Neuroradiologie Scan 2024; 14(04): 287-298
DOI: 10.1055/a-2371-7414
CME-Fortbildung

Progressive multifokale Leukenzephalopathie: Diagnostik und Therapieoptionen

Lea Grote-Levi
,
Nora Möhn
,
Mike P. Wattjes
,
Thomas Skripuletz

Das humane Polyomavirus 2 kann insbesondere bei immunkompromittierten Personen eine potenziell lebensgefährliche zerebrale opportunistische Infektion, die progressive multifokale Leukenzephalopathie (PML), auslösen. Bisher steht keine zugelassene wirksame kausale Therapie zur Verfügung. Dieser Beitrag zeigt, wie die Erkrankung diagnostiziert werden kann und welche aktuellen experimentellen Therapiemaßnahmen erfolgversprechend sind.

Fazit

Take Home Message

Das MRT des Gehirns ist eine sehr sensitive Methode zum Nachweis von PML Veränderungen, und das Protokoll sollte T2-FLAIR, konventionelle T2-gewichtete, diffusionsgewichtete (DWI) und kontrastmittelverstärkte T1-gewichtete Sequenzen beinhalten.

Fazit

Take Home Message

Bisher konnte für keinen der antiviralen Therapieansätze ein signifikanter positiver Wirkerfolg gezeigt werden.



Publication History

Article published online:
01 October 2024

© 2024. Thieme. All rights reserved.

