Abstract 192: The Relationship of Platelet-leukocyte Aggregates and Early Brain Injury After Subarachnoid Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jennifer A Frontera ◽  
Vladimir Katyshev ◽  
Thomas M McIntyre ◽  
Fatima A Sehba ◽  
Jonathan M Weimer ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Aneurysm Rupture ◽  
Acute Brain Injury ◽  
Unruptured Aneurysms ◽  
Major Predictor ◽  
A Prospective Study ◽  
And Control

Introduction: Acute brain injury incurred after aneurysm rupture in subarachnoid hemorrhage (SAH) is a major predictor of poor functional outcome. We hypothesize that platelet-leukocyte aggregates (PLA) form early after SAH and contribute to acute brain injury. Methods: A prospective study of antiplatelet-naive SAH patients and controls (patients with unruptured aneurysms undergoing repair) was conducted from 3/2014-3/2016. Platelet-monocyte, platelet-lymphocyte and platelet-neutrophil aggregates in whole blood were measured with and without exposure to a platelet agonist (Thrombin receptor activating peptide [TRAP]) using flow cytometry. PLA within 24h and averaged over 72h from ictus (prior to the onset of delayed cerebral ischemia/vasospasm) were compared between patients with mild (admission Hunt-Hess [HH] 1-3) versus severe early brain injury (EBI; HH 4-5). Results: We enrolled 60 SAH patients and 13 controls. PLA were significantly lower in those with severe EBI compared to those with mild EBI (Platelet-monocyte-aggregates 36% versus 53%, P=0.011; Platelet-neutrophil-aggregates 15.2 versus 23.1%, P=0.002) within 24h of ictus and prior to aneurysm repair and remained significantly lower over 72h (both P<0.05). Platelet-monocyte, platelet-neutrophil and platelet-lymphocyte aggregates were also significantly lower in those with severe EBI compared to controls (all P<0.05). The ability of platelets to be stimulated/activated by TRAP to form PLA was also lower in severe EBI patients compared to mild EBI and control patients over 72h (platelet-neutrophil-aggregates 79.7, 88.2 and 92.7%, respectively, P=0.003; platelet-lymphocyte aggregates 9.2, 11.0 and 14.6%, respectively, P=0.022), consistent with prior platelet activation/degranulation. Conclusions: PLA are lower, and respond less to stimulation in patients with severe EBI after SAH compared to those with mild EBI and controls. These data suggest that in severe EBI: PLA may form earlier and are cleared, are adherent to endothelium and not shed in the blood, or have migrated into the parenchyma. These hypotheses bear further study.

scholarly journals The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms

2015 ◽  
Vol 123 (4) ◽  
pp. 862-871 ◽  
Author(s):  
Matthew R. Reynolds ◽  
Robert T. Buckley ◽  
Santoshi S. Indrakanti ◽  
Ali H. Turkmani ◽  
Gerald Oh ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysms ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Patient Characteristics ◽  
Aneurysm Rupture ◽  
Unruptured Aneurysms ◽  
Size Number ◽  
Days Of Therapy ◽  
Induced Hypertension

OBJECT Vasopressor-induced hypertension (VIH) is an established treatment for patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and delayed cerebral ischemia (DCI). However, the safety of VIH in patients with coincident, unruptured, unprotected intracranial aneurysms is uncertain. METHODS This retrospective multiinstitutional study identified 1) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH group). All patients had previously undergone surgical or endovascular treatment for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH patients were made in terms of the patient characteristics, clinical and radiographic severity of SAH, total number of aneurysms, number of ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia, and degree and duration of VIH therapy. RESULTS For the VIH group (n = 176), 484 aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114 unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the mean sizes of the ruptured (7.2 ± 0.3 vs 7.8 ± 0.6 mm, respectively; p = 0.27) and unruptured (3.4 ± 0.2 vs 3.2 ± 0.2 mm, respectively; p = 0.40) aneurysms did not differ. The authors observed 1 new SAH from a previously unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p = 0.50). Baseline patient characteristics and comorbidities were similar between groups. While the degree of hypervolemia was similar between the VIH and non-VIH patients (fluid balance over the first 10 days of therapy: 3146.2 ± 296.4 vs 2910.5 ± 450.7 ml, respectively; p = 0.67), VIH resulted in a significant increase in mean arterial pressure (mean increase over the first 10 days of therapy relative to baseline: 125.1% ± 1.0% vs 98.2% ± 1.2%, respectively; p < 0.01) and systolic blood pressure (125.6% ± 1.1% vs. 104.1% ± 5.2%, respectively; p < 0.01). CONCLUSIONS For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during VIH therapy is rare. The authors do not recommend withholding VIH therapy from these patients.

Subarachnoid Hemorrhage

2016 ◽  
Author(s):  
Imoigele P Aisiku
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Three Dimensional ◽  
Aneurysm Rupture ◽  
World Federation ◽  
Neurogenic Pulmonary Edema ◽  
Systemic Complications ◽  
Unruptured Aneurysms ◽  
Risk Of Rupture ◽  
Anterior Communicating Aneurysm

Subarachnoid hemorrhage (SAH) represents a small portion of cerebrovascular disease but a disproportionally large percentage of the morbidity and mortality. The overall prognosis depends on the volume of the initial bleeding, rebleeding, and the degree of delayed cerebral ischemia. The presence of cardiac manifestations and neurogenic pulmonary edema at the initial presentation indicates a higher degree of severity and systemic complications. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of SAH. Figures show common saccular aneurysm locations, a noncontrast head computed tomographic scan of an SAH, an angiogram and surgical clipping of a broad-based anterior communicating aneurysm, and a three-dimensional reconstruction angiogram of a complex anterior communicating aneurysm with additional imaging of endoscopic stent-assisted coiling of the same aneurysm. Tables list the natural history of unruptured aneurysms and the annual risk of rupture, common clinical features and syndromes related to aneurysm location, the World Federation of Neurologic Surgeons grading system, the Hunt and Hess grading systems, and the Fisher scale. This review contains 4 highly rendered figures, 5 tables, and 144 references. Key words: aneurysm rupture, cerebral aneurysm, cerebral vasospasm, Fisher scale, Glasgow Coma Scale assessment, Hunt and Hess grading criteria, subarachnoid hemorrhage, World Federation of Neurologic Surgeons grading scale 

Emerging Markers of Early Brain Injury and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

2017 ◽  
Vol 107 ◽  
pp. 148-159 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
Krishna Amuluru ◽  
Brendan Smith ◽  
Nitesh Damodara ◽  
Mohammad El-Ghanem ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury

Assessment of tissue permeability by early CT perfusion as a surrogate parameter for early brain injury after subarachnoid hemorrhage

2020 ◽  
Vol 133 (3) ◽  
pp. 808-813 ◽  
Author(s):  
Vesna Malinova ◽  
Bogdan Iliev ◽  
Ioannis Tsogkas ◽  
Veit Rohde ◽  
Marios-Nikos Psychogios ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Predictive Value ◽  
Time Course ◽  
Ct Perfusion ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Tissue Permeability ◽  
Perfusion Deficits

OBJECTIVEThe severity of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) correlates with delayed cerebral ischemia (DCI) and outcome. A disruption of the blood-brain barrier is part of EBI pathophysiology. The aim of this study was to assess tissue permeability (PMB) by CT perfusion (CTP) in the acute phase after aSAH and its impact on DCI and outcome.METHODSCTP was performed on day 3 after aSAH. Qualitative and quantitative analyses of all CTP parameters, including PMB, were performed. The areas with increased PMB were documented. The value of an early PMB increase as a predictor of DCI and outcome according to the modified Rankin Scale (mRS) grade 3 to 24 months after aSAH was assessed. Possible associations of increased PMB with the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) and with early perfusion deficits, as radiographic EBI markers, were evaluated.RESULTSA total of 69 patients were enrolled in the study. An increased PMB on early CTP was detected in 10.1% (7/69) of all patients. A favorable outcome (mRS grade ≤ 2) occurred in 40.6% (28/69) of all patients. DCI was detected in 25% (17/69) of all patients. An increased PMB was a predictor of DCI (logistic regression, p = 0.03) but not of outcome (logistic regression, p = 0.40). The detection of increased PMB predicted DCI with a sensitivity of 25%, a specificity of 94%, a positive predictive value of 57%, and a negative predictive value of 79% (chi-square test p = 0.03). Early perfusion deficits were seen in 68.1% (47/69) of the patients, a finding that correlated with DCI (p = 0.005) but not with the outcome. No correlation was found between the SEBES and increased PMB.CONCLUSIONSChanges in PMB can be detected by early CTP after aSAH, which correlates with DCI. Future studies are needed to evaluate the time course of PMB changes and their interaction with therapeutic measures.

