Corpus callosum damage predicts disability progression and cognitive dysfunction in primary‐progressive MS after five years

Abstract

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability.

Early prognosis of multiple sclerosis

“…In addition, a recent study in RRMS patients, reported that, compared to healthy controls, there was a reduction in the connectivity of various regions in MS patients, particularly in the frontal and hippocampal regions, the motor strip, and occipital lobes (Li et al, 2013). Similarly, another recent study in PPMS patients found that a lower fractional anisotropy (FA) in the splenium of the corpus callosum predicted a greater progression of disability after 5 years (Bodini et al, 2013). Also, in this study a lower FA along the entire corpus callosum predicted worse verbal memory, attention, and information processing speed.…”

Early White Matter Changes in Childhood Multiple Sclerosis: A Diffusion Tensor Imaging Study

“…5 Recently, DTI studies in adult patients with MS demonstrated axonal and myelin injury occurring much earlier in the course of the disease than previously assumed. 6,7 Physiologic myelination is known to expand well into early adulthood in conjunction with cognitive, behavioral, emotional, and motor development. [8][9][10] Any pathology interfering with this process of myelination is likely to affect white matter integrity as has been shown in hypoxic-ischemic encephalopathy, former premature in-fants, and normal-pressure hydrocephalus.…”

Serum insulin‐like growth factor‐I levels are associated with improved white matter recovery after traumatic brain injury

“…Infarction of the SPCC and retrosplenial region can lead to verbal memory problems 52, 53, 54. In patients with multiple sclerosis, verbal learning performance was inversely associated with lesions in the SPCC, lower FA in SPCC predicted a greater progression of disability, and lower FA in the corpus callosum predicted worse verbal memory, longitudinally over 5 years 55, 56…”