HIV Viremia and Risk of Stroke Among People Living with HIV Who Are Using Antiretroviral Therapy.

BACKGROUND: Rates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined. METHODS: Between 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States. We considered three parameterizations of viral load (VL) including (1) baseline (most recent VL before study entry), (2) time-updated, and (3) cumulative VL (copy-days/mL of virus). We used Cox proportional hazards models to estimate hazard ratios (HRs) for stroke risk comparing the 75th percentile ("high VL") to the 25th percentile ("low VL") of baseline and time-updated VL. We used marginal structural Cox models, with most models adjusted for traditional stroke risk factors, to estimate HRs for stroke associated with cumulative VL. RESULTS: Among 15,974 people living with HIV, 139 experienced a stroke (113 ischemic; 18 hemorrhagic; eight were unknown type) over a median follow-up of 4.2 years. Median baseline VL was 38 copies/mL (interquartile interval: 24, 3,420). High baseline VL was associated with increased risk of both ischemic (HR: 1.3; 95% CI = 0.96-1.7) and hemorrhagic stroke (HR: 3.1; 95% CI = 1.6-5.9). In time-updated models, high VL was also associated with an increased risk of any stroke (HR: 1.8; 95% CI = 1.4-2.3). We observed no association between cumulative VL and stroke risk. CONCLUSIONS: Our findings are consistent with the hypothesis that elevated HIV VL may increase stroke risk, regardless of previous VL levels.

Impact of aging on the immune response to traumatic brain injury (AIm:TBI) study protocol.

BACKGROUND: Traumatic brain injury (TBI) in older adults leads to considerable morbidity and mortality. Outcomes among older adults with TBI are disparately worse than in younger adults. Differences in immunological response to injury may account for at least some of this disparity. Understanding how ageing differentially affects the immune response to TBI and how older age and these immunological changes affect the natural history of recovery following TBI are the goals of this study. DESIGN/METHODS: A prospective multiple cohort design is being used to assess the effects of ageing and TBI on immune makers and to test predictors of impairment and disability in older adults following mild TBI. Older adults (>55 years) with mild TBI are enrolled with three comparison groups: younger adults (21-54 years) with mild TBI, non-injured older adults (>55 years) and non-injured young adults (21-54 years). For the primary analysis, we will assess the association between immune markers and Glasgow Outcome Scale-Extended at 6 months, using logistic regression. Predictors of interest will be inflammatory biomarkers. Multivariate linear regression will be used to evaluate associations between biomarkers and other outcomes (symptoms, function and quality of life) at 3 and 6 months. Exploratory analyses will investigate the utility of biomarkers to predict outcome using receiver-operating characteristic curves. DISCUSSION: A better understanding of the recovery trajectory and biological rationale for disparate outcomes following TBI in older adults could allow for development of specific interventions aimed at reducing or eliminating symptoms. Such interventions could reduce impairment and healthcare costs.

Impact of Age on Plasma Inflammatory Biomarkers in the 6 Months Following Mild Traumatic Brain Injury.

OBJECTIVE: To compare plasma inflammatory biomarker concentrations to 6 months in young and older adults with and without mild traumatic brain injury (TBI). SETTING: Level 1 trauma center. PARTICIPANTS: Younger (21-54 years) and older (55+) adults diagnosed with mild TBI along with age-/sex-matched noninjured controls (n = 313). DESIGN: Prospective cohort study. MAIN MEASURES: Multiplex assays were used to quantify concentrations of selected plasma inflammatory markers at day 0, months 1 and 6. RESULTS: Persistent aging-related differences were found between control groups in concentrations of 4 cytokines up to 6 months. At day 0, interleukin-6 (IL-6), IL-8, and fractalkine were higher in the older TBI compared with older control as well as the younger TBI groups, while IL-10 was higher in older TBI compared with controls. At month 1, significantly higher concentrations of IL-8, fractalkine, and tumor necrosis factor-α (TNF-α) were seen. At 6 months postinjury, significantly higher concentrations of IL-6 and IL-8 were seen, while a lower concentration of IL-7 was found in older versus younger TBI groups. CONCLUSION: The neuroinflammatory signature that accompanies mild TBI in older adults differs from that of younger adults. The differences seen are notable for their roles in neutrophil attraction (IL-8), neuronal-microglial-immune cell interactions (fractalkine), and chronic inflammation (IL-6).

