Highest In-Hospital Glucose Measurements are Associated With Neurological Outcomes After Intracerebral Hemorrhage

Background and Purpose

The relationship between in-hospital hyperglycemia and neurological outcome after intracerebral hemorrhage (ICH) is not well studied.

Impact of early surgery after aneurysmal subarachnoid haemorrhage

Objectives – To investigate the effect of early aneurysm surgery (<72 h) on outcome in patients with subarachnoid haemorrhage (SAH). Materials and methods – We studied two consecutive series of patients with aneurysmal SAH [postponed surgery (PS) cohort, n = 118, 1989–1992: surgery was planned on day 12 and early surgery (ES) cohort, n = 85, 1996–1998: ES was performed only in patients with Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis to assess outcome at 3 months. Results – Favourable outcome (Glasgow Outcome Scale 4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly more often in the ES cohort. The occurrence of rebleeds was similar in both cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable outcome: 6.4, 95% confidence interval (CI) 1.0–39.8] and patients with both CSS <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5, 95% CI 1.1–99.4). Conclusions – Our results support the widely adopted practice of ES in good‐grade SAH patients.     

A Propensity Score-Matched Comparison of Readmission Rates Associated With Microsurgical Clipping and Endovascular Treatment of Ruptured Intracranial Aneurysms

Background: In the treatment of aneurysmal subarachnoid hemorrhage (aSAH), microsurgical clipping, and endovascular therapy (EVT) with coiling are modalities for securing the ruptured aneurysm. Little data is available regarding associated readmission rates. We sought to determine whether readmission rates differed according to treatment modality for ruptured intracranial aneurysms. Methods: The Nationwide Readmissions Database (NRD) was used to identify adults who experienced aSAH and underwent clipping or EVT. Primary outcomes of interest were the incidences of 30- and 90-day readmissions (30dRA, 90dRA). Propensity score matching was used to generate matched pairs based on age, comorbidities, hospital volume, and hemorrhage severity. Results: We identified 13,623 and 11,160 patients who were eligible for 30dRA and 90dRA analyses, respectively. Among the patients eligible for 30dRA and 90dRA, we created 4282 and 3518 propensity score-matched pairs, respectively. There was no difference in the incidence of 30dRA (12.4% for clipping versus 11.2% for EVT; P = .094). However, 90dRA occurred more frequently after clipping (22.5%) compared to EVT (19.7%; P = .003). Clipping was associated with poor outcome after 30dRA (odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.21-1.88, P < .001) and after 90dRA (OR = 1.60, 95% CI 1.34-1.91, P = .001). Mean duration to readmission and cost of readmission did not vary, but clipping was associated with longer lengths of stay during readmission. Conclusions: Microsurgical clipping of ruptured aneurysms is associated with a greater incidence of 90dRA, but not 30dRA, compared to EVT. Poor outcomes after readmission are more common following clipping.     

Cerebrospinal fluid creatine kinase-BB isoenzyme activity and outcome after subarachnoid hemorrhage.

BACKGROUND: The brain is rich in creatine kinase-BB isoenzyme activity (CK-BB), which is not normally present in cerebrospinal fluid (CSF). Results of previous studies have shown that CK-BB can be detected in the CSF of patients with aneurysmal subarachnoid hemorrhage (SAH), but whether CK-BB levels correlate with patients' neurologic outcomes is unknown. OBJECTIVE: To evaluate the relationship between CSF CK-BB level and outcome after SAH. DESIGN: Prospective observational cohort. SETTING: University-affiliated tertiary care center. PATIENTS: Convenience sample of 30 patients seen for cerebral aneurysm clipping. INTERVENTIONS: We sampled and assayed CSF for CK isoenzymes a median of 3 days after SAH in 27 patients, and at the time of unruptured aneurysm clipping in 3 patients. MAIN OUTCOME MEASURES: Without knowledge of CK results, we assigned the Glasgow Outcome Scale score early (approximately 1 week) and late (approximately 2 months) after surgery. RESULTS: Higher CSF CK-BB levels were associated with higher Hunt and Hess grades at hospital admission (Spearman rank correlation, p = 0.69; P<.001), lower Glasgow Coma Scale scores at hospital admission (p = -0.72; P<.001), and worse early outcomes on the Glasgow Outcome Scale (p = -0.64; P<.001). For patients with a favorable early outcome (Glasgow Outcome Scale score, 3-5), all CK-BB levels were less than 40 U/L. With a cutoff value of 40 U/L, CK-BB had a sensitivity of 70% and a specificity of 100% for predicting unfavorable early outcome (Glasgow Outcome Scale score, 1-2). Having a CK-BB level greater than 40 U/L increased the chance of an unfavorable early outcome, from 33% (previous probability) to 100%, whereas a CK-BB level of 40 U/L or less decreased it to 13%. Similar findings were obtained when considering late outcomes. CONCLUSION: The level of CSF CK-BB may help predict neurologic outcome after SAH.     

