Abstract: P1146

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Background: Different approaches have been suggested to dissect disease heterogeneity in multiple sclerosis (MS) with the goals to identify pathogenetically meaningful subtypes and to improve prediction of disease courses.
Methods: 84 early relapsing MS patients (median age at baseline: 32.0 years, interquartile range (IQR) [28.7, 38.6], median disease duration at baseline: 1.0 year, IQR [0.3, 3.3]), recruited at the University Hospital Zurich, and 14 healthy controls received standardized MRI examinations at baseline were included. Expanded disability status scale (EDSS) scores were assessed by an experienced neurologist at baseline and approximately every 6 months thereafter. Median follow-up time was 2.2 years (IQR [1.4, 3.1]). Thalamic volumes and total T2 lesion load were derived from 3D T1 gradient echo sequences using an automated processing pipeline. Thalamic brain volumes were transformed into z-scores using both a publicly available cohort of healthy controls and the locally recruited controls to correct z-scores for inter scanner effects. For each patient, the area under the curve (AUC) for EDSS was divided by the length of the individual observation period. Using the MRI baseline assessments, the cohort was stratified into four subtypes:
1. high degenerative (deg) and high inflammatory (inf),
2. high deg and low inf,
3. low deg and high inf,
4. low deg and low inf.
"High inf" was defined as lesion load above the mean lesion load of the cohort (2.6 ml). "High deg" was defined as z-scores of the thalamus below -1.28 (80th percentile). EDSS AUC were compared between subgroups using an ANOVA with a Tukey's post hoc test.
Results: 15 patients were allocated to group 1, 12 in groups 2 and 3 and 45 to group 4. The mean EDSS AUC was 1.8 (1.3 SD), 0.7 (0.9 SD), 1.0 (0.8 SD), and 0.9 (0.9 SD), for groups 1 to 4, respectively. The differences in the EDSS AUC were statistically significant (p=0.005). Post-hoc analysis showed that group 1 features a higher EDSS AUC than group 2 (p=0.01) and 4 (p=0.005).
Conclusions: Based on the stratification algorithm applied here, high inflammatory subtype at baseline appears to be associated with higher EDSS AUC when thalamic volumes, corrected for age and scanner offsets, indicate concomitant higher levels of degeneration. MRI based stratification may provide the basis for improved prognostic estimates, as well as for enriching study cohorts with either inflammatory and/or degenerative phenotypes.
Disclosure: Acknowledgments:
The project was supported by the Clinical Research Priority Project MS of the University Zurich.
Disclosures: SS is supported by the Swiss National Science Foundation, the Clinical Research Priority Program of the University of Zurich, the Myelin Repair Foundation and the Swiss Multiple Sclerosis Society. He has received research grants from Novartis and Sanofi Genzyme and consultancy and speaker fees from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva..
RM received unrestricted grants from Biogen and Novartis. Received financial compensation for lectures and advisory tasks from Biogen, Celgene, Merck, Novartis, Roche, Teva, Genzyme, Neuway and CellProtect. R. Martin is a co-founder/-owner of Cellerys. R. Martin has received royalties for an NIH-held patent on the use of daclizumab in MS.
PM and CW have received travel support from Sanofi Genzyme and Merck Serono. RO and ACO are employees of the company jung diagnostisc GmbH. CAW has received travel support from Teva.