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

Recently a hypothesis has arisen that the pathological processes of meningeal inflammation and cortical demyelination may be interconnected and in turn play a role in the development of a progressive disease course. It has been reported that in relapsing-remitting multiple sclerosis, meningeal inflammation may be present. To date the effect of multiple sclerosis on the spinal cord meninges has not been investigated in vivo. With the implementation of higher resolution structural and magnetization transfer ratio (MTR) acquisitions in the spinal cord, the potential to investigate the effects of multiple sclerosis on the outer region of the spinal cord (that would be expected to include the pia mater of the meninges) could provide further insights into the pathophysiology of multiple sclerosis.

The aims of this study were:

(1) To characterize the outermost region of the spinal cord, which is expected to include contributions from the pia mater and subpial region of the spinal cord, using high inplane resolution, magnetization transfer-weighted images to measure the MTR in healthy control subjects and in patients with multiple sclerosis or a clinically isolated syndrome.

(2) To compare the outer spinal cord MTR measures of people with a clinically isolated syndrome or multiple sclerosis with those of healthy controls.

(3) To compare outer spinal cord MTR findings seen in different clinical subgroups: clinically isolated syndrome, relapsing-remitting, primary- and secondary-progressive multiple sclerosis, and explore the relationship of outer cord MTR with measures of both spinal cord atrophy and physical disability.

The authors recruited 26 healthy controls, 22 patients with clinically isolated syndrome (CIS), 29 patients with relapsing-remitting multiple sclerosis (RRMS), 28 patients with secondary-progressive multiple sclerosis (SPMS), and 28 patients with primary-progressive multiple sclerosis (PPMS). All patients had Expanded Disability Status Scale (EDSS), multiple sclerosis functional composite (MSFC) and American Spinal Injury Association (ASIA). Assessment of physical function was performed immediately before the MRI. None of the subjects had experienced a relapse or received a course of corticosteroids within the month before imaging.

Subjects were scanned at 3 T. There were no significant differences in the cord area of healthy controls with either the clinically isolated syndrome or relapsing-remitting multiple sclerosis groups. The secondary-progressive, and primary-progressive multiple sclerosis groups both had lower cord areas than healthy controls. No significant difference was seen in brain parenchymal fraction in the clinically isolated syndrome group compared to controls, but  significant differences in brain parenchymal fraction were seen between controls and all subgroups of multiple sclerosis, with smaller brain parenchymal fractions in the multiple sclerosis subgroups. In each subject group, the MTR of the outer spinal cord was higher than the MTR of spinal cord white matter and the spinal cord white matter had higher MTR values than spinal cord grey matter. The outer spinal cord MTR and the spinal cord white matter values were higher in controls than all patient groups. The outer spinal cord MTR was lower in relapsing-remitting multiple sclerosis than clinically isolated syndrome. Both secondary-progressive and primary-progressive multiple sclerosis had lower outer spinal cord MTR values compared to relapsing-remitting multiple sclerosis. No significant difference was found between secondary- and primary-progressive multiple sclerosis. In the clinically isolated syndrome and relapsing-remitting multiple sclerosis groups, outer cord MTR was decreased in the absence of significant cord atrophy.

Authors: Kearney H, Yiannakas MC
Source: Brain. 2014 Jun 24. pii: awu171. [Epub ahead of print]
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