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Background and Purpose: Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal‐appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin. Mean MWF reflects average myelin content, while MWF standard deviation (SD) describes variation in myelin within regions. The myelin heterogeneity index (MHI = SD/mean MWF) is a composite metric of myelin content and myelin variability. We investigated how mean MWF, SD, and MHI compare in differentiating MS from controls and their associations with physical and cognitive disability. Methods: Myelin water imaging data were acquired from 91 MS participants and 31 healthy controls (HC). Segmented whole‐brain NAWM and corpus callosum (CC) NAWM, mean MWF, SD, and MHI were compared between groups. Associations of mean MWF, SD, and MHI with Expanded Disability Status Scale and Symbol Digit Modalities Test were assessed. Results: NAWM and CC MHI had the highest area under the curve:.78 (95% confidence interval [CI]:.69,.86) and.84 (95% CI:.76,.91), respectively, distinguishing MS from HC. Conclusions: Mean MWF, SD, and MHI provide complementary information when assessing regional and global NAWM abnormalities in MS and associations with clinical outcome measures. Examining all three metrics (mean MWF, SD, and MHI) enables a more detailed interpretation of results, depending on whether regions of interest include areas that are more heterogeneous, earlier in the demyelination process, or uniformly injured. [ABSTRACT FROM AUTHOR]

Background: Advanced magnetic resonance imaging (MRI) methods can provide more specific information about various microstructural tissue changes in multiple sclerosis (MS) brain. Quantitative measurement of T1 and T2 relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegeneration that occurs across the spectrum of MS. Objective: To use relaxation and DBSI MRI metrics to describe measures of neuroinflammation, myelin and axons in different MS subtypes. Methods: 103 participants (20 clinically isolated syndrome (CIS), 33 relapsing-remitting MS (RRMS), 30 secondary progressive MS and 20 primary progressive MS) underwent quantitative T1, T2, DBSI and conventional 3T MRI. Whole brain, normal-appearing white matter, lesion and corpus callosum MRI metrics were compared across MS subtypes. Results: A gradation of MRI metric values was seen from CIS to RRMS to progressive MS. RRMS demonstrated large oedema-related differences, while progressive MS had the most extensive abnormalities in myelin and axonal measures. Conclusion: Relaxation and DBSI-derived MRI measures show differences between MS subtypes related to the severity and composition of underlying tissue damage. RRMS showed oedema, demyelination and axonal loss compared with CIS. Progressive MS had even more evidence of increased oedema, demyelination and axonal loss compared with CIS and RRMS. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS.Methods: A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI).Results: In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108).Conclusion: Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS. [ABSTRACT FROM AUTHOR]

Background: Benign multiple sclerosis (BMS) is typically defined using the Expanded Disability Status Scale (EDSS), which relies heavily on ambulation. We set out to examine important psychosocial and cognitive outcomes in patients with longstanding BMS compared with patients who had recently progressed to ‘no longer benign’ (NLB).Methods: A previously reported cohort of BMS (EDSS ≤3 at 20 years disease duration) were re-assessed 25–30 years post-onset. Patients remaining benign (EDSS ≤3 at re-assessment) were compared with those NLB for: depression (Beck Depression Inventory), fatigue (Modified Fatigue Impact Scale), health-related quality of life (MSQoL-54), cognition (Rao’s Neuropsychological Screening Battery), and employment status.Results: A total of 75% (66/88) of the original cohort were located. A total of 61 patients were re-assessed. Twenty-five patients (41%) had progressed in EDSS and were NLB. Compared with benign patients, those NLB were more likely to have: significant fatigue (15/36 [42%] vs. 18/25 [72%], p = 0.019); poorer physical functioning (mean MSQoL-54 = 67.30 vs. 50.89, p = 0.002); an MS-related negative change in employment status (13/36 [36%] vs. 21/25 [84%], p < 0.0001) and cognitive impairment (3/28 [11%] vs. 5/19 [26%]; trend only, p = 0.317). Depression and mental health quality if life differed little between the benign and NLB patients (p > 0.6).Conclusions: Despite remaining benign for 20 years, a significant proportion of patients progressed with further follow up. While neither depression nor patient-reported mental health quality of life was associated with EDSS progression, patients with longstanding ‘benign’ MS (EDSS ≤3 for 25+ years) had less fatigue, better physical quality of life and employment outcomes and infrequent cognitive impairment. Remaining benign over the long term, as defined by the EDSS, carried some advantages beyond ambulation. [ABSTRACT FROM AUTHOR]

