Contributions
Abstract: P851
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: In multiple sclerosis (MS), chronic active/slowly expanding lesions - which previously could only be detected at autopsy - can now be identified on susceptibility-based MRI, in vivo, as non-gadolinium-enhancing lesions with a paramagnetic rim. Pathologically, these lesions feature smoldering inflammatory demyelination at the lesion edge, remyelination failure, and often ongoing axonal degeneration. However, the long-term effects of rim persistence in vivo are still uncertain.
Aim: We assessed whether the presence of paramagnetic rims is linked to patient disability and long-term lesion outcomes.
Methods: Chronic lesions with paramagnetic rims were identified on 7T or 3T susceptibility-based brain MRI in cross-sectional study of 191 MS cases. Correlations with clinical disability measures and brain volumes were assessed. A retrospective yearly evaluation of lesion volume change (27 chronic lesions with vs. 27 without rim) was performed in 23 MS cases with archival yearly scans for ≥10 years.
Results: Individuals with more than 4 chronic lesions with paramagnetic rims reached motor (EDSS and MSSS) and cognitive (SDMT and PASAT) disability at earlier age (p< 0.05). Normalized volumes of the brain, white matter, and caudate were lower in patients with rims than without rims (p< 0.05). At the lesion level, a dichotomy of longitudinal evolution of chronic MS lesions with and without rim was detected. Whereas lesions without rim shrank over time, chronic lesions with rim were stable in size or expanded into the surrounding tissue (p< 0.0001). This dichotomy was more pronounced before age 45 (p=0.04). On 7T T1-map, lesions with rim had higher T1 values (suggesting more tissue destruction) than lesions without rim (p=0.0025).
Conclusions: The presence of multiple chronic active lesions is associated with a more aggressive disease course. Persistent inflammation at the lesion edge - a major barrier for remyelination - can also exert ongoing damage on the surrounding tissue. These results support the use of paramagnetic-rim lesion development, or the resolution of such lesions, as outcome measures in MRI-based clinical trials aimed at treating perilesional chronic inflammation and its potential effects on remyelination.
Disclosure: The Intramural Research Program of NINDS supported this study. Absinta M is supported by grants from the National MS Society and from the Conrad N. Hilton Foundation. Reich DS received research support from collaborations with the Myelin Repair Foundation and Vertex Pharmaceuticals, unrelated to the present study. Masuzzo F, Sati P, Sethi V, Kolb H, Ohayon J, Cortese ICM: nothing to disclose.
Abstract: P851
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: In multiple sclerosis (MS), chronic active/slowly expanding lesions - which previously could only be detected at autopsy - can now be identified on susceptibility-based MRI, in vivo, as non-gadolinium-enhancing lesions with a paramagnetic rim. Pathologically, these lesions feature smoldering inflammatory demyelination at the lesion edge, remyelination failure, and often ongoing axonal degeneration. However, the long-term effects of rim persistence in vivo are still uncertain.
Aim: We assessed whether the presence of paramagnetic rims is linked to patient disability and long-term lesion outcomes.
Methods: Chronic lesions with paramagnetic rims were identified on 7T or 3T susceptibility-based brain MRI in cross-sectional study of 191 MS cases. Correlations with clinical disability measures and brain volumes were assessed. A retrospective yearly evaluation of lesion volume change (27 chronic lesions with vs. 27 without rim) was performed in 23 MS cases with archival yearly scans for ≥10 years.
Results: Individuals with more than 4 chronic lesions with paramagnetic rims reached motor (EDSS and MSSS) and cognitive (SDMT and PASAT) disability at earlier age (p< 0.05). Normalized volumes of the brain, white matter, and caudate were lower in patients with rims than without rims (p< 0.05). At the lesion level, a dichotomy of longitudinal evolution of chronic MS lesions with and without rim was detected. Whereas lesions without rim shrank over time, chronic lesions with rim were stable in size or expanded into the surrounding tissue (p< 0.0001). This dichotomy was more pronounced before age 45 (p=0.04). On 7T T1-map, lesions with rim had higher T1 values (suggesting more tissue destruction) than lesions without rim (p=0.0025).
Conclusions: The presence of multiple chronic active lesions is associated with a more aggressive disease course. Persistent inflammation at the lesion edge - a major barrier for remyelination - can also exert ongoing damage on the surrounding tissue. These results support the use of paramagnetic-rim lesion development, or the resolution of such lesions, as outcome measures in MRI-based clinical trials aimed at treating perilesional chronic inflammation and its potential effects on remyelination.
Disclosure: The Intramural Research Program of NINDS supported this study. Absinta M is supported by grants from the National MS Society and from the Conrad N. Hilton Foundation. Reich DS received research support from collaborations with the Myelin Repair Foundation and Vertex Pharmaceuticals, unrelated to the present study. Masuzzo F, Sati P, Sethi V, Kolb H, Ohayon J, Cortese ICM: nothing to disclose.