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

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in
  • Log out

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
  • Log out
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

June 13, 2000; 54 (11) Brief Communications

Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor

H. Openshaw, O. Stuve, J.P. Antel, R. Nash, B.T. Lund, L.P. Weiner, A. Kashyap, P. McSweeney, S. Forman
First published June 13, 2000, DOI: https://doi.org/10.1212/WNL.54.11.2147
H. Openshaw
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
O. Stuve
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J.P. Antel
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Nash
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B.T. Lund
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L.P. Weiner
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Kashyap
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. McSweeney
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Forman
From the Department of Neurology (Dr. Openshaw) and Division of Hematology and Bone Marrow Transplantation (Drs. Kashyap and Forman)City of Hope National Medical Center, Duarte, CA; the Departments of Neurology (Dr. Stuve) and Medical Oncology (Drs. Nash and McSweeney), Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle; the Neuroimmunology Unit (Dr. Antel), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Department of Neurology (Drs. Lund and Weiner), University of Southern California School of Medicine, Los Angeles.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor
H. Openshaw, O. Stuve, J.P. Antel, R. Nash, B.T. Lund, L.P. Weiner, A. Kashyap, P. McSweeney, S. Forman
Neurology Jun 2000, 54 (11) 2147-2150; DOI: 10.1212/WNL.54.11.2147

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
425

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Article abstract Four of 10 patients who were enrolled on protocols of high-dose immunosuppression with peripheral blood stem cell rescue for MS experienced neurologic worsening while receiving recombinant human granulocyte colony-stimulating factor. There was improvement when methylprednisolone was given to three of the patients, but one patient died of respiratory failure. The mechanism of the neurologic worsening is uncertain.

There has been recent interest in high-dose immunosuppression with peripheral blood stem cell support in MS and other autoimmune diseases.1 Approximately 74 patients with MS worldwide have received this investigational therapy, which is thought to be promising but is currently of unproven efficacy (personal communication, Alan Tyndall, MD, of the European Bone Marrow Transplant Association [EBMT] and European League Against Rheumatism [EULAR], 1999). In these patients, recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used first to mobilize progenitor and stem cells from the marrow and then later to hasten hematopoietic cell recovery after high-dose immunosuppression. In the last 34 months, 10 patients with MS have been given rhG-CSF at our three centers. We report the worsening of clinical status in four of these patients while receiving rhG-CSF.

Methods.

Recombinant human granulocyte colony-stimulating factor 10 to 16 μg/kg/day was administered subcutaneously or IV for 4 consecutive days. Apheresis commenced on day 5 and continued daily with rhG-CSF at the same dose until at least 6.5 × 106 CD34+ cells/kg were collected. Peripheral blood stem cells were infused, usually 2 to 4 weeks later, after patients received high-dose immunosuppression therapy. Anti-thymocyte globulin 10 to 15 mg/kg was given IV for 3 to 6 days with methylprednisolone premedication just before and after stem cell infusion. rhG-CSF 5 μg/kg/day IV was restarted on day +1 after stem cell infusion and continued until the absolute neutrophil count was greater than 1.0 K/μL for 3 consecutive days.

Results.

Table 1 presents clinical details before protocol enrollment of the four patients whose MS flared during rhG-CSF therapy (Patients 1 through 4) and the six patients whose disease did not flare (Patients 5 through 10). MRI gadolinium enhancement was present in all three patients whose disease flared, compared with one of six patients whose disease did not flare. None of the patients had repeat MRI at the time of neurologic worsening. In Patients 1 through 4, there appeared to be neurologic worsening from a pre-existing lesion rather than development of new lesions (table 2).

View this table:
  • View inline
  • View popup
Table 1.

Neurologic course before enrollment in stem cell transplantation protocol

View this table:
  • View inline
  • View popup
Table 2.

Neurologic worsening (flares) on rhG-CSF

Patient 1 became hemiplegic on the fifth day of rhG-CSF. Prior examination had shown upper motor neuron clumsiness and weakness, greater on the right side. Because of the neurologic worsening, the patient was taken off protocol and given methylprednisolone 1000 mg/day for 5 days. On the fourth day of methylprednisolone, there was improvement in right-sided strength, and in 3 more days her deficit had returned to the pre–rhG-CSF level.

