Intracranial volume (ICV) is often used as normalization factor in volumetrics and considered to be stable in young adults. We noticed thick skulls on MRI scans of leukodystrophy patients, suggesting potentially changing skull morphology. In this study we aimed to quantify skull thickness and ICV in metachromatic leukodystrophy (MLD) patients and people with multiple sclerosis (pwMS). We retrospectively analyzed single-center cross-sectional and longitudinal MRI scans. Skull thickness and ICV were determined using automated segmentation techniques. Participants included MLD (n=32, 11 male, scans=136, median age first scan=14.1 [IQR 7.9-25.7] years), MS (n=232, 78 male, median age first scan=47.3 [IQR 39.6-55.4] years, scans=431), and controls (n=139, 67 male, median age first scan=30.7 [IQR 10.7-48.9] years, scans=283). Both ICV and skull thickness showed natural growth in young controls. In young MLD participants, ICV decreased (-18.8±22.4mL/year, p<0.001). Above age 20, ICV and skull thickness remained stable in controls. In comparison to controls, we observed ICV loss in MLD participants (-4.01±8.29mL/year, p<0.001) and in pwMS (-2.99±2.69mL/year, p<0.001), as well as skull thickening (MLD: 0.16±0.14mm/year, p<0.001, pwMS: 0.04±0.09mm/year, p=0.009). In adult patient groups, negative correlations were found between ICV and skull thickness (MLD: -19.24mL/mm, p<0.001, pwMS: -11.56mL/mm, p<0.001), but not in controls (p=0.11). Despite limitations due to scanner variations, segmentation reliability and absence of validation against ground truth, these findings demonstrate a reduction in ICV in pathologies, already in young adulthood. Although the observed changes are small, they may lead to underestimations of atrophy when using ICV as a normalization factor.

Substantial brain volume loss is well-documented during acute anorexia nervosa (AN); however, longitudinal outcomes are unclear. Our comprehensive meta-analysis investigated global and regional structural brain alterations in adult and adolescent individuals with AN by extracting reported brain volume scores and neuroimaging coordinates from the literature. Results showed significant global brain volume reductions in gray matter (GM), white matter (WM), and increases in cerebrospinal fluid (CSF) in acute AN (N = 1130 patients; N = 40 papers), gradually improving upon weight rehabilitation. However, even after 1.5years of recovery, significantly lower global GM volume compared to healthy controls was found (N = 232 patients; N = 12 papers). Regarding potential regional changes, our search identified 35 eligible papers with neuroimaging coordinates for 412 foci as input for our anatomical likelihood estimation (ALE) analyses. The results revealed widespread reductions of GM volume and cortical thickness, but notably also identified consistently affected brain regions including the cingulate gyrus, precentral gyrus, and precuneus. Spatial colocalization analyses using the Neurosynth data base indicated brain areas associated with eating, food, threat, and reinforcement to be relatively preserved. The findings of our meta-analysis contribute to a better understanding of the underlying pathophysiology of AN, the time course and residuals of brain structural alterations during recovery and clinical implications potentially relevant for more-targeted treatment options.