scholarly journals Evidence-based cerebral vasospasm management

2006 ◽  
Vol 21 (3) ◽  
pp. 1-10 ◽  
Author(s):  
George W. Weyer ◽  
Colum P. Nolan ◽  
R. Loch Macdonald
Keyword(s):  
Clinical Trials ◽  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rescue Therapy ◽  
Delayed Cerebral Ischemia ◽  
Antiplatelet Agents ◽  
Fibrinolytic Therapy ◽  
Endothelin Antagonists ◽  
Steroid Drugs

✓Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness. The purpose of this work was to perform a systematic review of the literature on the treatment of cerebral vasospasm. A literature search for randomized controlled trials of therapies used for prevention or treatment of cerebral vasospasm and/or delayed cerebral ischemia was conducted, and 41 articles meeting the review criteria were found. Study characteristics and primary results of these articles are reviewed. Key indicators of quality were poor when averaged across all studies, but have improved greatly over time. The only proven therapy for vasospasm is nimodipine. Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium, statin medications, endothelin antagonists, steroid drugs, anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have yielded inconclusive results. The following conclusions were made: nimodipine is indicated after SAH and tirilazad is not effective. More study of hemodynamic maneuvers, the effectiveness of other calcium channel antagonists such as nicardipine delivered by other routes (for example intrathecally), magnesium, statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is warranted. There is less enthusiasm for the study of steroid drugs and anticoagulant/antiplatelet agents because they entail more risks and investigations so far have shown little evidence of efficacy. The study of rescue therapy such as balloon angioplasty and intraarterial vasodilating agents will be difficult. The quality of clinical trials should be improved.

scholarly journals Cerebral vasospasm following subarachnoid hemorrhage (SAH):

2018 ◽  
Vol 20 (3) ◽  
pp. 365-377
Author(s):  
Paulo Henrique Pires De Aguiar ◽  
Antônio Santos De Araújo Júnior ◽  
Mirella Martins Fazzito ◽  
Renata Simms ◽  
Miguel Melgar ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Antiplatelet Agents ◽  
Injured Brain ◽  
Endothelin Antagonists ◽  
Triple H ◽  
Proven Benefit ◽  
Improve Blood Flow

Cerebral vasospasm and the delayed cerebral ischemia remain a source of substantial morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Hemodynamic manipulation better known as ‘triple H’ therapy is routinely used in the management of patients with acute vasospasmfollowing SAH. The rationale of inducing hypertension, hypervolemia and hemodilution is to improve blood flow to the injured brain and to prevent secondary ischemia. While the Ca2+ antagonist Nimodipine is still the only drug with proven benefit on neurologic outcome following SAH, several alternatives are under research. Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium, statin medications, endothelin antagonists, steroid drugs, anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have yielded inconclusive and controversial results. Steroids drugs and anticoagulant/antiplatelet agents have been abandoned so far, because of the lack of efficacy. The purpose of the present paper is to provide a systematic review of the existing literature on the treatment of cerebral vasospasm.

Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 133 (6) ◽  
pp. 1786-1791 ◽  
Author(s):  
Kevin Kwan ◽  
Orseola Arapi ◽  
Katherine E. Wagner ◽  
Julia Schneider ◽  
Heustein L. Sy ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Significant Difference

OBJECTIVEIn patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration.METHODSIn this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures.RESULTSTwenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119).CONCLUSIONSPreliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

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.

scholarly journals Inflammation, Cerebral Vasospasm, and Evolving Theories of Delayed Cerebral Ischemia

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Kevin R. Carr ◽  
Scott L. Zuckerman ◽  
J Mocco
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Primary Role ◽  
Inflammatory Cascade ◽  
Exact Etiology ◽  
Intracellular Calcium Dynamics ◽  
Insight Into

