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To apply voxelwise analysis of diffusion-tensor (DT) magnetic resonance (MR) tractography and T2-weighted MR lesion measurements to characterize intrinsic damage to the brain white matter (WM) tracts and the relation of this damage to the presence and location of focal lesions among the main clinical phenotypes of multiple sclerosis (MS).The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Brain dual-echo and DT MR images were obtained in 172 patients with MS (22 [13%] with clinically isolated syndromes [CIS] suggestive of MS, 51 [30%] with relapsing-remitting [RR] MS, 44 [26%] with secondary progressive MS, 20 [12%] with benign MS, 35 [20%] with primary progressive MS) and 46 healthy control subjects. Probability maps of the major brain WM tracts were produced. Between-group comparisons were assessed by using analysis of covariance.Compared with the healthy control subjects, the patients with CIS had significantly increased (P.001) mean diffusivity, axial diffusivity, and radial diffusivity in the majority of WM tracts. The primary progressive MS group showed diffuse increases in mean, axial, and radial diffusivity, with fractional anisotropy (FA) damage involving the majority of WM tracts. No relevant difference in diffusivity measures was found between the CIS and RR-MS groups. Compared with the benign MS group, the RR-MS group had reduced FA values in all WM tracts and decreased axial diffusivity in the majority of tracts. The secondary progressive MS group had pronounced damage to the majority of tracts and, compared with the benign MS group, pronounced FA alteration of the tracts relevant for motor impairment.Voxelwise assessment of DT MR index abnormalities is a rewarding strategy for understanding the heterogeneity of clinical MS phenotypes.

To (a) apply an active surface method to map the regional distribution of cord atrophy across levels and sectors in a relatively large group of patients with multiple sclerosis (MS), (b) compare the anatomic location of cord atrophy between patients with relapsing-remitting (RR) MS and those with secondary progressive (SP) MS, and (c) assess correlations between atrophy and disability.This study was approved by the local ethical committee, and written informed consent was obtained from each participant. High-spatial-resolution magnetic resonance (MR) images of the cervical cord were acquired from 45 patients with RR MS, 26 patients with SP MS, and 67 age-matched healthy control subjects. The active surface method segmented the cord surface from C1 to C7 and created output images reformatted in planes perpendicular to the estimated cord center line. These unfolded cervical cord images were coregistered into a common standard space, and smoothed cord binary masks were used as input images for spatial statistics. Voxel-wise between-group comparisons and the correlation between regional cord atrophy versus clinical and conventional MR imaging variables were assessed with software.Compared with control subjects, patients with RR MS showed localized clusters of atrophy in the posterior cord. Conversely, patients with SP MS showed a widespread pattern of cord atrophy, predominantly in the posterior and lateral cord columns. In patients with MS, cervical cord atrophy was correlated with clinical disability, disease duration, and, to a lesser extent, conventional MR imaging measures of brain injury. No correlation was found between cord atrophy and the presence of focal cord lesions.Voxel-wise assessment of the regional distribution of damage in the cervical cord is feasible and might improve our understanding of the mechanisms related to the development of irreversible clinical disability in MS.

To elucidate the factors associated with the preservation of function in relapsing-remitting (RR) multiple sclerosis (MS) by investigating effective connectivity changes of the sensorimotor network in pediatric RR MS patients in comparison with adult patients with either clinically isolated syndromes (CIS) suggestive of MS or RR MS and in adult healthy control subjects by using functional magnetic resonance imaging (MR) imaging and a dynamic causal model approach and to assess the correlation between effective connectivity changes and structural damage to the corpus callosum and the corticospinal tracts (CSTs).The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Dual-echo, diffusion-tensor, and functional MR images were acquired from 17 pediatric RR MS patients, 16 adult patients with CIS, 14 adult RR MS patients, and 10 age-matched pediatric healthy control subjects during a simple motor task. Whole-brain, corpus callosum, and CST T2 lesion loads, as well as corpus callosum and CST diffusivity measures were determined. Functional MR imaging data were analyzed by using statistical parametric mapping.Coefficients of effective connectivity of the sensorimotor network were similar in control subjects and pediatric MS patients. In adult patients with CIS and even more evidently in those with RR MS, an increase of intra- and interhemispheric strengths of coefficients of effective connectivity was found (P = .05-.008). The increases in such coefficients were correlated with corpus callosum and CST damage, in terms of T2 lesion load and diffusion-tensor MR imaging quantities (r = -0.34 to 0.40).The preservation of brain adaptive properties might explain the favorable medium-term clinical outcome of pediatric MS patients. The progressive recruitment of cortical networks over time in patients with the adult RR forms of the disease might result in a loss of their plastic reservoir, thus possibly contributing to subsequent disease evolution.

To assess the extent of tactile-associated cervical spinal cord activation in patients with primary progressive (PP) multiple sclerosis (MS) and to investigate the relationship between spinal cord functional activation and the severity of cervical spinal cord and brain structural damage by using magnetic resonance (MR) images.The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Cervical spinal cord functional MR images were obtained in 23 patients with PP MS and 18 healthy control subjects during tactile stimulation of the right hand. Conventional and diffusion-tensor MR images of the brain and spinal cord were also acquired. Mean stimulus-related signal intensity change for all activated voxels and the distribution of functional MR activity at each spinal cord level were obtained. Univariate analysis was used to compare MR findings between groups. Between-group differences in topographic distribution of functional MR activity were evaluated by using random-effects logistic regression models.Patients with PP MS had higher mean spinal cord activity on functional MR images than did controls. A higher occurrence of functional MR activation in the right versus left side of the spinal cord and in the posterior versus anterior section of the spinal cord was found in both control subjects and patients with PP MS. Patients who were mildly disabled had a pattern of functional MR activity distribution similar to that of controls, but patients who were more severely disabled did not show differential activation between the right and left sides of the spinal cord. A higher occurrence of functional MR activity in the anterior section of the right side of the spinal cord at the level of the C6-7 intervertebral disk (P = .05) and the left side of the spinal cord at the level of the C7-T1 intervertebral disk (P = .03) was found in patients with PP MS than in control subjects. Mean spinal cord functional MR imaging signal intensity change correlated with spinal cord fractional anisotropy.Patients with PP MS showed tactile-associated cervical spinal cord overactivation. Spinal cord functional changes, possibly owing to injured interneurons, likely contribute to the complex process that leads to the accumulation of irreversible disability in patients with PP MS.