Minority Patients are Less Likely to Undergo Withdrawal of Care After Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Prior studies of patients in the intensive care unit have suggested racial/ethnic variation in end-of-life decision making. We sought to evaluate whether race/ethnicity modifies the implementation of comfort measures only status (CMOs) in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). METHODS: We analyzed data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a prospective cohort study specifically designed to enroll equal numbers of white, black, and Hispanic subjects. ICH patients aged ≥ 18 years were enrolled in ERICH at 42 hospitals in the USA from 2010 to 2015. Univariate and multivariate logistic regression analyses were implemented to evaluate the association between race/ethnicity and CMOs after adjustment for potential confounders. RESULTS: A total of 2705 ICH cases (912 black, 893 Hispanic, 900 white) were included in this study (mean age 62 [SD 14], female sex 1119 [41%]). CMOs patients comprised 276 (10%) of the entire cohort; of these, 64 (7%) were black, 79 (9%) Hispanic, and 133 (15%) white (univariate p < 0.001). In multivariate analysis, compared to whites, blacks were half as likely to be made CMOs (OR 0.50, 95% CI 0.34-0.75; p = 0.001), and no statistically significant difference was observed for Hispanics. All three racial/ethnic groups had similar mortality rates at discharge (whites 12%, blacks 9%, and Hispanics 10%; p = 0.108). Other factors independently associated with CMOs included age (p < 0.001), premorbid modified Rankin Scale (p < 0.001), dementia (p = 0.008), admission Glasgow Coma Scale (p = 0.009), hematoma volume (p < 0.001), intraventricular hematoma volume (p < 0.001), lobar (p = 0.032) and brainstem (p < 0.001) location and endotracheal intubation (p < 0.001). CONCLUSIONS: In ICH, black patients are less likely than white patients to have CMOs. However, in-hospital mortality is similar across all racial/ethnic groups. Further investigation is warranted to better understand the causes and implications of racial disparities in CMO decisions.

Cortisol is More Important than Metanephrines in Driving Changes in Leukocyte Counts after Stroke.

BACKGROUND: There are notable changes in the number of white blood cells (WBCs) after stroke, but the primary mediators of these changes are unclear. In this study, we assessed the role of the neuroendocrine and sympathetic nervous systems in stroke-induced changes of WBCs within distinct leukocyte subsets, as well as the effect of these changes on stroke outcomes. METHODS: Patients were recruited within 72 hours after ischemic stroke; complete blood count with differential was obtained at set time points. The relationships among leukocyte numbers, cortisol, adrenocorticotropic hormone, interleukin-6, and metanephrines were assessed at 72 hours after stroke. Associations between abnormal leukocyte counts at 72 hours, poststroke infection, and 3-month outcomes were determined. RESULTS: A total of 114 subjects were enrolled. Severe stroke was associated with leukocytosis, neutrophilia, monocytosis, lymphopenia, and eosinopenia. At 72 hours after stroke, increased serum cortisol was independently associated with neutrophilia and lymphopenia. Abnormal leukocyte counts were not independently predictive of poststroke infection, but lymphopenia was associated with poor outcome (modified Rankin score >3) at 3 months after stroke (odds ratio = 22.86 [1.95, 267.65]; P = .01). CONCLUSIONS: Increased serum cortisol is independently associated with neutrophilia and lymphopenia after stroke. Lymphopenia is not an independent predictor of infections but is independently associated with worse outcome.

Chemical Sympathectomy, but not Adrenergic Blockade, Improves Stroke Outcome.

