Quantitative evaluation of white matter hyperintensities in the central nervous system in infantile Pompe disease

Abstract

Pompe disease is a lysosomal storage disorder caused by deficiency of acid-alpha glucosidase. There are limited data on central nervous system (CNS) involvement in survivors of infantile Pompe disease (IPD). The objective of this cross-sectional study is to implement the Fazekas scale, a visual MRI rating scale, to quantify white matter hyperintensities (WMH) on T2-weighted-Fluid Attenuated Inversion Recovery (T2-FLAIR) brain MRI images and to determine the extent of white matter (WM) involvement in the CNS of patients with IPD. Twelve patients (aged 6.1-18.1 years, 7 males, 5 females) with IPD and on long-term enzyme replacement therapy were included in the study. We assessed WM involvement in ten anatomical areas of the brain- juxtacortical U-fibers, subcortical WM, periventricular WM in the centrum semiovale and in the frontal and parietal lobes at the level of corona radiata, corpus callosum, anterior and posterior limb of the internal capsule, external capsule, corticospinal tracts at cerebral peduncles, midbrain, and pons and the medullary decussation of corticospinal tracts. Based on the severity of WMH, each area was graded on the Fazekas scale from zero (absent) to 3 (severe) and a total score (range 0-30) was obtained. Ten patients (ages 6.6-18.1 years) had WMH on brain MRI (range of scores: 2-23) using the Fazekas scale. Five of the 10 patients (ages 6.7-18.1 years) had scores greater than 15 (range 16-23) indicating severe WMH and 2/10 patients (aged 6.1 years and 7.3 years) had no WM involvement with a score of zero. Our results provide a means to quantify WM involvement in the CNS of patients with IPD. Fazekas scale could serve as a biomarker for longitudinal follow up of WM abnormalities in patients with IPD and to better understand the extent of CNS involvement in IPD. [A portion of this study was funded by Genzyme Sanofi]