Factors Associated with Thrombolysis Outcome in Ischemic Stroke Patients with Atrial Fibrillation

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P < 0.001) and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were: heart failure (P = 0.045); high systolic pressure (P = 0.039); high blood glucose (P = 0.030); and a high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001). Moreover, high systolic pressure at admission (P = 0.007), high blood glucose (P = 0.027), and a high NIHSS score (P < 0.001) were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score (P = 0.006) and warfarin taken within 48 h before stroke onset (P = 0.032) were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke.     

Spontaneous cervical artery dissection is accompanied by a hypercoagulable state and simultaneous inflammatory condition

Background

Spontaneous cervical artery dissections (sCAD) are often preceded by infections. However, existing data about inflammatory parameters remained inconsistent. Remarkably, concurrent information about the coagulation system, whose affection seems also reasonable to cause ischaemic events, are still lacking in sCAD patients. Thus, this study explores the association between the inflammatory and coagulation system in patients with sCAD.

Methods

The parameters leukocyte and thrombocyte count, C-reactive protein, fibrinogen, D-dimer, activated partial thromboplastin time (aPTT) and prothrombin time were extracted from hospital-based medical records of patients (n = 60) with sCAD and compared with those of a control group (n = 97) from a prospective observational stroke study. Univariate analyses were added by multiple regression analyses.

Results

As compared with the control group, patients with sCAD had an increased leucocyte count (9.2 ± 3.2 vs. 7.9 ± 2.2 × 10⁹/l; p = 0.003), an increased thrombocyte count (252 ± 52 vs. 229 ± 64 × 10⁹/l; p = 0.021), a shortened aPTT 28.0 ± 3.5 vs. 29.9 ± 3.6 s; p = 0.001) and decreased D-dimer values (0.44 ± 0.29 vs. 0.76 ± 0.73 mg/l; p = 0.002). However, in multiple regression analyses adjusted for age, sex, initial stroke severity, arterial hypertension, diabetes mellitus and smoking only the shortened aPTT remained statistically significant (p = 0.045) between groups, while differences on leucocyte count (p = 0.087), thrombocyte count (p = 0.234) and D-dimer (p = 0.321) failed statistical significance.

Conclusion

We found evidence for a hypercoagulable state in patients with sCAD as indicated by a shortened aPTT, which was associated with a trend to an increased leucocyte count at the same time. Our findings first strengthen the hypothesis that inflammation critically impacts on the occurrence of sCAD, and second linked this condition with a marked affection of the coagulation system.

     

Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super-Refractory Status Epilepticus

Background

Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined.

Methods

Retrospective chart review including children age 0–17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated.

Results

Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths.

Conclusions

Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.

     

Systemic Inflammatory Response Syndrome (SIRS) Score Independently Predicts Poor Outcome in Isolated Traumatic Brain Injury

Introduction

Systemic inflammatory response syndrome (SIRS) is frequently observed after various types of acute cerebral injury and has been linked to clinical deterioration in non-traumatic brain injury (TBI). SIRS scores have also been shown to be predictive of length of stay and mortality in trauma patients. We aimed to determine the prognostic utility of SIRS present at admission in trauma patients with isolated TBI.

Methods

This was a 5-year retrospective cohort study of adults (≥18 years) with isolated TBI admitted to a Level II trauma center. The prognostic value of SIRS, total SIRS scores, and each SIRS criterion was examined by Χ ² and logistic regression analyses.

Results

Of the 330 patients identified, 50 (15.2%) met SIRS criteria. SIRS was significantly associated with poor outcome (P < 0.001). Relative risk of poor outcome was 2.7 times higher in patients with a SIRS score of 2 on admission (P = 0.007) and increased significantly to 6.5 times in patients with a SIRS score of 3 (P = 0.002). Logistic regression demonstrated SIRS and each criterion to be significant independent prognostic factors (SIRS, P = 0.030; body temperature, P = 0.006; tachypnea, P = 0.022, tachycardia P = 0.023).

Conclusion

SIRS at admission is an independent predictor of poor outcome in isolated TBI patients. These data demonstrate SIRS to be an important clinical tool that may be used in facilitating prognostication, particularly in elderly trauma patients. Future prospective studies aimed at therapeutic interventions to mitigate SIRS in TBI patients are warranted.

Level of Evidence

Prognostic, Level III.

     

Elevated serum IL-11, TNF α, and VEGF expressions contribute to the pathophysiology of hypertensive intracerebral hemorrhage (HICH)

To study the changes in serum interleukin-11 (IL-11), tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) expressions following hypertensive intracerebral hemorrhage (HICH), and explore their associations with disease severity and prognosis. Serum IL-11, TNF-α, and VEGF levels after 1, 3, 7, and 14 days after HICH were assayed using enzyme-linked immunosorbent assay (ELISA), and neurological deficit score (NDS) were recorded at admission and discharge for 99 HICH cases. Then 45 healthy controls were included and assayed for serum IL-11, TNF-α, and VEGF levels. Serum IL-11, TNF-α, and VEGF levels were higher in HICH patients than healthy controls (all P < 0.05). TNF-α was higher at the 3rd day following disease onset than other time points (all P < 0.05), while IL-11 and VEGF peaked at the 7th day and dropped below baseline values at the 14th day (all P < 0.05). Serum IL-11 was positively correlated with TNF-α (r = 0.70, P < 0.05) and VEGF (r = 0.72, P < 0.05). Serum TNF-α was positively correlated with VEGF (r = 0.46, P < 0.05). Serum IL-11, TNF-α, and VEGF were associated with disease severity in HICH patients. Patients with more severe disease tended to have higher NDS at admission, and higher IL-11, TNF-α, and VEGF during treatment were associated with higher NDS at discharge. Serum IL-11, TNF-α, and VEGF may involve in the pathophysiology of HICH, thus IL-11, TNF-α, and VEGF may be prognostic factors for post HICH neurologic damage.     

Cerebrospinal fluid levels of free fatty acid associated with ischemic stroke recurrence and functional outcome

The aim of this study was to evaluate the association between cerebrospinal fluid (CSF) levels of free fatty acid (FFA) and functional outcome and stroke recurrence in patients with ischemic stroke. In a prospective study, CSF levels of FFA were measured using an enzyme cycling method on admission in 217 consecutive patients with first-ever ischemic stroke. Clinical information was collected. Functional outcome and stroke recurrence were evaluated at 1-year follow-up. Multivariate analyses were performed using logistic regression models. The CSF FFA level was obtained in all patients with a median value of 0.22 (IQR 0.12–0.33) mmol/l. At admission, 89 patients (41.0 %) had a minor stroke (NIHSS < 5). In these patients, the median FFA level was lower than that observed in patients with moderate-to-high clinical severity (0.16 vs 0.27 mmol/l, p < 0.001). Patients with unfavorable outcomes and stroke recurrence had significantly higher FFA CSF levels on admission (all p < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that CSF FFA ≥ 0.33 mmol/l (third quarters) was an independent predictor of functional outcome (OR = 2.825; 95 % CI 1.502–5.313, p = 0.001) and stroke recurrence (OR = 7.862; 95 % CI 3.248–19.031, p < 0.0001). Our results demonstrate that high FFA SCF levels were independently associated with both the poor functional prognosis and stroke recurrence in patients with ischemic stroke.     

Acute Posterior Cranial Fossa Hemorrhage—Is Surgical Decompression Better than Expectant Medical Management?

Background

To compare the in-hospital mortality and institutional morbidity from medical therapy (MT), external ventricular drainage (EVD) and suboccipital decompressive craniectomy (SDC) following an acute hemorrhagic posterior cranial fossa stroke (PCFH) in patients admitted to the neurosciences critical care unit (NCCU). Retrospective observational single-center cohort study in a tertiary care center. All consecutive patients (n = 104) admitted with PCFH from January 1st 2005–December 31st 2011 were included in the study.

Methods

All patients with a PCFH were identified and confirmed by reviewing computed tomography of the brain reported by a specialist neuroradiologist. Management decisions (MT, EVD, and SDC) were identified from operative notes and electronic patient records.

Results

Following a PCFH, 47.8 % (n = 11) patients died after EVD placement without decompression, 45.7 % (n = 16) died following MT alone, and 17.4 % (n = 8) died following SDC. SDC was associated with lower mortality compared to MT with or without EVD (χ ² test p = 0.006, p = 0.008). Age, ICNARC score, brain stem involvement, and hematoma volume did not differ significantly between the groups. There was a statistically significant increase in hydrocephalus and intraventricular bleeds in patients treated with EVD placement and SDC (χ ² test p = 0.02). Median admission Glasgow Coma Scale scores for the MT only, MT with EVD, and SDC groups were 8, 6, and 7, respectively (ranges 3–15, 3–11 and 3–13) and did not differ significantly (Friedman test: p = 0.89). SDC resulted in a longer NCCU stay (mean of 17.4 days, standard deviation = 15.4, p < 0.001) and increased incidence of tracheostomy (50 vs. 17.2 %, p = 0.0004) compared to MT with or without EVD.

Conclusions

SDC following PCFH was associated with a reduction in mortality compared to expectant MT with or without EVD insertion. A high-quality multicenter randomized control trial is required to evaluate the superiority of SDC for PCFH.

     

Risk of Venous Thromboembolism in Patients with Large Hemispheric Infarction Undergoing Decompressive Hemicraniectomy

Background

Deep-venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute ischemic stroke. This study is the first to examine the risk of venous thromboembolism in patients with large hemispheric infarction undergoing decompressive hemicraniectomy.

Methods

The study population included 95 consecutive patients with a large hemispheric infarction who underwent decompressive hemicraniectomy between 2006 and 2014 at our institution. All patients received prophylactic unfractionated heparin and intermittent compression devices (SCD). Patients were systematically screened for DVT at 5-day interval using Duplex ultrasound. PE was diagnosed on chest CT angiography.

Results

Mean age was 57 ± 12 years; mean BMI was 28.3 ± 7.4 kg/m². 30.5 % of patients had infarction in the dominant hemisphere and 69.5 % in the non-dominant hemisphere. The mean NIHSS score was 16.0 ± 5 at admission. The mean length of stay was 22 ± 17 days. 35 % of patients developed a DVT including 27 % who developed above-knee DVT and required placement of an inferior vena cava filter. In multivariable analysis, predictors of DVT were an NIHSS ≥ 17 (p = 0.007), seizures (p = 0.003), hypertension (p = 0.03), and increasing length of stay (p = 0.01). The proportion of patients who developed PE was 13 %. In multivariate analysis, BMI ≥ 30 predicted PE (p = 0.05).

Conclusions

The rate of DVT and PE is remarkably high in patients with large hemispheric infarction undergoing decompressive hemicraniectomy despite prophylactic measures. We recommend routine screening for DVT in this population. Interventions beyond the standard prophylactic measures may be necessary in this high-risk group.

     

Brain-Specific Serum Biomarkers Predict Neurological Morbidity in Diagnostically Diverse Pediatric Intensive Care Unit Patients

Background

Unexpected neurological morbidity in Pediatric Intensive Care Units (PICUs) remains high and is difficult to detect proactively. Brain-specific biomarkers represent a novel approach for early detection of neurological injury. We sought to determine whether serum concentrations of neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, specific for neurons, oligodendrocytes, and glia, respectively, were predictive of neurological morbidity in critically ill children.

Methods

Serum was prospectively collected on days 1–7 from diagnostically diverse PICU patients (n = 103). Unfavorable neurological outcome at hospital discharge was defined as Pediatric Cerebral Performance Category (PCPC) score of 3–6 with a deterioration from baseline. NSE, MBP, and S100B concentrations were measured by enzyme-linked immunosorbent assay.

Results

Peak biomarker levels were greater in patients with unfavorable versus favorable neurological outcome [NSE 39.4 ± 44.1 vs. 12.2 ± 22.9 ng/ml (P = 0.005), MBP 9.1 ± 11.5 vs. 0.6 ± 1.3 ng/ml (P = 0.003), S100B 130 ± 232 vs. 34 ± 70 pg/ml (P = 0.04), respectively; mean ± SD]. Peak levels were each independently associated with unfavorable neurological outcome when controlling for presence of primary neurologic admission diagnosis and poor baseline PCPC using logistic regression analysis (NSE, P = 0.04; MBP, P = 0.004; S100B, P = 0.04), and had the following receiver operating characteristics: NSE 0.75 (0.58, 0.92), MBP 0.81 (0.66, 0.94), and S100B 0.80 (0.67, 0.93) (area under the curve [95% confidence intervals]).

Conclusions

Prospectively collected brain-specific serum biomarkers predict unfavorable neurological outcome in critically ill children. Serum biomarkers used in conjunction with clinical data could be used to generate models predicting early detection of neurological injury, allowing for more timely diagnostic and therapeutic interventions, potentially reducing neurological morbidity in the PICU.

