Time Course of Peripheral Leukocytosis and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage

Objective: Systemic inflammation after subarachnoid hemorrhage (SAH) is implicated in delayed cerebral ischemia (DCI) and adverse clinical outcomes. We hypothesize that early changes in peripheral leukocytes will be associated with outcomes after SAH.Methods: SAH patients admitted between January 2009 and December 2016 were enrolled into a prospective observational study and were assessed for Hunt Hess Scale (HHS) at admission, DCI, and modified Ranked Scale (mRS) at discharge. Total white blood cell (WBC) counts and each component of the differential cell count were determined on the day of admission (day 0) to 8 days after bleed (day 8). Global cerebral edema (GCE) was assessed on admission CT, and presence of any infection was determined. Statistical tests included student's t-test, Chi-square test, and multivariate logistic regression (MLR) models.Results: A total of 451 subjects were analyzed. Total WBCs and neutrophils decreased initially reaching a minimum at day 4–5 after SAH. Monocyte count increased gradually after SAH and peaked between day 6–8, while basophils and lymphocytes decreased initially from day 0 to 1 and steadily increased thereafter. Neutrophil to lymphocyte ratio (NLR) reached a peak on day 1 and decreased thereafter. WBCs, neutrophils, monocytes, and NLR were higher in patients with DCI and poor functional outcomes. WBCs, neutrophils, and NLR were higher in subjects who developed infections. In MLR models, neutrophils and monocytes were associated with DCI and worse functional outcomes, while NLR was only associated with worse functional outcomes. Occurrence of infection was associated with poor outcome. Neutrophils and NLR were associated with infection, while monocytes were not. Monocytes were higher in males, and ROC curve analysis revealed improved ability of monocytes to predict DCI and poor functional outcomes in male subjects.Conclusions: Monocytosis was associated with DCI and poor functional outcomes after SAH. The association between neutrophils and NLR and infection may impact outcomes. Early elevation in monocytes had an improved ability to predict DCI and poor functional outcomes in males, which was independent of the occurrence of infection.

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Association between HbA1C (glycated hemoglobin) and clinical outcomes in patients with subarachnoid hemorrhage after neuro-intervention

Current Neurovascular Research ◽

10.2174/1567202618666210225103057 ◽

2021 ◽

Vol 18 ◽

Author(s):

Chan Woong Park ◽

Ho Jun Yi ◽

Dong Hoon Lee ◽

Jae Hoon Sung

Keyword(s):

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Clinical Outcomes ◽

Glycated Hemoglobin ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Roc Curve Analysis ◽

Optimal Cutoff ◽

Cutoff Value ◽

Unfavorable Clinical Outcome ◽

High Hba1c

Objective: Our study investigated the association between level of HbA1c (glycated hemoglobin) at admission and the prognosis of aneurysmal subarachnoid hemorrhage (SAH). Methods: A total of 510 patients treated with neuro-intervention for aneurysmal SAH and with data for admission HbA1c (glycated hemoglobin) were included. Favorable clinical outcome was defined as Modified Rankin Scale (mRS) score of 0–2 at 3 months. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of HbA1C for unfavorable clinical outcomes. Logistic regression was used to evaluate the association between HbA1C level and outcomes. Results: The optimal cutoff value of HbA1C was identified as 6.0% (P < 0.001), and patients with a high HbA1C (≥ 6.0%) had a lower prevalence of favorable clinical outcomes than patients with low HbA1C (< 6.0%) (P < 0.001). High HbA1C (≥ 6.0%) was independently associated with unfavorable clinical outcome (OR 2.84; 95% CI: 1.52-5.44; P = 0.004). The risk of unfavorable clinical outcome was significantly increased in patients with HbA1C (≥ 7.0%, < 8%) and HbA1C (≥ 8.0%) compared with lower baseline HbA1C (≥ 6.0%, < 7%) values (OR 2.17; 95% CI: 1.87-5.13; P = 0.011 and OR 4.25; 95% CI: 3.17-8.41; P = 0.005). Conclusions: Our study showed that HbA1C could be an independent predictor of worse outcome following neuro-intervention for aneurysmal SAH. High HbA1C (≥ 6.0%) was associated with unfavorable clinical outcome, and gradual elevation of HbA1C contributed to an increase in the risk of worse clinical outcome after SAH.

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Deviation from Dynamic and Personalized Optimal Blood Pressure Targets is Associated With Worse Functional Outcomes After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyz310_186 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Andrew Silverman ◽

Sreeja Kodali ◽

Sumita Strander ◽

Emily Gilmore ◽

Alexandra Kimmel ◽

...

Keyword(s):

Blood Pressure ◽

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Functional Outcomes ◽

Near Infrared ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Time Correlation ◽

Blood Pressure Targets ◽

Percent Time

Abstract INTRODUCTION Effective blood pressure (BP) management after aneurysmal subarachnoid hemorrhage (aSAH) is critical for maintaining optimal cerebral perfusion and protecting the brain from further injury. How to best manage BP during the early stages of aSAH remains uncertain. In this study, we calculated individualized BP thresholds at which cerebral autoregulation was best preserved. We analyzed how deviating from these limits correlates with functional outcome. METHODS We prospectively enrolled 31 patients with aSAH. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation – a surrogate for cerebral blood flow – as well as intracranial pressure (ICP) in response to changes in mean arterial pressure (MAP) using time-correlation analysis. The resulting autoregulatory indices were used to trend BP ranges at which autoregulation was most preserved. The percent time that MAP exceeded limits of autoregulation (LA) was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale (mRS) at discharge and 90 d. Associations with outcome were analyzed using ordinal multivariate logistic regression. RESULTS Personalized LA were computed in all patients (age 57.5, 23F, mean WFNS 2, monitoring time 67.8 h). Optimal BP and LA were calculated on average for 89.5% of the total monitoring period. ICP- and NIRS-derived optimal pressures and LA strongly correlated with one another (P < .0001). Percent time that MAP deviated from LA significantly associated with worse functional outcome at discharge (NIRS P = .001, ICP P = .004) and 90 d (NIRS P = .002, ICP P = .003), adjusting separately for age, WFNS, vasospasm, or delayed cerebral ischemia. CONCLUSION Both invasive (ICP) and non-invasive (NIRS) determination of personalized BP thresholds for aSAH patients is feasible, and these 2 approaches revealed significant collinearity. Exceeding individualized autoregulatory thresholds may increase the risk of poor functional outcomes.

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Anesthesia modality does not affect clinical outcomes of intra-arterial vasodilator treatment in patients with symptomatic cerebral vasospasms

F1000Research ◽

10.12688/f1000research.52324.2 ◽

2021 ◽

Vol 10 ◽

pp. 417

Author(s):

Corinne Fischer ◽

Sonja Vulcu ◽

Johannes Goldberg ◽

Franca Wagner ◽

Belén Rodriguez ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

General Anesthesia ◽

Clinical Outcomes ◽

Cerebral Vasospasm ◽

Conscious Sedation ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Vasodilator Therapy ◽

Significant Difference ◽

Vasodilator Treatment

Background: Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Methods: Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. Results: A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. Conclusion: This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.

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Procalcitonin in the context of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2020.5.jns201337 ◽

2020 ◽

pp. 1-9

Author(s):

Michael Veldeman ◽

Daniel Lepore ◽

Anke Höllig ◽

Hans Clusmann ◽

Christian Stoppe ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Outcome Analysis ◽

Clinical Trial Registration ◽

Additional Increase ◽

Long Term Outcome

OBJECTIVEAneurysmal subarachnoid hemorrhage (aSAH) initiates a deleterious cascade activating multiple inflammatory processes, which can contribute to delayed cerebral ischemia (DCI). Procalcitonin (PCT) is an established marker for sepsis treatment monitoring, and its time course in the context of DCI after aSAH remains unclear. The aim of this trial was to assess the predictive and confirmative value of PCT levels in the context of DCI.METHODSAll patients admitted to the authors’ institution with aSAH between 2014 and 2018 were prospectively screened for eligibility. Daily PCT levels were recorded alongside relevant aSAH characteristics. The predictive and confirmative values of PCT levels were assessed using a receiver operating characteristic and area under the curve (AUC) analysis. The course of PCT levels around the DCI event was evaluated in an infection-free subgroup of patients.RESULTSA total of 132 patients with aSAH were included. Early PCT levels (first 3 days post-aSAH) had a low predictive value for the development of DCI (AUC 0.661, standard error [SE] 0.050; p = 0.003) and unfavorable long-term outcome (i.e., Glasgow Outcome Scale–Extended scores 1–4; AUC 0.674, SE 0.054; p = 0.003). In a subgroup analysis of infection-free patients (n = 72), PCT levels were higher in patients developing DCI (p = 0.001) and DCI-related cerebral infarction (p = 0.002). PCT concentrations increased gradually after DCI and decreased with successful intervention. In refractory cases progressing to cerebral infarction, PCT levels showed a secondary increase.CONCLUSIONSEarly higher PCT levels were associated with the later development of DCI and unfavorable outcome. Analysis of PCT beyond the first couple of days after hemorrhage is hampered by nosocomial infections. In infection-free patients, however, PCT levels rise during DCI and an additional increase develops in patients developing cerebral infarction.Clinical trial registration no.: NCT02142166 (clinicaltrials.gov)

