Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis.

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been studied. We apply tract-based spatial statistics (TBSS) to diffusion tensor imaging (DTI) in a cohort of multiple sclerosis patients to identify loci where reduced white matter tract fractional anisotropy (FA) predicts impaired performance in cognitive testing. Thirty-seven multiple sclerosis patients in remission (median age 43.5 years; Expanded Disability Status Scale range 1.5-6.5; 35 relapsing remitting, two secondary-progressive) underwent 3 T MRI including high-resolution DTI. Multiple sclerosis patients underwent formal testing of performance in multiple cognitive domains. Normalized cognitive scores were used for voxel-wise statistical analysis using TBSS, while treating age as a covariate of no interest. Permutation-based inference on cluster size (t > 2, P <0.05 corrected) was used to correct for multiple comparisons. Statistical mapping revealed differential patterns of FA reduction for tests of sustained attention, working memory and processing speed, visual working memory and verbal learning and recall. FA was not associated with frontal lobe function or visuospatial perception. Cognitively relevant tract localizations only partially overlapped with areas of high FLAIR lesion probability, confirming the contribution of normal-appearing white matter abnormality to cognitive dysfunction. Of note, tract localizations showing significant associations with cognitive impairment were found to interconnect cortical regions thought to be involved in processing in these cognitive domains, or involve possible compensatory processing pathways. This suggests that TBSS reveals functionally relevant tract injury underlying cognitive dysfunction in patients with multiple sclerosis.

Ehlers-Danlos syndrome and multiple sclerosis: a possible association.

Ehlers-Danlos syndrome (EDS) has various neurological manifestations. Here we present an association of EDS with multiple sclerosis (MS). Four MS patients from a total of 1892 followed up at our MS outpatient clinics had EDS. This frequency suggests 10-11 times increased prevalence of EDS in MS patients compared with the general population (P = 0.02). Suggested implications include a possible causal relationship on a connective tissue level with a higher susceptibility to MS in EDS. Diagnostic and management considerations are important in coexisting MS and EDS. Our patients had relatively florid lesions on brain MRIs and typical course and features of MS.