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

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

Share

July 2018; 5 (4) Clinical/Scientific NotesOpen Access

Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS

Seraj Makkawi, Carlos Camara-Lemarroy, Luanne Metz
First published April 3, 2018, DOI: https://doi.org/10.1212/NXI.0000000000000459
Seraj Makkawi
From the Department of Clinical Neurosciences (S.M., C.C.-L., L.M.), Cumming School of Medicine, University of Calgary, Alberta, Canada; and King Saud Bin Abdulaziz University for Health Sciences (S.M.), Jeddah, Saudi Arabia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos Camara-Lemarroy
From the Department of Clinical Neurosciences (S.M., C.C.-L., L.M.), Cumming School of Medicine, University of Calgary, Alberta, Canada; and King Saud Bin Abdulaziz University for Health Sciences (S.M.), Jeddah, Saudi Arabia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luanne Metz
From the Department of Clinical Neurosciences (S.M., C.C.-L., L.M.), Cumming School of Medicine, University of Calgary, Alberta, Canada; and King Saud Bin Abdulaziz University for Health Sciences (S.M.), Jeddah, Saudi Arabia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS
Seraj Makkawi, Carlos Camara-Lemarroy, Luanne Metz
Neurol Neuroimmunol Neuroinflamm Jul 2018, 5 (4) e459; DOI: 10.1212/NXI.0000000000000459

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
4220

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Several studies link the gut microbiome and MS immunopathogenesis. Fecal microbiota transplantation (FMT), the process of transferring fecal microbiota from a healthy donor to a patient, successfully treats recurrent Clostridium difficile enterocolitis and may benefit autoimmune diseases. The potential short-term efficacy of this procedure has been reported in MS. Here, we describe a patient with secondary progressive MS (SPMS) who achieved disease stability for over 10 years following FMT.

Case report

A 61-year-old woman with MS was followed up in the Calgary MS Clinic since 1988 (age 33 years). She had 7 relapses between 1998 and 2001, and her MRI showed numerous periventricular, juxtacortical, brainstem, and corpus callosum lesions confirming relapsing remitting MS (RRMS). CSF was not obtained. She started glatiramer acetate in 2001 and has remained on it since. She has been relapse-free and had stable brain MRI (no new lesions) since. However, between 2001 and 2005, her balance, ambulation, lower limb power, bladder function, and fatigue gradually worsened. Her Expanded Disability Status Scale (EDSS) increased from 2.0 to 3.0. Because of progressive symptom worsening, and stable MRI, this suggested a diagnosis of SPMS. During 2005 and 2006, she had several bouts of C difficile enterocolitis following clindamycin treatment of a gingival infection. Her EDSS score increased to 6.0. As she was resistant to multiple courses of metronidazole and vancomycin, she received a single FMT in 2006 from her partner via rectal enema using a standard protocol.1 Her EDSS score immediately stabilized without other treatment or lifestyle changes. Over the next 10 years, her Functional System scores minimally improved, as did Modified Multiple Sclerosis Functional Composite scores after 2012 when this measure was routine in our clinic (figure).

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure EDSS, FS scores, and Modified MSFC scores

(A) EDSS and FS scores. (B) Modified MSFC scores. All scores were recorded in the patient chart at the time of each visit. The first clinic visit after fecal microbiota transplantation was in 2007. Oral SDMT replaces the PASAT. EDSS = Expanded Disability Status Scale; FS = Functional System; MSFC = Multiple Sclerosis functional composite; SDMT = Symbol Digit Modalities Test; PASAT = Paced Auditory Serial Addition Test.

Discussion

The gut microbiome consists of billions of bacteria, fungi, and viruses, which participate in maintaining gut homeostasis. Recently, there has been explosion of interest in the gut microbiota and their impact on normal host immune function and in the development of autoimmune diseases such as MS.

Evidence suggesting a role for the gut microbiome in MS originated from preclinical investigations using the murine model of experimental autoimmune encephalomyelitis (EAE).2 Mice bred under germ-free conditions are resistant to EAE induction, and after induction, they have fewer activated pathogenic lymphocytes and increased T-regulatory cells. These changes, and resistance to EAE, can be reversed after recolonization with fecal microbiota from mice bred under standard conditions. Together, this evidence builds a case for the gut microbiome as a neuroimmune modulator in EAE.3

Recent studies have shown that gut microbiome compositions in patients with RRMS differ from those in controls. Some differences have been associated with relapse risk and peripheral immunologic derangements.4 However, a clear and consistent “MS microbiome phenotype” has not been described, and a myriad of different species have been implicated.