Cerebral vasospasm (CVS) is a potentially lethal complication of aneurysmal subarachnoid hemorrhage (aSAH). Recently, the symptomatic presentation of CVS has been termed delayed cerebral ischemia (DCI), occurring as early as 3-4 days after the sentinel bleed. For the past 5-6 decades, scientific research has promulgated the theory that cerebral vasospasm plays a primary role in the pathology of DCI and subsequently delayed ischemic neurological decline (DIND). Approximately 70% of patients develop CVS after aSAH with 50% long-term morbidity rates. The exact etiology of CVS is unknown; however, a well-described theory involves an antecedent inflammatory cascade with alterations of intracellular calcium dynamics and nitric oxide fluxes, though the intricacies of this inflammatory theory are currently unknown. Consequently, there have been few advances in the clinical treatment of this patient cohort, and morbidity remains high. Identification of intermediaries in the inflammatory cascade can provide insight into newer clinical interventions in the prevention and management of cerebral vasospasm and will hopefully prevent neurological decline. In this review, we discuss current theories implicating the inflammatory cascade in the development of CVS and potential treatment targets.

scholarly journals Non-cerebral vasospasm factors and cerebral vasospasm predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Yue Chen ◽  
Guanmin Li ◽  
Xiaoyong Chen ◽  
Dengliang Wang ◽  
Wenhua Fang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia

scholarly journals Milrinone for refractory cerebral vasospasm with delayed cerebral ischemia

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yasser B. Abulhasan ◽  
Johanna Ortiz Jimenez ◽  
Jeanne Teitelbaum ◽  
Gabrielle Simoneau ◽  
Mark R. Angle
Keyword(s):  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Cerebral Vasospasm ◽  
Standard Therapy ◽  
Therapy Group ◽  
Rescue Therapy ◽  
Delayed Cerebral Ischemia ◽  
World Federation ◽  
Study Cohort ◽  
Poor Grade

OBJECTIVEIntravenous (IV) milrinone is a promising option for the treatment of cerebral vasospasm with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, data remain limited on the efficacy of treating cases that are refractory to standard therapy with IV milrinone. The aim of this study was to determine predictors of refractory vasospasm/DCI despite treatment with IV milrinone, and to analyze the outcome of rescue therapy with intraarterial (IA) milrinone and/or mechanical angioplasty.METHODSThe authors conducted a retrospective cohort study of all patients with aSAH admitted between 2010 and 2016 to the Montreal Neurological Institute and Hospital. Patients were stratified into 3 groups: no DCI, standard therapy, and rescue therapy. The primary outcome was frequency of DCI-related cerebral infarction identified on neuroimaging before hospital discharge. Secondary outcomes included functional outcome reported as modified Rankin Scale (mRS) score, and segment reversal of refractory vasospasm.RESULTSThe cohort included 322 patients: 212 in the no DCI group, 89 in the standard therapy group, and 21 in the rescue therapy group. Approximately half (52%, 168/322) were admitted with poor-grade aSAH at treatment decision (World Federation of Neurosurgical Societies grade III–V). Among patients with DCI and imaging assessing severity of vasospasm, 62% (68/109) had moderate/severe radiological vasospasm on DCI presentation. Nineteen percent (21/110) of patients had refractory vasospasm/DCI and were treated with rescue therapy. Targeted rescue therapy with IA milrinone reversed 32% (29/91) of the refractory vasospastic vessels, and 76% (16/21) of those patients experienced significant improvement in their neurological status within 24 hours of initiating therapy. Moderate/severe radiological vasospasm independently predicted the need for rescue therapy (OR 27, 95% CI 8.01–112). Of patients with neuroimaging before discharge, 40% (112/277) had developed new cerebral infarcts, and only 21% (23/112) of these were vasospasm-related. Overall, 65% (204/314) of patients had a favorable functional outcome (mRS score 0–2) assessed at a median of 4 months (interquartile range 2–8 months) after aSAH, and there was no difference in functional outcome between the 3 groups (p = 0.512).CONCLUSIONSThe aggressive use of milrinone was safe and effective based on this retrospective study cohort and is a promising therapy for the treatment of vasospasm/DCI after aSAH.

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