Metabolic profile of PML lesions in patients with and without IRIS: an observational study

Neurology. 2012 Sep 4;79(10):1041-8. doi: 10.1212/WNL.0b013e318268465b. Epub 2012 Aug 22.

Abstract

Objective: To characterize progressive multifocal leukoencephalopathy (PML) lesions by contrast-enhanced MRI and evaluate their metabolism using proton magnetic resonance spectroscopy ((1)H- MRS) in the setting of immune reconstitution inflammatory syndrome (IRIS).

Methods: A total of 42 patients with PML underwent a clinical evaluation as well as brain MRI and (1)H-MRS at baseline and 3, 6, and 12 months later. The presence of IRIS was determined based on clinical and laboratory criteria. Ratios of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and lipid/lactate (Lip1 and Lip2) to creatine (Cr) were measured and correlated with the presence of contrast enhancement (CE) in PML lesions.

Results: IRIS occurred in 16 of 28 (57.1%) PML survivors (PML-S) and 1 of 14 (7.1%) PML progressors (PML-P). Lesions of patients with PML-IRIS showed significantly higher Cho/Cr (p = 0.0001), mI/Cr (p = 0.02), Lip1/Cr (p < 0.0001), and Lip2/Cr (p = 0.002) ratios and lower NAA/Cr (p = 0.02) ratios than patients with PML who did not have IRIS. An elevated Cho/Cr ratio was associated with CE within the (1)H-MRS voxel, whereas lipid/Cr ratios were elevated in PML-IRIS lesions independently of CE. Follow-up until 33 months from PML onset showed persistent elevation of the mI/Cr ratio in lesions of patients with PML-IRIS. A Lip1/Cr ratio greater than 1.5 combined with the presence of CE yielded a 79% probability of IRIS compared with 13% in the absence of these criteria.

Conclusion: (1)H-MRS is a valuable tool to recognize and track IRIS in PML and may prove useful in the clinical management of these patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain / metabolism*
  • Brain / pathology
  • Female
  • HIV Seropositivity / complications
  • HIV Seropositivity / metabolism
  • HIV Seropositivity / pathology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / complications
  • Immune Reconstitution Inflammatory Syndrome / metabolism*
  • Immune Reconstitution Inflammatory Syndrome / pathology
  • Leukoencephalopathy, Progressive Multifocal / complications
  • Leukoencephalopathy, Progressive Multifocal / metabolism*
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged