Patterns of white and gray structural abnormality associated with paediatric demyelinating disorders

Abstract

The impact of multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) - associated disorders (MOGAD) on brain structure in youth remains poorly understood. Reductions in cortical mantle thickness on structural MRI and abnormal diffusion-based white matter metrics (e.g., diffusion tensor parameters) have been well documented in MS but not in MOGAD. Characterizing structural abnormalities found in children with these disorders can help clarify the differences and similarities in their impact on neuroanatomy. Importantly, while MS and MOGAD affect the entire CNS, the visual pathway is of particular interest in both groups, as most patients have evidence for clinical or subclinical involvement of the anterior visual pathway. Thus, the visual pathway is of key interest in analyses of structural abnormalities in these disorders and may distinguish MOGAD from MS patients. In this study we collected MRI data on 18 MS patients, 14 MOGAD patients and 26 age- and sex-matched typically developing children (TDC). Full-brain group differences in fixel diffusion measures (fibre-bundle populations) and cortical thickness measures were tested using age and sex as covariates. Visual pathway analysis was performed by extracting mean diffusion measures within lesion free optic radiations, cortical thickness within the visual cortex, and retinal nerve fibre layer (RNFL) and ganglion cell layer thickness measures from optical coherence tomography (OCT). Fixel based analysis (FBA) revealed MS patients have widespread abnormal white matter within the corticospinal tract, inferior longitudinal fasciculus, and optic radiations, while within MOGAD patients, non-lesional impact on white matter was found primarily in the right optic radiation. Cortical thickness measures were reduced predominately in the temporal and parietal lobes in MS patients and in frontal, cingulate and visual cortices in MOGAD patients. Additionally, our findings of associations between reduced RNFLT and axonal density in MOGAD and TORT in MS patients in the optic radiations imply widespread axonal and myelin damage in the visual pathway, respectively. Overall, our approach of combining FBA, cortical thickness and OCT measures has helped evaluate similarities and differences in brain structure in MS and MOGAD patients in comparison to TDC.

Keywords: Cortical thickness; Diffusion; Fixel-based analysis; Multiple sclerosis; Myelin oligodendrocyte glycoprotein associated disorders; Optic neuritis.

Fig. 1

Whole-brain fixel-based analysis (FBA) revealed reductions in fixel metrics for paediatric patients with demyelinating syndromes when compared to typically developing children (TDC). All maps are superimposed on a study-specific template and colour-coded by effect size (F-statistic, thresholded at FWE-p < 0.05). Analysis accounted for effects of sex, age, and total intracranial volume. (A) MS patients revealed reductions in fibre density (FD), fibre-bundle cross section (FC) and fibre-density and fibre-bundle cross-section (FDC) when compared to TDC (B) MOGAD patients revealed reductions in FD and FDC when compared to TDC.

Fig. 2

Surface-based morphometry analysis revealed reductions in cortical thickness for (A) MS and (B) MOGAD patients when compared to typically developing children (TDC). Results were thresholded at voxel level with p < 0.05 and corrected with cluster level non-stationary cluster extent and superimposed on a template reconstruction of brain surface in MNI space. Analysis accounted for effects of sex and age.