Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis

Objectives-To assess (a) whether the changes in the normal appearing brain tissue (NABT), as revealed by magnetisation transfer (MT) histogram analysi s, correlates with cognitive dysfunction in patients with multiple sclerosi s and (b) the relative contribution of these changes by comparison with tha t of multiple sclerosis lesions visible on conventional MRI. Methods-Dual echo, T1 weighted and MT scans of the brain were obtained in 1 2 patients with multiple sclerosis with cognitive impairment and in seven w ithout cognitive impairment. Lesion loads were assessed from T2 and T1 weig hted scans. To create MT histograms of the NABT, multiple sclerosis lesion outlines from dual echo scans were superimposed automatically and nulled ou t from the coregistered and scalp stripped MTR maps. Average lesion MT rati o (MTR) and brain size were also measured. Results-T2 and T1 lesion loads were significantly higher and the average le sion MTR and brain size were significantly lower in the group of cognitivel y impaired patients. Patients with cognitive deficits also had significantl y lower average MTR and peak location of the NABT histogram. Logistic regre ssion analysis showed that 68% of the total variance was explained by avera ge NABT-MTR alone. A multivariable regression model showed that NABT-MTR wa s the only factor that significantly correlated with cognitive impairment i n these patients (p=0.001). Conclusions-The extent of abnormalities which go undetected when using conv entional MRI is relevant in determining cognitive impairment in multiple sc lerosis.