Relevance of brain lesion location to cognition in relapsing multiple sclerosis

Abstract

Objective: To assess the relationship between cognition and brain white matter (WM) lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS).

Methods: MRI-based T2 lesion probability map (LPM) was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP) and cognitively impaired (CI).

Results: Out of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001), T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major) than in CP patients (37% in the posterior corona radiata). The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected). Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions.

Conclusions: Overall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple) disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS.

Figure 1. LPM in cognitively impaired and cognitively preserved patients with MS.

T2-weighted lesion probability maps in cognitively impaired (upper panel, n = 36) and cognitively preserved (lower panel, n = 106) patients with MS. The color overlay created on top of the Montreal Neurological Institute standard brain shows the probability of each voxel containing a lesion in each patient group. The color bar denotes the probability range. The maximum local probability for lesions was higher in cognitively impaired patients (61% peak probability in the forceps major) than in cognitively preserved patients (37% peak probability in the posterior corona radiata). Images are shown in radiological convention.

Figure 2. Clusters of high lesion frequency in cognitively impaired MS patients.

Yellow shows the clusters of voxels where lesions, after controlling for age and sex, were more frequent (p<0.05, corrected) in cognitively impaired (n = 36) than in cognitively preserved (n = 106) patients with MS (forceps major in A and splenium of the corpus callosum in B). Red shows the clusters of voxels that also survived correction for T2-LV (forceps major, in A). Green represents the WM fiber tract (forceps major, in A) obtained from the FSL probabilistic tractography atlas. Background image is the MNI152 standard space image. Images are shown in radiological convention.