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JCV detection in multiple sclerosis patients treated with natalizumab

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Abstract

Natalizumab therapy is associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Because the prognosis of established PML is uniformly dismal, identification of highly susceptible patients to the disease may improve outcomes. We wanted to investigate whether serial plasma and cerebrospinal fluid (CSF) screening for polyomavirus would identify patients with laboratory evidence of viral infection prior to the development of clinical PML. Two hundred MS patients had pre-treatment CSF/plasma screening for JC virus (JCV) and BK virus (BKV) DNA, and thereafter every six treatments of natalizumab. In all positive patients treatment is stopped (due to potential risk of PML), they have follow-up clinical examinations and plasma/CSF JCV/BKV tests until all evaluations are normal. No patient developed clinical evidence of PML. Eight of the 200 patients had detectable JCV or BKV DNA. Five patients were positive for BKV DNA in the CSF and three patients were positive for JCV DNA (one in plasma, two in CSF). After cessation of natalizumab treatment, all patients converted to undetectable viral DNA. Screening for JCV in CSF in natalizumab-treated patients could help identify those at heightened risk for developing PML and discontinuing treatment in these patients may abort development of the clinical illness.

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References

  1. Aksamit A (2006) Review of progressive multifocal leukoencephalopathy and natalizumab. Neurologist 12(6):293–298

    Article  PubMed  Google Scholar 

  2. Alvarez-Lafuente R, Garcia-Montojo M, De Las Heras V, Bartolomé M, Arroyo R (2007) JC virus in cerebrospinal fluid samples of multiple sclerosis patients at the first demyelinating event. Mult Scler 13:590–595

    Article  CAS  PubMed  Google Scholar 

  3. Behzad-Behbahani A, Klapper PE, Vallely PJ, Cleator GM, Bonington A (2003) BKV-DNA and JCV-DNA in CSF of patients with suspected meningitis or encephalitis. Infection 31:374–378

    CAS  PubMed  Google Scholar 

  4. d’Arminio Monforte A, Cinque P, Vago L, Rocca A, Castagna A, Gervasoni C et al (1997) A comparison of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients. J Neurol 244:35–39

    Article  PubMed  Google Scholar 

  5. Elsner C, Dorries K (1992) Evidence of human polyomavirus BK and JC infection in normal brain tissue. Virology 191:72–80

    Article  CAS  PubMed  Google Scholar 

  6. Ferrante P, Caldarelli-Stefano R, Omodeo-Zorini E, Vago L, Boldorini R, Costanzi G et al (1995) PCR detection of JC virus DNA in brain tissue from patients with and without progressive multifocal leukoencephalopathy. J Med Virol 47:219–225

    Article  CAS  PubMed  Google Scholar 

  7. Fong IW, Britton CB, Luinstra KE, Tomas E, Mahony JB (1995) Diagnostic value of detecting JC virus DNA in cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. J Clin Microbiol 33:484–486

    CAS  PubMed  Google Scholar 

  8. Iacobaeus E, Ryschkewitsch C, Gravell M, Khademi M, Wallstrom E, Olsson T et al (2009) Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA. Mult Scler 15:28–35

    Article  CAS  PubMed  Google Scholar 

  9. Koralnik IJ, Boden D, Mai VX, Lord CI, Letvin NL (1999) JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy. Neurology 52:253

    CAS  PubMed  Google Scholar 

  10. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    CAS  PubMed  Google Scholar 

  11. Lindå H, von Heijne A, Major EO, Ryschkewitsch C, Berg J, Olsson T, Martin C (2009) Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med 361:1081–1087

    Article  PubMed  Google Scholar 

  12. Perrons CJ, Fox JD, Lucas SB, Brink NS, Tedder RS, Miller RF (1996) Detection of polyomaviral DNA in clinical samples from immunocompromised patients: correlation with clinical disease. J Infection 32:205–209

    Article  CAS  Google Scholar 

  13. Polman CH, O’Connor PW, Habrdova E, Hutchinson M, Kappos L, Miller DH et al (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910

    Article  CAS  PubMed  Google Scholar 

  14. Ransohoff RM (2007) Natalizumab for multiple sclerosis. N Engl J Med 356:2622–2629

    Article  CAS  PubMed  Google Scholar 

  15. Reploeg MD, Storch GA, Clifford D (2001) BK virus: a clinical review. Clin Infect Dis 33:191–202

    Article  CAS  PubMed  Google Scholar 

  16. Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW et al (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354:911–923

    Article  CAS  PubMed  Google Scholar 

  17. Tysabri full prescribing information. Biogen Idec. http://www.tysabri.com/tysbProject/tysb.portal/_baseurl/twoColLayout/SCSRepository/en_US/tysb/home/product-information/index.html. Accessed 11 Dec 2007

  18. Yousry TA, Major EO, Ryschkewitsch R, Fahle G, Fischer S, Hou J et al (2006) Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354:924–933

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The funding for this study was supported with MSRCNY funds and was approved by the MSRCNY Board of Directors.

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Correspondence to Saud A. Sadiq.

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Sadiq, S.A., Puccio, L.M. & Brydon, E.W.A. JCV detection in multiple sclerosis patients treated with natalizumab. J Neurol 257, 954–958 (2010). https://doi.org/10.1007/s00415-009-5444-4

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  • DOI: https://doi.org/10.1007/s00415-009-5444-4

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