Lesions may be located within the cortex, in the subcortical region, or around the ventricles. Subcortical lesions would preferentially affect U-fibers connecting adjacent cortex, while deeper lesions would disturb long-range connections. In MLD, it has been proposed that cortical demyelinization could explain the high rate of psychosis observed in this disease.96 Against such a proposal, it is worth remembering that cortical involvement could also be seen in MS, where it mainly provokes seizures without reported psychosis.97 Seizures also appear in the evolution of MLD, but after several years of psychosis. In MS, seizures are not associated with the occurrence of psychosis. Thus, cortex might not be the primary site for provoking psychosis. Lastly, MLD, like MS, mainly affects long-range connections while sparing U -fibers connecting adjacent areas.98
