Hyperintense Cortical Signal on Magnetic Resonance Imaging Reflects Focal Leukocortical Encephalitis and Seizure Risk in Progressive Multifocal Leukoencephalopathy

Abstract

Objective To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted pre-contrast MRI in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate.

Methods We reviewed clinical data including seizure history, presence of IRIS, and MRI scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either by CSF JC Virus (JCV) PCR, brain biopsy or autopsy, and who had MRI images available were included in the analysis (n=49). We characterized pathologic findings in areas of the brain displaying HCS in two patients and compared them with isointense cortex in the same individuals.

Results Of 49 patients, 17 (34.7%) had seizures and 30 (61.2%) had HCS adjacent to subcortical PML lesions on MRI. Of the 17 PML patients with seizures, 15 (88.2%) had HCS compared to 15/32 (46.9%) patients without seizures (p= 0.006). HCS was associated with seizure development with a relative risk (RR) of 4.75 (95% confidence interval of 1.2 to 18.5; p=0.006). Of the 20 patients with IRIS, 16 (80.0%) had HCS compared to 14/29 (49.3%) of those without IRIS (p=0.04). On histological examination, HCS areas were associated with striking JCV-associated demyelination of cortical and sub-cortical U-fibers, significant macrophage infiltration and a pronounced reactive gliosis in the deep cortical layers.

Interpretation Seizures are a frequent complication in PML. HCS is associated with seizures as well as IRIS, and correlates histologically with JCV focal leukocortical encephalitis (JCV FLE).