4.5 (0–18)5.0 (0–12)1.8 (0–10).008e
        CIS-20c (mean) (range)68.5 (14–125)86 (31–114)42.5 (17–85).002e
    MS characteristics
        EDSSb,c3.0 (1.5–6.5)2.5 (1.0–6.5)NA.615
        Disease duration since onset (yr)8.3 ± 6.29.1 ± 5.2NA.662
        Prior IFNb/GA duration at baseline (yr)2.9 ± 3.14.5 ± 4.0NA.169
    Volumes
        NGMV (L)0.75 ± 0.040.73 ± 0.060.77 ± 0.04.134
        NWMV (L)0.69 ± 0.040.69 ± 0.040.73 ± 0.03.020e
        NBV (L)1.44 ± 0.061.42 ± 0.081.50 ± 0.06.025f
        T2 lesion volume (mL)d6.2 (2.4–14.9)4.9 (2.5–12.0)NA.281
    Cognition z scores
        Symbol Digit Modalities Test−2.17 ± 0.92−1.71 ± 1.130.00 ± 1.00<.001e
        SPART-total recall−1.90 ± 1.94−0.82 ± 1.830.00 ± 1.00.021g
        SPART-delayed recall−1.42 ± 1.57−0.80 ± 1.930.00 ± 1.00.076
        VLGT–immediate recall−1.33 ± 1.84−1.66 ± 1.530.00 ± 1.00.052
        VLGT–short-term free recall−1.66 ± 1.89−1.40 ± 1.640.00 ± 1.00.068
        VLGT–long-term free recall−1.65 ± 1.86−1.48 ± 1.720.00 ± 1.00.070
        WLG–Animals−0.97 ± 0.73−0.75 ± 0.810.00 ± 1.00.019g
        WLG–Professions−1.69 ± 1.15−1.79 ± 1.580.00 ± 1.00.001e
        WLG–4 letter “M” words−0.81 ± 1.0−0.85 ± 0.940.00 ± 1.00.072
        Digit Span Forward−0.62 ± 1.06−0.29 ± 0.980.00 ± 1.00.670
        Digit Span Backward−0.96 ± 1.13−0.05 ± 1.360.00 ± 1.00.067
        TMT–Letter-Number Switching−2.33 ± 2.45−1.58 ± 2.080.00 ± 1.00.059
        Stroop-interference−0.28 ± 1.44−0.63 ± 1.250.00 ± 1.00.697
    Average cognition−1.61 ± 0.73−1.22 ± 1.010.00 ± 1.00<.001e
    • Note:—CIS-20 indicates Checklist for Individual Strength questionnaire; HADS, Hospital Anxiety and Depression Scale; A, Anxiety; D, Depression; SPART, Spatial Recall Task; NGMV, normalized gray matter volume; NWMV, normalized white matter volume; VLGT, Verbal Memory and Learning Task; WLG, Word List Generation; TMT, Trail-Making Test; L, liter; NA, not applicable.

    • ↵a When normally distributed, a multivariate General Linear Model was used with age, sex, and education included as covariates; General Linear Model main effect P values are shown. Nonparametric testing was performed using the Kruskall-Wallis and post hoc Mann-Whitney tests. P values < .05 are considered significant.

    • ↵b χ2 test.

    • ↵c Median and range.

    • ↵d Median and interquartile range.

    • ↵e Significant in both patient groups compared with healthy controls.

    • ↵f Only significant between patients receiving IFNb/GA and healthy controls.

    • ↵g Only significant between patients receiving natalizumab and healthy controls.