The potential role of the gut microbiome in MS pathogenesis has led to proposals for microbiome modification as a therapeutic strategy. Although dietary interventions and the use of probiotics have not been effective, FMT presents an ideal method of microbiome modification. Decades of safe use make it an attractive treatment option for autoimmune diseases, including MS.5

In a previous report, three people with MS had significant neurologic symptom improvement after FMT for constipation.6 To the best of our knowledge, this case is the first report suggesting the potential long-term benefit of FMT on MS disease progression. An inflammatory response, triggered by recurrent C difficile infections, likely led to rapid neurologic worsening in 2006 that stabilized after correction of gut dysbiosis by FMT. Her symptoms increased gradually, although her EDSS did not increase continuously before 2006, so it is possible that she did not have SPMS. Her neurologic deficits may have been more amenable to reversal than would be expected if they had been longstanding. We hypothesize that her transplanted gut microbiome failed to drive progression and possibly permitting limited endogenous repair. However, as we do not know the composition of her microbiome before she acquired C difficile, or after the FMT, this remains speculative. As no interventions have yet been shown to stimulate repair, the time course of recovery in MS remains unknown. Control of ongoing inflammation is, however, believed to be important.

The prospect of a novel treatment of MS based on a sound theoretical basis is encouraging. Clinical trials are required to guide the future use of FMT by evaluating its effectiveness, safety profile, and mechanism of action. Indeed, a phase-2 trial is ongoing.7 Challenges will include donor and patient selection, dosing, and selection of outcomes.

Author contributions

S.M. and C.C.-L. prepared the initial draft of the manuscript. S.M., C.C.-L., and L.M. contributed to the revision of the manuscript. S.M., C.C.-L., and L.M. agreed to the publication of this version of the manuscript.

Study funding

No targeted funding reported.

Disclosure

S. Makkawi and C. Camara-Lemarroy report no disclosures. L. Metz served on the scientific advisory board of DSMB and Rick Hansen Institute; has a patent pending for Combination of minocycline plus hydroxychloroquine in demyelinating disease; consulted for EMD Serono; and received research support from the Multiple Sclerosis Society of Canada. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

  • The Article Processing Charge was funded by the authors.

  • Received January 3, 2018.
  • Accepted in final form February 28, 2018.
  • Copyright © 2018 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. Louie T,
    2. Adams PC
    . Nature's therapy for recurrent Clostridium difficile diarrhea. Can J Gastroenterol Hepatol 2008;22:455–456.
    OpenUrl
  2. 2.↵
    1. Berer K,
    2. Mues M,
    3. Koutrolos M, et al
    . Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011;479:538–541.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Adamczyk-Sowa M,
    2. Medrek A,
    3. Madej P,
    4. Michlicka W,
    5. Dobrakowski P
    . Does the gut microbiota influence immunity and inflammation in multiple sclerosis pathophysiology? J Immunol Res 2017;2017:7904821.
    OpenUrl
  4. 4.↵
    1. Pröbstel AK,
    2. Baranzini SE
    . The role of the gut microbiome in multiple sclerosis risk and progression: towards characterization of the “MS microbiome”. Neurotherapeutics 2018;15:126–134.
    OpenUrl
  5. 5.↵
    1. Xu MQ,
    2. Cao HL,
    3. Wang WQ, et al
    . Fecal microbiota transplantation broadening its application beyond intestinal disorders. World J Gastroenterol 2015;21:102–111.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Borody TJ,
    2. Leis SM,
    3. Campbell J,
    4. Torres M,
    5. Nowak A
    . Fecal microbiota transplantation (FMT) in multiple sclerosis (MS) [abstract]. Am J Gastroenterol 2011;106:S352.
    OpenUrl
  7. 7.↵
    1. Kremenchutzky M
    . Fecal microbial transplantation in relapsing multiple sclerosis patients. In: ClinicalTrials.gov [online]. Available at: clinicaltrials.gov/ct2/show/NCT03183869. Accessed February 2, 2018.

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
    • Case report
    • Discussion
    • Author contributions
    • Study funding
    • Disclosure
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures

Related Articles

  • No related articles found.

Topics Discussed

  • All Demyelinating disease (CNS)
  • Multiple sclerosis

Alert Me

  • Alert me when eletters are published
Advertisement
Neurology - Neuroimmunology Neuroinflammation: 9 (4)

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: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • Neurology: Education
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2022 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise