Robust Perfusion Deficits in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

Abstract

BACKGROUND AND PURPOSE:Cognitive impairment is a common, disabling symptom of MS. We investigated the impact of cerebral perfusion and brain and lesion volumetry on cognitive performance in 45 patients with SPMS by using MR imaging.

Cerebral Hypoperfusion: A New Pathophysiologic Concept in Multiple Sclerosis?

“…From a clinical point of view, reduced white and gray matter CBF in patients with MS has thus far been associated with cognitive manifestations, [67][68][69][70] which are remarkably similar to those described in ischemic leukoencephalopathy. 71 One study found that reduced deep gray matter perfusion in MS negatively correlated with fatigue, 72 which is a very common but poorly understood cause of impaired activities of daily living in patients with MS.…”

Extensive White Matter Dysfunction in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

“…17 The skeletonized FA maps were compared between patients with and without cognitive impairment using FSL's Randomise tool, which conducts permutation-based nonparametric testing while correcting for multiple comparisons across space. 26 To be conservative and assumption free, voxelwise group analysis was conducted with 5000 permutations and threshold-free cluster enhancement (p corr Ͻ .05).…”

“…17 Briefly, regions of GM and WM were delineated algorithmically, and T2-weighted hyperintensities and T1-weighted hypointensities were hand traced using Medical Image Processing, Analysis, and Visualization version 4.0 (National Institutes of Health, Bethesda, Maryland). The FMRIB Software Library (FSL, http:// www.fmrib.ox.ac.uk/fsl) processed the DTI scans.…”

“…11,14 Given the recent emphasis on the role of GM pathology both in the etiology of MS and related cognitive dysfunction, FA was considered in the context of GM volume using multivariate regression. [15][16][17] Normal-appearing white matter has also been investigated using magnetization transfer ratio. 18 Tract-based spatial statistics (TBSS) is being increasingly utilized in DTI studies of MS and cognition.…”

Spatial Correlation of Pathology and Perfusion Changes within the Cortex and White Matter in Multiple Sclerosis

“…This assertion is supported by various pathological and imaging studies 8, 22–24 which have shown that cGM lesions may develop prior to the appearance of WM plaques 22 , arise independently of, and are poorly correlated with T2h-l formation 23,24 . A number of pathological and imaging papers have increasingly implicated an independent etiology for cGM lesion formation attributed either to the direct presence of meningeal-derived neurotoxic substances or secondary microglial activation mediated through meningeal/supbial inflammation and manifest as a gradient of demyelination centered upon the subpial cortex 24, 27 .…”