     

Serum levels of homocysteine at admission are associated with post-stroke depression in acute ischemic stroke

The primary purpose of this study was to assess the serum levels of homocysteine (HCY) at admission to the presence of post-stroke depression (PSD). From September 2014 to December 2015, first-ever acute ischemic stroke patients within the first 24 h after stroke onset were consecutively recruited and followed-up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression. By the time of 3 month after stroke, 238 had finished the follow-up and included in our study. Totally, 65 out of the 238 patients were diagnosed as depression (27.3%; 95% CI 19.6–35.4%). The results showed significantly higher HCY levels in patients with depression [21.4 (IQR 16.5–23.4) mmol/L vs. 14.1 (IQR 11.2–18.5) mmol/L, P < 0.0001) at admission than patients without depression. In multivariate logistic regression analysis, HCY was an independent predictor of PSD with an adjusted OR of 1.07 (95% CI 1.01–1.22; P = 0.013). Based on the ROC curve, the optimal cut-off value of serum HCY levels as an indicator for prediction of PSD was projected to be 16.5 mmol/L, which yielded a sensitivity of 82.5% and a specificity of 63.6%, with the area under the curve at 0.745 (95% CI 0.672–0.818; P < 0.0001). An increased risk of PSD was associated with serum HCY levels ≥16.5 mmol/L (adjusted OR 6.13, 95% CI 3.32–14.16; P < 0.001) after adjusting for above-recorded confounders. Elevated serum levels of HCY at admission were associated with depression 3-month after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.     

Clinical Value of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratio After Aneurysmal Subarachnoid Hemorrhage

Background

Inflammation and thrombosis are associated with the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are emerging as novel inflammatory markers in stroke. We aimed to identify the association of NLR and PLR with delayed cerebral ischemia (DCI) and 3-month outcome after aSAH.

Methods

Two hundred and forty-seven patients diagnosed with aSAH within 24 h of symptoms onset were enrolled. Clinical, neuroradiological, laboratory, and follow-up data were collected from electronic database. Functional outcome was assessed by modified Rankin Scale. Admission NLR, PLR, and combined NLR-PLR associated with outcomes were evaluated by logistic regression analysis, and we used receiver operating characteristic curves to detect the overall predictive accuracy of these markers.

Results

Fifty-five (22.3 %) patients had unfavorable outcome and 47 (19 %) developed DCI. Both NLR and PLR were correlated with WFNS grade (ρ = 0.35[p < 0.001], ρ = 0.28[p < 0.001]) and modified Fisher grade (ρ = 0.25[p = 0.001], ρ = 0.28[p = 0.003]) and independently related to DCI (OR 2.18, 95 %CI 1.51–3.15, p = 0.016; OR 2.21, 95 %CI 1.61–3.32, p = 0.008) and functional outcome (OR 1.89, 95 %CI 1.52–3.17, p = 0.015; OR 1.77, 95 %CI 1.48–3.21, p = 0.018) at 3 months after aneurysm repair. They had comparable predictive ability in DCI occurrence (area under the curve [AUC] 0.65, 95 %CI 0.55–0.74, p = 0.002; AUC 0.68, 95 %CI 0.60–0.76, p < 0.001) and poor outcome (AUC 0.70, 95 %CI 0.63–0.77, p < 0.001; AUC 0.65, 95 %CI 0.58–0.72, p = 0.001). However, combination of the two indexes showed a better predictive value than each alone (AUC 0.73, 95 %CI 0.66–0.81, p < 0.001 for DCI; AUC 0.76, 95 %CI 0.70–0.83, p < 0.001 for poor outcome).

Conclusions

NLR and PLR as novel inflammatory biomarkers are independent predictors of DCI development and functional outcome after acute aSAH. When combined together, they may help to identify high-risk patients more powerfully.

