Eldar Eftekhari1, Seyed-Parsa Hojjat1,2, Rita Vitorino1, Timothy J Carroll3, Charles Grady Cantrell3, Liesly Lee2,4, Matthew W Taylor2, Sarah A Morrow5, Haddas Benhabib6, Richard I Aviv7,8, Andrea Kassner2,9. 1. Sunnybrook Health Sciences Centre, Medical Imaging, 2075 Bayview Ave., Room AG-31, Toronto, ON, M4N 3M5, Canada. 2. University of Toronto, 27 Kings College Circle, Toronto, ON, M5S 1A1, Canada. 3. Department of Radiology, University of Chicago, Chicago, IL, 60637, USA. 4. Department of Neurology, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room AG-31, Toronto, ON, M4N 3M5, Canada. 5. University of Western Ontario, 1151 Richmond St, London, ON, N6A 3K7, Canada. 6. Queen's University, 99 University Ave, Kingston, ON, K7L 3N6, Canada. 7. Sunnybrook Health Sciences Centre, Medical Imaging, 2075 Bayview Ave., Room AG-31, Toronto, ON, M4N 3M5, Canada. richard.aviv@sunnybrook.ca. 8. University of Toronto, 27 Kings College Circle, Toronto, ON, M5S 1A1, Canada. richard.aviv@sunnybrook.ca. 9. The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada.
Abstract
PURPOSE: Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS). METHODS: Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression. RESULTS: rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impaired patients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068-2.956; p = 0.026), NAGM (OR 2.138; 1.100-4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120-4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups. CONCLUSION: rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.
PURPOSE: Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS). METHODS: Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression. RESULTS: rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impairedpatients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068-2.956; p = 0.026), NAGM (OR 2.138; 1.100-4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120-4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups. CONCLUSION: rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.
Entities:
Keywords:
Cognitive impairment; Normal appearing white matter; Relapsing-remitting multiple sclerosis; Relative recirculation; Symbol digit modalities test
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