Histological quantification of brain tissue inflammatory cell infiltration after focal cerebral infarction: a systematic review.

Ischemic stroke is a leading cause of death and disability, and current treatments to limit tissue injury and improve recovery are limited. Cerebral infarction is accompanied by intense brain tissue inflammation involving many inflammatory cell types that may cause both negative and positive effects on outcomes. Many potential neuroprotective and neurorestorative treatments may affect, and be affected by, this inflammatory cell infiltration, so that accurate quantification of this tissue response is needed. We performed a systematic review of histological methods to quantify brain tissue inflammatory cell infiltration after cerebral infarction. We found reports of multiple techniques to quantify different inflammatory cell types. We found no direct comparison studies and conclude that more research is needed to optimize the assessment of this important stroke outcome.

Pharmacological Management of Agitation and Delirium in Older Adults: a Survey of Practices in Canadian Emergency Departments.

Agitation is a common presenting symptom of delirium for older adults in the emergency department (ED). No medications have been found to reduce delirium severity, symptoms, or mortality, yet they may cause harm. Guidelines suggest using medications only when patients are posing a risk of harm, situations which may arise frequently in the ED. We sought to characterize prescribing patterns of medications for agitation by ED physicians in Canadian hospitals. In this multicenter study, we surveyed physicians in Vancouver, Toronto, and Sherbrooke. Descriptive statistics were used to summarize group characteristics and starting doses were compared to order sets. Fisher exact tests were used for demographic comparison. Ordinal linear regression models were run to identify a relationship between starting dose of medications and location. Of the 137 physicians invited, 77 (56%) completed the survey. Use of order sets was greatest in Sherbrooke and least in Vancouver. The most common medications used across sites were haloperidol, lorazepam, and quetiapine. Benzodiazepines were used across all sites but were used significantly more frequently in Vancouver than the other sites. Practice location was a significant predictor of starting dose of haloperidol, with Sherbrooke and Toronto having a lower starting dose than Vancouver. Higher use of order sets correlated with lower and more consistent starting doses. Benzodiazepines are used across EDs in Canada despite little evidence for efficacy in delirium and risk of harm. Implementation of order sets may be a useful way to standardize ED management of older adults experiencing hyperactive delirium.

Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration.

IMPORTANCE: Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms and improve clinicians' ability to predict disease course and to design targeted management strategies. OBJECTIVE: To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD using statistical classification approaches. DESIGN, SETTING AND PARTICIPANTS: In this retrospective observational study, 90 patients meeting the Frontotemporal Dementia Consortium consensus criteria for bvFTD underwent evaluation at the Memory and Aging Center of the Department of Neurology at University of California, San Francisco. Patients underwent a multidisciplinary clinical evaluation, including clinical demographics, genetic testing, symptom evaluation, neurologic examination, neuropsychological bedside testing, and socioemotional assessments. All patients underwent structural magnetic resonance imaging at their earliest evaluation at the memory clinic. From each patient's structural imaging scans, the mean volumes of 18 regions of interest (ROI) constituting the functional networks specifically vulnerable in bvFTD, including the salience network (SN), with key nodes in the frontoinsula and pregenual anterior cingulate, and the semantic appraisal network (SAN), anchored in the anterior temporal lobe and subgenual cingulate, were estimated. Principal component and cluster analyses of ROI volumes were used to identify patient clusters with anatomically distinct atrophy patterns. Data were collected from from June 19, 2002, to January 13, 2015. MAIN OUTCOMES AND MEASURES: Evaluation of brain morphology and other clinical features, including presenting symptoms, neurologic examination signs, neuropsychological performance, rate of dementia progression, and socioemotional function, in each patient cluster. RESULTS: Ninety patients (54 men [60%]; 36 women [40%]; mean [SD] age at evaluation, 55.1 [9.7] years) were included in the analysis. Four subgroups of patients with bvFTD with distinct anatomic patterns of network degeneration were identified, including 2 salience network-predominant subgroups (frontal/temporal [SN-FT] and frontal [SN-F]), a semantic appraisal network-predominant group (SAN), and a subcortical-predominant group. Subgroups demonstrated distinct patterns of cognitive, socioemotional, and motor symptoms, as well as genetic compositions and estimated rates of disease progression. CONCLUSIONS AND RELEVANCE: Divergent patterns of vulnerability in specific functional network components make an important contribution to the clinical heterogeneity of bvFTD. The data-driven anatomic classification identifies biologically meaningful anatomic phenotypes and provides a replicable approach to disambiguate the bvFTD syndrome.