Effects of body mass index on the immune response within the first days after major stroke in humans.

INTRODUCTION: Immunological alterations associated with increased susceptibility to infection are an essential aspect of stroke pathophysiology. Several immunological functions of adipose tissue are altered by obesity and are accompanied by chronic immune activation. The purpose of this study was to examine immune function (monocytes, granulocytes, cytokines) as a function of body mass index (BMI: 1st group: 25; 2nd group: 25 BMI 30; 3rd group: 30) and changes in body weight post stroke. METHOD: Fat status was assessed using standardized weight measurements on days 1, 2, 3, 4, 5, and 7 after ischemic stroke in a cohort of 40 stroke patients and 16 control patients. Liver fat and visceral fat were assessed by MRI on day 1 or 2 [I] and on day 5 or 7 [II]. Leukocyte subpopulations in peripheral blood, cytokines, chemokines, and adipokine concentrations in sera were quantified. In a second cohort (stroke and control group, n = 17), multiple regression analysis was used to identify correlations between BMI and monocyte and granulocyte subpopulations. RESULTS: Weight and fat loss occurred from the day of admission to day 1 after stroke without further reduction in the postischemic course. No significant changes in liver or visceral fat were observed between MRI I and MRI II. BMI was inversely associated with IL-6 levels, while proinflammatory cytokines such as eotaxin, IFN-ß, IFN -γ and TNF-α were upregulated when BMI increased. The numbers of anti-inflammatory CD14+CD16+ monocytes and CD16+CD62L- granulocytes were reduced in patients with higher BMI values, while that of proinflammatory CD16dimCD62L+ granulocytes was increased. CONCLUSION: A small weight loss in stroke patients was detectable. The data demonstrate a positive correlation between BMI and a proinflammatory poststroke immune response. This provides a potential link to how obesity may affect the clinical outcome of stroke patients.

A Managed Care System with Telemedicine Support for Neurological Emergencies.

OBJECTIVES: Telemedicine is frequently used to provide remote neurological expertise for acute stroke workup and was associated with better functional outcomes when combined with a stroke unit system-of-care. We investigated whether such system-of-care yields additional benefits when implemented on top of neurological competence already available onsite. METHODS: Quality improvement measures were implemented within a "hub-and-spoke" teleneurology network in 11 hospitals already provided with onsite or telestroke expertise. Measures included dedicated units for neurological emergencies, standardization of procedures, multiprofessional training, and quality-of-care monitoring. Intervention effects were investigated in a controlled study enrolling patients insured at 3 participating statutory health insurances diagnosed with acute stroke or other neurological emergencies. Outcomes during the intervention period between November 2017 and February 2020 were compared with those pre-intervention between October 2014 and March 2017. To control for temporal trends, we compared outcomes of patients with respective diagnoses in 11 hospitals of the same region. Primary outcome was the composite of up-to-90-day death, new disability with the need of ambulatory or nursing home care, expressed by adjusted hazard ratio (aHR). RESULTS: We included 1,418 patients post-implementation (55% female, mean age 76.7 ± 12.8 year) and 2,306 patients pre-implementation (56%, 75.8 ± 13.0 year, respectively). The primary outcome occurred in 479/1,418 (33.8%) patients post-implementation and in 829/2,306 (35.9%) pre-implementation. The aHR for the primary outcome was 0.89 (95% confidence interval [CI]: 0.79-0.99, p = 0.04) with no improvement seen in non-participating hospitals between post- versus pre-implementation periods (aHR 1.04; 95% CI: 0.95-1.15). INTERPRETATION: Implementation of a multicomponent system-of-care was associated with a lower risk of poor outcomes. ANN NEUROL 2023;93:511-521.

Predictors of post-stroke delirium incidence and duration: Results of a prospective observational study using high-frequency delirium screening.

BACKGROUND: Post-stroke delirium (PSD) is a modifiable predictor for worse outcome in stroke. Knowledge of its risk factors would facilitate clinical management of affected patients, but recently updated national guidelines consider available evidence insufficient. AIMS: The study aimed to establish risk factors for PSD incidence and duration using high-frequency screening. METHODS: We prospectively investigated patients with ischemic stroke admitted within 24 h. Patients were screened twice daily for the presence of PSD throughout the treatment period. Sociodemographic, treatment-related, and neuroimaging characteristics were evaluated as predictors of either PSD incidence (odds ratios (OR)) or duration (PSD days/unit of the predictor, b), using logistic and linear regression models, respectively. RESULTS: PSD occurred in 55/141 patients (age = 73.8 ± 10.4 years, 61 female, National Institutes of Health Stroke Scale (NIHSS) = 6.4 ± 6.5). Age (odds ratio (OR) = 1.06 (95% confidence interval (CI): 1.02-1.10), b = 0.08 (95% CI = 0.04-0.13)), and male gender (b = 0.99 (95% CI = 0.05-1.93)) were significant non-modifiable risk factors. In a multivariable model adjusted for age and gender, presence of pain (OR < sub > mvar = 1.75 (95% CI = 1.12-2.74)), urinary catheter (OR < sub > mvar = 3.16 (95% CI = 1.10-9.14)) and post-stroke infection (PSI; OR < sub > mvar = 4.43 (95% CI = 1.09-18.01)) were predictors of PSD incidence. PSD duration was impacted by presence of pain (b < sub > mvar = 0.49 (95% CI = 0.19-0.81)), urinary catheter (b < sub > mvar = 1.03 (95% CI = 0.01-2.07)), intravenous line (b < sub > mvar = 0.36 (95% CI = 0.16-0.57)), and PSI (b < sub > mvar = 1.60 (95% CI = 0.42-2.78)). PSD (OR = 3.53 (95% CI = 1.48-5.57)) and PSI (OR = 5.29 (95% CI = 2.92-7.66)) independently predicted inferior NIHSS at discharge. Insular and basal ganglia lesions increased the PSD risk about four- to eight-fold. DISCUSSION/CONCLUSION: This study identified modifiable risk factors, the management of which might reduce the negative impact PSD has on outcome.

Course and Recognition of Poststroke Delirium: A Prospective Noninferiority Trial of Delirium Screening Tools.

BACKGROUND AND PURPOSE: Poststroke delirium (PSD) is an independent predictor of unfavorable outcome. Despite its individual and socioeconomic burden, its frequency, clinical course, and routine detection remain unresolved. This study aimed to assess psychometric properties of established delirium screening tools and investigate the natural course of PSD. METHODS: This study investigated patients presenting with high-risk transient ischemic attacks or ischemic stroke within 24 hours during a 3-month period. Twice-daily screenings for PSD were done using the confusion assessment method, nursing delirium scale, and rapid delirium assessment, and evaluated for noninferiority against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. We investigated demographic and stroke characteristics as predictors of PSD, neurological deficits as predictors of false screening results, and conducted a simulation study to estimate the best timing to identify PSD. RESULTS: We enrolled 141 patients (73.8±10.4 years of age, 61 female) with a mean National Institutes of Health Stroke Scale score of 6.4±6.5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based PSD incidence was 39%, which manifested within 24 hours in 25% and 72 hours in almost all cases. The confusion assessment method was the only screening tool noninferior to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ratings providing a sensitivity of 82% and specificity of 80%. Age (odds ratio, 1.07 [1.02-1.13] per year, P=0.004) and National Institutes of Health Stroke Scale (odds ratio, 1.24 [1.15-1.34] per point, P<0.001) were predictors of PSD. False-positive screening results were associated with stroke-induced disorientation (odds ratio, 6.1 [3.2-11.61], P<0.001) and neglect (odds ratio, 2.17 [1.22-3.87], P=0.008). Simulations revealed that one in 4 cases is missed with less than daily screenings. CONCLUSIONS: PSD is a common complication of stroke and transient ischemic attack. Detection is challenged by confounding effects such as focal neurological deficits and the necessity for at least daily screenings. Future studies are required to investigate implementation of these findings in clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03930719.

Corrigendum: Clinical Improvement Following Stroke Promptly Reverses Post-stroke Cellular Immune Alterations.

[This corrects the article DOI: 10.3389/fneur.2019.00414.].

Clinical Improvement Following Stroke Promptly Reverses Post-stroke Cellular Immune Alterations.

Background and Purpose: Stroke induces immediate profound alterations of the peripheral immune system rendering patients more susceptible to post-stroke infections. The precise mechanisms maintaining stroke-induced immune alterations (SIIA) remain unknown. High-Mobility-Group-Protein B1 (HMGB-1) is elevated for at least 7 days post-stroke and has been suggested to mediate SIIA. Patients with rapid clinical recovery of neurological deficits rarely develop severe infections. We therefore investigated whether rapid neurological recovery (either spontaneous or secondary to neurovascular recanalization therapy) alters the course of SIIA. National Institutes of Health Stroke Scale (NIHSS) served as surrogate marker for neurological improvement. Methods: Fluorescence-activated cell sorting was used to define leukocyte subpopulations. C-reactive protein (CRP), procalcitonin (PCT), HMGB-1, GM-CSF; IFN-ß, IFN-γ, IL-1ß, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, IL-17F, IL-18, TNF-α, MIF, IL-8, MCP-1, MCP-4, MIP-3α, MIP-3ß, Eotaxin, soluble IL-6 receptor, E-selectin, and P-selectin were analyzed by ELISA or Multiplex Assays. Serum miRNA expression changes were analyzed by qPCR. Results: Cellular parameters were similar in the improved and non-improved cohort on admission. In patients with rapid clinical recovery absolute and relative leukocyte, neutrophil, and lymphocyte numbers normalized promptly overnight. In contrast, HMGB-1 serum levels did not differ between the two groups. Nine miRNA were found to be differentially expressed between improved and non-improved patients. Conclusions: SIIA are detectable on admission of acute stroke patients. While it was assumed that post-stroke immunosuppression is rapidly reversed with improvement this is the first data set that shows that improvement actually is associated with a rapid reversal of SIIA demonstrating that SIIA require a constant signal to persist. The observation that HMGB-1 serum concentrations were similar in improved and non-improved cohorts argues against a role for this pro-inflammatory mediator in the maintenance of SIIA. Serum miRNA observed to be regulated in stroke in other publications was counter regulated with improvement in our cohort.