Broad rim lesions correlate with a rapidly progressive MS phenotype

Rim activity extends into the normal-appearing white matter (NAWM) in a proportion of lesions, observed a Finnish research group. The authors concluded that the broad rim lesion (BRL) is a novel phenotype that is directly related to disease progression.

In MS, the Expanded Disability Status Scale (EDSS) score correlates relatively poorly with overall lesion load, but correlates significantly with rim-active lesion load, based on voxel-level 18 kDa translocator protein (TSPO) availability. Dr Jussi Lehto (University of Turku, Finland) and colleagues further investigated PET-measurable rim activity [1]. They included NAWM in the perilesional area and explored correlations between rim activity and biomarkers of progression, such as PET distribution volume ratio (DVR) in the NAWM, as well as overall T1 lesion load.

A total of 114 MS patients underwent MRI and [¹¹C]PK11195 TSPO-PET. Of this cohort, 83 (73%) patients had relapsing-remitting MS and 31 (27%) had secondary progressive MS. By dilating parametric DVR maps, they obtained 0–2 mm, 2–4 mm, and 4–6 mm perilesional masks from each patient. Based on its average DVR, each 2 mm rim was categorised as HIGH or LOW. Lesions were considered BRLs if they exhibited a HIGH-HIGH-HIGH pattern within each 2 mm segment.

In 34 of 114 (38.8%) patients, BRLs were seen. Disease duration and EDSS score were significantly higher among patients with BRLs. Perhaps even more interesting, according to Dr Lehto, was that the mean [¹¹C]PK11195 DVRs in the NAWM and thalamus were significantly higher in patients with BRLs. The proportion of BRLs correlated with overall T1-lesion volume (r=0.53; P<0.0001). Moreover, patients with ≥1 BRL did worse on almost every imaging-related biomarker of progression. Dr Lehto added that the 19 slowly progressing patients (with an EDSS score ≤1.5 after 12 years from onset) were very unlikely (11%) to have a BRL, whereas 50% of rapid progressors (EDSS score 4 after 12 years from onset) had ≥1 BRL (P=0.013). BRLs partially overlap with so-called iron-rim lesions, which are white matter lesions surrounded by a rim of iron containing microglia.

“Broad perilesional distribution of innate immune cells seen in neuropathological preparations is quantifiable in vivo with TSPO PET,” concluded Dr Letho. “Similarly to the previously categorised phenotypes ‘PET rim active’ and ‘PET-overall active,’ broad perilesional activity correlates with progression. Patients with BRLs progress more rapidly.”

1. Lehto J, et al. PET-based characterization of the broad rim lesion, a novel progression-related lesion phenotype. O018, MSMilan 2023, 11–13 October, Milan, Italy.

 

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Posted on 4 December 20234 December 2023