Regional diffusion tensor imaging differences in multiple sclerosis patients with little focal damage and the relation to ncurocognition

Background: Focal damage, reflected as T2 hyperintense and T1 hypointense lesions, cannot fully account for cognitive impairment in multiple sclerosis (MS), which is a frequent symptom occurring early in the disease. The investigation and localization of damage in the total white matter (WM) could provide more knowledge on the roots of cognitive deficits in MS. Diffusion tensor imaging (DTI) measures have shown to be sensitive for WM damage, not only inside lesions but also for damage in the so-called normal-appearing white matter (NAWM). Objective: To localize WM damage in MS patients using a new hypothesis-free, post-processing technique, tract-based spatial statistics (TBSS), and relate it to neurocognitive deficits. Methods: DTI data was investigated in 30 MS patients (median Expanded Disability Status Scale (EDSS) 3.0, range 0-6.5, mean disease duration 3.6 years, SD 3.5), which were selected to have little focal WM damage (mean 5.6 mL, SD 7.7) on standard T2-weighted images, and 31 age-matched healthy controls. The letter digit substitution test (LDST) was used to assess processing speed, Stroop test to evaluate inhibition and attention, and the location learning test (LLT) for visu-ospatial memory. Cognitive tests were controlled for fatigue, depression and premorbid IQ where appropriate. Results: Patients were found to have a lower fractional anlsotropy (FA) compared with controls in the fornices, left corona radiata, inferior longitudinal fascicles of both hemispheres, both optic radiations and parts of the forceps major and the genu of the corpus callosum. Patients showed just-normal inhibition and attention and impaired processing speed compared with controls. In patients, processing speed correlated with abnormal FA in the corpus callosum (Pearson's r = 0.26; P = 0.05). Despite the damage in the fornices, known to be involved in memory function, patients exhibited normal visuospatial memory, which may indicate (partial) reorganization of memory function. Conclusions: We found 12 areas of FA decrease using a hypothesis-free method of analyzing DTI images of MS patients with little focal WM damage. Impaired processing speed was associated with reduced FA in the corpus callosum.