    • View popup
    Table 2:

    Clinical scales of baseline and month 12 (median and range)a

    Time PointBaselineMonth 12P Value
    Patients on natalizumab
        EDSS3.0(1.5–6.5)3.0(1.0–6.5)1.0
        HADS-A6.0(1–13)6.0(0–15)1.0
        HADS-D4.5(0–18)2.0(0–17).012b
        CIS-2068.5(14–125)62.0(10–117).036
    Patients on IFNb/GA (n = 17)
        EDSS2.5(1.0–6.5)3.0(1.5–7.0).006b
        HADS-A7.0(1–14)5.0(1–11).609
        HADS-D5.0(0–12)3.0(0–14).855
        CIS-2086.0(31–114)81.0(16–105).177
    Healthy controls (n = 12)
        HADS-A3.5(1–12)2.5(0–9)1.0
        HADS-D1.0(0–10)0.0(0–5)1.0
        CIS-2042.5(17–85)52.0(17–82).744
    • Note:—CIS-20 indicates Checklist Individual Strength questionnaire; HADS, Hospital Anxiety and Depression Scale; A, Anxiety; D, Depression.

    • ↵a EDSS, HADS, and CIS were tested with the related-samples Wilcoxon signed rank test (Bonferroni-corrected).

    • ↵b Significant difference.

    • View popup
    Table 3:

    DTI and volumetric variables of baseline and month 12 visit (mean)

    BaselineMonth 12P Value
    Patients on natalizumab (n = 22)
        FA severity (z score)−0.67 ± 0.65−0.59 ± 0.69.02a
        MD severity (z score)0.89 ± 0.920.93 ± 0.98.81
        AD severity (z score)0.36 ± 0.400.43 ± 0.39.34
        RD severity (z score)0.94 ± 1.000.94 ± 1.071.0
        NGMV (L)0.75 ± 0.040.75 ± 0.051.0
        NWMV (L)0.69 ± 0.040.67 ± 0.03.008a
        NBV (L)1.44 ± 0.061.42 ± 0.06.036a
        T2 lesion volume (mL)b6.2 (2.4–14.9)6.9 (2.2–13.6).644
    Patients on IFNb/GA (n = 17)
        FA severity (z score)−0.64 ± 0.43−0.67 ± 0.48.94
        MD severity (z score)0.74 ± 0.580.78 ± 0.58.64
        AD severity (z score)0.26 ± 0.350.26 ± 0.281.0
        RD severity (z score)0.82 ± 0.590.87 ± 0.62.43
        NGMV (L)0.73 ± 0.060.74 ± 0.051.0
        NWMV (L)0.69 ± 0.040.67 ± 0.03.004a
        NBV (L)1.42 ± 0.081.41 ± 0.07<.001a
        T2 lesion volume (mL)b4.9 (0.25–12.0)5.4 (0.28–13.3).012a
    • Note:—NGMV indicates normalized gray matter volume; NWMV, normalized white matter volume.

    • ↵a Significant difference between the time points (Bonferroni-corrected).

    • ↵b Median and interquartile range.

    • View popup
    Table 4:

    RCI (mean) of patients on natalizumab and IFNb/GA between baseline and month 12

    RCI Baseline–Month 12Patients on NatalizumabPatients on IFNb/GAP Value
    Symbol Digit Modalities Test−0.02 ± 0.68−0.04 ± 0.77.993
    SPART-total0.18 ± 1.46−0.49 ± 1.42.432
    SPART-delayed0.54 ± 1.690.06 ± 1.99.629
    VLGT–immediate recall−0.67 ± 0.880.20 ± 1.03.024a
    VLGT–short-term free recall−0.15 ± 1.010.06 ± 0.75.575
    VLGT–long-term free recall−0.21 ± 1.360.47 ± 0.84.211
    WLG–Animals0.15 ± 0.90−0.40 ± 0.81.185
    WLG–Professions−0.19 ± 0.880.04 ± 1.17.835
    WLG–4 letter “M” words−0.61 ± 0.88−0.36 ± 1.08.129
    Digit Span Forward−0.01 ± 0.870.06 ± 0.85.842
    Digit Span Backward−0.31 ± 0.89−0.34 ± 1.42.572
    TMT–Letter-Number Switching0.41 ± 3.230.59 ± 2.91.922
    Stroop-interference−1.00 ± 2.14−0.78 ± 1.63.595
    • Note:—SPART indicates Spatial Recall Task; VLGT, Verbal Memory and Learning Task; WLG, Word List Generation; TMT, Trail-Making Test.

