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Metabolic profile of PML lesions in patients with and without IRIS: an observational study
Sarah Gheuens1, Long Ngo, Xiaoen Wang
1Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA., USA.
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.
Insights
Proton magnetic resonance spectroscopy ((1)H-MRS) can identify immune reconstitution inflammatory syndrome (IRIS) in progressive multifocal leukoencephalopathy (PML) lesions. This technique aids in recognizing and tracking IRIS for better patient management.
Area of Science:
- Neuroimaging
- Neurology
- Biochemistry
Background:
- Progressive multifocal leukoencephalopathy (PML) is a serious opportunistic infection.
- Immune reconstitution inflammatory syndrome (IRIS) can complicate PML treatment.
- Characterizing PML lesions and their metabolic changes is crucial for understanding IRIS.
Purpose of the Study:
- To characterize progressive multifocal leukoencephalopathy (PML) lesions using contrast-enhanced MRI.
- To evaluate the metabolism of PML lesions in the context of immune reconstitution inflammatory syndrome (IRIS) using proton magnetic resonance spectroscopy ((1)H-MRS).
Main Methods:
- 42 patients with PML underwent MRI and (1)H-MRS at baseline and follow-up.
- (1)H-MRS measured metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr, Lip/Cr).
- Metabolite ratios were correlated with contrast enhancement (CE) and IRIS presence.
Main Results:
- PML-IRIS lesions showed higher Cho/Cr, mI/Cr, and lipid/Cr ratios, and lower NAA/Cr compared to non-IRIS PML.
- Elevated Cho/Cr correlated with CE; elevated lipid/Cr was independent of CE.
- A combination of elevated Lip1/Cr and CE predicted IRIS with 79% probability.
Conclusions:
- (1)H-MRS is a valuable tool for recognizing and monitoring IRIS in PML patients.
- Metabolic profiles from (1)H-MRS can differentiate PML-IRIS from non-IRIS PML.
- This technique may assist in the clinical management of PML-IRIS.

