Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS

Cognitive dysfunction is increasingly recognized in multiple sclerosis MS, and the role of cortical gray matter lesions as possible causative factors for cognitive dysfunction, and possibly as a main disease initiating factor has recently been proposed, partially by our teams observations in MS neuropathology studies. Our main hypothesis is that cortical lesions determine the formation of white matter lesions along tracts directly originating from them, and that the extent of cortical dysfunction will be directly proportional to the location and overall load of cortical lesions. In order to detect cortical lesions more efficiently, our team has developed a customized pulse sequence we termed GM-DIR, with increased sensitivity for cortical lesion detection. Utilizing standard DIR, our custom-made GM-DIR and 60-direction DTI studies, we have been able to determine in an early pilot study that connections between lesions do exist. During the study period, we have processed data on 25 early MS patients less than 5 years of disease activity and compared that with 24 controls, and concluded that white matter lesions do in deed appear to be connected with cortical lesions. Our first abstract related to these novel observations has been submitted to the upcoming ACTRIMSECTRIMS meeting. Furthermore, we started collecting and analyzing neuropsychiatric outcome measures using the MACFIMS battery. Our first results are presented herein this report. Correlative analysis of MRI and MACFIMS data has been initiated and is ongoing in our laboratory. Enrollment has been steady we dont anticipate any problems meeting our target during the study duration. We believe that our observations will meaningfully contribute not only to our understanding of cognitive dysfunction in early MS, but also to key disease initiating events, which may pave the way to the development of more specific disease modifying therapies.