Person:

Ngo, Long

INTRODUCTION Since the relationship between delirium and long-term cognitive decline has not been well-explored, we evaluated this association in a prospective study.

METHODS SAGES is an on-going study involving 560 adults age 70+ without dementia scheduled for major surgery. Delirium was assessed daily in the postoperative period using the Confusion Assessment Method. General Cognitive Performance (GCP) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were assessed preoperatively then repeatedly out to 36 months.

RESULTS On average, patients with post-operative delirium had significantly lower preoperative cognitive performance, greater immediate (1 month) impairment, equivalent recovery at 2 months, and significantly greater long-term cognitive decline relative to the non-delirium group. Proxy reports corroborated the clinical significance of the long-term cognitive decline in delirious patients.

DISCUSSION Cognitive decline following surgery is biphasic and accelerated among persons with delirium. The pace of long-term decline is similar to that seen with Mild Cognitive Impairment.

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).