Posterior brain damage and cognitive impairment in pediatric multiple sclerosis
Related Experiment Video
Updated: May 2, 2026
A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)
Published on: February 7, 2025
Maria A Rocca1, Martina Absinta, Maria Pia Amato
1From the Neuroimaging Research Unit (M.A.R., M.A., M.F.), Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience (M.A.R., M.A., L.M., A. Fiorino, G.C., M.F.), and Department of Neurology (M.P.A., E.P.), University of Florence; the Multiple Sclerosis Center (A.G., L.P.), Ospedale di Gallarate; Fondazione "Istituto Neurologico Casimiro Mondino" (P.V., M.C.P.), Pavia; Multiple Sclerosis Center (R.C.), Spedali Civili of Brescia, Italy; Department of Cardiovascular Sciences (M.A.H.), University of Leicester, UK; and the Department of Neuroradiology (A. Falini), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Insights
Cognitive impairment in pediatric multiple sclerosis (MS) is linked to structural and functional brain changes. Specifically, damage in the posterior Default Mode Network (DMN) correlates with cognitive deficits in these young patients.
Area of Science:
- Neuroscience
- Radiology
- Pediatric Neurology
Background:
- Pediatric multiple sclerosis (MS) can lead to significant cognitive impairment.
- Understanding the underlying neurobiological mechanisms is crucial for effective management.
Purpose of the Study:
- To investigate the relationship between structural and functional brain abnormalities and cognitive impairment in pediatric MS patients.
- To identify specific brain regions and network alterations associated with cognitive dysfunction.
Main Methods:
- Combined structural MRI (dual-echo, diffusion tensor, T1-weighted) and resting-state functional MRI (RS-fMRI) in 35 pediatric MS patients and 16 controls.
- Assessed white matter (WM) and gray matter (GM) damage using voxel-wise analyses.
- Measured Default Mode Network (DMN) resting-state functional connectivity (FC).
Main Results:
- 45% of pediatric MS patients exhibited cognitive impairment.
- Cognitively impaired patients showed more severe WM/GM damage in posterior DMN regions (precuneus, posterior cingulum, corpus callosum) and reduced precuneus RS-FC.
- Cognitive impairment was strongly associated with cingulum/corpus callosum diffusivity abnormalities and precuneus RS-FC.
Conclusions:
- Cognitive dysfunction in pediatric MS is associated with structural and functional abnormalities in posterior DMN core regions.
- Co-occurring white matter structural damage in these areas likely underlies the observed cognitive deficits.
Objective:
We combined structural and functional MRI to better understand the mechanisms responsible for cognitive impairment in pediatric patients with multiple sclerosis (MS).
Methods:
Brain dual-echo, diffusion tensor, 3D T1-weighted, and resting-state (RS) fMRI scans were acquired from 35 consecutive pediatric patients with MS and 16 sex- and age-matched healthy controls. Patients with abnormalities in ≥2 neuropsychological tests were classified as cognitively impaired. The regional distribution of white matter (WM) and gray matter (GM) damage was assessed using voxel-wise analyses. Default mode network (DMN) RS functional connectivity (FC) was also measured.
Results:
Sixteen patients (45%) were classified as cognitively impaired. Compared to cognitively preserved (CP) patients, cognitively impaired patients with MS had higher occurrence of T2 lesions as well as more severe damage to the WM and GM, as measured by atrophy and diffusivity abnormalities, in the posterior regions of the parietal lobes close to the midline (precuneus, posterior cingulum, and corpus callosum). Compared to the other study groups, they also showed reduced RS FC of the precuneus, whereas CP patients experienced an increased RS FC of the anterior cingulate cortex. A multivariable model identified diffusivity abnormalities of the cingulum and corpus callosum and RS FC of the precuneus as the covariates more strongly associated with cognitive impairment (C-index = 0.99).
Conclusions:
In pediatric patients with MS, cognitive dysfunction is associated with structural and functional abnormalities of the posterior core regions of the DMN. WM structural abnormalities co-occurring at this level are likely to be the substrate of such modifications.
Related Concept Videos
01:19Multiple Sclerosis l: Introduction
01:28Traumatic Brain Injury l: Introduction