The sequence of regional structural disconnectivity due to multiple sclerosis lesions.

TitleThe sequence of regional structural disconnectivity due to multiple sclerosis lesions.
Publication TypeJournal Article
Year of Publication2023
AuthorsTozlu C, Olafson E, Jamison K, Demmon E, Kaunzner U, Marcille M, Zinger N, Michaelson N, Safi N, Nguyen T, Gauthier S, Kuceyeski A
JournalbioRxiv
Date Published2023 Jan 27
Abstract

OBJECTIVE: Prediction of disease progression is challenging in multiple sclerosis (MS) as the sequence of lesion development and retention of inflammation within a subset of chronic lesions is heterogeneous among patients. We investigated the sequence of lesion-related regional structural disconnectivity across the spectrum of disability and cognitive impairment in MS.

METHODS: In a full cohort of 482 patients, the Expanded Disability Status Scale was used to classify patients into (i) no or mild vs (ii) moderate or severe disability groups. In 363 out of 482 patients, Quantitative Susceptibility Mapping was used to identify paramagnetic rim lesions (PRL), which are maintained by a rim of iron-laden innate immune cells. In 171 out of 482 patients, Brief International Cognitive Assessment was used to identify subjects with cognitive impairment. Network Modification Tool was used to estimate the regional structural disconnectivity due to MS lesions. Discriminative event-based modeling was applied to investigate the sequence of regional structural disconnectivity due to all representative lesions across the spectrum of disability and cognitive impairment.

RESULTS: Structural disconnection in the ventral attention and subcortical networks was an early biomarker of moderate or severe disability. The earliest biomarkers of disability progression were structural disconnections due to PRL in the motor-related regions. Subcortical structural disconnection was an early biomarker of cognitive impairment.

INTERPRETATION: MS lesion-related structural disconnections in the subcortex is an early biomarker for both disability and cognitive impairment in MS. PRL-related structural disconnection in the motor cortex may identify the patients at risk for moderate or severe disability in MS.

DOI10.1101/2023.01.26.525537
Alternate JournalbioRxiv
PubMed ID36747675
PubMed Central IDPMC9900990
Related Institute: 
MRI Research Institute (MRIRI) Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065