scholarly journals Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

2013 ◽  
Vol 2013 ◽  
pp. 1-42
Author(s):  
Jennifer A. Frontera
Keyword(s):  
Clinical Trials ◽  
Cardiac Arrest ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Randomized Clinical Trials ◽  
Early Brain Injury ◽  
Aneurysm Rupture ◽  
Neurological Outcomes ◽  
Injury Research ◽  
The Brain

Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH).Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included.Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically.Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.

scholarly journals Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH)

2018 ◽  
Vol 19 (7) ◽  
pp. 2035 ◽  
Author(s):  
Shafqat Chaudhry ◽  
Ahmad Hafez ◽  
Behnam Rezai Jahromi ◽  
Thomas Kinfe ◽  
Alf Lamprecht ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Therapy Monitoring ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Endovascular Coiling ◽  
Molecular Pattern ◽  
Extracellular Matrix Components

Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide. Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes. The mechanisms leading to these complications are complex and poorly understood. Early brain injury resulting from transient global ischemia can release molecules that may be critical to initiate and sustain inflammatory response. Hence, the events during early brain injury can influence the occurrence of delayed brain injury. Since the damage associated molecular pattern molecules (DAMPs) might be the initiators of inflammation in the pathophysiology of aSAH, so the aim of this review is to highlight their role in the context of aSAH from diagnostic, prognostic, therapeutic, and drug therapy monitoring perspectives. DAMPs represent a diverse and a heterogenous group of molecules derived from different compartments of cells upon injury. Here, we have reviewed the most important DAMPs molecules including high mobility group box-1 (HMGB1), S100B, hemoglobin and its derivatives, extracellular matrix components, IL-1α, IL-33, and mitochondrial DNA in the context of aSAH and their role in post-aSAH complications and clinical outcome after aSAH.

scholarly journals Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2021 ◽  
Author(s):  
Jane Y. Yuan ◽  
Yasheng Chen ◽  
Atul Kumar ◽  
Zach Zlepper ◽  
Keshav Jayaraman ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Characteristic Curve ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Younger Patients ◽  
Poor Outcome ◽  
Dependent Relationship ◽  
Relationship Of

Background and Purpose: Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH. Methods: We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome. Results: Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3–11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients. Conclusions: Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

scholarly journals The Updated Role of the Blood Brain Barrier in Subarachnoid Hemorrhage: From Basic and Clinical Studies

2020 ◽  
Vol 18 (12) ◽  
pp. 1266-1278
Author(s):  
Sheng Chen ◽  
PengLei Xu ◽  
YuanJian Fang ◽  
Cameron Lenahan
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Ct Perfusion ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Brain Barrier ◽  
Blood Brain

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke associated with high mortality and morbidity. The blood-brain-barrier (BBB) is a structure consisting primarily of cerebral microvascular endothelial cells, end feet of astrocytes, extracellular matrix, and pericytes. Post-SAH pathophysiology included early brain injury and delayed cerebral ischemia. BBB disruption was a critical mechanism of early brain injury and was associated with other pathophysiological events. These pathophysiological events may propel the development of secondary brain injury, known as delayed cerebral ischemia. Imaging advancements to measure BBB after SAH primarily focused on exploring innovative methods to predict clinical outcome, delayed cerebral ischemia, and delayed infarction related to delayed cerebral ischemia in acute periods. These predictions are based on detecting abnormal changes in BBB permeability. The parameters of BBB permeability are described by changes in computed tomography (CT) perfusion and magnetic resonance imaging (MRI). Kep seems to be a stable and sensitive indicator in CT perfusion, whereas Ktrans is a reliable parameter for dynamic contrast-enhanced MRI. Future prediction models that utilize both the volume of BBB disruption and stable parameters of BBB may be a promising direction to develop practical clinical tools. These tools could provide greater accuracy in predicting clinical outcome and risk of deterioration. Therapeutic interventional exploration targeting BBB disruption is also promising, considering the extended duration of post-SAH BBB disruption.

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