    • ↵a A significant difference between the patient groups.

PreviousNext
Back to top

In this issue

American Journal of Neuroradiology: 37 (6)
American Journal of Neuroradiology
Vol. 37, Issue 6
1 Jun 2016
  • Table of Contents
  • Index by author
  • Complete Issue (PDF)
Advertisement
Print
Download PDF
Email Article

Thank you for your interest in spreading the word on American Journal of Neuroradiology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
White Matter Diffusion Changes during the First Year of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis
(Your Name) has sent you a message from American Journal of Neuroradiology
(Your Name) thought you would like to see the American Journal of Neuroradiology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Cite this article
O.T. Wiebenga, M.M. Schoonheim, H.E. Hulst, G.J.A. Nagtegaal, E.M.M. Strijbis, M.D. Steenwijk, C.H. Polman, P.J.W. Pouwels, F. Barkhof, J.J.G. Geurts
White Matter Diffusion Changes during the First Year of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis
American Journal of Neuroradiology Jun 2016, 37 (6) 1030-1037; DOI: 10.3174/ajnr.A4690

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
0 Responses
Respond to this article
Share
Bookmark this article
White Matter Diffusion Changes during the First Year of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis
O.T. Wiebenga, M.M. Schoonheim, H.E. Hulst, G.J.A. Nagtegaal, E.M.M. Strijbis, M.D. Steenwijk, C.H. Polman, P.J.W. Pouwels, F. Barkhof, J.J.G. Geurts
American Journal of Neuroradiology Jun 2016, 37 (6) 1030-1037; DOI: 10.3174/ajnr.A4690
del.icio.us logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Purchase

Jump to section

  • Article
    • Abstract
    • ABBREVIATIONS:
    • Materials and Methods
    • Results
    • Discussion
    • Conclusions
    • Footnotes
    • References
  • Figures & Data
  • Supplemental
  • Info & Metrics
  • Responses
  • References
  • PDF

Related Articles

  • PubMed
  • Google Scholar

Cited By...

  • Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis
  • Crossref
  • Google Scholar

This article has not yet been cited by articles in journals that are participating in Crossref Cited-by Linking.

More in this TOC Section

  • Diagnostic Neuroradiology of Monoclonal Antibodies
  • Clinical Outcomes After Chiari I Decompression
  • Segmentation of Brain Metastases with BLAST
Show more Adult Brain

Similar Articles

Advertisement

Indexed Content

  • Current Issue
  • Accepted Manuscripts
  • Article Preview
  • Past Issues
  • Editorials
  • Editor's Choice
  • Fellows' Journal Club
  • Letters to the Editor
  • Video Articles

Cases

  • Case Collection
  • Archive - Case of the Week
  • Archive - Case of the Month
  • Archive - Classic Case

More from AJNR

  • Trainee Corner
  • Imaging Protocols
  • MRI Safety Corner
  • Book Reviews

Multimedia

  • AJNR Podcasts
  • AJNR Scantastics

Resources

  • Turnaround Time
  • Submit a Manuscript
  • Submit a Video Article
  • Submit an eLetter to the Editor/Response
  • Manuscript Submission Guidelines
  • Statistical Tips
  • Fast Publishing of Accepted Manuscripts
  • Graphical Abstract Preparation
  • Imaging Protocol Submission
  • Evidence-Based Medicine Level Guide
  • Publishing Checklists
  • Author Policies
  • Become a Reviewer/Academy of Reviewers
  • News and Updates

About Us

  • About AJNR
  • Editorial Board
  • Editorial Board Alumni
  • Alerts
  • Permissions
  • Not an AJNR Subscriber? Join Now
  • Advertise with Us
  • Librarian Resources
  • Feedback
  • Terms and Conditions
  • AJNR Editorial Board Alumni

American Society of Neuroradiology

  • Not an ASNR Member? Join Now

© 2025 by the American Society of Neuroradiology All rights, including for text and data mining, AI training, and similar technologies, are reserved.
Print ISSN: 0195-6108 Online ISSN: 1936-959X

Powered by HighWire