Investigation of magnetization transfer ratio-derived pial and subpial abnormalities in the multiple sclerosis spinal cord

Neuropathological studies in multiple sclerosis have suggested that meningeal inflammation in the brain may be linked to disease progression. Inflammation in the spinal cord meninges has been associated with axonal loss, a pathological substrate for disability. Quantitative magnetic resonance imaging facilitates the investigation of spinal cord microstructure by approximating histopathological changes. We acquired structural and quantitative imaging of the cervical spinal cord from which we calculated magnetization transfer ratio in the outer spinal cord-an area corresponding to the expected location of the pia mater and subpial region-and in spinal cord white and grey matter. We studied 26 healthy controls, 22 people with a clinically isolated syndrome, 29 with relapsing-remitting, 28 with secondary-progressive and 28 with primary-progressive multiple sclerosis. Magnetization transfer ratio values in the outermost region of the spinal cord were higher than the white matter in controls and patients: controls (51.35 +/- 1.29 versus 49.87 +/- 1.45, P < 0.01), clinically isolated syndrome (50.46 +/- 1.39 versus 49.13 +/- 1.19, P < 0.01), relapsing-remitting (48.86 +/- 2.89 versus 47.44 +/- 2.70, P < 0.01), secondary-progressive (46.33 +/- 2.84 versus 44.75 +/- 3.10, P < 0.01) and primary-progressive multiple sclerosis (46.99 +/- 3.78 versus 45.62 +/- 3.40, P < 0.01). In linear regression models controlling for cord area and age, higher outer spinal cord magnetization transfer ratio values were seen in controls than all patient groups: clinically isolated syndrome (coefficient = -0.32, P = 0.03), relapsing-remitting (coefficient = -0.48, P < 0.01), secondary-progressive (coefficient = -0.51, P < 0.01) and primary-progressive multiple sclerosis (coefficient = -0.38, P < 0.01). In a regression analysis correcting for age and cord area, magnetization transfer ratio values in the outer cord were lower in relapsing-remitting multiple sclerosis compared with clinically isolated syndrome (coefficient = -0.28, P = 0.02), and both primary and secondary-progressive compared to relapsing-remitting multiple sclerosis (coefficients = -0.29 and -0.24, respectively, P = 0.02 for both). In the clinically isolated syndrome and relapsing-remitting multiple sclerosis groups, outer cord magnetization transfer ratio was decreased in the absence of significant cord atrophy. In a multivariate regression analysis an independent association was seen between outer cord magnetization transfer ratio and cord atrophy (coefficient = 0.40, P < 0.01). Our in vivo imaging observations suggest that abnormalities in a region involving the pia mater and subpial cord occur early in the course of multiple sclerosis and are more marked in those with a progressive course.