Background: Advanced magnetic resonance imaging (MRI) methods can provide more specific information about various microstructural tissue changes in multiple sclerosis (MS) brain. Quantitative measurement of T 1 and T 2 relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegeneration that occurs across the spectrum of MS., Objective: To use relaxation and DBSI MRI metrics to describe measures of neuroinflammation, myelin and axons in different MS subtypes., Methods: 103 participants (20 clinically isolated syndrome (CIS), 33 relapsing-remitting MS (RRMS), 30 secondary progressive MS and 20 primary progressive MS) underwent quantitative T 1 , T 2 , DBSI and conventional 3T MRI. Whole brain, normal-appearing white matter, lesion and corpus callosum MRI metrics were compared across MS subtypes., Results: A gradation of MRI metric values was seen from CIS to RRMS to progressive MS. RRMS demonstrated large oedema-related differences, while progressive MS had the most extensive abnormalities in myelin and axonal measures., Conclusion: Relaxation and DBSI-derived MRI measures show differences between MS subtypes related to the severity and composition of underlying tissue damage. RRMS showed oedema, demyelination and axonal loss compared with CIS. Progressive MS had even more evidence of increased oedema, demyelination and axonal loss compared with CIS and RRMS.

Background: Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability., Objective: To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) participants and evaluate the correlation between myelin measures and clinical disability., Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner. Myelin heterogeneity index (MHI), a measurement of myelin variability, was calculated for whole cervical cord, global white matter, dorsal column, lateral and ventral funiculi. Correlations were assessed between MHI and Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), timed 25-foot walk, and disease duration., Results: In various regions of the cervical cord, ProgMS MHI was higher compared to HC (between 9.5% and 31%, p  ⩽ 0.04) and RRMS (between 13% and 26%, p  ⩽ 0.02), and ProgMS MHI was associated with EDSS ( r  = 0.42-0.52) and 9HPT ( r  = 0.45-0.52)., Conclusion: Myelin abnormalities within clinically eloquent areas are related to clinical disability. MWI metrics have a potential role for monitoring subclinical disease progression and adjudicating treatment efficacy for new therapies targeting ProgMS.

Background/objective: Retinal nerve fiber layer (RNFL) thickness has been linked to brain atrophy in multiple sclerosis (MS). However, little is known about retinal atrophy in 'benign' MS. We compared RNFL thickness in benign MS with healthy controls., Methods: Patients with benign MS (Expanded Disability Status Scale (EDSS) ≤ 3; ≥15 years' disease duration), identified through the British Columbia MS database, along with age-matched healthy controls, were recruited. RNFL thickness was measured using spectral-domain optical coherence tomography. Analysis of variance (ANOVA) was used to compare groups. The association between RNFL thickness and MS patient characteristics was examined via linear mixed-effects models (adjusting for within-patient inter-eye correlations and history of optic neuritis (ON), where appropriate)., Results: Overall, 29 benign MS patients and 29 healthy controls were included, totaling 116 eyes. RNFL thickness was lowest for the benign MS eyes, with and then without a history of ON, followed by healthy controls (mean=73.2 µm, SD ± 0.4; 89.9 µm, SD ± 12.5; 96.7 µm, SD ± 10.4; p<0.02). RNFL thickness was associated with a history of ON (p<0.0001), but not EDSS or disease duration (p>0.1)., Conclusions: RNFL thickness was lower in patients with benign MS than healthy controls, regardless of the previous history of ON. However, no association was found between RNFL values and disability or MS disease duration.