Fasting Hyperglycemia and Long-term Outcome in Patients with Acute Ischemic Stroke Treated with Mechanical Thrombectomy

BackgroundLittle is known about the prognostic role of fasting glucose after mechanical thrombectomy (MT).AimsWe investigated whether fasting glucose on the next day after MT was associated with long-term outcome in acute ischemic stroke patients according to diabetes.MethodsWe retrospectively analyzed 181 consecutive patients with acute anterior circulation ischemic stroke who underwent MT in 2 comprehensive stroke centers in Poland. Glucose levels were evaluated on admission and on the next day after MT. Fasting hyperglycemia (FHG) was defined as the glucose level above 5.5 mmol/L. Unfavorable outcome was defined as modified Rankin scale (mRS) of 3-6 at day 90 from stroke onset.ResultsPatients with FHG had higher mRS at 3-month follow-up compared with those without FHG (3.71 ± 2.56 versus 1.87 ± 2.22, P < .001). In the subgroup analyses, FHG was associated with poor neurological outcome in the group without diabetes (3.74 ± 2.52 versus 1.81 ± 3.74, P < .001) but not with diabetes (3.64 ± 2.67 versus 2.30 ± 3.74, P= .11). Patients without diabetes who had FHG were older, had higher glucose on admission, higher prevalence of atrial fibrillation, cardioembolic stroke etiology and bleeding brain complications compared with the group with normal fasting glucose. After adjustment for potential confounders, fasting glucose (odds ratio [OR] 1.46; 95% CI 1.19-1.79, P < .001), age (OR 1.06; 95% CI 1.02-1.10, P = .001), successful reperfusion (OR 0.09; 95% CI 0.04-0.22, P < .001) and baseline NIHSS score (OR 1.18; 95% CI 1.08-1.29, P < .001) were predictors of mRS 3-6 at 3-month follow-up in the whole group. In the subgroup without diabetes, fasting glucose (OR 1.57; 95% CI 1.17-2.11, P = .002), age (OR 1.05; 95% CI 1.01-1.08, P = .008), successful reperfusion (OR 0.11; 95% CI 0.04-0.30, P < .001) and baseline NIHSS score (OR 1.14; 95% CI 1.04-1.26, P = .011) were independent predictors of unfavorable 3-month outcome.ConclusionsFasting glucose on the next day after MT in patients with acute ischemic stroke is an independent risk factor for worse 3-month outcome.     

Acute Ischemic Stroke Outcome and Preceding Anticoagulation: Direct Oral Anticoagulants Versus Vitamin K Antagonists

Background and Purpose: Acute ischemic stroke (AIS) severity and clinical course are less known in direct oral anticoagulants (DOAC) users. We aimed to explore the outcome of AIS in patients pretreated with vitamin-K-antagonists (VKA) and DOAC. Methods: A retrospective study was performed. Patients pretreated with oral anticoagulants (OAC) for nonvalvular atrial fibrillation admitted for AIS in a stroke unit between 2016-01-01 and 2018-08-31 were included. The primary endpoint was mortality during the hospital stay, and secondary endpoints were neurologic improvement at stroke unit discharge and good functional outcome 90 days after AIS. Results: A total of 156 patients were included (83 on VKA and 73 on DOAC). Stroke severity (defined by NIHSS on admission) was comparable in both groups (AVK 13.0 [4.0-20.0] versus DOAC 11.0 [4.0-17.0], P = .435). Infratherapeutic levels and/or inappropriate low dose of OAC was also similar between groups (P = .152) and was not associated with stroke severity (P = .631) or mortality (P = .788). VKA (OR 12.616, P = .035, 95%CI 1.19-133.64) and PH2 hemorrhagic transformation (OR 7.516, P = .024, 95%CI 1.31-43.20) were associated with higher mortality in multivariate analysis. Higher stroke severity (OR .101, P < .001, 95%CI .037-.279) and VKA usage (OR .212, P = .003, 95%CI .08-.58) were associated with worse functional outcome at 3 months. Reperfusion therapy was significantly associated with neurologic improvement during stroke unit stay (OR 3.969, P = .009, 95%CI 1.42-11.11) but not with the functional outcome (P = .063). Conclusions: Nonvalvular atrial fibrillation patients pretreated with DOAC admitted for AIS had a better outcome when compared to VKA, although stroke severity was similar between groups.     

Factors Associated with Inpatient Mortality after Intracerebral Hemorrhage: Updated Information from the United States Nationwide Inpatient Sample

Background: To use a nationwide database of hospital admissions to assess for trends in inpatient mortality from acute spontaneous intracerebral hemorrhage as well as associated potentially contributing factors. Methods: Adults with intracerebral hemorrhage in the US National Inpatient Sample database from 2012 to 2015 were included in this study. We assessed for mortality rate as well as potential impact of various comorbidities and demographic factors such as ethnicity and median house hold income on inpatient mortality rate. Results: A total of 47,700 patients were identified with a mean age of 68 years. The overall mortality rate was 24%. Hypertension was the commonest comorbidity (84%) followed by diabetes mellitus (28%). Positive associated factors for mortality rate were coagulopathy (OR 1.28, 95% CI 1.19-1.38, P < .001), female gender (OR 1.12, 95% CI 1.08-1.17, P < .001), and congestive heart failure (OR 1.16, 95% CI 1.08-1.24, P < .001). Age greater than 75 was also associated with higher mortality (P < .001). Factors associated with reduced mortality were hypertension (OR .76, 95% CI .72-0.81, P < .001), hypothyroidism (OR .87, 95% CI .81-.93, P < .001) and obesity (OR .64, 95% CI .59-.69, P < .001). Conclusions: The inpatient mortality of 24% represents a decline when compared to previous years. Attention to the associated factors with mortality, that we report, could have some potential impact on management. Of interest, we found support for obesity paradox in which obesity may have an actual salutary effect on vascular disease outcome. Our observed paradoxical effects, not only for obesity, but also hypertension and hypothyroidism, warrant further study.     

Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage

The findings of various studies reporting temporal changes in CSF total nitrite/nitrate (NOx) levels after subarachnoid hemorrhage (SAH) vary considerably. The study group comprised 10 patients with SAH and 10 control subjects. Total nitrite/nitrate concentration was measured by a vanadium-based assay with the colorimetric Griess reaction. CSF oxyhemoglobin level was assessed by spectrophotometry. After an initial peak (22.6+/-10.1 microM) within first 24 h after SAH, CSF NOx decreased gradually during the period of observation. There was a significant correlation between CSF concentrations of NOx and OxyHb in the entire observation period (R=0.87, p<0.001). When the impact of bleeding into CSF was considered, patients with very good outcome [Glasgow Outcome Scale (GOS)=5] had significantly lower CSF NOx (11.1+/-1.3 microM) than those with worse outcome (GOS<5) (21.8+/-11.2 microM, p<0.01). In conclusion, this study demonstrates that after aneurysm rupture CSF NOx levels correlate with OxyHb. We suggest this as a novel interpretation of other variable findings in relation to NO metabolites in the central nervous system (CNS) post SAH, and hence it could usefully be incorporated into the planning of future studies, correlating NOx with clinical outcome.     

Changes in the metabolism of sphingolipids after subarachnoid hemorrhage

We previously described how ceramide (Cer), a mediator of cell death, increases in the cerebrospinal fluid (CSF) of subarachnoid hemorrhage (SAH) patients. This study investigates the alterations of biochemical pathways involved in Cer homeostasis in SAH. Cer, dihydroceramide (DHC), sphingosine‐1‐phosphate (S1P), and the activities of acid sphingomyelinase (ASMase), neutral sphingomyelinase (NSMase), sphingomyelinase synthase (SMS), S1P‐lyase, and glucosylceramide synthase (GCS) were determined in the CSF of SAH subjects and in brain homogenate of SAH rats. Compared with controls (n = 8), SAH patients (n = 26) had higher ASMase activity (10.0 ± 3.5 IF/µl· min vs. 15.0 ± 4.6 IF/µl ? min; P = 0.009) and elevated levels of Cer (11.4 ± 8.8 pmol/ml vs. 33.3 ± 48.3 pmol/ml; P = 0.001) and DHC (1.3 ± 1.1 pmol/ml vs. 3.8 ± 3.4 pmol/ml; P = 0.001) in the CSF. The activities of GCS, NSMase, and SMS in the CSF were undetectable. Brain homogenates from SAH animals had increased ASMase activity (control: 9.7 ± 1.2 IF/µg ? min; SAH: 16.8 ± 1.6 IF/µg ? min; P < 0.05) and Cer levels (control: 3,422 ± 26 fmol/nmol of total lipid P; SAH: 7,073 ± 2,467 fmol/nmol of total lipid P; P < 0.05) compared with controls. In addition, SAH was associated with a reduction of 60% in S1P levels, a 40% increase in S1P‐lyase activity, and a twofold increase in the activity of GCS. In comparison, NSMase and SMS activities were similar to controls and SMS activities similar to controls. In conclusion, our results show an activation of ASMase, S1P‐lyase, and GCS resulting in a shift in the production of protective (S1P) in favor of deleterious (Cer) sphingolipids after SAH. Additional studies are needed to determine the effect of modulators of the pathways described here in SAH. © 2015 Wiley Periodicals, Inc.     

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage

Background and purpose

Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients.

Methods

A total of 121 consecutive spontaneous SAH patients were retrospectively analyzed. CSF was collected from external ventricular drain as part of routine diagnostic procedures. We used multivariable binary logistic regression to investigate associations between CSF RBC counts and functional outcome 3 months after SAH or hospital survival. Good functional outcome was defined as modified Rankin Scale ≤ 2.

Results

Patients' age was 60 ± 14 years, and the median admission Hunt & Hess grade (H&H) was 4. CSF samples were collected 2 days after intensive care unit admission. High CSF RBC counts positively correlated with radiological measurements for SAH volume, for example, modified Fisher score (p = 0.002) and Hijdra ventricle score (p = 0.016). Multivariable regression analysis adjusted for age, H&H grade, modified Fisher and Hijdra scores showed that low CSF RBC counts predicted hospital survival (per 100,000 CSF RBCs: adjusted odds ratio [adjOR] = 0.74, 95% confidence interval [CI] = 0.61–0.89, p = 0.001) and good functional outcome after 3 months (per 100,000 CSF RBC: adjOR = 0.76, 95% CI = 0.60–0.96, p = 0.020).

Conclusions

CSF RBC counts correlate with radiographic scores quantifying SAH volume and may serve as an early independent biomarker for hospital survival and good functional 3-month outcome in patients requiring ventriculostomy after SAH.     

Pre-Existing Cerebral Small Vessel Disease Limits Early Recovery in Patients with Acute Lacunar Infarct

Background and Purpose: To assess whether neuroimaging markers of chronic cerebral small vessel disease (cSVDm) influence early recovery after acute ischemic stroke (AIS). Methods: Retrospective analysis of patients diagnosed with AIS and included in the Spanish Neurological Society Stroke Database. Inclusion criteria: (1) Brain MRI performed after acute stroke and (2) Premorbid modified Rankin scale (mRS) = 0. Exclusion criteria: (1) Uncommon stroke etiologies, (2) AIS not confirmed on neuroimaging, or (3) Old territorial infarcts on neuroimaging. Patients scored from 0 to 2 according to the amount of cSVDm. Patients were divided into lacunar ischemic stroke (LIS) and nonlacunar ischemic stroke (NLIS) groups according to TOAST classification. Primary outcome: Distribution of mRS at discharge. Secondary outcomes: NIHSS improvement more than or equal to 3 at 24 hours and at discharge, NIHSS worsening more than or equal to 3 points at 24 hours. Results: We studied 4424 patients (3457 NLIS, 967 LIS). The presence of cSVDm increased the risk of worsening 1 category on the mRS at discharge in the LIS group ([1] cSVDm: OR 1.89 CI 95% 1.29-2.75, P = .001. [2] cSVDm: OR 1.87, CI 95% 1.37-2.56 P = .001) and was an independent factor for not achieving an improvement more than or equal to 3 points on the NIHSS at discharge for all the patients and the LIS group (all stroke patients: [1] cSVDm: OR 0.81 CI 95% .68-.97 P = .022. [2] cSVD: OR 0.58 CI95% .45-.77, P = .001./LIS: [1] cSVDm: OR 0.64, CI 95% .41-.98, P = .038. [2] cSVDm: OR 0.43, CI 95% .24-.75 P = .003). Conclusions: Pre-existing SVD limits early functional and neurological recovery after AIS, especially in LIS patients.     

Elevated C-reactive protein and white blood cell count at admission predict functional outcome after non-aneurysmal subarachnoid hemorrhage

Introduction

Patients with non-aneurysmal subarachnoid hemorrhage (SAH) are considered to have an overall benign course of disease compared to patients suffering from aneurysmal SAH. Nevertheless, a small but significant number of such patients might only achieve unfavorable outcome. Therefore, the purpose of the present study was to determine if routine laboratory markers of acute phase response are associated with unfavorable outcome in patients with non-aneurysmal SAH.

Methods

From 2006 to 2017, 154 patients suffering from non-aneurysmal SAH were admitted to our institution. Patients were stratified according to the distribution of cisternal blood into patients with perimesencephalic SAH (pSAH) versus non-perimesencephalic SAH (npSAH). C-reactive protein (CRP) and white blood cells (WBC) assessments were performed within 24 h of admission as part of routine laboratory workup. Outcome was assessed according to the modified Rankin Scale (mRS) after 6 months and stratified into favorable (mRS 0–2) vs. unfavorable (mRS 3–6).

Results

The multivariate regression analysis revealed “CRP?>?5 mg/l” (p?=?0.004, OR 143.7), “WBC count?>?12.1 G/l” (p?=?0.006, OR 47.8), “presence of IVH” (p?=?0.02, OR 13.5), “poor-grade SAH” (p?=?0.01, OR 45.2) and “presence of CVS” (p?=?0.003, OR 149.9) as independently associated with unfavorable outcome in patients with non-aneurysmal SAH.

Conclusion

Elevated C-reactive protein and WBC count at admission were associated with unfavorable outcome after non-aneurysmal SAH.

     

Infarct Volume Predicts Delayed Recovery in Patients with Subarachnoid Hemorrhage and Severe Neurological Deficits

Background

Recovery is common after subarachnoid hemorrhage (SAH), even in patients who are severely disabled at hospital discharge. Little is known about predictors of late recovery in such patients, even though such knowledge may influence treatment decisions. We hypothesized that cerebral infarction volume would be associated with 3 months outcomes in patients who are severely disabled at 14 days.

Methods

We prospectively identified consecutive aneurysmal SAH patients, documented the development of cerebral infarction, and ascertained the modified Rankin Scale (mRS) at 14 days and 3 months. We included patients with mRS 4 or 5 and NIH Stroke Scale (NIHSS) at least 8 on hospital day 14 (i.e., severe neurologic impairment) and calculated infarct volume in a semi-automated fashion using CT imaging. We explored outcome determinants with ordinal regression.

Results

At 14 days, 66 patients were severely disabled, 65 (98.5 %) of whom had mRS of 5; the median NIHSS was 21 [14–24]. At 3 months, 20 (32.8 %) of the 61 patients with known outcomes were independent. Larger infarction volumes were associated with death (20.4 vs. 0.85 mL, P = 0.02). In ordinal regression, increased infarct volume was associated with the worse mRS after correction for WFNS grade, age, and withdrawal of life support (OR 1.01 per mL of infarct, 95 % CI 1.01–1.03, P = 0.01).

Conclusions

After SAH, even with severe neurological injury at 14 days, good recovery is frequent and is associated with lower infarction volume. These data may help clinicians inform surrogate decision makers as they plan the future care of such severely disabled patients.     

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage

Abstract

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm. [Neurol Res 2001; 23: 715-720]     

Prognostic Value of NT-proBNP After Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Cohort Studies

Background: Many studies have evaluated the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and its prognostic value in ischemic stroke. However, a widespread consensus has not been reached. Therefore, we completed a meta-analysis to evaluate the prognostic significance of NT-proBNP for mortality and functional outcome in patients with ischemic stroke. Methods: We performed a systematic search and review using the PubMed and EMBASE databases to identify literature that reported a correlation between NT-proBNP and mortality and functional outcome in ischemic stroke patients. Results: Eleven studies inclusive of 10,498 patients met the inclusion criteria. Elevated plasma NT-proBNP levels were associated with increased risk of mortality in ischemic stroke patients (all-cause mortality: odds ratio [OR] = 2.43, 95% confidence interval [CI] 1.62-3.64, P < .001, I²=74.3%; cardiovascular mortality: OR = 2.01, 95% CI 1.55-2.61, P < .001, I² = 42.6%). In addition, unfavorable functional outcomes were observed in patients with higher levels of NT-proBNP (OR = 1.68, 95% CI 1.13-2.50, P = .01, I² = 90.8%) after ischemic stroke. Conclusions: This meta-analysis demonstrates that NT-proBNP could be a predictor of mortality and functional outcome in ischemic stroke patients.     

Prognostic Value of Serum S100 Protein by Elecsys S100 Immunoassay in Patients with Spontaneous Subarachnoid and Intracerebral Hemorrhages

Objective

The serum S100 protein has been known to reflect the severity of neuronal damage. The purpose of this study was to assess the prognostic value of the serum S100 protein by Elecsys S100 immunoassay in patients with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) and to establish reference value for this new method.

Methods

Serum S100 protein value was measured at admission, day 3 and 7 after bleeding in 42 consecutive patients (SAH : 20, ICH : 22) and 74 healthy controls, prospectively. Admission Glasgow coma scale (GCS) score, Hunt & Hess grade and Fisher grade for SAH, presence of intraventricular hemorrhage, ICH volume, and outcome at discharge were evaluated. Degrees of serum S100 elevation and their effect on outcomes were compared between two groups.

Results

Median S100 levels in SAH and ICH groups were elevated at admission (0.092 versus 0.283 µg/L) and at day 3 (0.110 versus 0.099 µg/L) compared to healthy controls (0.05 µg/L; p<0001). At day 7, however, these levels were normalized in both groups. Time course of S100 level in SAH patient was relatively steady at least during the first 3 days, whereas in ICH patient it showed abrupt S100 surge on admission and then decreased rapidly during the next 7 days, suggesting severe brain damage at the time of bleeding. In ICH patient, S100 level on admission correlated well with GCS score (r=-0.859; p=0.0001) and ICH volume (r=0.663; p=0.001). A baseline S100 level more than 0.199 µg/L predicted poor outcome with 92% sensitivity and 90% specificity. Logistic regression analyses showed Ln (S100) on admission as the only independent predictor of poor outcome (odd ratio 36.1; 95% CI, 1.98 to 656.3).

Conclusion

Brain damage in ICH patient seems to develop immediately after bleeding, whereas in SAH patients it seems to be sustained for few days. Degree of brain damage is more severe in ICH compared to SAH group based on the S100 level. S100 level is considered an independent predictor of poor outcome in patient with spontaneous ICH, but not in SAH. Further study with large population is required to confirm this result.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

Race is a Predictor of Withdrawal of Life Support in Patients with Intracerebral Hemorrhage

Introduction: Medical and socioeconomic factors may impact decisions to change the goals of care for patients with intracerebral hemorrhage (ICH) to comfort measures only. Methods: We reviewed prospectively collected data on patients with ICH, including baseline patient demographics, Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), and ICH score. We conducted multivariable logistic regression analysis to identify predictors of change to comfort measures only status. Results: Of 198 patients included in the analysis, 39 (19.7%) were made comfort measures only. Age, gender, insurance status, substance use, and medical comorbidities were similar between groups. Race was significantly different between the comfort measures only (black 15.4%, white 51.3%, other 33.3%) and noncomfort measures only groups (black 39.6%, white 45.9%, other 14.5%; P?=?.003). Patients changed to comfort measures only had higher mean income based on zip code ($59,264 versus $49,916; P?=?.021), higher median NIHSS (23 versus 16; P?=?.0001), higher ICH score (2.7 versus 1.5; P < .0001), lower median GCS (7 versus 13; P < .0001). Following multivariable analysis, factors associated with comfort measures only were GCS odds ratio (OR) 0.77, 95% confidence interval (CI) 0.68-0.86, P < .0001), intraventricular hemorrhage (IVH) volume (OR 1.03, 95% CI 1.01-1.06, P?=?.002), and black race (OR 0.24, 95% CI 0.07-0.82, P?=?.022). Mortality, poor outcome, and hospital length of stay were not significantly different between black and white patients. Conclusions: Lower GCS score, higher IVH volume, and race were independent predictors of comfort measures only. Black patients were 76% less likely to withdraw life support than white patients. There were no significant differences in mortality between black and white patients. Providers should be aware of potential racial disparities.     

Predictors of 30-Day Readmission After Subarachnoid Hemorrhage

Background

Readmission within 30 days is increasingly evaluated as a measure of quality of care. There are few data on the rates of readmission after subarachnoid hemorrhage (SAH).

Objective

We sought to determine the predictors of 30-day readmission in patients with SAH.

Methods

We prospectively identified 283 patients with SAH admitted between 2006 and 2012. Readmission was determined by means of an automated query with confirmation in the electronic medical record.

Results

Overall, 21 (8 %) patients were readmitted for infection (n = 8), headache (n = 5), hydrocephalus (n = 4), cardiovascular causes (n = 2), medication-related complications (n = 1), and cerebral ischemia (n = 1). Readmission was associated with longer intensive care unit (ICU) length of stay (LOS) (15.4 [13.4–19.3] vs. 12.2 [8.2–18.5] days, P = 0.02), hospital LOS (22.2 [17.4–23.0] vs. 16.8 [12.0–24.1] days, P = 0.01), and placement of an external ventricular drain (EVD, OR 3.9, 95 % CI 1.3–12.0, P = 0.01). Readmission was not associated with admission neurologic grade, NIH Stroke scale at 14 days, modified Rankin scale at 3 months, history of cardiovascular disease, or radiographic cerebral infarction (P > 0.1).

Conclusions

Demographics, severity of neurologic injury, radiographic cerebral infarction, and outcomes were not associated with readmission after SAH. Markers of a more complicated hospital course (ICU and hospital LOS, EVD placement) were associated with 30-day readmission. Most readmissions were for infections acquired after discharge. Readmission within 30 days is difficult to predict, and, since the most common reason was infection acquired after discharge, it may be difficult to prevent without an integrated health system and coordinated care.     

The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage

Background

Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI.

Methods

A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted. Platelet activation [thromboelastography maximum amplitude (MA)] and inflammation [C-reactive protein (CRP)] were measured serially over time during the first 72 h following SAH onset. Platelet activation and inflammatory markers were compared between controls and SAH patients with mild [Hunt–Hess (HH) 1–3] versus severe (HH 4–5) EBI. The association of these biomarkers with 3-month functional outcomes was evaluated.

Results

We enrolled 127 patients (106 SAH; 21 controls). Platelet activation and CRP increased incrementally with worse EBI/HH grade, and both increased over 72 h (all P < 0.01). Both were higher in severe versus mild EBI (MA 68.9 vs. 64.8 mm, P = 0.001; CRP 12.5 vs. 1.5 mg/L, P = 0.003) and compared to controls (both P < 0.003). Patients with delayed cerebral ischemia (DCI) had more platelet activation (66.6 vs. 64.9 in those without DCI, P = 0.02) within 72 h of ictus. At 3 months, death or severe disability was more likely with higher levels of platelet activation (mRS4–6 OR 1.18, 95 % CI 1.05–1.32, P = 0.007) and CRP (mRS4–6 OR 1.02, 95 % CI 1.00–1.03, P = 0.041).

Conclusions

Platelet activation and inflammation occur acutely after SAH and are associated with worse EBI, DCI and poor 3-month functional outcomes. These markers may provide insight into the mechanism of EBI following SAH.