Abstract
The progressive multifocal leukoencephalopathy is a demyelinating disease secondary to infection to John Cunningham Virus, it has a low incidence despite a high seroprevalence in the general population. The principal risk factor for its development is an immunosuppression, including Human Immunodeficiency Virus infection, hematologic neoplasms, chronic inflammatory diseases and systemic immunosuppressive drugs. After the primary infection, the virus stays in a latent state, acquiring a neuroinvasive capacity following a set of mutations in its genome. After infecting oligodendrocytes it takes them to destruction with the consequent demyelinating process whilst its fight to the host's cellular immune system. The diagnosis is based on a set of clinical findings secondary to encephalic compromise, classically supratentorial, in addition to a demonstration of viral genome or antibodies in serum or cerebrospinal fluid and the presence of diagnostic images and histopathologic findings on the cerebral white matter. Its treatment is based on the enhancement of the disturbed immune function, with the exception of immune reconstitution state where other strategies are applied. In this paper we will review the more relevant basic and clinical aspects of this disease.
References
Corral IC, Quereda C. Cap. 15. The neurological spectrum of HIV infection. En: García-Monco JC. CNS infections. A clinical approach. Vizcaya, España: Springer; 2014. p. 299-327.
Marra CM. Cap. 19. Human immunodeficiency virus. En: Scheld WM, Marra CM, Whitley RJ. Infections of the central nervous system. Cuarta edición. Philadelphia: Wolters Kluwer Health; 2014; p. 286-98.
Ropper AH, Samuels MA, Klein JP. Adams and Victors. Principles of neurology. Décima edición. Mc-Graw Hill; 2017.
Saylor D. Neurologic complications of human immunodeficiency virus infection. Continuum (Minneap Minn). 2018;24 (5, Neuroinfectious Disease):1397-421. doi: 10.1212/CON.0000000000000647.
Camporro J, Bruno V, Cammarota A, Del Castillo M, Alessandro L. Espectro clínico de la leucoencefalopatía multi-focal progresiva: diferencias y similitudes en pacientes con y sin virus de la inmunodeficiencia humana. Rev Neurol. 2019;69:152-8. doi: 10.33588/rn.6904.2019040.
Iacobaeus E, Burkill S, Bahmanyar S, Hakim R, Bys-tròm C, Fored M, Olsson T, Brundin L, Montgomery S. The national incidence of PML in Sweden, 1988-2013. Neurology. 2018;6;90(6):e498-506. doi: 10.1212/WNL.0000000000004926.
Sipilä JOT, Soilu-Hänninen M, Rautava P, Kytö V. Progressive multifocal leukoencephalopathy in Finland: a cross-sectional registry study. J Neurol. 2019;266(2):515-21. doi: 10.1007/s00415-018-09167-y.
Zhai S, Brew BJ. Progressive multifocal leukoencephalopathy. Handb Clin Neurol. 2018;152:123-37. doi: 10.1016/B978-0-444-63849-6.00010-4.
Anand P, Hotan GC, Vogel A, Venna N, Mateen FJ. Progressive multifocal leukoencephalopathy: A 25-year retrospective cohort study. Neurol Neuroimmunol Neuroinflamm. 2019;25;6(6):e618. doi: 10.1212/NXI.0000000000000618.
Grebenciucova E, Berger JR. Progressive multifocal leukoencephalopathy. Neurol Clin. 2018;36(4):739-50. doi: 10.1016/j.ncl.2018.06.002.
Koralnik IJ. Leucoencefalopatía multifocal progresiva (LMP): epidemiología, manifestaciones clínicas y diagnóstico. UpTo-Date. 2020. p. 1-25.
Kartau M, Sipilä JO, Auvinen E, Palomäki M, Verkkoniemi-Ahola A. Progressive multifocal leukoencephalopathy: current insights. Degener Neurol Neuromuscul Dis. 2019;9:109-21. doi: 10.2147/DNND.S203405.
