Background Cognitive impairment affects 40%–68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. Methods Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. Results No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale–Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). Conclusion Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Purpose The role of gray matter in Multiple sclerosis (MS) is increasingly evident; however conventional magnetic resonance (MR) images demonstrate limitations in cortical lesion (CL) identification. Perfusion imaging appears sensitive to changes in tissue type and disease severity in MS. We sought to utilize bookend perfusion to quantify parameters in healthy controls (HC), normal appearing and lesional tissue at different RRMS stages. Methods Thirty-nine RRMS patients and 19 age-matched HC were prospectively recruited. MACFIMS battery was used to assess cognitive performance. Perfusion parameters including cerebral blood flow (CBF) and volume (CBV) and mean transit time (MTT) were compared for HC, normal appearing and lesional tissue for all study groups. Dispersion of perfusion measures for white matter lesion (WML) and CLs were assessed. Results Twenty of the 39 RRMS patients were cognitively impaired (RRMS-I). Significant differences were displayed between all RRMS subgroups and HC except for normal appearing gray matter (NAGM) CBV between HC and unimpaired RRMS patients (RRMS-NI) and for all normal appearing white matter (NAWM) perfusion parameters between HC and RRMS-NI. WML but not CL perfusion was significantly reduced in RRMS-I versus RRMS-NI. Perfusion reduction with disease progression was greater in NAGM and NAWM compared to CL and WML. Smaller dispersion was observed for CLs compared to WML for each perfusion parameter. Conclusion Quantitative GM and WM analysis demonstrates significant but disproportionate WML, CL, NAWM and NAGM changes present between healthy controls and RRMS patients with and without cognitive impairment necessitating absolute rather than relative lesion perfusion measurement.

Background and Purpose Cortical dysfunction, quantifiable by cerebral perfusion techniques, is prevalent in MS patients contributing to cognitive impairment. We sought to localize perfusion distribution differences in relapsing-remitting MS patients with and without cognitive impairment, and healthy controls. Materials and Methods 39 relapsing-remitting MS patients (20 cognitively impaired, 19 non-impaired) and 19 age and gender-matched healthy controls underwent a neurocognitive battery and MRI scanning. Voxel-based analysis compared regional deep and cortical GM perfusion and volume among the cohorts. Results Adjusting for localized volumetric differences in the right frontal, temporal and occipital lobes, progressive CBF and CBV deficits were present in the left middle frontal cortex for all cohorts and in the left superior frontal gyrus for cognitively impaired patients compared to unimpaired patients and controls. Compared to healthy controls, reduced CBF was present in the limbic regions of cognitively impaired patients and reduced CBV in the right middle frontal gyrus of cognitively impaired and temporal gyrus of non-impaired relapsing-remitting MS patients. Conclusions Consistent regional frontal cortical perfusion deficits are present in relapsing-remitting MS patients, with more widespread hypoperfusion in cognitively impaired patients, independent of structural differences indicating that cortical perfusion may be a useful biomarker of cortical dysfunction and cognitive impairment in MS.