Metabolic profile of PML lesions in patients with and without IRIS

Objective: To characterize progressive multifocal leukoencephalopathy (PML) lesions by contrast-enhanced MRI and evaluate their metabolism using proton magnetic resonance spectroscopy ((HMRS)-H-1) 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 H-1-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 (ml), 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), ml/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 H-1-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 ml/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: H-1-MRS is a valuable tool to recognize and track IRIS in PML and may prove useful in the clinical management of these patients. Neurology (R) 2012;79:1041-1048