Patient 2 was stable while receiving rhG-CSF for stem cell mobilization, during immunosuppression therapy with busulfan and cyclophosphamide, and while receiving rhG-CSF from day +1 to day +15. However, on day +25, her white cell count decreased to 1.7 K/μL and one dose of rhG-CSF at 5 μg/kg was given subcutaneously. The following day, the patient could no longer lift her right leg and could barely raise her right arm. With no improvement on day +27, she was admitted to the hospital and methylprednisolone was started at 1000 mg/day IV. Her deficit improved to the pretransplantation level after 3 days of methylprednisolone.

Patient 3 experienced symptomatic worsening of leg strength on the second day of rhG-CSF and became bed-bound 2 days later. Immunosuppression was given according to protocol with total-body irradiation and cyclophosphamide. Antithymocyte globulin with methylprednisolone premedication was then started, and six doses were administered 1, 3, and 5 days both before and after stem cell infusion. Leg strength and function began to improve 3 days after stem cell infusion. rhG-CSF was not given after transplantation in this patient.

Patient 4 had been ambulatory with a walker until 6 months before enrollment on the study, when she became paraplegic and experienced increasing weakness in her arms with a sensory level at C2-3. After completion of 6 days of rhG-CSF for stem cell collection, she experienced respiratory difficulties requiring intubation. There was no evidence of active infection or pulmonary embolism. Her clinicians attributed the breathing difficulty to the high cervical cord lesion and suspected that the combined effects of analgesics and progression of respiratory compromise after rhG-CSF resulted in pulmonary failure. Because of persistent respiratory instability, the patient was removed from the investigational study, and in accordance with her request, she was extubated. Death occurred 14 days after hospital admission for stem cell collection.

Discussion.

Neurologic problems associated with rhG-CSF mobilization in patients with MS have not, to our knowledge, been reported previously (Burt et al.1 and personal communication, Dr. Alan Tyndall of the EBMT and EULAR registry, 1999). Over 90% of patients with MS reported to the registry received cyclophosphamide just before rhG-CSF for stem cell mobilization. Our patients, however, and those of Burt et al.1 received rhG-CSF alone. The presence of gadolinium enhancement on the pretransplantation MRIs of patients whose disease later flared (see table 1) suggests that active MS may predispose to rhG-CSF–induced flares.

The possibility that these flares were fortuitous and not caused by rhG-CSF cannot be excluded. However, there have been reports in other autoimmune diseases of rhG-CSF triggering or worsening immune phenomena. These include anecdotal reports of rhG-CSF triggering cutaneous vasculitis and arthritis, as well as a report of exacerbation of neurologic symptoms in systemic lupus erythematosus.2 The mechanism is uncertain. In another patient with MS and in control subjects, we found that 5 days of rhG-CSF administration suppressed rather than activated peripheral blood lymphoproliferative responses to myelin protein epitopes (data not shown). Suppression may be mediated by monocytes, found in peripheral blood at twofold greater amounts after rhG-CSF, and reported to suppress alloantigen responses.3 rhG-CSF has also been shown to alter T cell subsets in favor of CD4−/CD8− T cells,4 a population known in experimental systems to suppress graft-versus-host disease.

There is an extensive literature on cytokines in MS.5 In general, an increase in inflammatory cytokines—particularly tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), and interleukin (IL)-12—correlates with disease activity, whereas an increase in anti-inflammatory cytokines—particularly IL-10—correlates with remission. In normal volunteers receiving rhG-CSF, ex vivo release of stimulated peripheral blood mononuclear cells showed increased IL-10 and decreased or attenuated TNFα and IFNγ.6 In addition, rhG-CSF treatment has been shown to shift splenocyte cytokines to a type 2 helper T-cell pattern in mice.7 However, another group measuring plasma levels reported a 25-fold increase in the type 1 helper T-cell cytokine TNFα in normal volunteers, with the rise starting within 24 hours of the first rhG-CSF dose.8 The role of cytokine release in MS disease activity in transplant recipients clearly needs further investigation.

Another possible mechanism involves a neutrophil effect. With daily rhG-CSF treatment, there is an eightfold increase in neutrophil count by 3 days, compared with only a 1.5- to 2-fold increase in T-cell counts. Neutrophils infiltrate the parenchyma in some patients after stem cell transplantation for oncologic disease, producing the so-called engraftment syndrome (fever, skin rash, capillary leak, and pulmonary infiltrates), a condition that occurs more often when rhG-CSF is used after transplantation.9 Corticosteroids also produce leukocytosis but, unlike rhG-CSF, corticosteroids decrease the capacity of neutrophils to migrate from the vascular space,10 and methylprednisolone is used therapeutically in the engraftment syndrome. Both the neurologic worsening in Patient 2 on day +25 (a time when the engraftment syndrome occurs) and this patient’s response to methylprednisolone support a possible role of neutrophil infiltration in regions of demyelinating plaques with local release of toxic mediators.

