Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

2019 ◽  
Vol 31 (3) ◽  
pp. 466-475 ◽  
Author(s):  
Yu Zhu ◽  
Hao Jiang ◽  
Yongda Li ◽  
Yuxiang Weng ◽  
Kangli Xu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Alkaline Phosphatase Level ◽  
Serum Alkaline Phosphatase ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Serum Alkaline Phosphatase Level ◽  
Angiographic Vasospasm

scholarly journals Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage

2017 ◽  
Vol 126 (5) ◽  
pp. 1545-1551 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
David Roh ◽  
Shouri Lahiri ◽  
Emma Meyers ◽  
Jens Witsch ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Functional Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Angiographic Vasospasm ◽  
Increased Risk ◽  
Address Data

OBJECTIVEThe clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome.METHODSThe authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up.RESULTSThe cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4–3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0–3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4–1.6, p = 0.5).CONCLUSIONSUEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.

scholarly journals Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

2021 ◽  
Author(s):  
Claudia Ditz ◽  
Björn Machner ◽  
Hannes Schacht ◽  
Alexander Neumann ◽  
Peter Schramm ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Antiplatelet Therapy ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Control Group ◽  
Lesion Volume ◽  
Single Center ◽  
Single Center Experience

AbstractPlatelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

scholarly journals Associations between endothelin polymorphisms and aneurysmal subarachnoid hemorrhage, clinical vasospasm, delayed cerebral ischemia, and functional outcome

2018 ◽  
Vol 128 (5) ◽  
pp. 1311-1317 ◽  
Author(s):  
Christoph J. Griessenauer ◽  
Robert M. Starke ◽  
Paul M. Foreman ◽  
Philipp Hendrix ◽  
Mark R. Harrigan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Multivariate Logistic Regression Analysis ◽  
Renin Angiotensin System ◽  
Nucleotide Polymorphisms ◽  
Endothelin 1 ◽  
Potent Vasoconstrictor

OBJECTIVEEndothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated.METHODSBlood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation. The CARAS study prospectively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015. Common endothelin SNPs were detected using 5′ exonnuclease (TaqMan) genotyping assays. Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed.RESULTSSamples from 149 patients with aSAH and 50 controls were available for analysis. In multivariate logistic regression analysis, the TG (odds ratio [OR] 2.102, 95% confidence interval [CI] 1.048–4.218, p = 0.036) and TT genotypes (OR 7.884, 95% CI 1.003–61.995, p = 0.05) of the endothelin-1 T/G SNP (rs1800541) were significantly associated with aSAH. There was a dominant effect of the G allele (CG/GG genotypes; OR 4.617, 95% CI 1.311–16.262, p = 0.017) of the endothelin receptor A G/C SNP (rs5335) on clinical vasospasm. Endothelin SNPs were not associated with DCI or functional outcome.CONCLUSIONSCommon endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm. Further studies are required to elucidate the relevant pathophysiology and its potential implications in the treatment of patients with aSAH.

Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission

2017 ◽  
Vol 97 ◽  
pp. 199-204 ◽  
Author(s):  
Abdulrahman Aldakkan ◽  
Alireza Mansouri ◽  
Blessing N.R. Jaja ◽  
Naif M. Alotaibi ◽  
R. Loch Macdonald ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Angiographic Vasospasm

Gain-of-function polymorphisms of cystathionine β-synthase and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage

2011 ◽  
Vol 115 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Bartosz T. Grobelny ◽  
Andrew F. Ducruet ◽  
Peter A. DeRosa ◽  
Ivan S. Kotchetkov ◽  
Brad E. Zacharia ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Intracellular Signaling ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Gain Of Function ◽  
Functional Polymorphisms ◽  
Angiographic Vasospasm ◽  
Serum Homocysteine ◽  
Buccal Swabs

Object Cystathionine β-synthase (CBS) is an enzyme that metabolizes homocysteine to form H2S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H2S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C→T, 844ins68, and 1080C→T) by polymerase chain reaction. Serum homocysteine levels (μmol/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI. Results There were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT/ins genotypes were less likely to experience DCI relative to those with the 844 WT/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis. Conclusions Polymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H2S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.

