Skip to main content

Fungal infection in cerebrospinal fluid from some patients with multiple sclerosis


Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system and spinal cord, leading to axonal demyelination of neurons. Recently, we have found a correlation between fungal infection and MS in peripheral blood of patients. The present work provides evidence of fungal infection in the cerebrospinal fluid (CSF) of some MS patients. Thus, fungal antigens can be demonstrated in CSF, as well as antibodies reacting against several Candida species. Comparison was made between CSF and blood serum for the presence of fungal antigens (proteins) and antibodies against different Candida spp. Analyses of both CSF and serum are complementary and serve to better evaluate for the presence of disseminated fungal infection. In addition, PCR analyses indicate the presence of DNA from different fungal species in CSF, depending on the patient analyzed. Overall, these findings support the notion that fungal infection can be demonstrated in CSF from some MS patients. This may constitute a risk factor in this disease and could also help in understanding the pathogenesis of MS.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Barnett MH, Sutton I (2006) The pathology of multiple sclerosis: a paradigm shift. Curr Opin Neurol 19(3):242–247

    PubMed  Article  Google Scholar 

  2. 2.

    Hawker K (2011) Progressive multiple sclerosis: characteristics and management. Neurol Clin 29(2):423–434

    PubMed  Article  Google Scholar 

  3. 3.

    Stadelmann C (2011) Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications. Curr Opin Neurol 24(3):224–229

    PubMed  CAS  Article  Google Scholar 

  4. 4.

    Burrell AM, Handel AE, Ramagopalan SV, Ebers GC, Morahan JM (2011) Epigenetic mechanisms in multiple sclerosis and the major histocompatibility complex (MHC). Discov Med 11(58):187–196

    PubMed  Google Scholar 

  5. 5.

    Giovannoni G, Ebers G (2007) Multiple sclerosis: the environment and causation. Curr Opin Neurol 20(3):261–268

    PubMed  Article  Google Scholar 

  6. 6.

    Holmoy T, Harbo H, Vartdal F, Spurkland A (2009) Genetic and molecular approaches to the immunopathogenesis of multiple sclerosis: an update. Curr Mol Med 9(5):591–611

    PubMed  Article  Google Scholar 

  7. 7.

    Kakalacheva K, Munz C, Lunemann JD (2011) Viral triggers of multiple sclerosis. Biochim Biophys Acta 1812(2):132–140

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Marrie R (2011) Demographic, genetic, and environmental factors that modify disease course. Neurol Clin 29(2):323–341

    PubMed  Article  Google Scholar 

  9. 9.

    Van der Mei IA, Simpson S Jr, Stankovich J, Taylor BV (2011) Individual and joint action of environmental factors and risk of MS. Neurol Clin 29(2):233–255

    PubMed  Article  Google Scholar 

  10. 10.

    Goverman JM (2011) Immune tolerance in multiple sclerosis. Immunol Rev 241(1):228–240

    PubMed  CAS  Article  Google Scholar 

  11. 11.

    Hollifield RD, Harbige LS, Pham-Dinh D, Sharief MK (2003) Evidence for cytokine dysregulation in multiple sclerosis: peripheral blood mononuclear cell production of pro-inflammatory and anti-inflammatory cytokines during relapse and remission. Autoimmunity 36(3):133–141

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    McCoy L, Tsunoda I, Fujinami RS (2006) Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity 39(1):9–19

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Westall FC (2006) Molecular mimicry revisited: gut bacteria and multiple sclerosis. J Clin Microbiol 44(6):2099–2104

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Kuhle J, Pohl C, Mehling M, Edan G, Freedman MS, Hartung HP, Polman CH, Miller DH, Montalban X, Barkhof F, Bauer L, Dahms S, Lindberg R, Kappos L and Sandbrink R (2007) Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 356(4):371–378

    PubMed  CAS  Article  Google Scholar 

  15. 15.

    Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128(Pt 11):2705–2712

    PubMed  Article  Google Scholar 

  16. 16.

    D’Haeseleer M, Cambron M, Vanopdenbosch L, De Keyser J (2011) Vascular aspects of multiple sclerosis. Lancet Neurol 10(7):657–666

    PubMed  Article  Google Scholar 

  17. 17.

    Carrasco L, Ramos M, Galisteo R, Pisa D, Fresno M, Gonzalez ME (2005) Isolation of Candida famata from a patient with acute zonal occult outer retinopathy. J Clin Microbiol 43(2):635–640

    PubMed  Article  Google Scholar 

  18. 18.

    Pisa D, Ramos M, Garcia P, Escoto R, Barraquer R, Molina S, Carrasco L (2008) Fungal infection in patients with serpiginous choroiditis or acute zonal occult outer retinopathy. J Clin Microbiol 46(1):130–135

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    Gass JD (2003) Are acute zonal occult outer retinopathy and the white spot syndromes (AZOOR complex) specific autoimmune diseases? Am J Ophthalmol 135(3):380–381

    PubMed  Article  Google Scholar 

  20. 20.

