Nucleus-specific thalamic volumes and retinal thickness in pediatric-onset multiple sclerosis: a cross-sectional study.

UNLABELLED: This study aimed to (i) compare nucleus-specific thalamic volumes between patients with pediatric-onset multiple sclerosis (POMS) and controls and (ii) examine relationships between lesion burden, thalamic volume, and optical coherence tomography (OCT) measures of retinal neuroaxonal structure. In this single-center retrospective cross-sectional study, we included 119 patients with POMS and 120 clinically referred controls with structurally normal brain MRI. DeepThalamus was used to derive total and nucleus-wise thalamic volumes from volumetric 3D T1-weighted MRI, with additional intracranial volume (ICV) normalization. In patients with POMS, DeepLesionBrain was used to quantify white matter lesion volume, count, and load from 3D T1-weighted and FLAIR images. Available OCT-derived peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were analyzed in relation to thalamic volumes and lesion burden using regression, correlation, and linear mixed-effects models, with FDR correction. Total, right, and left thalamic volumes were smaller in POMS than in controls, with a 0.9 cm3 (~ 7%) lower mean total thalamic volume in the POMS group (all FDR q < 0.05). The pattern of between-group thalamic volume differences was regionally specific, with the largest relative volume differences observed in posterior and visual relay nuclei (particularly pulvinar and LGN), while anterior nuclei were relatively spared. Greater lesion burden showed stronger and more consistent inverse associations with thalamic volume, whereas associations with lower retinal layer thickness (GC-IPL and pRNFL) were statistically significant but generally modest (FDR q < 0.05).

CONCLUSION

POMS is associated with smaller thalamic volumes, with larger observed relative between-group differences in posterior and visual relay nuclei, particularly the pulvinar and LGN. Smaller thalamic volumes were consistently associated with lesion burden and showed modest but consistent ipsilateral associations with lower retinal thickness.

WHAT IS KNOWN: • POMS shows early deep gray matter involvement, and thalamic volume loss can be detected within the first years after diagnosis. • The thalamus is functionally heterogeneous, but nucleus-level vulnerability patterns in POMS and their relationship to lesion burden and OCT measures remain insufficiently characterized.

WHAT IS NEW: • Larger observed between-group thalamic volume differences were found in the pulvinar and other posterior thalamic nuclei, while greater lesion burden was associated with smaller thalamic volumes. • Lower retinal thickness on OCT showed ipsilateral associations with smaller volumes of posterior and visual relay thalamic nuclei in POMS.