Motor callosal disconnection in early relapsing‐remitting multiple sclerosis

Abstract

In relapsing-remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0-2.0) to an age-matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA-CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short-interval interhemispheric inhibition (S-IHI), an established measure of CMF effective connectivity. FA-CC and S-IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA-CC) and function (S-IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine-hole-peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S-IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion.

Callosal anatomical and effective connectivity between primary motor cortices predicts visually cued bimanual temporal coordination performance

“…Concerning the RRMS group, 11 patients had participated and their S-IHI and FA-hCMF data had been reported already in our previous study (Wahl et al 2011). Written informed consent was obtained from all subjects prior to participation.…”

“…FA and S-IHI data of the healthy subjects have been reported earlier (Wahl et al 2007(Wahl et al , 2011. Among the patients, 7 were diagnosed with CIS, and 15 had RRMS, according to the revised McDonald criteria (Polman et al 2011).…”

“…We chose multiple sclerosis as a model disease of callosal damage, given the findings of frequent and early callosal affection in RRMS (Evangelou et al 2000a, b;Pelletier et al 2001;Zito et al 2014). We have shown previously, that impaired S-IHI along with reduced FA-hCMF is already present in the earliest stages of RRMS (Wahl et al 2011), but the behavioral implications of these findings have not been tested. We tested here the hypothesis that relative to healthy controls MS patients show reduced between-hand offsets due to reduced anatomical and effective interhemispheric connectivity.…”

“…MRI was acquired in a 3-Tesla Magnetom Trio (Siemens Medical Solutions, Erlangen, Germany) as described earlier (Wahl et al 2007(Wahl et al , 2011. Structural T1-weighted images were acquired with a magnetization-prepared rapidacquisition gradient echo (MPRAGE) sequence [repetition time (TR) 2250 ms, echo time (TE) 26 ms, inversion time 900 ms, flip angle 9°, 192 sagittal slices, field of view 256 9 256 mm, voxel size 1 9 1 9 1 mm].…”

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

“…The ipsilateral CSP probably reflects transcallosal inhibition as it is absent or abnormal in patients with corpus callosum lesions [56,57]. Separately, noncallosal neural pathways may also generate ipsilateral CSPs [58].…”