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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Neuroimmunology Unit, National Institute of Neurology and Neurosurgery, Center for Research and Advanced Studies, Mexico City, Mexico. jsotelo@servidor.unam.mx

    , ,

    Source

    Annals of neurology 63:3 2008 Mar pg 303-11

    MeSH

    Adolescent
    Adult
    Aged
    Cohort Studies
    DNA, Viral
    Female
    Herpesvirus 3, Human
    Humans
    Male
    Middle Aged
    Multiple Sclerosis, Relapsing-Remitting
    Viral Load

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18306233

    Citation

    Sotelo, Julio, et al. "Varicella-zoster Virus in Cerebrospinal Fluid at Relapses of Multiple Sclerosis." Annals of Neurology, vol. 63, no. 3, 2008, pp. 303-11.
    Sotelo J, Martínez-Palomo A, Ordoñez G, et al. Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis. Ann Neurol. 2008;63(3):303-11.
    Sotelo, J., Martínez-Palomo, A., Ordoñez, G., & Pineda, B. (2008). Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis. Annals of Neurology, 63(3), pp. 303-11. doi:10.1002/ana.21316.
    Sotelo J, et al. Varicella-zoster Virus in Cerebrospinal Fluid at Relapses of Multiple Sclerosis. Ann Neurol. 2008;63(3):303-11. PubMed PMID: 18306233.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis. AU - Sotelo,Julio, AU - Martínez-Palomo,Adolfo, AU - Ordoñez,Graciela, AU - Pineda,Benjamin, PY - 2008/2/29/pubmed PY - 2008/4/19/medline PY - 2008/2/29/entrez SP - 303 EP - 11 JF - Annals of neurology JO - Ann. Neurol. VL - 63 IS - 3 N2 - 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. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/18306233/full_citation L2 - https://doi.org/10.1002/ana.21316 DB - PRIME DP - Unbound Medicine ER -