Introduction

In multiple sclerosis (MS), persistent chronic inflammation and remyelination failure at the edges of old non-gadolinium (Gd)-enhancing white matter (WM) lesions, is identified with a paramagnetic rim on susceptibility-based MRI sequences (1, 2). On the other hand, serum neurofilaments (sNfL) levels are associated with disease activity and neurodegeneration in both acute and chronic phases of MS (3, 4). Yet, whether the presence of chronic (“smoldering”) inflammation (as measured by susceptibility-based MRI) is accompanied by increased in neuroaxonal destruction (as assessed by sNfL) in living patients is currently unknown. The goal of this study was to assess the relationship between the presence and number of paramagnetic rims and the level of sNfL (3) in MS patients.

Methods

Patients with relapsing remitting MS (RRMS) and primary or secondary progressive MS (PMS) (5) were recruited from the Neuroimmunology/MS outpatient center at the University Hospital of Lausanne, Switzerland. Patients featuring visible contrast enhancing lesions on post-Gd T1-weighted images were excluded from the analysis. For each patient, expanded disability status scale (EDSS), blood sample, and MRI data were collected within a time window of 13, 4-22 days (median, IQR). A 3D segmented EPI(6) sequence giving high resolution (0.65 mm3 voxels) T2*-weighted and phase images was acquired during the intravenous injection of Gd on a 3T Siemens (Skyra or Prisma) MRI scanner. Phase postprocessing and image coregistration were performed as previously described (1, 7, 8). Phase images were analyzed independently by two raters (P.M. and M.A.) for the presence of paramagnetic rims in chronic non-Gd enhancing WM lesions, as previously described (8). Serum neurofilament analysis was performed with the Single Molecule Array (Simoa) assay (SIMOA) at the Basel University Hospital, Switzerland (3).

Results

Twenty-eight patients were included (RRMS: n=18 and PMS: n=10). Eleven of 28 patients (39%; “rim-positive”) had at least one chronic WM lesion featuring a paramagnetic rim. The agreement between raters was 91%. The level of sNfL was significantly higher in rim-positive compared to rim-negative cases (mean±SD: 54±29 and 14±5 pg/ml respectively, p<0,0001; Figure 1A). Interestingly, in the subgroup of 10 progressive PMS, the level of sNfL was higher in all rim-positive (n=7) compared to rim-negative (n=3) patients (mean 69±25 and 12±3 pg/ml respectively; Figure 1B). No age difference was observed between rim-positive and rim-negative patients (mean 46±11 and 48±13 years old, respectively). Also, we observed a positive correlation between the number of paramagnetic rims and the level of sNfL (p<0,0001) and between the number of rims and the EDSS per patient (p<0,001; Figure 2). Examples of paramagnetic rims in RRMS, SPMS, and PPMS patients are shown in Figures 3 and 4.

Conclusions

Our results show that MS patients featuring chronic smoldering inflammation at the edges of some lesions have higher neuroaxonal destruction than patients without. This is particularly relevant since our cohort of patients did not include subjects with active inflammation as measured by the presence of Gd enhancing lesions. While these results should be confirmed in larger MS cohorts, they suggest that the combination of paramagnetic rim and serum NfL assessment may help in the selection of “chronically” active MS patients who may benefit from disease-modifying treatments.

Acknowledgements

No acknowledgement found.

References

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