Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical status in multiple sclerosis: A retrospective cross-sectional study

Abstract

Background: Paramagnetic rims have been observed as a feature of some multiple sclerosis (MS) lesions on susceptibility-sensitive magnetic resonance imaging (MRI) and indicate compartmentalized inflammation. Objective: To investigate clinical, MRI, and intrathecal (cerebrospinal fluid, CSF) associations of paramagnetic rim lesions (PRLs) using 3T MRI in MS. Methods: This is a retrospective, cross-sectional analysis. All patients underwent 3T MRI using a T2*-weighted sequence with susceptibility postprocessing (susceptibility-weighted angiography (SWAN) protocol, GE). SWAN-derived filtered-phase maps and corresponding T2-FLAIR images were manually reviewed to determine PRL. Descriptive statistics, t-tests, and regression determined demographic, clinical, MRI, and CSF associations with PRL. Results: A total of 147 MS patients were included; 79 of whom had available CSF. Forty-three percent had at least one PRL. PRL status (presence/absence) did not vary by sex or Expanded Disability Status Scale (EDSS) but was associated with younger age, shorter disease duration, worse disease severity, high-efficacy therapy use, and poorer dexterity, as well as lower age-adjusted brain volumes and cognitive processing speeds. PRL status was moreover associated with blood–brain barrier disruption as determined by pathologically elevated albumin quotient. Sensitivity analyses remained supportive of these findings. Conclusion: PRLs, an emerging noninvasive biomarker of chronic neuroinflammation, are confirmed to be associated with greater disease severity and newly shown to be preliminarily associated with blood–brain barrier disruption.

Cerebrospinal fluid–related tissue damage in multiple sclerosis patients with iron rim lesions

“…A recent study also investigated the relationship between IRLs and clinical, MRI and CSF profiles. 18 Besides an association of IRLs with worse disease severity and lower brain volumes, the authors also found a pathologically elevated albumin quotient as a marker of blood–CSF barrier disruption in MS patients with IRLs. 18 We now provide some additional observations regarding the association between IRLs, pathogenic CSF profiles and a CSF-related tissue injury.…”

“…However, the average interval between CSF analysis and time point of MRI in this study was similar to that in a previous study. 18 Patients with acute relapses have higher CSF leukocyte counts than patients with chronic progressive or inactive disease, 29 and previous studies demonstrated that the CSF leukocyte count and the albumin CSF/serum quotient correlate with proximity of lesions to the lumbar CSF space and the temporal latency of the LP at the time of relapse. 30 , 31 While CSF leukocyte counts might decrease under DMTs, the humoral response (IgG synthesis) usually remains unchanged.…”

“…In cases CSF was obtained more than once, the data closest to the time of MRI were used for further analysis as suggested previously. 18 , 19 Signs of acute inflammatory activity (relapses and/or presence of acute contrast-enhancing lesions) at the time point of lumbar puncture (LP) were manually recorded from medical and radiology reports. Exclusion criteria were the presence of neurological diseases other than MS, cardiovascular or respiratory disease and missing or insufficient MRI data.…”

Association of paramagnetic rim lesions and retinal layer thickness in patients with multiple sclerosis

“…35 However, most recently, elevated albumin quotient, a subtle biomarker of impaired BBB, has been detected in patients with PRLs, confirming that impaired BBB that leads to chronic inflammation is most probably insidious and omnipresent, yet invisible to the naked eye in terms of gadolinium enhancement. 36…”

“…35 However, most recently, elevated albumin quotient, a subtle biomarker of impaired BBB, has been detected in patients with PRLs, confirming that impaired BBB that leads to chronic inflammation is most probably insidious and omnipresent, yet invisible to the naked eye in terms of gadolinium enhancement. 36 Although the pathophysiology underlying GCIPL and pRNFL thinning is not entirely clear, the currently prevailing concept comprises retrograde degeneration secondary to axonal damage occurring at any point within the brain. 37 In previous studies, GCIPL thinning and to a lesser degree pRNFL thinning have shown marked associations with both level of disability and clinical progression of MS, as well as brain atrophy.…”