BACKGROUND: A robust adrenergic response following stroke impairs lymphocyte function, which may prevent the development of autoimmune responses to brain antigens. We tested whether inhibition of the sympathetic response after stroke would increase the propensity for developing autoimmune responses to brain antigens. METHODS: Male Lewis rats were treated with 6-hydroxydopamine (OHDA) prior to middle cerebral artery occlusion (MCAO), labetalol after MCAO, or appropriate controls. Behavior was assessed weekly and animals survived to 1 month at which time ELISPOT assays were done on lymphocytes from spleen and brain to determine the Th1 and Th17 responses to myelin basic protein (MBP), ovalbumin (OVA), and concanavalin A. A subset of animals was sacrificed 72 hours after MCAO for evaluation of infarct volume and lymphocyte responsiveness. Plasma C-reactive protein (CRP) was measured as a biomarker of systemic inflammation. RESULTS: Despite similar initial stroke severity and infarct volumes, 6-OHDA-treated animals lost less weight and experienced less hyperthermia after stroke. 6-OHDA-treated animals also had decreased CRP in circulation early after stroke and experienced better neurological outcomes at 1 month. The Th1 and Th17 responses to MBP did not differ among treatment groups at 1 month, but the Th1 response to OVA in spleen was more robust in labetalol and less robust in 6-OHDA-treated animals. CONCLUSIONS: Chemical sympathectomy with 6-OHDA, but not treatment with labetalol, decreased systemic markers of inflammation early after stroke and improved long-term outcome. An increase in Th1 and Th17 responses to MBP was not seen with inhibition of the sympathetic response.

Labetalol Use Is Associated With Increased In-Hospital Infection Compared With Nicardipine Use in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Increased sympathetic tone causes hypertension after intracerebral hemorrhage, and blood pressure reduction has been studied as a way to decrease hemorrhage growth and improve outcomes. It is unknown if the antihypertensive used to achieve blood pressure goals influences either. Because sympatholytic drugs reduce death and infection in animal models, we hypothesized that labetalol would improve outcomes compared with nicardipine. METHODS: Prospective data from a single center were retrospectively reviewed. Patients receiving labetalol, nicardipine, or both during their first 3 days of hospitalization were included. Outcomes included in-hospital death; discharge modified Rankin Score >2; and in-hospital urinary tract infection, pneumonia, or bacteremia. Patients were compared with propensity scoring and analyzed with linear models adjusted for significant confounders. RESULTS: Of 1066 admissions, 525 were treated with labetalol or nicardipine and are included; 229 (43.6%) received labetalol, 107 (20.4%) received nicardipine, and 189 (36.0%) received both. Mortality and infection rates were 40.2% and 15.8%, respectively, 77.2% had a modified Rankin Score >2. After adjustment, compared with nicardipine alone, labetalol alone was associated with infection (odds ratio, 3.12; confidence interval, 1.27-7.64; P=0.013) but not when combined with nicardipine (odds ratio, 2.44; confidence interval, 0.98-6.07; P=0.055). Labetalol, with or without nicardipine, was not associated with death or discharge modified Rankin Score >2. CONCLUSIONS: Compared with nicardipine, labetalol was associated with increased in-hospital infections, but not mortality or modified Rankin Score >2. These findings do not support our hypothesis that labetalol use improves outcomes relative to nicardipine in intracerebral hemorrhage.

Splenectomy Does Not Improve Long-Term Outcome After Stroke.

BACKGROUND AND PURPOSE: Immune responses to brain antigens after stroke contribute to poor outcome. We hypothesized that splenectomy would lessen the development of such responses and improve outcome. METHODS: Male Lewis rats (275-350 g) underwent 2-hour middle cerebral artery occlusion immediately after splenectomy or sham splenectomy. Animals were survived to 4 weeks (672 hrs), and immune responses to myelin basic protein determined at euthanasia. Infarct volume was determined in a subset of animals euthanized at 72 hours. Behavioral outcomes were assessed to 672 hours. RESULTS: Splenectomy was associated with worse neurological scores early after stroke, but infarct size at 72 hours was similar in both groups. Behavioral outcomes and immune responses to myelin basic protein were also similar among splenectomized and sham-operated animals 672 hours after middle cerebral artery occlusion. CONCLUSIONS: Splenectomy did not alter the immune responses to brain antigens or improve outcome after stroke. Differences between this study and other studies of splenectomy and stroke are examined.

Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Statement for Healthcare Professionals From the American Heart Association.

At least half of all stroke survivors experience fatigue; thus, it is a common cause of concern for patients, caregivers, and clinicians after stroke. This scientific statement provides an international perspective on the emerging evidence surrounding the incidence, prevalence, quality of life, and complex pathogenesis of poststroke fatigue. Evidence for pharmacological and nonpharmacological interventions for management are reviewed, as well as the effects of poststroke fatigue on both stroke survivors and caregivers.

Added Value of Vessel Wall Magnetic Resonance Imaging for Differentiation of Nonocclusive Intracranial Vasculopathies.

BACKGROUND AND PURPOSE: Our goal is to determine the added value of intracranial vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive vasculopathies compared with luminal imaging alone. METHODS: We retrospectively reviewed images from patients with both luminal and IVWI to identify cases with clinically defined intracranial vasculopathies: atherosclerosis (intracranial atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and inflammatory vasculopathy. Two neuroradiologists blinded to clinical data reviewed the luminal imaging of defined luminal stenoses/irregularities and evaluated the pattern of involvement to make a presumed diagnosis with diagnostic confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in addition to IVWI for the pattern of wall involvement, presence and pattern of postcontrast enhancement, and presumed diagnosis and confidence. Analysis was performed on per-lesion and per-patient bases. RESULTS: Thirty intracranial atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47 inflammatory vasculopathy lesions) were included. For both per-lesion and per-patient analyses, there was significant diagnostic accuracy improvement with luminal imaging+IVWI when compared with luminal imaging alone (per-lesion: 88.8% versus 36.1%; P<0.001 and per-patient: 96.3% versus 43.5%; P<0.001, respectively). There was substantial interrater diagnostic agreement for luminal imaging+IVWI (κ=0.72) and only slight agreement for luminal imaging (κ=0.04). Although there was a significant correlation for both luminal and IVWI pattern of wall involvement with diagnosis, there was a stronger correlation for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease diagnosis than for luminal imaging (κ=0.69 versus 0.18; P<0.001). CONCLUSIONS: IVWI can significantly improve the differentiation of nonocclusive intracranial vasculopathies when combined with traditional luminal imaging modalities.

Increased infections with ß-blocker use in ischemic stroke, a ß2-receptor mediated process?

Strokes promote immunosuppression, partially from increased sympathetic activity. Altering sympathetic drive with ß-blockers has variably been shown to improve stroke outcomes. This study adds to this literature using propensity score matching to limit confounding and by examining the effects of selective and non-selective ß-blockers. Prospective data from acute ischemic stroke admissions at a single center from July 2010-June 2015 were analyzed. Outcomes included infection (urinary tract infection [UTI], pneumonia, or bacteremia), discharge modified Rankin Score (mRS), and in-hospital death. Any selective and non-selective ß-blocker use during the first 3 days of admission were investigated with propensity score matching. A sensitivity analysis was also performed. This study included 1431 admissions. Any ß-blocker use was associated with increased infections (16.4 vs. 10.7%, p = 0.030). Non-selective ß-blocker use was associated with increased infections (18.9 vs. 9.7%, p = 0.005) and UTIs (13.0 vs. 5.5%, p = 0.009). Selective ß-blocker use was not associated with infection. There were no associations between ß-blocker use and in-hospital death or discharge mRS. In the sensitivity analysis, the association between non-selective ß-blocker use and urinary tract infections persisted (12.5 vs. 4.2%, p = 0.044). No associations with death or mRS were found. Early ß-blocker use after ischemic stroke may increase the risk of infection but did not change disability or mortality risk. The mechanism may be mediated by ß2-adrenergic receptor antagonism given the different effects seen with selective versus non-selective ß-blocker use.

Added Value of Vessel Wall Magnetic Resonance Imaging in the Differentiation of Moyamoya Vasculopathies in a Non-Asian Cohort.

BACKGROUND AND PURPOSE: Although studies have evaluated the differential imaging of moyamoya disease and atherosclerosis, none have investigated the added value of vessel wall magnetic resonance imaging (MRI). This study evaluates the added diagnostic value of vessel wall MRI in differentiating moyamoya disease, atherosclerotic-moyamoya syndrome (A-MMS), and vasculitic-MMS (V-MMS) with a multicontrast protocol. METHODS: We retrospectively reviewed the carotid artery territories of patients with clinically defined vasculopathies (moyamoya disease, atherosclerosis, and vasculitis) and steno-occlusive intracranial carotid disease. Two neuroradiologists, blinded to clinical data reviewed the luminal imaging of each carotid, evaluating collateral extent and making a presumed diagnosis with diagnostic confidence. After 3 weeks, the 2 readers reviewed the luminal imaging+vessel wall MRI for the presence, pattern and intensity of postcontrast enhancement, T2 signal characteristics, pattern of involvement, and presumed diagnosis and confidence. RESULTS: Ten A-MMS, 3 V-MMS, and 8 moyamoya disease cases with 38 affected carotid segments were included. There was significant improvement in diagnostic accuracy with luminal imaging+vessel wall MRI when compared with luminal imaging (87% versus 32%, P<0.001). The most common vessel wall MRI findings for moyamoya disease were nonenhancing, nonremodeling lesions without T2 heterogeneity; for A-MMS eccentric, remodeling, and T2 heterogeneous lesions with mild/moderate and homogeneous/heterogeneous enhancement; and for V-MMS concentric lesions with homogeneous, moderate enhancement. Inter-reader agreement was moderate to substantial for all vessel wall MRI characteristics (κ=0.46-0.86) and fair for collateral grading (κ=0.35). There was 11% inter-reader agreement for diagnosis on luminal imaging when compared with 82% for luminal imaging+vessel wall MRI (P<0.001). CONCLUSIONS: Vessel wall MRI can significantly improve the differentiation of moyamoya vasculopathies when combined with traditional imaging techniques.

Weekend Discharge and Stroke Quality of Care: Get With The Guidelines-Stroke Data from a Comprehensive Stroke Center.

OBJECTIVE: Get With The Guidelines-Stroke collects data on hospital compliance with evidence-based stroke quality of care indicators. Prior work has investigated a link between weekend hospital admission and increased mortality after stroke. There is, however, a paucity of work investigating a similar association between weekend hospital discharge and quality of care. We aimed to determine if weekend discharge affects care to enlighten opportunities for quality improvement. MATERIALS AND METHODS: Through a retrospective analysis of records from a Comprehensive Stroke Center from July 2010 to June 2015, we identified patients with ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage. Our quality of care indicators were dysphagia screening, rehabilitation assessment, smoking cessation counseling, stroke education, and weight reduction counseling. We created regression models to find adjusted differences in quality of care measure compliance for patients discharged on the weekend. RESULTS: Our analysis included 2737 patients, of which 431 were discharged on the weekend. After adjustment, weekend discharge was significantly associated with reduced stroke education (odds ratio .67, confidence interval .51-0.88, P = .004) and reduced weight reduction counseling (odds ratio .65, confidence interval .45-0.93, P = .018). CONCLUSIONS: Hospital discharge on the weekend was associated with an adjusted one-third decrease in odds of stroke education and weight reduction counseling. There is an opportunity for quality improvement in educating stroke patients before hospital discharge on the weekend.

Multicontrast high-resolution vessel wall magnetic resonance imaging and its value in differentiating intracranial vasculopathic processes.

BACKGROUND AND PURPOSE: Although studies have attempted to differentiate intracranial vascular disease using vessel wall magnetic resonance imaging (VWI), none have incorporated multicontrast imaging. This study uses T1- and T2-weighted VWI to differentiate intracranial vasculopathies. METHODS: We retrospectively reviewed patients with clinically defined intracranial vasculopathies causing luminal stenosis/irregularity who underwent VWI studies. Two blinded experts evaluated T1 precontrast and postcontrast and T2-weighted VWI characteristics, including the pattern of wall thickening; presence, pattern, and intensity of postcontrast enhancement; and T2 signal characteristics. RESULTS: Twenty-one cases of atherosclerosis (intracranial atherosclerotic disease [ICAD]), 4 of reversible cerebral vasoconstriction syndrome, and 4 of vasculitis were identified, with a total of 118 stenotic lesions (81 ICAD, 22 reversible cerebral vasoconstriction syndrome, and 15 vasculitic lesions). There was substantial to excellent inter-reader agreement for the assessment of lesional T2 hyperintensity (κ=0.80), pattern of wall thickening (κ=0.87), presence (κ=0.90), pattern (κ=0.73), and intensity (κ=0.77) of enhancement. ICAD lesions were significantly more likely to have eccentric wall involvement (90.1%) than reversible cerebral vasoconstriction syndrome (8.2%; P<0.001) and vasculitic lesions (6.7%; P<0.001) and were also more likely to have T2 hyperintensity present than the other 2 vasculopathies (79% versus 0%; P<0.001). There were also significant differences in the presence, intensity, and pattern of enhancement between all lesion types. Combining T1 and T2 VWI increased the sensitivity of VWI in differentiating ICAD from other vasculopathies from 90.1% to 96.3%. CONCLUSIONS: Multicontrast VWI can be a complementary tool for intracranial vasculopathy differentiation, which often leads to more invasive workups when reversible cerebral vasoconstriction syndrome and vasculitis are in the differential diagnosis.