Bartsch T, Rempe T, Leypoldt F, Riedel C, Jansen O, Berg D, Deuschl G. The spectrum of progressive multifocal leukoencephalopathy: a practical approach. Eur J Neurol. 2019;26(4):566-e41. doi: 10.1111/ene.13906.
Cortese I, Reich D S, Nath A. Progressive multifocal leuko-encephalopathy and the spectrum of JC virus-related disease. Nat Rev Neurol. 2021;17(1):37-51. doi: 10.1038/s41582-020-00427.
Pietropaolo V, Prezioso C, Bagnato F, Antonelli G. John Cunningham virus: an overview on biology and disease of the etiological agent of the progressive multifocal leukoencephalopathy. New Microbiol. 2018;41(3):179-86.
Takahashi K, Sato Y, Sekizuka T, Kuroda M, Suzuki T, Hasegawa H, Katano H. High expression of JC polyoma-virus-encoded microRNAs in progressive multifocal leuko-encephalopathy tissues and its repressive role in virus replication. PLoS Pathog. 2020;16(4):e1008523. doi: 10.1371/journal.ppat.1008523.
Khalili A, Craigie M, Donadoni M, Sariyer IK. Host-immune interactions in JC virus reactivation and development of progressive multifocal leukoencephalopathy (PML). J Neuroimmune Pharmacol. 2019;14(4):649-60. doi: 10.1007/s11481-019-09877-8.
Mockus TE, Netherby-Winslow CS, Atkins HM, Lauver MD,Jin G, Ren HM, Lukacher AE. CD8 T cells and STAT1 signaling are essential codeterminants in protection from polyomavirus encephalopathy. J Virol. 2020;31;94(8):e02038-19. doi: 10.1128/JVI.02038-19.
Major EO, Yousry TA, Clifford DB. Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned. Lancet Neurol. 2018;17(5):467-80. doi: 10.1016/51474-4422(18)30040-1. Erratum in: Lancet Neurol. 2018 Jul;17(7):578.
Berger JR, Pall L, Lanska D, Whiteman M. Progressive multifocal leukoencephalopathy in patients with HIV infection. J Neurovirol. 1998;4(1):59-68. doi: 10.3109/13550289809113482.
Gasnault J, Costagliola D, Hendel-Chavez H, Dulioust A, Pakianather S, Mazet AA, et al. Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early S-drug combination antiretroviral therapy. PLoS One. 2011;6(6):e20967. doi: 10.1371/journal.pone.0020967.
Berenguer J, Miralles P, Arrizabalaga J, Ribera E, Dronda F, Baraia-Etxaburu J, et al. Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy. Clin Infect Dis. 2003;36(8):1047-52. doi: 10.1086/374048.
Tyler KL, Vollmer TL. To PLEX or not to PLEX in natali zumab-associated PML. Neurology. 2017;88(12):1108-9. doi: 10.1212/WNL.0000000000003747.
Pham HP, Raju D, Schwartz J. Do we have enough evidence for recommending therapeutic plasma exchange for patients with natalizumab-associated progressive multifocal leukoencephalopathy? J Clin Apher. 2018;33(3):452-3. doi: 10.1002/jca.21617.
Stefoski D, Balabanov R, Waheed R, Ko M, Koralnik IJ, Sierra Morales F. Treatment of natalizumab-associated PML with filgrastim. Ann Clin Transl Neurol. 2019;6(5):923-31. doi: 10.1002/acn3.776.
Tan K, Roda R, Ostrow L, McArthur J, Nath A. PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids. Neurology. 2009;72(17):1458-64. doi: 10.1212/01.wnl.0000343510.08643.74.
Muftuoglu M, Olson A, Marin D, Ahmed S, Mulanovich V, Tummala S, Chi TL, Ferrajoli A, Kaur I, Li L, Champlin R, Shpall EJ, Rezvani K. Allogeneic BK Virus-Specific T Cells for Progressive Multifocal Leukoencephalopathy. N Engl J Med. 2018; 11;379(15):1443-1451. doi: 10.1056/NEJ-Moa1801540.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.