2025 American Academy of Neurology Abstract Website

Andrei Miclea¹, Jonathan Zurawski², Brian C. Healy³, Shrishti Saxena², Hrishikesh Lokhande², Molly Quattrucci², Renxin Chu², Howard L. Weiner², Rohit Bakshi², Tanuja Chitnis²
¹Brigham MS Center, Brigham and Women’s Hospital, Boston, MA, USA, ²Brigham MS Center, Brigham and Women’s Hospital; Department of Neurology, Harvard Medical School; Boston, MA, USA, ³Brigham MS Center, Brigham and Women’s Hospital; Department of Neurology, Harvard Medical School; Biostatistics Center, Massachusetts General Hospital; Boston, MA, USA

Objective:

Because of the persisting unmet need to identify biomarkers with prognostic clinical utility in MS, the objective of the present study is to characterize the relationship between 7 Tesla MRI-defined measures of disease severity (gray matter demyelinating lesions, brain atrophy, and meningeal inflammation) and serological immune alterations in patients with early MS.

Background:

Due to substantially higher sensitivity of 7T MRI, there is new technical capability to non-invasively identify biomarker-MRI patterns relevant to clinical status and prognosis. In the present study, we therefore leverage clinical 7T MRI and blood biomarker analysis from a large cohort study to characterize patterns of 7T MRI-proteomic association in early-stage MS.

Design/Methods:

Patients with CIS or MS having a 7 Tesla brain MRI and blood sample both within five years of MS diagnosis were included in the analysis (n=57). Correlational analysis was adjusted for sex, age, and disease duration. Correlation between serum proteins and MRI-defined cortical and thalamic gray matter lesions, leptomeningeal enhancement (presence and foci number), deep gray matter (DGM) structure volumes, whole brain parenchymal volume and total T2 white matter lesion volume was assessed.

Results:

Cortical lesions were associated with higher IL-15, TNF-alpha, and BAFF levels, and lower levels of FcRL2. Leptomeningeal enhancement was associated with higher levels of PLXNB3 and lower levels of nCDase and CNTN5. Higher IL-1B levels correlated with lower DGM volume while higher levels of CDH6, SIGLEC9, and HAGH correlated with higher DGM volume.

Conclusions:

Our study identifies several novel associations between serum immune proteins and 7T MRI outcomes, which may have relevance as disease biomarkers in early stages of MS.