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). Desi gn: CSF polymerase chain reaction (PCR) detection for JC viral (JCV) D NA; MRI and localized H-1 MRS in the PML lesions, normal-appearing con tralateral brain regions (CONTRA), and in matched brain regions of nor mal subjects. Setting: University-affiliate medical center. Patients o r participants: 20 AIDS patients with clinical diagnosis of PML, 16 ha d tissue and/or CSF evidence of JCV infection; 20 age-matched normal s ubjects. Main outcome measures: Metabolites from H-1 MRS: N-acetyl asp artate (NA), creatine (CR), choline-containing compounds (CHO), myoino sitol (MI), glutamine/glutamate (GLX), lactate, and lipids. Results: C SF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic d emyelinating lesions; commonest locations were frontal lobe and cerebe llum. H-1 MRS in the lesions showed decreased NA (-35%; p < 0.0001) an d CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional i ncreased 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 longitud inally (4-18 months), showed progressive spectroscopic changes; two pa tients with longest survival showed the highest MI. Conclusions: These MRS findings are consistent with neuropathologic observations of neur onal loss, cell membrane and myelin breakdown, and increased glial act ivity in PML lesions. The CONTRA abnormalities may be due to remote ef fects of PML or direct HIV-1 infection. H-1 MRS may be useful for char acterization and follow-up evaluation of PML lesions.