Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepine
Article first published online: 25 JUL 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 62, Issue 1, pages 21–33, July 2007
How to Cite
Black, J. A., Liu, S., Carrithers, M., Carrithers, L. M. and Waxman, S. G. (2007), Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepine. Ann Neurol., 62: 21–33. doi: 10.1002/ana.21172
- Issue published online: 27 JUL 2007
- Article first published online: 25 JUL 2007
- Manuscript Accepted: 1 MAY 2007
- Manuscript Revised: 10 APR 2007
- Manuscript Received: 23 JAN 2007
- National Multiple Sclerosis Society. Grant Numbers: RG1912, RG3888-A-2
- NIH (National Institute of Neurological Disorders and Stroke). Grant Number: K02 NS047457-01
- Medical Research Service and Rehabilitation Service, Department of Veterans Affairs
- Dana Foundation
- Nancy Davis Foundation and Destination Cure
In vitro observations and studies in murine experimental autoimmune encephalomyelitis (EAE) have shown protective effects of sodium channel blockers on central nervous system axons and improved clinical status when treatment is continued throughout the period of observation. Several clinical studies of sodium channel blockers are under way in patients with multiple sclerosis. Here we asked whether a protective effect would persist after withdrawal of a sodium channel blocker.
We studied a mouse model of myelin oligodendrocyte glycoprotein–induced EAE treated with phenytoin or carbamazepine.
Both phenytoin and carbamazepine significantly improved the clinical course of the disease. Withdrawal of phenytoin resulted in acute exacerbation, accompanied by a significantly increased inflammatory infiltrate within the central nervous system and the death of nearly 60% of EAE mice. There were no clinical worsening or deaths in control mice after withdrawal of phenytoin. Withdrawal of carbamazepine led to acute worsening of EAE symptoms, increased inflammatory infiltrate, and was associated with the death of 8% of mice.
These results, together with results showing effects of sodium channel blockers in immune cells, raise questions about the long-term effects of sodium channel blockers in neuroinflammatory disorders, and suggest that clinical studies of sodium channel blockers in these disorders should be planned carefully. Ann Neurol 2007