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Pediatric patients with clinically isolated syndromes who had brain lesions had supratentorial lesion volumes similar to adult multiple sclerosis patients, but greater infratentorial lesion volumes (<jats:italic>p<\/jats:italic> &lt; 0.009), particularly in the pons of male patients. The predilection for infratentorial lesions the pediatric patients with clinically isolated syndromes may reflect immunological differences or differences in myelin, possibly related to the caudorostral temporal gradient in myelin maturation. 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