Long-term prognosis of patients surviving progressive multifocal leukoencephalopathy
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ID: 317752
2026
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Abstract
Abstract Despite improved survival in recent years, long-term outcomes in patients surviving progressive multifocal leukoencephalopathy beyond the first year remain poorly defined. This international multicenter retrospective study aimed to characterize the three-year prognosis of patients with progressive multifocal leukoencephalopathy who had survived at least one year, identify factors associated with favorable outcomes and late mortality, and determine recurrence rate. Data were collected through standardized questionnaires across forty-one centers in twelve countries. Patients were eligible if they met the 2013 diagnostic criteria for definite progressive multifocal leukoencephalopathy of the American Academy of Neurology, survived at least one year after diagnosis, and had documented follow-up three years after diagnosis. Demographic, clinical, virological, and radiological data were retrieved at diagnosis, one year, and three years. Functional status was assessed using the modified Rankin Scale, with scores of 0-2 defining a favorable outcome. Generalized linear mixed models identified independent predictors of three-year functional status and late mortality. Among 1877 screened cases, 245 patients met inclusion criteria. The most common underlying causes of immunosuppression were HIV infection (48%), autoimmune/inflammatory diseases (26%), and hematological malignancies (18%). At three years, 220 patients (89.8% of the cohort) were alive and 188 (85.5% of survivors) had neurological sequelae, most frequently motor or cognitive impairment. Overall, 112/245 (45.7%) achieved a favorable functional outcome. HIV-associated progressive multifocal leukoencephalopathy (OR 2.36, 95% CI 1.05-5.28) was associated with a favourable outcome, whereas higher modified Rankin Scale score at diagnosis (OR 0.48, 95% CI 0.35-0.66) and higher number of affected brain regions on baseline MRI (OR 0.78, 95% CI 0.64-0.95) were independently associated with poorer functional outcome. Among variables collected one year after diagnosis, good functional status at that time was significantly associated with long-term favorable outcome (OR 0.01, 95% CI <0.01-0.03). Twenty-five patients (10.2%) died after the first year, with mortality associated with higher lesion burden at diagnosis and primary immunodeficiency as underlying disease. Even beyond the first year, progressive multifocal leukoencephalopathy remained the leading cause of death (11/25). Recurrence occurred in seven patients (2.9%) and was almost always fatal (6/7). This study provides a comprehensive evaluation of long-term outcomes among survivors of progressive multifocal leukoencephalopathy. These findings present a nuanced picture: while most remain neurologically impaired, nearly half achieve functional independence at three years. The results emphasize the prognostic relevance of the initial clinical and radiological burden and early functional trajectory and highlight the need for research into mechanisms driving disease recurrence.
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| Authors | Nicolas Lambert, Majdouline El Moussaoui, Adèle Le Guilloux, Marine Joly, Maria del Carmen Garcia Martearena, Ilaria Mainardi, Raphaël Bernard‐Valnet, Carmela Pinnetti, Andrea Antinori, Annalisa Mondi, Kirsten Felicity Greve, Xavier Brousse, Willeke F. Westendorp, Martijn T Wijburg, Lea Grote‐Levi, Nora Möhn, Valérie Pourcher, Simon B. Gressens, Claudina Vicente Cruz, Vincent van Pesch, M. Vidal, Alexis Redor, Alain Makinson, Agni M Konitsioti, Baptiste Hoellinger, Louisa Nitsch, Douglas Ney, Emmanuel Faure, Karl Bjørnar Alstadhaug, M. Martinot, Francesco Genderini, Joseph Legras, Margaux Garzaro, Sophie Blanchi, Sandrine Gazaignes, Serena Borrelli, S. Patrat-Delon, David Vydrář, Paul Nicolas-Vullierme, Marin Moutel, Tom Cartau, Frédéric London, André Cabie, Kévin Bouiller, Alexis Montcuquet, Paul Loubet, Naomi Sayre, Marion Le Maréchal, David B. Clifford, Thomas Skripuletz, Matthijs C. Brouwer, Jacob Bodilsen, Renaud Pasquier, Irene Cortese, Paola Cinque, Agnès Sommet, Guillaume Martin-Blondel |
| Journal | Brain research |
| Year | 2026 |
| DOI |
10.1093/brain/awag213
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| URL | |
| Keywords | Keywords not found |
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