Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy

Objective: To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (H-1 MRS). Design: CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized H-1 MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects. Setting: University-affiliate medical center. Patients or participants: 20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects. Main outcome measures: Metabolites from H-1 MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids. Results: CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. H-1 MRS in the lesions showed decreased NA (-35%; p < 0.0001) and CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+15%), MI (+13%), and lower GLX (-9%; p = 0.02), Six patients, studied longitudinally (4-18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI. Conclusions: These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. H-1 MRS may be useful for characterization and follow-up evaluation of PML lesions.