Inflammatory CNS demyelination: Histopathologic correlation with in vivo quantitative proton MR spectroscopy

BACKGROUND AND PURPOSE: The mechanisms behind the demyelination that is cha racteristic of multiple sclerosis (MS) are still poorly understood, The pur pose of this study was to compare immunopathologic findings in demyelinatin g lesions of three patients with in vivo assessments obtained by quantitati ve proton MR spectroscopy (MRS), METHODS: Between four and seven stereotactic needle brain biopsies were per formed in three young adults with diagnostically equivocal findings for MS, Axonal density, gliosis, blood brain-barrier breakdown, and demyelinating activity of lesions were determined, Combined MR/MRS studies were performed (T1-weighted fast low-angle shot and single-voxel stimulated-echo acquisit ion mode), and absolute metabolite levels were obtained with a user-indepen dent fitting routine, Metabolite control values were obtained from a group of age-matched healthy volunteers (n=40, age range, 20-25 years old). Alter ations of metabolite levels of control subjects were considered significant when exceeding two standard deviations. RESULTS: There were parallel decreases of N-acetylaspartate (21%-82%) and r eductions of axonal density (44%-74%) in demyelinating plaques, Concomitant increases of choline (75%-152%) and myo-inositol (84%-160%) corresponded t o glial proliferation. Elevated lactate was associated with inflammation. CONCLUSION: The present data suggest that in vivo MRS indicates key patholo gic features of demyelinating lesions.