Palliative Care Needs in the Neuro-ICU.

OBJECTIVES: Patients admitted to the neurological or neurosurgical ICU are likely to have palliative care needs. The goals of this project are to encourage the ICU team to identify palliative care needs for patients and their families and potential ways to meet those needs. DESIGN: Quality improvement project using a parallel-group prospective cohort design. SETTING: Single neuro-ICU at a large, academic medical center. PATIENTS: All patients admitted to the neuro-ICU from September 1, 2013, to November 30, 2013. INTERVENTIONS: We developed a palliative care needs screening tool consisting of four questions: 1) Does the patient have distressing physical or psychological symptoms? 2) Are there specific support needs for patient or family? 3) Are treatment options matched with patient-centered goals? 4) Are there disagreements among teams and family? We implemented this daily screening tool on morning rounds for one of two neurocritical care services that alternate admitting days to a single neuro-ICU. We examined prevalence and nature of palliative care needs and actions to address those needs, comparing the services with and without screening. MEASUREMENTS AND MAIN RESULTS: Over the 3-month period, 130 patients were admitted to the service with screening and 132 patients to the service without screening. The two groups did not differ with regard to age, gender, Glasgow Coma Scale, or diagnosis. Palliative care needs were identified in 62% of screened patients (80/130). Needs were mainly social support (53%) and establishing goals of care (28%). Screening was associated with more documented family conferences (p = 0.019) and a trend toward more palliative care consultations (p = 0.056). CONCLUSIONS: We developed a brief palliative care needs screening tool that identified palliative care needs for 62% neuro-ICU patients. This tool was associated with actions to meet these needs, potentially improving care for patients and their families.

Stroke, IL-1ra, IL1RN, infection and outcome.

BACKGROUND: Infection is a common phenomenon following stroke, and adversely affects outcome. Previous studies suggest that interleukin-1 receptor antagonist (IL-1ra) and single nucleotide polymorphisms (SNPs) in the IL1RN gene might influence the risk of post-stroke infection and outcome. In this study, we addressed the effects of the rs4251961 SNP in IL1RN on infection risk and outcome. METHODS: Subjects with acute ischemic stroke were enrolled within 72 h of symptom onset and followed up to 1 year. Plasma IL-1ra was measured at multiple time points and outcome assessed at 1, 3, 6, and 12 months. Active surveillance for infection occurred while subjects were hospitalized. Subjects were genotyped for the IL1RN rs4251961 polymorphism. RESULTS: In the population of 113 subjects for this study, those with the minor C allele of rs4251961 polymorphism in IL1RN were more likely to be Caucasian, hypertensive, and to be afflicted with coronary heart disease. Higher plasma IL-1ra was associated with an increased risk of infection (other than pneumonia), and the minor C allele of rs4251961 was independently associated with a decreased risk of infection (other than pneumonia). Initial plasma IL-1ra was not predictive of long-term outcome, but patients with the minor C allele of rs4251961 were more likely to experience good (modified Rankin Score <2) long-term outcome. CONCLUSIONS: These data indicate that IL-1ra and IL1RN may influence the risk of infection after stroke, but this influence seems limited to infections other than pneumonia. Further studies are needed to better understand the complexities of immune regulation on infection and outcome after stroke.

Associations Between Measures of Disability and Quality of Life at Three Months After Stroke.

