Citations

Objectives: There is a paucity of data on patients with new-onset status epilepticus in patients without a prior history of epilepsy; we aimed to describe clinical characteristics and assess variables predictive of outcomes. Design: Retrospective cohort. Setting: Quaternary academic medical center. Patients: Adult patients with new-onset status epilepticus. Methods: Retrospective review of adults with new-onset status epilepticus admitted to Mayo Clinic, Rochester MN between January 1, 1990, and December 31, 2015, was performed. Patient demographics, status epilepticus etiology, Status Epilepticus Severity Score, and status epilepticus classification per the Status Epilepticus Severity Score were recorded. Six-month mortality and functional outcomes defined as modified Rankin scale (≥3 at last follow-up was considered poor) were primary outcomes. Refractory status epilepticus was a secondary outcome. Interventions: None. Measurements and Main Results: One-hundred seventy-seven patients were included. Status epilepticus was convulsive in 124 (70.1%) and nonconvulsive in 53 (29.9%); 96 cases (54.2%) were refractory status epilepticus. Mean age at onset was 63 ± 18 years; 52.5% were greater than or equal to 65 years. Etiologies were acute in 50.8%, progressive in 18.1%, remote in 19.2%, and unknown in 11.9% patients. Six-month mortality was 32.2%, and 70.1% had poor modified Rankin scale at mean follow-up 3.1 ± 3.5 years. Age greater than or equal to 65 was a significant predictor of poor functional outcome and 6-month mortality. Loss of consciousness, status epilepticus classification, or age greater than or equal to 65 did not predict progression to refractory status epilepticus. Progression to refractory status epilepticus did not impact functional outcome or mortality at last follow-up. Conclusions: Poor outcomes in new-onset status epilepticus were associated with older age as well as predominantly progressive or remote symptomatic disease. Further prospective investigations assessing the course and outcomes of these patients would be useful in management and prognostication.

SummaryObjectiveIn patients with status epilepticus (SE) without prior epilepsy, there are limited data on the safety of discontinuing antiseizure drugs (ASDs) after seizure control. We aimed to describe seizure recurrence when weaning from ASDs following new onset SE (NOSE).MethodsRetrospective review of adult patients with NOSE admitted to Mayo Clinic, Rochester, Minnesota between January 1, 1990 and December 31, 2015 was performed. Weaning was defined as a discontinuation of ASDs following discharge. Patient demographics, SE characteristics, timing of ASD withdrawal, and seizure recurrence were collected.ResultsOne hundred seventy‐seven patients with mean age 63 ± 18 years were identified; 96 (54.2%) patients had refractory SE (RSE), and 81 (45.8%) had nonrefractory SE. Mean follow‐up was 3.8 ± 3.2 years for those successfully weaned off ASDs. One hundred thirty (73.4%) with outpatient follow‐up were included in the analysis; 128 (98.5%) patients were discharged on an ASD; 44 of 128 (34.4%) patients underwent weaning from at least 1 ASD following discharge, including 27 of 128 (21.1%) who were completely weaned off of all ASDs. Younger patients (P = 0.009) and those with RSE (P = 0.048, odds ratio = 2.12, 95% confidence interval = 1.00‐4.48) tended to undergo weaning. Six of 44 (13.6%) patients had seizure recurrence when weaned off of any ASD, and two of 27 (7.4%) patients completely weaned off all ASDs had seizure recurrence. Two of seven (28.6%) patients who underwent attempted barbiturate weaning experienced seizure recurrence.SignificanceWe found a rate of 13.6% for late seizure recurrence after weaning from at least one ASD in patients with NOSE; seizure recurrence was more likely in patients with RSE treated with barbiturates. Systematic collection of longitudinal data in patients requiring multiple ASDs for NOSE control will provide more conclusive guidance on weaning from ASDs.

Glioma incidence is highest in non‐Hispanic Whites, and to date, glioma genome‐wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case–Control Study and GliomaSE Case–Control Study previously estimated to have <80% EA, or self‐identify as non‐White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR ≥0.4 ), and ≥15% NAA (AMR ≥0.15 ), genome‐wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10 −4 ; 11p11.12, p = 7.0 × 10 −4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR ≥0.4 . In addition, we identified a peak at rs1620291 ( p = 4.36 × 10 −6 ) in 7q21.3. Among AMR ≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10 −4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10 −4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.

Abstract White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.

Purpose The purpose of this study was to examine the relationship between manifestations of racism in medical school and subsequent changes in graduating medical students’ intentions to practice in underserved or minority communities, compared with their attitudes and intentions at matriculation. Method The authors used repeated-measures data from a longitudinal study of 3,756 students at 49 U.S. medical schools that were collected from 2010 to 2014. They conducted generalized linear mixed models to estimate whether manifestations of racism in school curricula/policies, school culture/climate, or student attitudes/behaviors predicted first- to fourth-year changes in students’ intentions to practice in underserved communities or primarily with minority populations. Analyses were stratified by students’ practice intentions (no/undecided/yes) at matriculation. Results Students’ more negative explicit racial attitudes were associated with decreased intention to practice with underserved or minority populations at graduation. Service learning experiences and a curriculum focused on improving minority health were associated with increased intention to practice in underserved communities. A curriculum focused on minority health/disparities, students’ perceived skill at developing relationships with minority patients, the proportion of minority students at the school, and the perception of a tense interracial environment were all associated with increased intention to care for minority patients. Conclusions This study provides evidence that racism manifested at multiple levels in medical schools was associated with graduating students’ decisions to provide care in high-need communities. Strategies to identify and eliminate structural racism and its manifestations in medical school are needed.