    Heckenlively JR, Ferreyra HA (2008) Autoimmune retinopathy: a review and summary. Semin Immunopathol 30(2):127–134

    PubMed  Article  Google Scholar 

  21. 21.

    Jacobson DM (1996) Acute zonal occult outer retinopathy and central nervous system inflammation. J Neuroophthalmol 16(3):172–177

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    Monson DM, Smith JR (2011) Acute zonal occult outer retinopathy. Surv Ophthalmol 56(1):23–35

    PubMed  Article  Google Scholar 

  23. 23.

    Benito-León J, Pisa D, Alonso R, Calleja P, Díaz-Sánchez M, Carrasco L (2010) Association between multiple sclerosis and Candida species: evidence from a case–control study. Eur J Clin Microbiol Infect Dis:1139–1145

  24. 24.

    Ramos M (2007) Diagnóstico de candidiasis mediante técnicas de PCR y de detección de antígenos fúngicos. Facultad de Ciencias. Universidad Autónoma de Madrid, Madrid

    Google Scholar 

  25. 25.

    Pisa D, Ramos M, Molina S, Garcia P, Carrasco L (2007) Evolution of antibody response and fungal antigens in the serum of a patient infected with Candida famata. J Med Microbiol 56(Pt 5):571–578

    PubMed  CAS  Article  Google Scholar 

  26. 26.

    Purzycki CB, Shain DH (2010) Fungal toxins and multiple sclerosis: a compelling connection. Brain Res Bull 82(1–2):4–6

    PubMed  CAS  Article  Google Scholar 

  27. 27.

    Malcus-Vocanson C, Giraud P, Broussolle E, Perron H, Mandrand B, Chazot G (1998) A urinary marker for multiple sclerosis. Lancet 351(9112):1330

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    Avni T, Leibovici L, Paul M (2011) PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 49(2):665–670

    PubMed  Article  Google Scholar 

  29. 29.

    Bretagne S, Costa JM (2005) Towards a molecular diagnosis of invasive aspergillosis and disseminated candidosis. FEMS Immunol Med Microbiol 45(3):361–368

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Khan ZU, Mustafa AS (2001) Detection of Candida species by polymerase chain reaction (PCR) in blood samples of experimentally infected mice and patients with suspected candidemia. Microbiol Res 156(1):95–102

    PubMed  CAS  Article  Google Scholar 

  31. 31.

    Gilden DH (2005) Infectious causes of multiple sclerosis. Lancet Neurol 4(3):195–202

    PubMed  CAS  Google Scholar 

  32. 32.

    Giovannoni G, Cutter GR, Lunemann J, Martin R, Munz C, Sriram S, Steiner I, Hammerschlag MR, Gaydos CA (2006) Infectious causes of multiple sclerosis. Lancet Neurol 5(10):887–894

    PubMed  Article  Google Scholar 

  33. 33.

    Wingerchuk DM (2011) Environmental factors in multiple sclerosis: Epstein-Barr virus, vitamin D, and cigarette smoking. Mt Sinai J Med NY 78(2):221–230

    Article  Google Scholar 

  34. 34.

    Cermelli C, Jacobson S (2000) Viruses and multiple sclerosis. Viral Immunol 13(3):255–267

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    Pisa D, Alonso R, Carrasco L (2011) Fungal infection in a patient with multiple sclerosis. Eur J Clin Microbiol Infect Dis 30(10):1173–1180

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    Rieger F, Amouri R, Benjelloun N, Cifuentes-Diaz C, Lyon-Caen O, Hantaz-Ambroise D, Dobransky T, Perron H, Gemy C (1996) Gliotoxic factor and multiple sclerosis. CR Acad Sci 319(4):343–350

    CAS  Google Scholar 

  37. 37.

    Wu GF, Alvarez E (2011) The immunopathophysiology of multiple sclerosis. Neurol Clin 29(2):257–278

    PubMed  Article  Google Scholar 

  38. 38.

    Gutwinski S, Erbe S, Munch C, Janke O, Muller U, Haas J (2010) Severe cutaneous Candida infection during natalizumab therapy in multiple sclerosis. Neurology 74(6):521–523

    PubMed  CAS  Article  Google Scholar 

Download references


The study was supported by a grant from the Fundación de Investigación Médica Mutua Madrileña. We also acknowledge an institutional grant to Centro de Biología Molecular from the Fundación Ramón Areces.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information



Corresponding author

Correspondence to L. Carrasco.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pisa, D., Alonso, R., Jiménez-Jiménez, F.J. et al. Fungal infection in cerebrospinal fluid from some patients with multiple sclerosis. Eur J Clin Microbiol Infect Dis 32, 795–801 (2013).

Download citation


  • Multiple Sclerosis
  • Fungal Infection
  • Multiple Sclerosis Patient
  • Blood Serum
  • Fungal Species