During the past years treatment of multiple sclerosis (MS) has critically improved with the introduction of new and very effective drugs. These modern MS therapeutics selectively interfere with immune cell trafficking resulting in substantial shifts in leukocyte counts in peripheral blood. Strikingly, investigations of cerebrospinal fluid (CSF) also revealed immunological changes behind the blood-CSF barrier which might contribute to the increased effectiveness of these drugs. By contrast, these changes might account for a reduced immune surveillance of the central nervous system (CNS) and favor the occurrence of opportunistic infections such as progressive multifocal leukoencephalopathy. In this review, we focus on immunological changes induced by two approved agents in the treatment of highly active MS, natalizumab and fingolimod, and outline the current knowledge about their impact in the CSF compartment of the CNS. Further investigations and monitoring of immunological changes in CSF under MS therapy might help to provide further information about immunological changes.
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