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Multiple sclerosis (MS) is considered an inflammatory autoimmune disease of CNS white matter. Quantitative MRI measures of visible white matter lesion load, however, have shown that the burden of inflammatory disease is a relatively insensitive metric of physical disability, cognitive impairment, or long-term prognosis.
While MRI has proven to be an invaluable tool for MS diagnosis and response to anti-inflammatory based therapies, 1 the relatively poor correlation between measures of inflammation and clinical sequelae has prompted revitalized recognition of the neurodegenerative aspects of MS. Pathologic studies have emphasized the extensive network of axonal transactions and neuronal cell loss in lesional and normal-appearing white matter (NAWM), and have confirmed that a significant aspect of MS pathology also resides in cortical and subcortical gray matter.
Advances in MR imaging are ever-increasingly able to detect lesions in the cerebral mantle and in deep gray structures,2 gray matter loss can be detected even at the time of an initial demyelinating event,3 and apparently NAWM in patients with MS has been shown to have reduced structural integrity. …
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