Background: Paramagnetic Rim Lesions (PRL) are a subset of chronic demyelinating lesions in Multiple Sclerosis (MS), characterized by iron-rich, pro-inflammatory microglia encircling the periphery. These lesions have recently been shown to predict poorer overall prognosis. They have also been associated with elevated levels of cerebrospinal fluid (CSF) total protein, neurofilament light, and chitinase-3-like protein suggestive of a perpetuating or causative role in intrathecal inflammation.
Objectives: We sought to explore inflammatory CSF correlates of PRL to better elucidate their underlying associated pathophysiology. We hypothesized that patients with PRL would exhibit greater CSF inflammation associated with dysregulated microglial activity.
Methods: This is a retrospective, cross-sectional cohort study. We assessed cellular and soluble mediators of inflammation in CSF by employing 1) spectral flow cytometry and 2) oligonucleotide-linked-antibody proteomics (Olink Proteomics) of 96 cytokines/chemokines. PRL were identified on standardized clinical 3T MRI collected in close proximity to CSF sample acquisition.
Results: 27 Patients with diagnosed MS were analyzed via Olink and assessed for PRL status. Of this cohort, 6 were additionally assessed by flow cytometry. We found that patients with PRL had higher Interferon-Gamma (IFN-g) and STAM Binding Protein (STAMBP) in CSF. We also observed increased Oligoclonal Bands and an over-representation of CD138+ CD19+ plasma cells within CSF.
Conclusions: PRL are associated with increased intrathecal IFN-g, STAMBP, and plasma cells in MS. Whether these inflammatory mediators drive the formation of PRL, are a consequence of PRL formation, or are the result of a parallel inflammatory process is a promising subject for future study.
