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Clinical outcome of long-term survivors of progressive multifocal leukoencephalopathy
  1. M A Lima1,2,3,
  2. F Bernal-Cano1,2,4,
  3. D B Clifford5,6,
  4. R T Gandhi7,8,
  5. I J Koralnik1,2
  1. 1Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, USA
  2. 2Harvard Medical School, USA
  3. 3Neuroinfections and HTLV laboratory, Fundação Oswaldo Cruz, Brazil
  4. 4Division of Infectious Diseases, Hospital San Ignacio, Bogota Colombia
  5. 5Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
  6. 6Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
  7. 7Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, USA
  8. 8Ragon Institute of MGH, MIT and Harvard, USA
  1. Correspondence to Igor J Koralnik, Neurology Department, Beth Israel Deaconess Medical Center; E/CLS 1005, 330 Brookline Avenue Boston, MA 02215, USA; ikoralni{at}bidmc.harvard.edu

Abstract

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the polyomavirus JC (JCV) in immunosuppressed people. There is no cure for PML but 1-year survival has increased from 10% to 50% in HIV-infected individuals treated with highly active antiretroviral therapy. We describe herein the clinical outcome of 24 PML patients whose survival exceeded 5 years, with a mean follow-up of 94.2 months (range, 60–188 months). Of all patients, only two were females including one who had non-Hodgkin's lymphoma and was HIV negative. All 23 HIV-positive patients received highly active antiretroviral therapy, and additional experimental therapies were not associated with a better clinical outcome.

Marked neurological improvement occurred in 4/24 (17%) of patients, while 11/24 (46%) had partial improvement and 9/24 (37%) remained stable. By the end of the period of observation, 8/24 (33%) of patients had no significant disability despite persistent symptoms (modified Rankin disability scale (MRDS) =1), 6/24 (25%) had slight disability and were living independently (MRDS=2), 5/24 (21%) were moderately disabled, requiring some help during activities of daily living (MRDS=3) and 5/24 (21%) had moderately severe disability, requiring constant help or institutionalisation (MRDS=4). Patients with cerebellar lesions tended to have a worse clinical outcome.

MRI showed leukomalacia with ventricular enlargement secondary to destruction of the white matter at the site of previous PML lesions, and focal areas of subcortical atrophy with preservation of the cortical ribbon.

Of 20 patients tested, 19(95%) had detectable CD8+ cytotoxic T-lymphocytes against JCV in their blood. In absence of a specific treatment, immunotherapies aiming at boosting the cellular immune response against JCV may improve the prognosis of PML.

  • Neuroimmunology
  • neurovirology

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Footnotes

  • M A Lima, F Bernal-Cano Contributed equally.

  • Funding Other Funders: NIH.

  • Competing interests IJK has received research grant support from Biogen Idec, and has received consultancy fees from Bristol Myers Sqibb, Ono Pharmaceuticals, Merck Serono, Antisense and Alnylam. RTG has received grant support from Tibotec and Gilead. DBC has advisory board membership with Genzyme and Bristol Myers Squibb, and has received consultancy fees from BiogenIdec, Genentech, Pfizer, and Millennium. He has received speaking fees from GlaxoSmithKline and from Millennium. He has received travel expenses from and has grants or grants pending from Biogen Idec. FBC has received grant support from Pfizer Therapeutics and has received consultancy fees from Abbott laboratories. MAL has no competing interests.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Beth Israel Deaconess Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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