Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis.

Abstract

The present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS). PedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K-means clustering on cognitive scores. MRI metrics included brain T2-hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting-state (RS) functional connectivity (FC) were estimated. Three cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005). We identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.