     

Early elevated levels of soluble triggering receptor expressed on myeloid cells-1 in subarachnoid hemorrhage patients

Early brain injury (EBI) contributes to poor prognosis of subarachnoid hemorrhage (SAH). This study aimed to clarify whether triggering receptor expressed on myeloid cells-1 (TREM-1) was implicated in the inflammatory mechanisms of EBI. The cerebrospinal fluid (CSF) levels of soluble TREM-1 (sTREM-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as plasma levels of white blood cells (WBC) count and C-reactive protein in 17 SAH patients at early stage (within the EBI period) and 9 volunteers were observed. Also World Federation of Neurosurgical Societies (WFNS) scale of SAH patients was calculated on admission. Compared to controls, increased CSF levels of sTREM-1 (t = 5.66, P < 0.001), TNF-α (t = 5.41, P < 0.001) and IL-6 (t = 2.98, P = 0.007) as well as elevated plasma WBC counts (t = 7.61, P < 0.001) and C-reactive protein levels (t = 3.91, P = 0.001) were found in SAH patients. Considering the increased WBC counts in SAH group, covariate analysis was also performed when comparing patients’ sTREM-1 levels with respect to controls and no obvious difference was found (F = 0.982, P = 0.332). For SAH group, early CSF concentrations of sTREM-1 were correlated with those of both TNF-α (r = 0.582, P = 0.014) and IL-6 (r = 0.593, P = 0.012). Also the CSF sTREM-1 levels were positively correlated with WBC counts (r = 0.629, P = 0.007) and C-reactive protein levels (r = 0.804, P < 0.001) as well as WFNS scale (r = 0.835, P < 0.001). This study showed an early increased sTREM-1 CSF level in SAH patients, which correlated with inflammation intensity post-SAH and clinical severity, indicating that TREM-1 may participate in the inflammatory mechanisms of EBI.     

Lymphocyte-to-monocyte ratio on day 7 is associated with outcomes in acute ischemic stroke

The main features of stroke-induced immunosuppression are lymphopenia and deactivation of monocytes in peripheral blood. We hypothesized that lymphocyte-to-monocyte ratio (LMR) in peripheral blood may represent the degree of stroke-induced immunosuppression. To prove this hypothesis, we evaluated whether LMR is associated with risk of post-stroke infection and clinical outcome at 3 months in patients with acute ischemic stroke. We selected patients with stroke in anterior circulation within 24 h from onset. Peripheral blood sampling for differential blood count was performed on days 1 and 7. The LMRs on days 1 and 7 were analyzed to determine associations with excellent outcomes (modified Rankin Scale of score 0–1 at 3 months). One hundred and two patients were included. The initial National Institutes of Health Stroke Scale score (adjusted odd ratio [OR] 0.89; 95% confidence interval [CI], 0.83–0.95; P = 0.001) and LMR on day 7 (adjusted OR 1.49; 95% CI, 1.09–2.02; P = 0.011) were associated with excellent outcomes. LMRs on day 1 were significantly lower in stroke patients with pneumonia (P = 0.007) and pneumonia or urinary tract infection (P = 0.012) than those without infections. LMRs on day 7 were also significantly lower in stroke patients with infection (P = 0.005 in pneumonia, P = 0.003 in urinary tract infection, and P < 0.001 in pneumonia or urinary tract infection) than those without infections. Lower LMRs on day 7 are associated with worse outcomes at 3 months after stroke onset. LMR may be a useful marker for assessing the stroke-induced immunosuppression.     

Role of <Emphasis Type="Italic">TLR4</Emphasis> (C1196T) and <Emphasis Type="Italic">CD14</Emphasis> (C-260T) Polymorphisms in Development of Ischemic Stroke,Its Subtypes and Hemorrhagic Stroke

In the present study, we evaluated the association of TLR4 and CD14 polymorphisms, i.e. C1196T and C-260T, respectively, with ischemic stroke (n = 700), its subtypes and hemorrhagic stroke (n = 300) in a South Indian population from Telangana. The genotypes were determined using PCR–RFLP, and the strength of association between genotypes and stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. The results revealed a lack of association for TLR4 variant with ischemic stroke and hemorrhagic stroke, although a significant association was observed with the subtypes extracranial large artery (p = 0.008), other determined aetiology (p = 0.03) and undetermined aetiology (p = 0.01). Investigations on the variant of CD14 gene revealed negative association among ischemic stroke patients; however, a significant association was observed for hemorrhagic stroke following dominant and recessive genotypic model (p = 0.05, p = 0.02). Among ischemic stroke subtype, a significant association was observed with intracranial large artery, extracranial large artery, other determined aetiology and undetermined aetiology form of stroke (p < 0.01). Further, analysis of the CD14 variant between the two major stroke types revealed a significant difference in genotype distribution following the co-dominant genotypic model (p = 0.01).     