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  • Literatur

  • 1 Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol 2010; 9: 425-437
  • 2 Cortese I, Reich DS, Nath A. Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease. Nat Rev Neurol 2021; 17: 37-51
  • 3 Weber T, Trebst C, Frye S. et al. Analysis of the systemic and intrathecal humoral immune response in progressive multifocal leukoencephalopathy. J Infect Dis 1997; 176: 250-254
  • 4 Eng PM, Turnbull BR, Cook SF. et al. Characteristics and antecedents of progressive multifocal leukoencephalopathy in an insured population. Neurology 2006; 67: 884-886
  • 5 Zhai S, Brew BJ. Progressive multifocal leukoencephalopathy. Handb Clin Neurol 2018; 152: 123-137
  • 6 Mateen FJ, Muralidharan R, Carone M. et al. Progressive multifocal leukoencephalopathy in transplant recipients. Ann Neurol 2011; 70: 305-322
  • 7 Arkema EV, van Vollenhoven RF, Askling J. et al. Incidence of progressive multifocal leukoencephalopathy in patients with rheumatoid arthritis: a national population-based study. Ann Rheum Dis 2012; 71: 1865-1867
  • 8 Bartsch T, Rempe T, Leypoldt F. et al. The spectrum of progressive multifocal leukoencephalopathy: a practical approach. Eur J Neurol 2019; 26: 566-e541
  • 9 Blair NF, Brew BJ, Halpern JP. Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance. Neurology 2012; 78: 507-508
  • 10 Wattjes MP, Vennegoor A, Steenwijk MD. et al. MRI pattern in asymptomatic natalizumab-associated PML. J Neurol Neurosurg Psychiatry 2015; 86: 793-798
  • 11 Wattjes MP, Barkhof F. Diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy using MRI. Curr Opin Neurol 2014; 27: 260-270
  • 12 Bergui M, Bradac GB, Oguz KK. et al. Progressive multifocal leukoencephalopathy: diffusion-weighted imaging and pathological correlations. Neuroradiology 2004; 46: 22-25
  • 13 Baldassari LE, Wattjes MP, Cortese ICM. et al. The neuroradiology of progressive multifocal leukoencephalopathy: a clinical trial perspective. Brain 2021;
  • 14 Wijburg MT, Witte BI, Vennegoor A. et al. MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance. J Neurol Neurosurg Psychiatry 2016; 87: 1138-1145
  • 15 Wijburg MT, van Oosten BW, Murk JL. et al. Heterogeneous imaging characteristics of JC virus granule cell neuronopathy (GCN): a case series and review of the literature. J Neurol 2015; 262: 65-73
  • 16 Ngouth N, Monaco MC, Walker L. et al. Comparison of qPCR with ddPCR for the Quantification of JC Polyomavirus in CSF from Patients with Progressive Multifocal Leukoencephalopathy. Viruses 2022; 14
  • 17 Warnke C, von Geldern G, Markwerth P. et al. Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 2014; 76: 792-801
  • 18 Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 2005; 353: 369-374
  • 19 Bloomgren G, Richman S, Hotermans C. et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366: 1870-1880
  • 20 Sriwastava S, Kataria S, Srivastava S. et al. Disease-modifying therapies and progressive multifocal leukoencephalopathy in multiple sclerosis: A systematic review and meta-analysis. J Neuroimmunol 2021; 360: 577721
  • 21 Gieselbach RJ, Muller-Hansma AH, Wijburg MT. et al. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol 2017; 264: 1155-1164
  • 22 Rosenkranz T, Novas M, Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med 2015; 372: 1476-1478
  • 23 Schwab N, Schneider-Hohendorf T, Hoyt T. et al. Anti-JCV serology during natalizumab treatment: Review and meta-analysis of 17 independent patient cohorts analyzing anti-John Cunningham polyoma virus sero-conversion rates under natalizumab treatment and differences between technical and biological sero-converters. Mult Scler 2018; 24: 563-573
  • 24 Jamilloux Y, Kerever S, Ferry T. et al. Treatment of Progressive Multifocal Leukoencephalopathy With Mirtazapine. Clin Drug Investig 2016; 36: 783-789
  • 25 Hou J, Major EO. The efficacy of nucleoside analogs against JC virus multiplication in a persistently infected human fetal brain cell line. J Neurovirol 1998; 4: 451-456
  • 26 Hall CD, Dafni U, Simpson D. et al. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team. N Engl J Med 1998; 338: 1345-1351
  • 27 Clifford DB, Nath A, Cinque P. et al. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol 2013; 19: 351-358
  • 28 De Luca A, Ammassari A, Pezzotti P. et al. Cidofovir in addition to antiretroviral treatment is not effective for AIDS-associated progressive multifocal leukoencephalopathy: a multicohort analysis. AIDS 2008; 22: 1759-1767
  • 29 Darvin P, Toor SM, Sasidharan Nair V. et al. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018; 50: 1-11
  • 30 Tan CS, Bord E, Broge TA. et al. Increased program cell death-1 expression on T lymphocytes of patients with progressive multifocal leukoencephalopathy. J Acquir Immune Defic Syndr 2012; 60: 244-248
  • 31 Cortese I, Muranski P, Enose-Akahata Y. et al. Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy. N Engl J Med 2019; 380: 1597-1605
  • 32 Boumaza X, Bonneau B, Roos-Weil D. et al. Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors. Ann Neurol 2022;
  • 33 Mani J, Jin N, Schmitt M. Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses after transplantation. Cytotherapy 2014; 16: 1325-1335
  • 34 Balduzzi A, Lucchini G, Hirsch HH. et al. Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient. Bone Marrow Transplant 2011; 46: 987-992
  • 35 Muftuoglu M, Olson A, Marin D. et al. Allogeneic BK Virus-Specific T Cells for Progressive Multifocal Leukoencephalopathy. N Engl J Med 2018; 379: 1443-1451
  • 36 Cortese I, Beck ES, Al-Louzi O. et al. BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study. Lancet Neurol 2021; 20: 639-652
  • 37 Krymskaya L, Sharma MC, Martinez J. et al. Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides. J Virol 2005; 79: 11170-11178
  • 38 Hopfner F, Mohn N, Eiz-Vesper B. et al. Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy. Neurol Neuroimmunol Neuroinflamm 2021; 8
  • 39 Blankenbach K, Schwab N, Hofner B. et al. Natalizumab-associated progressive multifocal leukoencephalopathy in Germany. Neurology 2019; 92: e2232-e2239
  • 40 Carson KR, Evens AM, Richey EA. et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood 2009; 113: 4834-4840