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Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage

Scientific Reports ◽

10.1038/s41598-020-79586-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sami Ridwan ◽

Alexander Grote ◽

Matthias Simon

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Interleukin 6 ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Interindividual Variations ◽

Potential Biomarker ◽

Diagnostic Usefulness

AbstractInterleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4–14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4–14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4–14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

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Role of ABO blood type in delayed cerebral ischemia onset and clinical outcomes after aneurysmal subarachnoid hemorrhage in an ethnic minority urban population

Surgical Neurology International ◽

10.25259/sni_10_2020 ◽

2020 ◽

Vol 11 ◽

pp. 108

Author(s):

Santiago René Unda ◽

Tarini Vats ◽

Rafael De la Garza Ramos ◽

Phillip Cezaryirli ◽

David J. Altschul

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Clinical Outcomes ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Univariate Analysis ◽

Delayed Cerebral Ischemia ◽

Blood Type ◽

Academic Center ◽

Abo Blood Type

Background: In recent years, the role of ABO blood type moved into focus through the discovery of different hemostaseologic properties with importance in many diseases including subarachnoid hemorrhage (SAH). However, the role of ABO blood type in delayed cerebral ischemia (DCI) onset, clinical progress, and outcome after SAH is to date largely unexplored. Our aim was to explore the role of ABO blood group in DCI and clinical outcomes after aneurysmal SAH (aSAH). Methods: A retrospective analysis was made with data collected from patients who presented aSAH at our single- academic center from 2015 to 2018. We included demographic, clinical, and imaging variables in the univariate analysis and in the subsequent multivariate analysis. Results: A total of 204 patients were included in this study. About 17.9% of “O” type patients developed a DCI while DCI was reported in only 8.2% of non-O type patients (P = 0.04). “O” type was an independent risk after in the logistic regression after adjusting for significant factors in the univariate analysis (OR=2.530, 95% CI: 1.040- 6.151, P = 0.41). Compared to “non-O” type patients, “O” type patients had a trend to have poorer outcomes at discharge (25.5% vs. 21.3%, P = 0.489) and at 12–18 months (21.1% vs. 19.5%, P = 0.795). However, there were no significant differences. Conclusion: Our study evidenced that patients with “O” blood type have higher risk of DCI onset after aSAH. Although these findings need to be confirmed, they may aid to improve DCI prevention and outcome predictions.

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Abstract TP463: Treatment of Asymptomatic Angiographic Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage May Prevent Progression to Delayed Cerebral Ischemia

Stroke ◽

10.1161/str.51.suppl_1.tp463 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Tania Rebeiz ◽

Tagir Sabirov ◽

Sheshali Wanchoo ◽

Jung-Min Kim ◽

Richard Temes

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Endovascular Treatment ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Treated Group ◽

Untreated Group ◽

Chi Square ◽

Asymptomatic Patients ◽

Chi Square Test

Objective: Endovascular treatment of angiographic cerebral arterial vasospasm (CVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH), who do not fulfill criteria for delayed cerebral ischemia (DCI), remains controversial. We sought to investigate the relationship of endovascular intervention with the development of DCI. Method: Consecutive patients admitted between 2017 and 2019 with aSAH were analyzed retrospectively. Rates of development of DCI were compared between two groups - the treated group: patients not in DCI who underwent conventional digital subtraction angiography (DSA) between days 3 and 14 of ictus and were treated endovascularly for CVS, - the untreated group: patients who did not undergo DSA or did get DSA but did not receive endovascular treatment for CVS. Pearson’s chi-square test for independence was used to compare progression to DCI and t-test for independent samples was used to compare modified fisher scale (mFS) among the 2 groups. Multivariate logistic regression using stepwise backward selection was used to evaluate the predictors of DCI. Results: A total of 83 patients were analyzed. 21 patients (25%) were treated for angiographic vasospasm. 70% of these patients had moderate or severe CVS. 15 (15%) underwent DSA but were not treated angiographically. DSA was performed on an average of day 8 [5-12] post-ictus. 47 (57%) did not received DSA. Although, patients treated for angiographic CVS had higher modified Fisher Scale mFS (p=0.11), the rate of progression to DCI was higher among the untreated group 20 (32%) compared to the treated group (10%) (p =0.04). Delayed cerebral ischemia occurred at an average of day 6 [2-16] post-ictus. Although 15 out of 36 (42%) had DSA but were untreated due to absence or visualization of non-significant CVS, the treated group (68%) had significantly higher mFS (p=0.02) and elevated TCD velocities (p=0.03). mFS (p=0.04) and lack of past medical history of hypertension (p=0.03) were predictors of DCI. Conclusion: Endovascular treatment of angiographic CVS in asymptomatic patients was associated with lower risk of progression to DCI. A large prospective study is needed to evaluate its potential to prevent progression to DCI in high risk patients.

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Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1412833112 ◽

2015 ◽

Vol 112 (4) ◽

pp. 1155-1160 ◽

Cited By ~ 33

Author(s):

Jenna L. Leclerc ◽

Spiros Blackburn ◽

Dan Neal ◽

Nicholas V. Mendez ◽

Jeffrey A. Wharton ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Functional Outcomes ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Free Hemoglobin ◽

Disease States ◽

Critical Care Management ◽

Poor Outcomes ◽

Harmful Effects

Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI) significantly contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb, thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1-1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been associated with reduced ability to protect against toxic free Hb. We hypothesized that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2 phenotype was significantly associated with increased focal moderate (P= 0.014) and severe (P= 0.008) CV and more global CV (P= 0.014) after controlling for covariates. Strong trends toward increased mortality (P= 0.079) and worse functional outcomes were seen for the Hp2-2 patients with modified Rankin scale at 6 wk (P= 0.076) and at 1 y (P= 0.051) and with Glasgow Outcome Scale Extended at discharge (P= 0.091) and at 1 y (P= 0.055). In conclusion, Hp2-2 phenotype is an independent risk factor for the development of both focal and global CV and also predicts poor functional outcomes and mortality after aSAH. Hp phenotyping may serve as a clinically useful tool in the critical care management of aSAH patients by allowing for early prediction of those patients who require increased vigilance due to their inherent genetic risk for the development of CV and resulting DCI and poor outcomes.

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Computed tomography perfusion imaging after aneurysmal subarachnoid hemorrhage can detect cerebral vasospasm and predict delayed cerebral ischemia after endovascular treatment

Surgical Neurology International ◽

10.25259/sni_14_2020 ◽

2020 ◽

Vol 11 ◽

pp. 233

Author(s):

Koji Omoto ◽

Ichiro Nakagawa ◽

Fumihiko Nishimura ◽

Shuichi Yamada ◽

Yasushi Motoyama ◽

...

Keyword(s):

Computed Tomography ◽

Subarachnoid Hemorrhage ◽

Endovascular Treatment ◽

Clinical Outcomes ◽

Cerebral Vasospasm ◽

Cerebral Blood Volume ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Mean Transit Time ◽

Delayed Cerebral Ischemia ◽

Computed Tomography Perfusion

Background: Endovascular treatment (ET) can improve angiographic cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage, but was unrelated to clinical outcomes in previous analyses. Appropriate detection of CV and precise indications for ET are required. This study investigated whether changes in computed tomography perfusion (CTP) parameter can determine indications for ET in CV and predict its effectiveness. Methods: Participants comprised 140 patients who underwent neck clipping or coil embolization. CTP was performed a week after aneurysmal treatment or when clinical deterioration had occurred. Patients were divided into ET and non-ET groups by propensity score matching. In addition, the ET group was divided into subgroups with and without new cerebral infarction (CI). All CTP images in the three groups were retrospectively investigated qualitatively and quantitatively. CI was diagnosed from CT at 3 months postoperatively. Results: Of the 121 patients examined, 15 patients (11%) needed ET. In qualitative analysis, all ET group patients displayed extension of time-to-peak (TTP) at the region of vasospastic change, regardless of the presence of CI. Quantitative analysis showed significant decreases in cerebral blood volume (P < 0.01), cerebral blood flow (CBF) (P < 0.001), and extension in TTP (P < 0.01) in the ET group compared with the non-ET group. A significant decrease in CBF (P < 0.001) and extension in mean transit time (P < 0.001) was seen in the ET with CI subgroup compared with the ET without CI subgroup. Conclusion: CTP in the vasospastic period may be an indication for ET and predict the effectiveness of ET for CV to improve clinical outcomes.

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