Rabinstein, Alejandro A.

Objectives: To determine the causes of death in patients with status epilepticus. To analyze the relative contributions of seizure etiology, seizure refractoriness, use of mechanical ventilation, anesthetic drugs for seizure control, and medical complications to in-hospital and 90-day mortality, hospital length of stay, and discharge disposition. Design: Retrospective cohort. Setting: Single-center neuroscience ICU. Participants: Patients with status epilepticus were identified by retrospective search of electronic database from January 1, 2011, to December 31, 2016. Interventions: Review of electronic medical records. Measurements and Main Results: Demographics, clinical characteristics, treatments, and outcomes were collected. Univariable and multivariable logistic regression analysis were used to determine whether the use of anesthetic drugs, mechanical ventilation, Status Epilepticus Severity Score, refractoriness of seizures, etiology of seizures, or medical complications were associated with in-hospital, 90-day mortality or discharge disposition. Among 244 patients with status epilepticus (mean age was 64 yr [interquartile range, 42–76], 55% male, median Status Epilepticus Severity Score 3 [interquartile range, 2–4]), 24 received anesthetic drug infusions for seizure control. In-hospital and 90-day mortality rates were 9.2% and 19.2%, respectively. Death was preceded by withdrawal of life-sustaining treatment in 19 patients (86.3%) and cardiac arrest in three (13.7%). Only Status Epilepticus Severity Score was associated with in-hospital and 90-day mortality, whereas the use of anesthetic drugs for seizure control, mechanical ventilation, medical complications, etiology, and refractoriness of seizures were not. Hospital length of stay was longer in patients with medical complications ( p = 0.0091), refractory seizures ( p = 0.0077), and in those who required anesthetic drugs for seizure control ( p = 0.0035). Patients who had refractory seizures were less likely to be discharged home (odds ratio, 0.295; CI, 0.143–0.608; p = 0.0009). Conclusions: In this cohort, death primarily resulted from the underlying neurologic disease and withdrawal of life-sustaining treatment and not from our treatment choices. Use of anesthetic drugs, medical complications, and mechanical ventilation were not associated with in-hospital and 90-day mortality.

Background and Purpose— Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods— As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results— One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P =0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P =0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P =0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P =0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions— High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

Abstract Although white matter hyperintensities have traditionally been viewed as a marker of vascular disease, recent pathology studies have found an association between white matter hyperintensities and Alzheimer’s disease pathologies. The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer’s disease biomarkers measured using PET. From the population-based Mayo Clinic Study of Aging, 434 participants without dementia (55% male) with FLAIR and gradient recall echo MRI, tau-PET (AV-1451) and amyloid-PET scans were identified. A subset had cerebral microbleeds detected on T2* gradient recall echo scans. White matter hyperintensities were semi-automatically segmented using FLAIR MRI in participant space and normalized to a custom template. We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer’s biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Topographic patterns of amyloid-associated white matter hyperintensities included periventricular white matter hyperintensities (frontal and parietal lobes). White matter hyperintense volumes in the detected topographic pattern correlated strongly with lobar cerebral microbleeds (P < 0.001, age and sex adjusted Cohen’s d = 0.703). In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis. Among non-demented elderly, amyloid load correlated with a topographic pattern of white matter hyperintensities. Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities. The study did not support an association between increased tau burden and white matter hyperintense burden.

Objectives: Patients requiring admission to an ICU may subsequently experience cognitive decline. Our objective was to investigate longitudinal cognitive trajectories in older adults hospitalized in ICUs. We hypothesized that individuals hospitalized for critical illness develop greater cognitive decline compared with those who do not require ICU admission. Design: A retrospective cohort study using prospectively collected cognitive scores of participants enrolled in the Mayo Clinic Study of Aging and ICU admissions retrospectively ascertained from electronic medical records. A covariate-adjusted linear mixed effects model with random intercepts and slopes assessed the relationship between ICU admissions and the slope of global cognitive z scores and domains scores (memory, attention/executive, visuospatial, and language). Setting: ICU admissions and cognitive scores in the Mayo Clinic Study of Aging from October 1, 2004, to September 11, 2017. Patients: Nondemented participants age 50 through 91 at enrollment in the Mayo Clinic Study of Aging with an initial cognitive assessment and at least one follow-up visit. Interventions: None. Measurements and Main Results: Of 3,673 participants, 372 had at least one ICU admission with median (25–75th percentile) follow-up after first ICU admission of 2.5 years (1.2–4.4 yr). For global cognitive z score, admission to an ICU was associated with greater decline in scores over time compared with participants not requiring ICU admission (difference in annual slope = –0.028; 95% CI, –0.044 to –0.012; p < 0.001). ICU admission was associated with greater declines in memory (–0.029; 95% CI, –0.047 to –0.011; p = 0.002), attention/executive (–0.020; 95% CI, –0.037 to –0.004; p = 0.016), and visuospatial (–0.013; 95% CI, –0.026 to –0.001; p = 0.041) domains. ICU admissions with delirium were associated with greater declines in memory (interaction p = 0.006) and language (interaction p = 0.002) domains than ICU admissions without delirium. Conclusions: In older adults, ICU admission was associated with greater long-term cognitive decline compared with patients without ICU admission. These findings were more pronounced in those who develop delirium while in the ICU.

Objective: To determine the frequency and characteristics of symptomatic intracerebral hemorrhage in a population-based study Patients and Methods: The population-based Mayo Clinic Study of Aging included 4,994 participants age ≥50 years entered from 11/29/2004 to 3/11/2017. Participants with intracranial hemorrhage were identified using the Rochester Epidemiology Project medical records linkage system. Medical records of these individuals were reviewed. Each hemorrhage was classified as deep, lobar, or cerebellar intracerebral hemorrhage (ICH) or convexity subarachnoid hemorrhage (cSAH). Traumatic, subdural, non-convexal SAH, and epidural hemorrhages were excluded. Patient demographics, presence of hypertension, antithrombotic regimen, APOE genotype, and amyloid PET scan results were collected when available. Individuals with hemorrhages were matched 3:1 on age and gender to controls without symptomatic hemorrhage. Analyses within the cases and between the groups were performed. Results: Symptomatic hemorrhages were identified in 57 individuals for a frequency of 1.14%. Twenty-one were classified as deep, 26 lobar, 5 cerebellar, and 5 cSAH. Mean age at the time of hemorrhage was 80.9 years (SD ±7.9). 54.4% of hemorrhages occurred in men. Hypertension was present in 45.6%. Of those with lobar ICH or cSAH, 87.1% were on an antithrombotic compared to 65.6% of controls (p=0.02) and 32.3% of these were on warfarin compared to 12.9% of controls (p=0.01). APOE genotype was available in 54 of the 57. APOE e2 and/or e4 was found in 46.7% of those with lobar ICH/cSAH compared to 39.1% of controls (p=0.47) and 35.0% of those with deep ICH versus 39.3% of controls (p=0.73). Of the 31 with either lobar ICH or cSAH, 7 underwent amyloid PET scans; of these, 71.4% were abnormal compared to 42.9% of controls with mean SUVR of 1.911 and 1.565, respectively (p=0.08). Conclusions: Symptomatic ICH occurred in approximately 1 in 100 individuals age 50-94 years in this population-based study. In a matched case-control study, antithrombotic use (particularly warfarin) was statistically associated with the development of an ICH. While only a subset underwent amyloid PET, there was a trend towards greater amyloid load in those who developed a lobar or cSAH compared to controls.