This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
The attention of researchers and clinicians specializing in both multiple sclerosis (MS) and JC virus (JCV), the etiologic agent of progressive multifocal leukoencephalopathy (PML), was rekindled by the development of PML in two patients with MS enrolled in a clinical trial of combination therapy with natalizumab (Tysabri) and interferon β-1A (Avonex) in recent years. PML had not been previously reported with either MS or treatment with interferon β alone. This occurrence of PML with α4β1-integrin inhibition in MS raised a number of issues in terms both of the scientific understanding of these diseases and for the future of immunomodulatory treatment for MS. In this review, we examine the current status of knowledge of the virus, its molecular biology, life cycle, and pathogenetic mechanisms, and how this relates to the basic science and clinical perspectives of MS. A better understanding of the specific steps from JCV infection to the development of PML is key to this issue. Other critical issues for further investigation include the role of α4β1-integrin inhibition by natalizumab in the re-expression of JCV from latent sites and in the inhibition of entry into the brain and peripheral sites.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
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.
You May Also be Interested in
- Article
- Abstract
- PML: Pathology and epidemiology.
- Life cycle of JCV: Latency and reactivation.
- JCV and the immune system.
- Detection of JCV and quantification of viral load.
- Therapeutic targets in PML.
- JCV in MS.
- MRI considerations in MS and PML.
- PML in patients with MS.
- Summary and future research directions.
- Acknowledgment
- Footnotes
- References
- Info & Disclosures
Hastening the Diagnosis of Amyotrophic Lateral Sclerosis
Dr. Brian Callaghan and Dr. Kellen Quigg