SSRI/SNRI Use is Not Associated with Increased Risk of Delayed Cerebral Ischemia After aSAH

Background

To determine the effect of selective serotonin reuptake inhibitor (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) use on the risk of symptomatic vasospasm and delayed cerebral ischemia (DCI) in patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH).

Methods

Retrospective review of consecutive patients with aSAH at Mayo Clinic, Rochester from January 2001 to December 2013. The variables collected and analyzed included age, sex, SSRI/SNRI use, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3–6) within 1 year.

Results

579 [females 363 (62.7 %)] patients with a median age of 55 (IQR 47–65) years were admitted with aSAH during the study period. WFNS at nadir was IV–V in 240 (41.5 %), and modified Fisher score was 3–4 in 434 (75.0 %). 81 (13.9 %) patients had been prescribed an SSRI or SNRI prior to admission and all continued to receive these medications during hospitalization. Symptomatic vasospasm was present in 154 (26.4 %), radiological infarction in 172 (29.5 %), and DCI in 250 (42.9 %) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p = 0.458), symptomatic vasospasm (p = 0.097), radiological infarction (p = 0.972), or poor functional outcome at 3 months (p = 0.376).

Conclusions

The use of SSRI/SNRI prior to and during hospitalization is not associated with DCI or functional outcome in patients with aSAH.

     

Association between cerebral dopamine neurotrophic factor (<Emphasis Type="Italic">CDNF</Emphasis>) 2 polymorphisms and schizophrenia susceptibility and symptoms in the Han Chinese population

Background

Schizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels. Cerebral dopamine neurotrophic factor (CDNF) 2 is known to protect and repair the dopaminergic system. Dopamine dysfunction is one of the pathogenesis of SZ. However, the relationship between CDNF2 and SZ has not been previously investigated. We speculated that CDNF2 may be a susceptibility factor for SZ.

Methods

To address this issue, we carried out a study to investigate the association between CDNF2 and SZ in the total sample 1371 (670 SZ patients and 701 healthy controls) Han Chinese population. Stage 1 included 528 SZ patients and 528 healthy controls; and stage 2 included 142 SZ patients and 173 healthy controls. The allele and genotype frequencies of five single nucleotide polymorphisms (rs2577074, rs2577075, rs2249810, rs6506891, and rs2118343) of CDNF2 were compared between patients and controls.

Results

We found a significant association in allele and genotype frequencies between the two groups at rs2249810 (χ² = 4.38 and 6.45, respectively; P = 0.03 and 0.04, respectively). An association was also observed in males at rs2249810 (χ² = 8.76; P = 0.03). Haplotype TGATC differed between SZ and controls in stage 2 samples (χ² = 6.38; P = 0.01), and rs2118343 genotypes were associated with negative factor scores (F = 4.396; P = 0.01).

Conclusions

These results suggest that rs2249810 and haplotype TGATC of CDNF2 are an SZ susceptibility locus and factor, respectively, and that rs2118343 genotypes are associated with negative symptoms of SZ in the Han Chinese population.

     

Socioeconomic Status Interacts with Conscientiousness and Neuroticism to Predict Circulating Concentrations of Inflammatory Markers

Background

Socioeconomic health disparities research may benefit from further consideration of dispositional factors potentially modifying risk associated with low socioeconomic status, including that indexed by systemic inflammation.

Purpose

This study was conducted to investigate interactions of SES and the Five-Factor Model (FFM) personality traits in predicting circulating concentrations of the inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP).

Method

Using a sample of middle-aged and older adults from the Midlife in the United States Survey (MIDUS) biomarker project (N = 978), linear regression models tested interactions of each FFM trait with a composite measure of SES in predicting IL-6 and CRP, as well as the explanatory role of medical morbidity, measures of adiposity, and health behaviors.

Results

SES interacted with conscientiousness to predict levels of IL-6 (interaction b = .03, p = .002) and CRP (interaction b = .04, p = .014) and with neuroticism to predict IL-6 (interaction b = ?.03, p = .004). Socioeconomic gradients in both markers were smaller at higher levels of conscientiousness. Conversely, the socioeconomic gradient in IL-6 was larger at higher levels of neuroticism. Viewed from the perspective of SES as the moderator, neuroticism was positively related to IL-6 at low levels of SES but negatively related at high SES. Interactions of SES with both conscientiousness and neuroticism were attenuated upon adjustment for measures of adiposity.

