Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis

Objective Recent studies in peripheral blood mononuclear cells (PBMCs) have indicated that exacerbations of multiple sclerosis (MS) could be associated with the reactivation of latent varicella‐zoster virus (VZV). Methods Ultrastructural observations for viral particles were made by electron microscopy in cerebrospinal fluid (CSF) from 15 MS patients during relapse, 19 MS patients during remission, and 28 control subjects. Initial findings were reproduced in a confirmation cohort. In addition, DNA from VZV was quantified by real‐time polymerase chain reaction in PBMCs and CSF from a large number of MS patients (n = 78). Results We found by electron microscopy the presence of abundant viral particles identical to VZV in CSF obtained from MS patients within the first few days of an acute relapse. In contrast, viral particles were not seen in CSF samples from MS patients in remission or from neurological control subjects. Also, DNA from VZV was present in CSF and in PBMCs during relapse, disappearing in most patients during remission. The mean viral load was 542 times greater in CSF at relapse than in CSF at remission and 328 times greater in CSF at relapse than in PBMCs at relapse. Interpretation The ultrastructural finding of viral particles identical to VZV, together with the simultaneous presence of large quantities of DNA from VZV in the subarachnoid space, almost restricted to the periods of exacerbation, as well as its steady diminution and eventual disappearance from clinical relapse to clinical remission are surprising and constitute the strongest evidence to support the participation of VZV in the pathogenesis of MS. Ann Neurol 2008