In order to test the hypothesis that in primary open angle glaucoma (POAG), an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC). Altered integrity (decreased fractional anisotropy or increased diffusivities) of white matter (WM) tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle). POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM) regions (frontoparietal cortex, hippocampi and cerebellar cortex), decreased functional connectivity (FC) in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition.

Our aim was to assess in primary open angle glaucoma (POAG), a major cause of irreversible blindness worldwide, whether diffuse brain changes recently shown in advanced stage can be detected since the early stage. We used multimodal magnetic resonance imaging (MRI) in 57 patients with the three POAG stages and in 29 age-matched normal controls (NC). Voxelwise statistics was performed with nonparametric permutation testing. Compared with NC, disrupted anatomical connectivity (AC) was found in the whole POAG group along the visual pathway and in nonvisual white matter tracts (P < 0.001). Moreover, POAG patients showed decreased functional connectivity (FC) in the visual (P = 0.004) and working memory (P < 0.001) networks whereas an increase occurred in the default mode (P = 0.002) and subcortical (P < 0.001) networks. Altered AC and FC were already present in early POAG (n = 14) in both visual and nonvisual systems (P ≤ 0.01). Only severe POAG (n = 30) showed gray matter atrophy and this mapped on visual cortex (P < 0.001) and hippocampus (P < 0.001). Increasing POAG stage was associated with worsening AC in both visual and nonvisual pathway (P < 0.001), progressive atrophy in the hippocampus and frontal cortex (P < 0.003). Most of the structural and functional alterations within and outside the visual system showed correlation (P < 0.001 to 0.02) with computerized visual field and retinal nerve fiber layer thickness. In conclusion, the complex pathogenesis of POAG includes widespread damage of AC and altered FC within and beyond the visual system since the early disease stage. The association of brain MRI changes with measures of visual severity emphasizes the clinical relevance of our findings. Hum Brain Mapp 37:4581-4596, 2016. © 2016 Wiley Periodicals, Inc.

In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This is particularly true for hypointense, destructive lesions.

Background:Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage.Methods:In the CLARITY study (ClinicalTrials.gov NCT00213135), the effect of 2 years’ treatment with cladribine tablets on annualized percentage brain volume change (PBVC/y) was evaluated in patients with relapsing MS (RMS).Results:Compared with placebo (–0.70% ± 0.79), PBVC/y was reduced in patients treated with cladribine tablets 3.5 mg/kg (–0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (–0.57% ± 0.72, p = 0.019). After adjusting for treatment group, PBVC/y showed a significant correlation with the cumulative probability of disability progression (HR = 0.67, 95% CI = 0.571, 0.787; p < 0.001), with patients with lower PBVC/y showing the highest probability of remaining free from disability progression at 2 years and vice versa.Conclusions:Cladribine tablets given annually for 2 years in short-duration courses in patients with RMS in the CLARITY study significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates.

Higher frequency of lesion occurrence in clinically eloquent WM tracts can characterize CIS subjects with different types of onset. The involvement of specific WM tracts, in particular those traversed by fibers involved in motor function and near the corpus callosum, seems to be associated with a higher risk of clinical conversion to MS in the short term.