Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles.

Ventricular enlargement (VE) is commonly observed in aging and fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. VE may generate a mechanical force causing structural deformation. In this longitudinal study, we examined the relationships between VE and structural changes in the corpus callosum (CC) and putamen. MRI scans (2-7/person over 0.2-7.5 years) were acquired from 22 healthy controls, 26 unaffected premutation carriers (PFX-), and 39 carriers affected with FXTAS (PFX+). Compared with controls, PFX- demonstrated enlarged fourth ventricles, whereas PFX+ displayed enlargement in both third and fourth ventricles, CC thinning, putamen atrophy/deformation (thinning and increased distance), and accelerated expansions in lateral ventricles. Common for all groups, baseline VE predicted accelerated CC thinning and putamen atrophy/deformation and conversely, baseline CC and putamen atrophy/deformation and enlarged third and fourth ventricles predicted accelerated lateral ventricular expansion. The results suggest a progressive VE within the 4 ventricles as FXTAS develops and a deleterious cycle between VE and brain deformation that may commonly occur during aging and FXTAS progression but become accelerated in FXTAS.