Rebleeding drives poor outcome in aneurysmal subarachnoid hemorrhage independent of delayed cerebral ischemia: a propensity-score matched cohort study

2020 ◽  
Vol 133 (2) ◽  
pp. 360-368
Author(s):  
Victor M. Lu ◽  
Christopher S. Graffeo ◽  
Avital Perry ◽  
Lucas P. Carlstrom ◽  
Leonardo Rangel-Castilla ◽  
...  
Keyword(s):  
Cohort Study ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Propensity Score ◽  
Functional Outcome ◽  
Treatment Modality ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Poor Functional Outcome ◽  
Poor Outcome

OBJECTIVEDelayed cerebral ischemia (DCI) and aneurysm rebleeding contribute to morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH); however, the relationship between their impacts on overall functional outcome is incompletely understood.METHODSThe authors conducted a cohort study of all aSAH during the study period from 2001 to 2016. Primary end points were overall functional outcome and ischemic aSAH sequelae, defined as delayed cerebral ischemia (DCI), DCI with infarction, symptomatic vasospasm (SV), and global cerebral edema (GCE). Outcomes were compared between the rebleed and nonrebleed cohorts overall and after propensity-score matching (PSM) for risk factors and treatment modality. Univariate and multivariate ordered logistic regression analyses for functional outcomes were performed in the PSM cohort to identify predictors of poor outcome.RESULTSFour hundred fifty-five aSAH cases admitted within 24 hours of aneurysm rupture were included, of which 411 (90%) experienced initial aneurysm ruptures only, while 44 (10%) had clinically confirmed rebleeding. In the overall cohort, rebleeding was associated with significantly worse functional outcome, longer intensive care unit length of stay (LOS), and GCE (all p < 0.01); treatment modality, overall LOS, DCI, DCI with infarction, and SV were nonsignificant. In the PSM analysis of 43 matched rebleed and 43 matched nonrebleed cases, only poor functional outcome and GCE remained significantly associated with rebleeding (p < 0.01 and p = 0.02, respectively). Multivariate regression identified that both rebleeding (HR 21.5, p < 0.01) and DCI (HR 10.1, p = 0.01) independently predicted poor functional outcome.CONCLUSIONSRebleeding and DCI after aSAH are highly morbid and potentially deadly events after aSAH, which appear to have independent negative impacts on overall functional outcome. Early rebleeding did not significantly affect the risk of delayed ischemic complications.

scholarly journals Delayed Cerebral Ischemia and Spreading Depolarization in Absence of Angiographic Vasospasm after Subarachnoid Hemorrhage

2011 ◽  
Vol 32 (2) ◽  
pp. 203-212 ◽  
Author(s):  
Johannes Woitzik ◽  
Jens P Dreier ◽  
Nils Hecht ◽  
Ingo Fiss ◽  
Nora Sandow ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Digital Subtraction Angiography ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Prolonged Release ◽  
Digital Subtraction ◽  
Angiographic Vasospasm ◽  
Electrode Strip ◽  
Subdural Electrode

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2020 ◽  
Vol 88 (1) ◽  
pp. E13-E26
Author(s):  
R Loch Macdonald ◽  
Daniel Hänggi ◽  
Nerissa U Ko ◽  
Tim E Darsaut ◽  
Andrew P Carlson ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Internal Carotid ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rescue Therapy ◽  
Delayed Cerebral Ischemia ◽  
Phase 2 ◽  
Open Label ◽  
Angiographic Vasospasm ◽  
Basal Cisterns

ABSTRACT BACKGROUND A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. METHODS Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. RESULTS The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. CONCLUSION Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.

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