Three patients improved on methylprednisolone. Consequently, we have amended our protocols to include corticosteroid administration concurrently with rhG-CSF during stem cell mobilization. In addition, we believe it prudent to use a minimum duration of rhG-CSF to achieve early granulocyte recovery after transplantation and to avoid altogether post-transplantation rhG-CSF in those patients whose disease flared during mobilization.

Acknowledgments

Supported in part by CA33572 and CA30206 from the National Cancer Institute.

Footnotes

  • Presented in part at the annual meeting of the American Academy of Neurology; Toronoto, Canada; April 17–24, 1999.

  • Received January 20, 2000.
  • Accepted in final form February 10, 2000.

References

  1. ↵
    Burt RK, Traynor AE, Pope R, et al. Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation. Blood 1998;92:3505–3514.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Euler HH, Harten P, Zeuner RA, Schwab UM. Recombinant human granulocyte colony stimulating factor in patients with systemic lupus erythematosus associated neutropenia and refractory infections. J Rheumatol 1997;24:2153–2157.
    OpenUrlPubMed
  3. ↵
    Mielcarek M, Martin PJ, Torok-Storb B. Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. Blood 1997;89:1629–1634.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Kusnierz-Glaz CR, Still BJ, Amano M, et al. Granulocyte colony-stimulating factor-induced co-mobilization of CD4− CD8− T cells and hematopoietic progenitor cells (CD34+) in the blood of normal donors. Blood 1997;89:2586–2595.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    Hohlfeld R. Biotechnological agents for the immunotherapy of multiple sclerosis: principles, problems, and perspectives. Brain 1997;120:865–916.
    OpenUrlCrossRefPubMed
  6. ↵
    Hartung T, Docke WD, Gantner F, et al. Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers. Blood 1995;85:2482–2489.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    Pan L, Delmonte J Jr, Jalonen CK, Ferrara JLM. Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood 1995;86:4422–4429.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Xu S, Hoglund M, Venge P. The effect of granulocyte colony-stimulating factor (G-CSF) on the degranulation of secondary granule proteins from human neutrophils in vivo may be indirect. Br J Haematol 1996;93:558–568.
    OpenUrlCrossRefPubMed
  9. ↵
    Lee CK, Gingrich RD, Hohl RJ, Ajram KA. Engraftment syndrome in autologous bone marrow and peripheral stem cell transplantation. Bone Marrow Transplant 1995;16:175–182.
    OpenUrlPubMed
  10. ↵
    Crockard AD, Boylan MT, Droogan AG, McMillan SA, Hawkins SA. Methylprednisolone-induced neutrophil leukocytosis down-modulation of neutrophil L-selectin and Mac-1 expression and induction of granulocyte-colony stimulating factor. Int J Clin Lab Res 1998;28:110–115.
    OpenUrlCrossRefPubMed

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
    • Methods.
    • Results.
    • Discussion.
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

SARS-CoV-2 Vaccination Safety in Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Multifocal Motor Neuropathy

Dr. Jeffrey Allen and Dr. Nicholas Purcell

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Articles
    Neurologic improvement after peripheral blood stem cell transplantation in POEMS syndrome
    S. Kuwabara, S. Misawa, K. Kanai et al.
    Neurology, October 01, 2008
  • Brief Communications
    Autologous peripheral blood stem cell transplantation for POEMS syndrome
    S. Kuwabara, S. Misawa, K. Kanai et al.
    Neurology, November 16, 2005
  • Articles
    Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis
    S. H. Appel, J. I. Engelhardt, J. S. Henkel et al.
    Neurology, October 20, 2008
  • Clinical Scientific Notes
    Demyelinating Brachial Neuropathy Complicating Syngeneic Graft-versus-host Disease
    Yasumasa Yoshiyama, Masashi Nakajima, Satoshi Kuwabara et al.
    Neurology, January 01, 1997
Neurology: 100 (13)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

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
  • Activate a Subscription
  • 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 | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise