Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study

Vacuolating megalencephalic leukoencephalopathy (VML) with subcortical cyst s is a neurodegenerative disorder clinically characterized by megalencephal y with onset in the first year of life, progressive ataxia, spasticity and relatively spared cognitive function. Conventional MRI findings consist of diffusely abnormal cerebral white matter with subcortical cysts. Recent sin gle-voxel proton MR spectroscopy studies have shown mild metabolic abnormal ities in the white matter. We report here a combined proton MR imaging and MR spectroscopic imaging (H-1-MRSI) study on new, unrelated patients with t his rare disorder. H-1-MRSI examinations, which can provide simultaneously metabolic information from many different brain regions, showed inhomogeneo us decreases in all normally detected metabolites with significant widespre ad decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine and concomitant small increases in lactate in the white matter of both hemi spheres. Metabolic abnormalities were milder in the frontal white matter an d more severe in the posterior white matter. The H-1-MRSI pattern of the gr ay matter was normal in both patients. In one patient, a subsequent H-1-MRS I examination (performed 3 years after the first) confirmed the presence of widespread decreases in the ratio of N-acetylaspartate to creatine+phospho creatine in the white matter. We conclude that severe metabolic abnormaliti es can be found in the white matter of VML patients. This suggests that, de spite the apparently mild clinical course, a severe neurodegenerative proce ss may occur in the white matter of these patients.