Conclusions

Conscientiousness may buffer, and neuroticism amplify, excess inflammatory risk associated with low SES, in part through relationships with adiposity. Neuroticism may be associated with lower levels of inflammation at high levels of SES.

     

Depression and Smoking Cessation: Evidence from a Smoking Cessation Clinic with 1-Year Follow-Up

Background

Smoking is more prevalent among people with depression. Depression may make cessation more difficult and cessation may affect depression symptoms.

Purpose

The aims of this study were to assess the associations between (1) baseline depression and 1-year smoking abstinence and (2) abstinence and change in depression.

Methods

Observational study using data collected routinely in a smoking cessation clinic in the Czech Republic from 2008 to 2014. Aim 1: N = 3775 patients; 14.3% reported mild and 15.4% moderate/severe baseline depression levels measured using Beck’s Depression Inventory (BDI-II). Logistic regressions assessed if depression level predicted 1-year biochemically verified abstinence while adjusting for patient and treatment characteristics. Aim 2: N = 835 patients abstinent at 1 year; change in depression was analysed using Chi-square statistics, t test and mixed method analyses of variance.

Results

Rate of abstinence was lower for patients with mild (32.5%, OR = 0.68; 95% CI: 0.54 to 0.87, p = 0.002) and moderate/severe depression (25.8%; OR = 0.57, 95% CI: 0.45 to 0.74, p < 0.001) compared with patients without depression (40.5%).Across abstinent patients, the majority with baseline depression reported lower depression levels at follow-up. Overall mean (SD) BDI-II scores improved from 9.2 (8.6) to 5.3 (6.1); t(834) = 14.6, p < 0.001. There were significant main effects of time (F(1832) = 880.8, p < 0.001, partial η² = 0.51) and baseline depression level (F(2832) = 666.4, p < 0.001, partial η² = 0.62) on follow-up depression and a significant depression * time interaction (F(2832) = 296.5, p < 0.001, partial η² = 0.42).

Conclusions

In this effective smoking cessation clinic, depression at the start of treatment predicted reduced smoking abstinence 1 year later. Patients abstinent from smoking experienced considerable improvement in depression.

     

Albumin-Induced Neuroprotection in Focal Cerebral Ischemia in the ALIAS Trial: Does Severity,Mechanism, and Time of Infusion Matter?

Objective

To determine whether there is any differential benefit of albumin administration within 2 h of onset of ischemia and in settings (severe ischemia with reperfusion in cardioembolic strokes with National Institutes of Health Stroke Scale [NIHSS] ≥15), most representative of experimental models of cerebral ischemia in which albumin was effective in reducing neurological injury.

Background

High-dose intravenous (IV) albumin treatment for acute ischemic stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke patients in contrast to preclinical studies; however, models of preclinical studies were not completely followed.

Methods

A total of 1275 patients combined from ALIAS trials I and II were included in our analysis. We analyzed preclinical studies and selected patients with large ischemic stroke (NIHSS ≥15) related to cardioembolic etiology (n = 189). Outcomes were then studied including time from onset to IV albumin administration.

Results

The odds of excellent outcome (mRS 0–1) at 3 months was not different with high-dose IV albumin infusion (n = 100) compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719–3.708], p value 0.2419). When we further classified these subjects according to time of IV albumin administration, we observed significantly higher odds of excellent outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI 1.040–84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS score, and any therapeutic procedure.

Conclusion

A trend for benefit is noted in ischemic stroke patients with large cardioembolic stroke (NIHSS ≥15) when high-dose albumin was initiated within 2 h, suggesting that certain ischemic stroke subgroups of patients most representative of preclinical settings may benefit from such a treatment. Additional clinical trials maybe needed to stratify subjects and treatment assignments according to NIHSS severity and timely randomization to evaluate this concept further.

     

Decannulation and Functional Outcome After Tracheostomy in Patients with Severe Stroke (DECAST): A Prospective Observational Study

Background

Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH).

Methods

In this retrospective single-center cohort of aSAH patients (October 2009–September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death.

Results

Of 179 patients, 27 % had a high Hunt–Hess grade (IV–V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07–6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30–7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt–Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04–629], p = 0.040).

Conclusions

RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.