To date, no studies have explored the relationship between brain atrophy and MS disability using differing MRI protocols and scanners at multiple sites.
To assess the association between brain atrophy and MS disability, as measured by EDSS and 6-month confirmed disability progression (CDP).
In this retrospective study at 4 MS centres, a total of 1300 patients had brain MRI imaging assessed by icobrain. Relapse-onset MS patients were included if they had two clinical MRIs 12 (±3) months apart and ≥2 EDSS scores post MRI-2, the first ≤3 months from MRI-2, with ≥6 months between first and last EDSS. Volumetric data were analysed if the alignment similarity between two images was as good as that of same-scanner scan-rescan images (normalised mutual information ≥0.2). The percentage brain volume change (PBVC), percentage grey matter change (PGMC), FLAIR lesion volume change, whole brain volume, grey matter volume, FLAIR lesion volume and T1 hypointense lesion volume at MRI-2 were calculated. Ordinal mixed effect models were used to determine the association between these volumetric MRI measures and all EDSS scores post MRI-2. Cox proportional hazards models were used for the 6-month CDP outcome, using a subset of patients with ≥3 EDSS. Models were adjusted for proportion of time spent on disease-modifying therapy during MRIs ± whole brain/grey matter volume at baseline MRI.
Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. During the follow-up period (median 3.8 years, range 1.3-8.9), 29 of 244 (12%) patients experienced 6-month CDP. There was no evidence for association between annualised PBVC or PGMC and CDP or EDSS (p>0.05). Cross-sectional whole brain and grey matter volume (at MRI-2) tended to associate with CDP (HR 0.99, 95% CI 0.98-1.00, p=0.06). Every 1ml of whole brain or grey matter volume lost represented a 1% higher chance of reaching 6-month CDP. Only whole brain volume (at MRI-2) was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the slope of EDSS change over time (β -0.001, SE 0.0003, p=0.02). On average, every 33ml reduction of brain volume was associated with a 1 step increase in EDSS.
In this real-world clinical setting where a fifth of the brain atrophy analysis were performed on different scanners, we found no association between individual brain atrophy and MS disability. However, there was an association between cross-sectional whole brain volume with EDSS and slope of EDSS change.