Mri natural history of the leukodystrophy vanishing white matter

Background: In vanishing white matter (VWM), a form of leukodystrophy, earlier onset is associated with faster clinical progression. MRI typically shows rarefaction and cystic destruction of the cerebral white matter. Information on the evolution of VWM according to age at onset is lacking. Purpose: To determine whether nature and progression of cerebral white matter abnormalities in VWM differ according to age at onset. Materials and Methods: Patients with genetically confirmed VWM were stratified into six groups according to age at onset: Younger than 1 year, 1 year to younger than 2 years, 2 years to younger than 4 years, 4 years to younger than 8 years, 8 years to younger than 18 years, and 18 years or older. With institutional review board approval, all available MRI scans obtained between 1985 and 2019 were retrospectively analyzed with three methods: (a) ratio of the width of the lateral ventricles over the skull (ventricle-to-skull ratio [VSR]) was measured to estimate brain atrophy; (b) cerebral white matter was visually scored as percentage normal, hyperintense, rarefied, or cystic on fluid-attenuated inversion recovery (FLAIR) images and converted into a white matter decay score; and (c) the intracranial volume was segmented into normal-appearing white and gray matter, abnormal but structurally present (FLAIRhyperintense) and rarefied or cystic (FLAIR-hypointense) white matter, and ventricular and extracerebral cerebrospinal fluid (CSF). Multilevel regression analyses with patient as a clustering variable were performed to account for the nested data structure. Results: A total of 461 examinations in 270 patients (median age, 7 years [interquartile range, 3-18 years]; 144 female patients) were evaluated; 112 patients had undergone serial imaging. Patients with later onset had higher VSR [F(5) = 8.42; P <.001] and CSF volume [F(5) = 21.7; P <.001] and lower white matter decay score [F(5) = 4.68; P <001] and rarefied or cystic white matter volume [F(5) = 13.3; P <001]. Rate of progression of white matter decay scores [b = -1.6, t(109) = -3.9; P , .001] and VSRs [b = -0.05, t (109) = -3.7; P<.001] were lower with later onset. Conclusion: A radiologic spectrum based on age at onset exists in vanishing white matter. The earlier the onset, the faster and more cystic the white matter decay, whereas with later onset, white matter atrophy and gliosis predominate