Background: The modified Rankin Scale (mRS), which measures degree of disability in daily activities, is the most common outcome measure in stroke research. Quality of life (QoL), however, is impacted by factors other than disability. The goal of this study was to assess the correlation between functional dependence and a more patient-centered QoL measure, the European QoL visual analog scale (EQ VAS). Methods: We reviewed prehospital and hospital records from 11 acute care hospitals in Seattle, Washington (USA) from June 2000 to January 2003 for this cohort study. Patients with a final diagnosis of stroke were contacted three to four months after stroke, and mRS and EQ VAS were assessed. Good QoL was defined as EQ VAS ≥65. Results: Of 760 patients with stroke, 346 were available at three to four months. Most (296, 85.5%) had ischemic stroke. Overall, mRS and QoL were negatively correlated (Spearman's ρ -0.53, p < 0.001). Percentage of good QoL decreased as mRS increased from 0 to 5 (88%, 70%, 52%, 50%, 31%, 20%, respectively, p < 0.001). However, 36% (n = 62) of patients with dependent mRS (3-5, n = 174) reported good QoL, and 30% (n = 52) of patients with independent mRS (0-2, n = 172) reported poor QoL. In multivariable analysis, older age, male gender, and absence of dementia, were associated with good QoL despite dependent mRS; atrial fibrillation was associated with poor QoL despite independent mRS. Conclusions: QoL decreases with increasing mRS, but exceptions exist with good QoL despite high mRS. To provide patient-centered care, clinicians and researchers should avoid equating disability with QoL after stroke.

Fatigue, Toll-Like Receptor 4, and Pro-Inflammatory Cytokines in Adults With Subarachnoid Hemorrhage: A 6-Month Longitudinal Study.

BACKGROUND: Fatigue is prevalent in subarachnoid hemorrhage (SAH) survivors. Biological mechanisms underlying fatigue post-SAH are not clear. Inflammation may contribute to the development of fatigue. This study aimed to examine the associations between inflammatory markers and fatigue during the first 6 months post-SAH. Specific biomarkers examined included both early and concurrent expression of Toll-Like Receptor 4 (TLR4) messenger RNA (mRNA) and plasma concentrations of pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)1ß, and IL6. METHODS: We conducted a 6-month longitudinal study with a convenience sample of 43 SAH survivors. We collected blood samples on days 2, 3, and 7 and 2, 3, and 6 months post-SAH to assess biomarkers. Fatigue was assessed by the PROMIS Fatigue Scale at 2, 3, and 6 months. Linear mixed models were used to test the associations between early (days 2, 3, and 7) and concurrent (2, 3, and 6 months) TLR4 mRNA expression (TagMan gene expression assays) and TNF-α, IL1ß, and IL6 plasma concentrations (multiplex assays) and concurrent fatigue. RESULTS: 28% of SAH survivors experienced fatigue during the first 6 months post-SAH. Fatigue levels in SAH survivors were higher than those of the U.S. population and consistent during the 6 months. Experience of fatigue during the 6 months post-SAH was associated with higher IL1ß plasma concentrations on day 7 and IL1ß, IL6, and TNF-α plasma concentrations during the 6 months post-SAH. CONCLUSION: Inflammation appears to underlie the development of fatigue in SAH survivors.

Higher plasma fractalkine is associated with better 6-month outcome from ischemic stroke.

BACKGROUND AND PURPOSE: Fractalkine (CX3CL1) is a unique chemokine that is constitutively expressed on neurons where it serves as an adhesion molecule for lymphocytes and monocytes. CX3CL1 may also be cleaved from the surface of these cells and enter the circulation to act as a traditional chemokine. CX3CL1 could thus influence the inflammatory response after stroke. We hypothesized that patients with higher plasma CX3CL1 after stroke would have a more robust inflammatory response and experience worse outcome. METHODS: Plasma CX3CL1 concentrations were assessed in 85 patients who were part of a larger study evaluating immune responses after ischemic stroke; CX3CL1 values were available from Day 1 to Day 180 after stroke onset. CX3CL1 was correlated to measures of inflammation and its effect on outcome assessed. RESULTS: At 1 day after stroke, CX3CL1 was lower in patients with severe strokes. At 180 days after stroke, CX3CL1 concentrations were lower in patients with poor outcome. The association of CX3CL1 and outcome at 180 days was independent of initial stroke severity. Plasma CX3CL1 at 180 days was inversely associated with systemic markers of inflammation, including white blood cell counts and high-sensitivity C-reactive protein. CONCLUSIONS: In contrast to our original hypothesis, lower concentrations of CX3CL1 are associated with worse stroke outcome. In light of recent studies suggesting an immunomodulatory and neuroprotective role for CX3CL1 in a variety of neurodegenerative diseases, a therapeutic role for CX3CL1 in stroke recovery should be considered.