Cortical lesions are common in a longitudinal progressive multifocal leukoencephalopathy cohort

Progressive multifocal leukoencephalopathy (PML) cortical lesions have been noted on pathology but have not been studied in vivo. We aimed to characterize cortical lesions in PML and their clinical associations using in vivo MRI. Cortical lesions were identified by two independent raters on 3 tesla inversion-prepared T1-weighted MRI images from 44 participants enrolled in a PML natural history study, 10 healthy individuals and 5 HIV-infected individuals without PML. Follow-up imaging was evaluated for 10 participants with stable PML and 10 with worsening PML. Multiple sclerosis-related PML cases were excluded. In addition, cortical lesions identified on post-mortem 7T MRI from three individuals with PML were examined histopathologically. The primary outcome was the median number of cortical lesions per person. Secondary outcomes included change in lesion number and volume over time and associations between lesions and clinical measures. Cortical lesions were detected in 39/44 individuals with PML (median 6, range 0-136, interquartile range 16). No cortical lesions were identified in healthy or HIV-only participants. Cortical lesions identified on post-mortem MRI in 3 individuals with PML corresponded to areas of demyelination containing nuclei with immunoreactivity to JC virus Viral Protein 1 on histopathology. In 20 people with PML with follow-up evaluation (median follow-up interval 3 months, range 1-48, interquartile range 4), cortical lesion burden remained stable over time in both stable and worsening PML groups. There was no association between cortical lesion volume and cerebrospinal fluid viral load, survival, or cortical dysfunction signs. Cortical lesions are a common finding in PML and can be detected with 3 tesla MRI. Cortical lesions were not associated with distinct clinical characteristics and may form early in the disease with little subsequent expansion, providing insight into PML progression.