Brain Pathology Case of the Month - November 2013


Progressive multifocal leukoencephalopathy (PML) in Systemic Lupus Erythematosus (SLE)

A real-time PCR Assay was performed and JC Polyomavirus DNA was detected


The authors described a case of Progressive Multifocal Leukoencephalopathy (PML) in an adult woman. PML is a rare and fatal demyelinating disease of the central nervous system caused by JC polyomavirus (JCV) reactivation (10). JCV is ubiquitous within the human population (11). The primary JCV infection normally takes place during childhood, usually without clinical symptoms and remains latent in the urinary tract and lymphoid organs. 92% of adults are reported to be JCV-seropositive (6). Reactivation of the JCV infection has been more commonly attributed to severe immunosuppression, e.g., HIV infection, hematologic cancers, chronic diseases and organ transplantations treated with fludarabine (9), rituximab, natalizumab and efalizumab (1,5,12). The particular feature of this case is the absence of all these elements. The patient was not under immunosuppressive treatment, was HIV-negative and the blood tests demonstrated the competency of the immune system. The only clinical features that could be related to PML were SLE and the use of low-dose prednisone (25 mg). Furthermore, PML has been associated with many rheumatological diseases: among them, SLE is the most commonly associated (4). Cases of PML onset in patients with SLE who did not receive any immunosuppressive therapy are reported. Some authors suggest that SLE is associated with a specific predisposition to the development of PML (8), as well as with a higher risk of PML associated with novel biologic therapies (7). Therefore, a high index of suspicion should be maintained in SLE patients presenting with neurologic decline. If PML is suspected in a rheumatic disease patient presenting with unexplained neurologic symptoms or signs, detection of JCV in brain tissue is needed to confirm diagnosis. Neuronavigation brain biopsy must be considered; the sensitivity of this examination is higher if compared to PCR analysis of cerebrospinal fluid (3) with a low rate of complications (2).


  1. Carson KR, Focosi D, Major EO, Petrini M, Richev EA, West DP, Bennett CL (2009) Monoclonal antibody-associated progressive multifocal leukoencephalopathy in patients treated with rituximab, natalizumab and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncology 10:816-24.
  2. Dammers R, Haitsma IK, Schouten JW, Kros JM, Avezaat CJ, Vincent AJ (2008) Safety and efficacy of frameless and frame-based intracranial biopsy techniques. Acta Neurochir (Wien) 150:23-9.
  3. Gibson PE, Gardner SD, Field AM (1986) Use of a molecular probe for detecting JCV DNA directly in human brain material. J Med Virol 18: 87-95.
  4. Govindappa V, Hicks S, Wichter M, Jolly M (2007) Progressive multifocal leukoencephalopathy in systemic lupus erythematosus. Arthritis Rheum 57:352-4.
  5. Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D (2005) Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353: 375-381.
  6. Major EO, Amemiya K, Tornatore CS, Houff SA, Berger JR (1992) Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 5: 49-73.
  7. Molloy ES , Calabrese LH (2009) Progressive multifocal leukoencephalopathy: A national estimate of frequency in systemic lupus erythematosus and other rheumatic diseases. Athritis Rheum 60: 3761-3765.
  8. Power C, Gladden JG, Halliday W, Del Bigio MR, Nath A, Ni W, et al (2000) AIDS- and non-AIDS related PML association with distinct p53 polymorphism. Neurology 54: 743-746.
  9. Vidarsson B, Mosher DF, Salamat MS, Isaksson HJ, Onundarson PT (2002) Progressive multifocal leukoencephalopathy after fludarabine therapy for low-grade lymphoproliferative disease. Am J Hematol 70: 51-54.
  10. Weber T, Major EO (1997) Progressive multifocal leukoencephalopathy: molecular biology, pathogenesis and clinical impact. Intervirology 40: 98-111.
  11. White MK, Khalili K (2011) Pathogenesis of progressive multifocal leukoencephalopathy - revisited. J Infect Dis 203:578-86.
  12. Yokoyama H, Watanabe T, Maruyama D, Kim SW, Kobayashi Y, Tobinai K (2008) Progressive multifocal leukoencephalopathy in a patient with B-cell lymphoma during rituximab-containing chemotherapy: case report and review of the literature. Int J Hematol 88: 443-447.

Contributed by Pasquale Donnarumma, Angelo Pichierri, Roberto Tarantino, Andrea Gennaro Ruggeri, Manila Antonelli, Roberto Delfini

International Society of Neuropathology