Men Experience Higher Risk of Pneumonia and Death After Intracerebral Hemorrhage

Background

Infectious complications worsen outcome after intracerebral hemorrhage (ICH). We investigated the impact of sex on post-ICH infections and mortality.

Methods

Consecutive ICH patients (admitted to a single hospital between 1994 and 2015) were retrospectively assessed via chart review to ascertain the following in-hospital infections: urinary tract infection (UTI), pneumonia, and sepsis. Adjusted logistic regression was performed to identify associations between sex, infection, and mortality at 90 days.

Results

Two thousand and four patients were investigated, 1071 (53.7%) males. Men were more likely to develop pneumonia (21.9 vs 15.5% p < 0.001) and sepsis (3.4 vs 1.6%, p = 0.009), whereas women had higher risk of UTI (19.9 vs 11.7% p < 0.001). Multivariate analyses confirmed association between male sex and pneumonia (Odds Ratio (OR) 1.37, 95% confidence interval (CI) 1.08–1.74, p = 0.011). Male sex (OR 1.40; CI 1.07–1.85; p = 0.015) and infection (OR 1.56; CI 1.11–1.85; p = 0.011) were independently associated with higher 90-day mortality.

Conclusions

Types and rates of infection following ICH differ by sex. Male sex independently increases pneumonia risk, which subsequently increases 90-day mortality. Sex-specific preventive strategies to reduce the risk of these complications may be one strategy to improve ICH outcomes.

     

Lymphopenia,Infectious Complications,and Outcome in Spontaneous Intracerebral Hemorrhage

Background

Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH).

Methods

We retrospectively analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. We identified subjects with lymphocyte count obtained within 24 h from onset, and AL was defined as lymphocyte count <1000/μL. Infectious complications were assessed through retrospective chart review. Association between AL, infections, and mortality was investigated using multivariable logistic regression.

Results

Of the 2014 patients meeting inclusion criteria, 548 (27.2%) had AL and 605 (30.0%) developed an infectious complication. Case-fatality at 90 days was 36.9%. Patients with AL had larger hematoma volumes, higher frequency of intraventricular hemorrhage, and lower Glasgow Coma Scale score on presentation (all p < 0.001). AL was independently associated with increased risk of pneumonia [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50–2.58, p < 0.001] and multiple infections (OR 1.84, 95% CI 1.24–2.71, p = 0.003). AL was also an independent predictor of 90-day mortality (OR 1.55, 95% CI 1.18–2.04, p = 0.002) after adjusting for confounders.

Conclusions

AL is common in ICH patients and independently associated with increased risk of infectious complications and poor outcome. Further studies will be needed to determine whether prophylactic antibiotics in ICH patients with AL can improve outcome.

     

Seizures Among Long-Term Survivors of Conservatively Treated ICH Patients: Incidence,Risk Factors,and Impact on Functional Outcome

Background

Seizures are a common complication after intracerebral hemorrhage (ICH) but there is a substantial lack of information on the long-term incidence in ICH survivors and whether post-ICH seizures affect functional long-term outcome.

Methods

Over a five-year period 464 consecutive patients with spontaneous ICH were analyzed. Focussing on 1-year ICH survivors, clinical, and radiological parameters were retrieved from institutional prospective databases. The occurrence of seizures was categorized as early (≤7 days) or late (>7 days). Functional outcome was assessed by mailed questionnaires and telephone interviews, and was categorized into good vs. poor (mRS: 0–2 vs. 3–5) and favorable vs. unfavorable (mRS: 0–3 vs. 4–5). Multivariate regression models were calculated to investigate risk factors associated with post-ICH seizures including an a priori defined subgroup analysis of lobar ICH patients.

Results

Among 203 long-term ICH survivors, 19.7 % developed seizures of which 55 % occurred late. Factors associated with seizures were lobar location (OR 8.10; 95 % CI 3.04–21.59; p < 0.001), sepsis (OR 4.59; 95 % CI 1.20–17.53; p = 0.026), and history of alcohol abuse (OR 3.36; 95 % CI 1.25–9.06; p = 0.017). Subgroup analysis of lobar ICH patients revealed history of alcohol abuse as the only independent predictor of post-ICH seizures (OR 5.22; 95 % CI 1.25–21.78; p = 0.024). Functional long-term outcome among survivors was slightly worse in patients with post-ICH seizures (p = 0.059). In multivariate regression modeling for prediction of poor outcome, the parameter “post-ICH seizures” again reached a statistical trend (p = 0.065), and established parameters such as age, GCS, and hemorrhage volume were independently related to poor outcome.

Conclusions

Post-ICH seizures among long-term ICH survivors are common and may contribute to unfavorable functional outcome. Especially lobar ICH patients with a history of alcohol abuse are at risk to develop post-ICH seizures. Therefore, this subgroup may represent a target population for a prophylactic anticonvulsive treatment approach, preferably investigated in a prospective randomized trial.

     

Prior antiplatelet therapy is not associated with larger hematoma volume or hematoma growth in intracerebral hemorrhage

Hematoma volume (HV) and hematoma growth (HG) predict mortality and poor outcome in intracerebral hemorrhage (ICH). While the influence of oral anticoagulation on HV, HG and outcome is well established, the effect of prior antiplatelet therapy (APT) remains uncertain. We retrospectively examined data from all patients with acute, primary ICH, and baseline head CT admitted to our department between January 2005 and February 2014. HV were calculated by ABC/2 method. HG was defined as present if HV increased between baseline and follow-up CT ≥?30% or ≥?6 mL. We analyzed the influence of APT on HV, HG, and in-hospital mortality using univariate and multivariate analyses. In addition, we used propensity score matching to assess differences in in-hospital mortality rates. From 668 screened patients, 343 had primary ICH and fulfilled all inclusion criteria. APT was present in 99 patients (29%). Baseline median HV was 16 mL (IQR 6–46). HG occurred in 44 of 160 patients with follow-up CT (28%). In-hospital mortality was 10% (n?=?36). APT was associated with older age, a mRS score before admission (pre-mRS) of >?2, and presence of cardiovascular comorbidities. We did not find an association between APT and larger baseline HV (p?=?0.32), or HG (OR 0.8, 95% CI 0.4–1.9). After propensity score matching for age, pre-mRS, gender, and cardiovascular comorbidities, APT was not associated with higher in-hospital mortality (OR 1.90, 95% CI 0.85–4.24, p?=?0.117). This study did not show a higher risk for larger HV, HG, or in-hospital mortality in primary ICH patients with APT.     

Nosocomial Infections and Outcomes after Intracerebral Hemorrhage: A Population-Based Study

Background

Infections after intracerebral hemorrhage (ICH) may be associated with worse outcomes. We aimed to evaluate the association between nosocomial infections (>48 h) and outcomes of ICH at a population level.

Methods

We identified patients with ICH using ICD-9-CM codes in the 2002–2011 Nationwide Inpatient Sample. Demographics, comorbidities, surgical procedures, and hospital characteristics were compared between patients with and without concomitant nosocomial infections. Primary outcomes were in-hospital mortality and home discharge. Secondary outcome was permanent cerebrospinal shunt placement. Logistic regression analyses were used to analyze the association between infections and outcomes.

Results

Among 509,516 ICH patients, infections occurred in 117,636 (23.1 %). Rates of infections gradually increased from 18.7 % in 2002–2003 to 24.1 % in 2010–2011. Pneumonia was the most common nosocomial infection (15.4 %) followed by urinary tract infection (UTI) (7.9 %). Patients with infections were older (p < 0.001), predominantly female (56.9 % vs. 47.9 %, p < 0.001), and more often black (15.0 % vs. 13.4 %, p < 0.001). Nosocomial infection was associated with longer hospital stay (11 vs. 5 days, p < 0.001) and a more than twofold higher cost of care (p < 0.001). In the adjusted regression analysis, patients with infection had higher odds of mortality [odds ratio (OR) 2.11, 95 % CI 2.08–2.14] and cerebrospinal shunt placement (OR 2.19, 95 % CI 2.06–2.33) and lower odds of home discharge (OR 0.49, 95 % CI 0.47–0.51). Similar results were observed in subgroup analyses of individual infections.

Conclusions

In a nationally representative cohort of ICH patients, nosocomial infection was associated with worse outcomes and greater resource utilization.

     

Joint Effects of GWAS SNPs in Coagulation System Confer Risk to Hypertensive Intracerebral Hemorrhage

Recent genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with coagulation system, including hemostatic factors and hematological phenotypes. However, few articles described the relationships between these SNPs and the risk of hemorrhagic stroke. The aim of our study was to evaluate the roles of these SNPs as risk factors and survival predictors for hemorrhagic stroke. Thirteen SNPs from GWAS in coagulation system were genotyped in a Chinese Han population including 1000 patients with hemorrhagic stroke (intracerebral hemorrhage, ICH = 743; subarachnoid hemorrhage, SAH = 257) and 1044 population-based controls. The associations between the genetics risk score (GRS) and risk of hemorrhagic stroke as well as post-stroke adverse outcomes were determined. No individual SNP was associated with the risk of hemorrhagic stroke. The GRS was calculated by summing the number of risk alleles of each SNP, and a total of 13 SNPs were included. Meanwhile, the GRS cutoffs values were defined to be close to quartiles or tertiles in control subjects. For quartiles, individuals with GRS about 8–9, 10–11, ≥12 had 1.28 (OR 1.28, 95% CI 0.98–1.68, p = 0.067)-, 1.36 (OR 1.36, 95% CI 1.04–1.79, p = 0.026)-, 1.53 (OR 1.53, 95% CI 1.13–2.07, p = 0.006)-fold increase in ICH risk compared to those with GRS ≤7, respectively; for tertiles, individuals with GRS about GRS 9–10, ≥11 had 0.98 (OR 0.98, 95% CI 0.78–1.23, p = 0.067)- and 1.26 (OR 1.26, 95% CI 1.00–1.59, p = 0.048)-fold increase in ICH risk compared to those with GRS ≤8, respectively. Further stratification analyses indicated that this association was only found in hypertensive ICH subjects. However, no statistical difference was found in the volume of hematoma, activities of daily living scale as well as hospital death in the ICH patients based on GRS values. Joint effects of SNPs associated with low coagulation factor levels might confer risk to ICH patients with hypertension. However, the clinical value on risk stratification and survival prediction was limited.     

Factors associated with fatal outcome in posterior reversible encephalopathy syndrome: a retrospective analysis of the Berlin PRES study

Although often reversible, fatal outcome in posterior reversible encephalopathy syndrome (PRES) is well known. However, data on predictors of PRES-associated in-hospital death are scarce. In this study, we aimed to investigate predictors of in-hospital death in a large cohort. Radiological report databases between January 1999 and February 2015 were retrospectively searched for patients with PRES. Patients were included if they met criteria for PRES after detailed investigation of clinical charts and imaging studies. Various clinical, paraclinical and brain MRI data as well as data on in-hospital mortality were analyzed. 151 patients were included into the study, 64% were female. Seventeen (11.2%) patients died during hospital stay. In univariate analyses, higher age (p = 0.04), higher levels of C-reactive protein (p < 0.001), etiology of PRES (sepsis and chemotherapy; p = 0.02), altered coagulation (p = 0.002), altered mental state at onset (p = 0.03), and subarachnoid hemorrhage (SAH; p = 0.01) were related to in-hospital death. In multivariate analyses adjusted for age and sex, elevated CRP levels (OR 1.1 95% CI 1.1–1.2), altered coagulation (OR 5.1 95% CI 1.8–14.7), subarachnoid hemorrhage (OR 10.1 95% CI 2.2–46.1) and altered mental state (OR 3.3; 95% CI 1.1–9.4) were independently associated with in-hospital death. Altered mental state, subarachnoid hemorrhage as well as the higher levels of CRP and altered coagulation were significantly more frequent in patients who died in hospital. However, prospective studies are warranted to establish predictors of fatality in patients with PRES.     

Prophylactic Anticonvulsants in Intracerebral Hemorrhage

Background and Purpose

Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome.

Methods

We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score.

Results

We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95–0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76–4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40–3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51–6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10–5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4–6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication.

Discussion

Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.

     

Incidence,Predictors, and Outcomes of Ventriculostomy-Associated Infections in Spontaneous Intracerebral Hemorrhage

Background

The impact of ventriculostomy-associated infections (VAI) on intracerebral hemorrhage (ICH) outcomes has not been clearly established, although prior studies have attempted to address the incidence and predictors of VAI. We aimed to explore VAI characteristics and its effect on ICH outcomes at a population level.

Methods

ICH patients requiring ventriculostomy with and without VAI were identified from 2002 to 2011 Nationwide Inpatient Sample using ICD-9 codes. A retrospective cohort study was performed. Demographics, comorbidities, hospital characteristics, inpatient outcomes, and resource utilization measures were compared between the two groups. Pearson’s Chi-square and Wilcoxon–Mann–Whitney tests were used for categorical and continuous variables, respectively. Logistic regression was used to analyze the predictors of VAI.

Results

We included 34,238 patients in the analysis, of whom 1934 (5.6 %) had VAI. The rate of ventriculostomy utilization in ICH increased from 5.7 % in 2002–2003 to 7.0 % in 2010–2011 (trend p < 0.001) and the rate of VAI also showed a gradual upward trend from 6.1 to 7.0 % across the same interval (trend p < 0.001). The VAI group had significantly higher inpatient mortality (41.2 vs. 36.5 %, p < 0.001) and it remained higher after controlling for baseline demographics, hospital characteristics, comorbidity, and systemic infections (adjusted OR 1.38, 95 % CI 1.22–1.46, p < 0.001). The VAI group had longer length of hospital stay and higher inflation adjusted cost of care. Predictors of VAI included higher age, males, higher Charlson’s comorbidity scores, longer length of stay, and presence of systemic infections mainly pneumonia and sepsis.

Conclusion

VAI resulted in higher inpatient mortality, more unfavorable discharge disposition, and higher resource utilization measures in ICH patients. Steps to mitigate VAI may help improve ICH outcomes and decrease hospital costs.

     

Safety of Chemical DVT Prophylaxis in Severe Traumatic Brain Injury with Invasive Monitoring Devices

Background

Patients with traumatic brain injuries (TBIs) have an increased risk of developing a deep vein thrombosis (DVT), but the risk of hemorrhage expansion with intracranial monitoring devices remains unknown. We sought to determine the safety of chemical DVT prophylaxis in severe TBI patients with invasive intracranial pressure monitors.

Methods

We retrospectively reviewed all patients with severe TBI admitted to the neurosurgical intensive care unit of a large tertiary care center over a three-year period.

Results

155 patients were included with an incidence of DVT of 12 %. The median length of time to a stable head CT was 2 days, and the median time to initiation of chemical DVT prophylaxis was 3.6 days. The odds of DVT increased with intraparenchymal hemorrhage [OR 7.21, 95 % CI (1.43–36.47), p = 0.0169], non-White ethnicity [OR 7.86, 95 % CI (1.23–50.35), p = 0.0295], female gender [OR 13.93, 95 % CI (2.47–78.73), p = 0.0029], smoking [OR 4.32, 95 % CI (1.07–17.51), p = 0.0405], no anticoagulation [OR 25.39, 95 % CI (4.26–151.48), p < 0.001], and an IVC filter [OR 15.82, 95 % CI (3.14–79.76), p < 0.001]. Twenty-eight (18 %) of these subjects experienced in-hospital mortality. The risk of in-hospital death was significantly increased among those who did not receive anticoagulation. This study found no association between DVT formation, hemorrhage expansion, or increased risk from invasive monitoring devices between various doses of unfractionated heparin (UH) and low-molecular-weight heparin (LMWH).

Conclusion

We conclude that DVT prophylaxis with either LMWH or UH is safe with intracranial pressure monitors in place.

     

TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis

Background and Purpose

Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema.

Methods

We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC).

Results

Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63–0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61–0.73).

Conclusions

Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.

     

Intracerebral haemorrhage in a population-based stroke registry (LuSSt): incidence, aetiology, functional outcome and mortality

Data on incidence of intracerebral haemorrhage (ICH) vary widely. Population-based data on predictors of ICH survival and functional outcome are rare. The Ludwigshafen Stroke Study is a prospective, population-based stroke registry which started in January 2006. All residents of the city of Ludwigshafen, Germany, who suffer from acute stroke or transient ischaemic attack are registered. Patients with first-ever primary intracerebral haemorrhage (FE-pICH) between 2006 and 2010 were included in the present analysis. Between January 1st, 2006 and December 31st, 2010, 152 patients suffered a FE-pICH. Crude and age-adjusted incidence rates per 100,000 for FE-pICH were 18.7 (95 % CI 15.9–21.9) and 11.9 (95 % CI 10.2–14.0), respectively, and remained stable over time. Case-fatality rates for FE-pICH were 27.0, 34.9 and 44.1 % at days 28, 90 and 365, respectively. In 21 patients, an (21.3 %) early do-not resuscitate-order was documented. Excluding these patients from multivariate analyses, National Institute of Health Stroke Scale (NIHSS) (OR 1.22, 95 % CI 1.08–1.36), hypercholesterolemia (OR 0.16, 95 % CI 0.05–0.55) and modified Rankin Scale (mRS) prior to stroke (OR 1.56, 95 % CI 1.06–2.3) were independently associated with risk of 1-year mortality, whereas NIHSS (OR 1.41, 95 % CI 1.20–1.66) and leukocyte count on admission (OR 1.48, 95 % CI 1.16–1.89) were independently associated with good or moderate functional outcome (mRS ≤ 3) after 1 year. Incidence of FE-ICH is in the lower range of those reported from other registries and remained stable over the observation period. Higher treatment rates for hypertension might partly account for this. Stroke severity as indicated by NIHSS was independently associated with mortality and functional outcome after 1 year. We found no association between aetiology and outcome in ICH patients.     

Acutely Trapped Ventricle: Clinical Significance and Benefit from Surgical Decompression

Background

Focal ventricular obstruction—trapped ventricle—results in cerebrospinal fluid accumulation, mass effect and possible clinical deterioration. There are no systematic studies on the benefit of surgical decompression in adults.

Methods

We reviewed patients admitted with acutely trapped ventricle on brain imaging to assess their prognosis and the effect of surgical intervention on 30-day mortality.

Results

Of the 392 patients with trapped ventricle, the most common causes were brain tumor (45 %), intracerebral hemorrhage (ICH) (20 %), and subdural hematoma (SDH) (14 %). Lateral ventricle trapping accounted for 97 % of cases. Two hundred and twenty-one patients (56 %) received a surgical intervention for trapped ventricle or its causes; 126 (83 %) were treated with craniotomy, 26 (17 %) with craniectomy, 30 (14 %) with external ventricular drain (EVD) alone, 23 (10 %) with ventriculoperitoneal shunt alone, and 16 (7 %) with endoscopic fenestration of the septum pellucidum. Surgical intervention was associated with mortality reduction from 95 % (n = 54) to 48 % (n = 11) in the ICH group, from 47 % (n = 27) to 12 % (n = 15) in the tumor group and from 90 % (n = 18) to 20 % (n = 7) in the SDH group (p < 0.001 for all comparisons). Univariate logistic analysis showed that surgical intervention and tumor etiology were associated with decreased mortality while age, ICH etiology, intraventricular hemorrhage, midline shift, and anticoagulation were associated with increased mortality. On multivariate logistic regression, surgical intervention remained associated with decreased mortality (p < 0.0001; OR 0.20, 95 % CI 0.09–0.42). On subgroup analysis of the ICH cohort, surgical intervention was also associated with decreased mortality (p = 0.028).

Conclusions

Neurosurgical intervention for decompression in patients with trapped ventricle can have a measurable beneficial effect on early mortality.

     

Perihematomal Edema Expansion Rates and Patient Outcomes in Deep and Lobar Intracerebral Hemorrhage

Background

Perihematomal edema (PHE) expansion rate may predict functional outcome following spontaneous intracerebral hemorrhage (ICH). We hypothesized that the effect of PHE expansion rate on outcome is greater for deep versus lobar ICH.

Methods

Subjects (n = 115) were retrospectively identified from a prospective ICH cohort enrolled from 2000 to 2013. Inclusion criteria were age ≥ 18 years, spontaneous supratentorial ICH, and known onset time. Exclusion criteria were primary intraventricular hemorrhage (IVH), trauma, subsequent surgery, or warfarin-related ICH. ICH and PHE volumes were measured from CT scans and used to calculate expansion rates. Logistic regression assessed the association between PHE expansion rates and 90-day mortality or poor functional outcome (modified Rankin Scale > 2). Odds ratios are per 0.04 mL/h.

Results

PHE expansion rate from baseline to 24 h (PHE24) was associated with mortality for deep (p = 0.03, OR 1.13[1.02–1.26]) and lobar ICH (p = 0.02, OR 1.03[1.00–1.06]) in unadjusted regression and in models adjusted for age (deep p = 0.02, OR 1.15[1.02–1.28]; lobar p = 0.03, OR 1.03[1.00–1.06]), Glasgow Coma Scale (deep p = 0.03, OR 1.13[1.01–1.27]; lobar p = 0.02, OR 1.03[1.01–1.06]), or time to baseline CT (deep p = 0.046, OR 1.12[1.00–1.25]; lobar p = 0.047, OR 1.03[1.00–1.06]). PHE expansion rate from baseline to 72 h (PHE72) was associated with mRS > 2 for deep ICH in models that were unadjusted (p = 0.02, OR 4.04[1.25–13.04]) or adjusted for ICH volume (p = 0.02, OR 4.3[1.25–14.98]), age (p = 0.03, OR 5.4[1.21–24.11]), GCS (p = 0.02, OR 4.19[1.2–14.55]), or time to first CT (p = 0.03, OR 4.02[1.19–13.56]).

Conclusions

PHE72 was associated with poor functional outcomes after deep ICH, whereas PHE24 was associated with mortality for deep and lobar ICH.

     

Three-Factor Versus Four-Factor Prothrombin Complex Concentrate for the Emergent Management of Warfarin-Associated Intracranial Hemorrhage

Background

Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH).

Methods

This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, discharge location, intensive care unit (ICU) and hospital-free days, INR reversal, and thromboembolic (TE) events at 90 days. Each was analyzed using regression analysis. Continuous and binary outcomes were analyzed using linear and logistic regression, respectively, while ordinal regression was used for discharge location.

Results

Of the 103 patients, 63 received 4-factor PCC. Median age was 79 years [interquartile intervals(IQI 73–84)], median presenting INR was 2.7 (2.2–3.3), and presenting ICH was intraparenchymal in 51% of patients. In-hospital and 30-day mortality were 25 and 35%, respectively. In-hospital mortality was greater among those who received 4-factor PCC, yet was not statistically significant (OR 2.2, 95% CI 0.59–9.4, p = 0.26), as having Glasgow Coma Scale (GCS) ≤8 explained most of the difference (OR 48, 95% CI 14–219, p <0.001). The effect of 4-factor PCC was not statistically significant in any of the secondary analyses. Crude rates of TE events were higher in the 4-factor PCC group (19 vs. 10%), though not significantly.

Conclusions

In-hospital mortality was not improved with the use of 4- versus 3-factor PCC in the emergent reversal of warfarin-associated ICH. Secondary clinical outcomes were similarly nonsignificant.

     

Mortality and functional disability after spontaneous intracranial hemorrhage: the predictive impact of overall admission factors

To determine the effects of different prognostic factors, including previous antiplatelet therapy, admission data, and radiographic findings on discharge and 3-month neurological condition using modified Rankin scale (mRS) and mortality at 30 days and 3-month follow-up in patients presenting to the emergency department with spontaneous intracranial hemorrhage (sICH). Between January and July 2012, 120 consecutive patients (males 62 %, females 38 %), who were admitted within 48 h of symptoms onset, were included. We recorded the following data on admission: demographics; functional scores of ICH, Glasgow Coma Scale, and National Institutes of Health Stroke Scale; vital signs; smoking status; use of illicit drug; preadmission antiplatelet treatment; results of laboratory tests (platelet count, serum glucose, sodium and creatinine levels, and prothrombin time); and primary neuroimaging findings [intraventricular hemorrhage (IVH), midline shift, and hydrocephalus]. In multivariate analysis using adjusted model for demographics and prior antiplatelet therapy; functional scores, laboratory results, and diabetes history correlated with mortality during 30 days after the event. Moreover, the parameters on the initial computed tomography scan significantly increased 30-day fatality rate and was correlated with increase in the discharge mRS score of survivors. The odds ratio (OR) and 95 % confidence interval (CI) of early mortality associated with IVH presentation was 2.34 (CI 1.76–3.02, p = 0.003). The corresponding ORs in those with midline shift displacement and hydrocephalus were 2.18 (95 % CI 2.08–3.80, p = 0.01) and 1.62 (95 % CI 1.01–2.63, p = 0.02), respectively. In patients with ICH, prognostic factors, include various clinical parameters and paraclinical findings of admission time.     

Factors Associated with the Need for Intensive Care Unit Admission Following Supratentorial Intracerebral Hemorrhage: The Triage ICH Model

Background

Providing the correct level of care for patients with intracerebral hemorrhage (ICH) is crucial, but the level of care needed at initial presentation may not be clear. This study evaluated factors associated with admission to intensive care unit (ICU) level of care.

Methods

This is an observational study of all adult patients admitted to our institution with non-traumatic supratentorial ICH presenting within 72 h of symptom onset between 2009–2012 (derivation cohort) and 2005–2008 (validation cohort). Factors associated with neuroscience ICU admission were identified via logistic regression analysis, from which a triage model was derived, refined, and retrospectively validated.

Results

For the derivation cohort, 229 patients were included, of whom 70 patients (31 %) required ICU care. Predictors of neuroscience ICU admission were: younger age [odds ratio (OR) 0.94, 95 % CI 0.91–0.97; p = 0.0004], lower Full Outline of UnResponsiveness (FOUR) score (0.39, 0.28–0.54; p < 0.0001) or Glasgow Coma Scale (GCS) score (0.55, 0.45–0.67; p < 0.0001), and larger ICH volume (1.04, 1.03–1.06; p < 0.0001). The model was further refined with clinician input and the addition of intraventricular hemorrhage (IVH). GCS was chosen for the model rather than the FOUR score as it is more widely used. The proposed triage ICH model utilizes three variables: ICH volume ≥30 cc, GCS score <13, and IVH. The triage ICH model predicted the need for ICU admission with a sensitivity of 94.3 % in the derivation cohort [area under the curve (AUC) = 0.88; p < 0.001] and 97.8 % (AUC = 0.88) in the validation cohort.

Conclusions

Presented are the derivation, refinement, and validation of the triage ICH model. This model requires prospective validation, but may be a useful tool to aid clinicians in determining the appropriate level of care at the time of initial presentation for a patient with a supratentorial ICH.

     

Integrins AV and B8 Gene Polymorphisms and Risk for Intracerebral Hemorrhage in Greek and Polish Populations

Α limited number of genetic variants have been linked to the development of intracerebral hemorrhage (ICH). Ιntegrin AV and/or B8-deficient mice were found to develop ICH. The present candidate gene association study was designed to investigate possible influence of integrin AV (ITGAV) and integrin B8 (ITGB8) gene region polymorphisms on the risk of ICH. 1015 participants (250 Greek and 193 Polish patients with primary ICH and 250 Greek and 322 Polish controls) were included in the study. Using logistic regression analyses, 11 tag single nucleotide polymorphisms (SNPs) for ITGAV and 11 for ITGB8 gene were tested for associations with ICH risk, lobar ICH risk and non-lobar ICH after adjustment for age, gender, history of hypertension and country of origin. Linear regression models were used to test the effect of tag SNPs on the ICH age of onset. Correction for multiple comparisons was carried out. The rs7565633 tag SNP of the ITGAV gene was independently associated with the risk of lobar ICH in the codominant model of inheritance [odds ratio (95 % confidence interval (CI)) 0.56 (0.36–0.86), p = 0.0013]. Furthermore, heterozygous individuals of the rs10251386 and the rs10239099 of the ITGB8 gene had significantly lower age of ICH onset compared to the wild-type genotypes [regression coefficient (b) ?3.884 (95 % CI ?6.519, ?1.249), p = 0.0039 and b = ?4.502 (95 % CI ?7.159, ?1.845), p = 0.0009, respectively]. The present study provides preliminary indication for an influence of ITGAV gene tag SNP in the development of lobar ICH and of ITGB8 gene variants in the age of ICH onset.     

The impact of cerebral microbleeds on intracerebral hemorrhage and poor functional outcome of acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis

It is still controversial whether pre-existing cerebral microbleeds (CMBs) increase the risks of intracranial hemorrhage (ICH) and poor functional outcome (PFO) in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Therefore, we performed a systematic review and meta-analysis to determine the impact of CMBs on ICH and PFO of AIS patients with IVT. We searched PubMed, EMBASE and Web of Science from inception to August 3, 2016, with language restriction in English. We included studies that reported the relationship between CMBs and ICH or PFO after thrombolysis. Two retrospective and nine prospective studies met inclusion criteria (total 2702 patients). The overall prevalence of CMBs on pre-IVT MRI scans was 24.0%. Pre-existing CMBs on MRI scans were not significantly associated with a higher risk of early sICH (OR 1.74; 95% CI 0.91–3.33; I ² = 44.5%). Subgroup analyses did not substantially influence these associations. The presence of CMBs was associated with the increased risk of 3-month PFO (OR 1.58; 95% CI 1.08–2.31; I ² = 54.2%), PH (OR 2.14; 95% CI 1.34–3.42; I ² = 11.0%) and any ICH (OR 1.42; 95% CI 1.04–1.95; I ² = 0.0%), respectively. This meta-analysis showed that CMBs presence was not significantly associated with the increased risk of early sICH after IVT. However, the results also demonstrated that CMBs presence increased the risks of 3-month PFO, PH and any ICH after IVT. Due to a small number of included studies and methodological limitations, the results of this meta-analysis should be interpreted cautiously. CMBs presence should not be a contraindication to IVT for AIS patients based on the existing evidence.     

The Prevalence and Impact of Status Epilepticus Secondary to Intracerebral Hemorrhage: Results from the US Nationwide Inpatient Sample

Background

Status epilepticus (SE) has been identified as a predictor of morbidity and mortality in many acute brain injury patient populations. We aimed to assess the prevalence and impact of SE after intracerebral hemorrhage (ICH) in a large patient sample to overcome limitations in previous small patient sample studies.

Methods

We queried the Nationwide Inpatient Sample for patients admitted for ICH from 1999 to 2011, excluding patients with other acute brain injuries. Patients were stratified into SE diagnosis and no SE diagnosis cohorts. We identified independent risk factors for SE and assessed the impact of SE on morbidity and mortality with multivariable logistic regression models. Logistic regression was used to evaluate the trend in SE diagnoses over time as well.

Results

SE was associated with significantly increased odds of both mortality and morbidity (odds ratios (OR) 1.18 [confidence intervals (CI) 1.01–1.39], and OR 1.53 [CI 1.22–1.91], respectively). Risk factors for SE included female sex (OR 1.17 [CI 1.01–1.35]), categorical van Walraven score (vWr 5–14: OR 1.68 [CI 1.41–2.01]; vWr > 14: OR 3.77 [CI 2.98–4.76]), sepsis (OR 2.06 [CI 1.58–2.68]), and encephalopathy (OR 3.14 [CI 2.49–3.96]). Age was found to be associated with reduced odds of SE (OR 0.97 [CI 0.97–0.97]). From 1999 to 2011, prevalence of SE diagnosis increased from 0.25 to 0.61% (p < 0.001). Factors associated with SE were female sex, medium and high risk vWr score, sepsis, and encephalopathy. Independent predictors associated with increased mortality from SE were increased age, pneumonia, myocardial infarction, cardiac arrest, and sepsis.

Conclusions

SE is a significant, likely underdiagnosed, predictor of morbidity and mortality after ICH. Future studies are necessary to better identify which patients are at highest risk of SE to guide resource utilization.