Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms due to the physicians’ unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.
AgostiniHT, YanagiharaR, DavisV, RyschkewitschCF, StonerGL. Asian genotypes of JC virus in Native Americans and in a Pacific Island population: markers of viral evolution and human migration. Proc Natl Acad Sci USA. 1997;94(26):14542-6. [https://doi.org/10.1073/pnas.94.26.14542]. [PMID:9405649]
TanCS, KoralnikIJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010;9(4):425-37. [https://doi.org/10.1016/S1474-4422(10)70040-5]. [PMID:20298966]
Ahsan N, Shah KV. Polyomaviruses and human diseases. In: Ahsan N, editor. Polyomaviruses and human diseases: advances in experimental medicine and biology. New York: Springer; 2006. (vol. 577). [https://doi.org/10.1007/0-387-32957-9_1]
RyschkewitschC, JensenP, HouJ, FahleG, FischerS, MajorEO. Comparison of PCR-southern hybridization and quantitative real-time PCR for the detection of JC and BK viral nucleotide sequences in urine and cerebrospinal fluid. J Virol Methods. 2004;121(2):217-21. [https://doi.org/10.1016/j.jviromet.2004.06.021]. [PMID:15381359]
Cayres-VallinotoIMV, VallinotoAC, PenaGP, et al. JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region. Braz J Infect Dis. 2016;20(4):360-4. [https://doi.org/10.1016/j.bjid.2016.05.005]. [PMID:27266589]
EngsigFN, HansenAB, OmlandLH, et al. Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study. J Infect Dis. 2009;199(1):77-83. [https://doi.org/10.1086/595299]. [PMID:19007313]
KhannaN, ElziL, MuellerN, et al. Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV cohort study. Clin Infect Dis. 2009;48(10):1459-66. [https://doi.org/10.1086/598335]. [PMID:19348592]
VidalJE, OliveiraACP, FinkMCDS, PannutiCS, TrujilloJR. AIDS-related progressive multifocal leukoencephalopathy: a retrospective study in a referral center in São Paulo, Brazil. Rev Inst Med Trop São Paulo. 2008;50(4):209-12. [https://doi.org/10.1590/S0036-46652008000400004]. [PMID:18813759]
BergerJR, KaszovitzB, PostMJ, DickinsonG. Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection: a review of the literature with a report of sixteen cases. Ann Intern Med. 1987;107(1):78-87. [https://doi.org/10.7326/0003-4819-107-1-78]. [PMID:3296901]
LuftBJ, HafnerR, KorzunAH, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team. N Engl J Med. 1993;329(14):995-1000. [https://doi.org/10.1056/NEJM199309303291403]. [PMID:8366923]
MiskinDP, NgoLH, KoralnikIJ. Diagnostic delay in progressive multifocal leukoencephalopathy. Ann Clin Transl Neurol. 2016;3(5):386-91. [https://doi.org/10.1002/acn3.301]. [PMID:27231708]
LeeAM, BaiHX, ZouY, et al. Safety and diagnostic value of brain biopsy in HIV patients: a case series and meta-analysis of 1209 patients. J Neurol Neurosurg Psychiatry. 2016;87(7):722-33. [https://doi.org/10.1136/jnnp-2015-312037]. [PMID:26758989]
ZhangJ, LiuX, FuK, et al. Diagnostic value and safety of stereotactic biopsy in acquired immune deficiency syndrome patients with intracranial lesions: systematic review and meta-analysis. World Neurosurg. 2017;98:790-799.e13. [https://doi.org/10.1016/j.wneu.2016.11.151]. [PMID:27965075]
ZivanovicM, SavsekL, PoljakM, PopovicM. Possible pitfalls in the diagnostic of progressive multifocal leukoencephalopathy. Clin Neuropathol. 2016;35(2):66-71. [PMID:26754416]
Muñoz-MármolAM, MolaG, Fernández-VasaloA, VelaE, MateJL, ArizaA. JC vírus early protein detection by immunohistochemistry in progressive multifocal encephalopathy: a comparative study with in-situ hybridization and polymerase chain reaction. J Neuropathol Exp Neurol. 2004;63(11):1124-30. [https://doi.org/10.1093/jnen/63.11.1124]. [PMID:15581180]
MarzocchettiA, Di GiambenedettoS, CingolaniA, AmmassariA, CaudaR, De LucaA. Reduced rate of diagnostic positive detection of JC virus DNA in cerebrospinal fluid in cases of suspected progressive multifocal leukoencephalopathy in the era of potent antiretroviral therapy. J Clin Microbiol. 2005;43(8):4175-7. [https://doi.org/10.1128/JCM.43.8.4175-4177.2005]. [PMID:16081969]
McGuireD, BarhiteS, HollanderH, MilesM. JC virus DNA in cerebrospinal fluid of human immunodeficiency virus-infected patients: predictive value for progressive multifocal leukoencephalopathy. Ann Neurol. 1995;37(3):395-9. [https://doi.org/10.1002/ana.410370316]. [PMID:7695239]
BossolascoS, CaloriG, MorettiF, et al. Prognostic Significance of JC Virus DNA Levels in Cerebrospinal Fluid of Patients with HIV-Associated Progressive Multifocal Leukoencephalopathy. Clin Infect Dis. 2005;40(5):738-44. [https://doi.org/10.1086/427698]. [PMID:15714422]
SahraianMA, RadueE-W, EshaghiA, BesliuS, MinagarA. Progressive multifocal leukoencephalopathy: a review of the neuroimaging features and differential diagnosis. Eur J Neurol. 2012;19(8):1060-9. [https://doi.org/10.1111/j.1468-1331.2011.03597.x]. [PMID:22136455]
SmithAB, SmirniotopoulosJG, RushingEJ. Central nervous system infections associated with human immunodeficiency virus infection: radiologic-pathologic correlation. Radiographics. 2008;28(7):2033-58. [https://doi.org/10.1148/rg.287085135]. [PMID:19001657]
WhitemanML, PostMJ, BergerJR, TateLG, BellMD, LimonteLP. Progressive multifocal leukoencephalopathy in 47 HIV-seropositive patients: neuroimaging with clinical and pathologic correlation. Radiology. 1993;187(1):233-40. [https://doi.org/10.1148/radiology.187.1.8451420]. [PMID:8451420]
FournierA, Martin-BlondelG, Lechapt-ZalcmanE, et al. Immune reconstitution inflammatory syndrome unmasking or worsening aids-related progressive multifocal leukoencephalopathy: a literature review. Front Immunol. 2017;8:577. [https://doi.org/10.3389/fimmu.2017.00577]. [PMID:28588577]
FalcóV, OlmoM, del SazSV, et al. Influence of HAART on the clinical course of HIV-1-infected patients with progressive multifocal leukoencephalopathy: results of an observational multicenter study. J Acquir Immune Defic Syndr. 2008;49(1):26-31. [https://doi.org/10.1097/QAI.0b013e31817bec64]. [PMID:18667930]
GasnaultJ, CostagliolaD, Hendel-ChavezH, et al. Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy. PLoS One. 2011;6(6):e20967. [https://doi.org/10.1371/journal.pone.0020967]. [PMID:21738597]
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