Some of you may have not yet heard about paramagnetic rims in MS lesions.
Their presence on MRI scans is felt to represent iron rich microglial inflammation in the brain occurring in a subset of individuals. Pathologically iron rims reflect slowly expanding chronically active MS lesions (see below).
Figure: Paramagnetic lesion arrowed in (a) in a 34 y with RRMS. [Source-this article]
The presence of these lesions have been linked to a greater disability and disease severity, as well as brain volume loss. By all means this is unlikely to be the only process that leads to this, but it is something of interest as there are currently drugs in clinical trial partially targeting microglial activity – the BTK inhibitors. BTKi also target B cells.
In this new study, the investigators again studied the clinical outcomes of having iron rims on scans, as well as some biological parameters, such as oligoclonal bands and blood brain barrier dysfunction. Other biomarkers, such as GFAP (a microglial marker) and neurofilament levels have not been assessed, which is a shame as the findings would have been more informative. Also, not certain what the relevance of OCBs in this context is as antibody production is a hallmark of B-cell and plasma cell activation and therefore highly sensitive and specific for MS, but what they’re not are markers of microglial activation.
Nonetheless, the authors demonstrate that those with iron rims tended to have more CSF-specific Oligoclonal bands (93.5% in those with iron rimmed lesions vs 72.7% without) and less significantly also had evidence of blood brain dysfunction as depicted by the albumin quotient (see Figure below).
Personally, I don’t think that the Oligoclonal band status of the participants really links it to the iron rims, since the prevalence of oligoclonal bands is almost certainly a diagnostic entity within MS (i.e. you’re more likely to be diagnosed with MS if you have positive bands) and therefore a proportion of these individuals are going to have iron rims.
Clinically they also noted that those with iron rims tended to have larger lesions (as depicted by T2 Lesion Volumes), decreased brain volume and were more likely to have underlying tissue damage (as depicted by black holes, see [c] on the first figure).
Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical status in multiple sclerosis: A retrospective cross-sectional study
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.