Impact of thyroid hormone replacement therapy on the course and functional outcome of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Thyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling. OBJECTIVE: We aimed to analyze the value of thyroid hormone replacement therapy (THRT) due to pre-existing hypothyroidism on the clinical course and outcome of aneurysmal subarachnoid hemorrhage (SAH). METHODS: SAH individuals treated between January 2003 and June 2016 were included. Data on baseline characteristics of patients and SAH, adverse events and functional outcome of SAH were recorded. Study endpoints were cerebral infarction, in-hospital mortality and unfavorable outcome at 6 months. Associations were adjusted for outcome-relevant confounders. RESULTS: 109 (11%) of 995 individuals had THRT before SAH. Risk of intracranial pressure- or vasospasm-related cerebrovascular events was inversely associated with presence of THRT (p = 0.047). In multivariate analysis, THRT was independently associated with lower risk of cerebral infarction (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.41-0.99, p = 0.045) and unfavorable outcome (aOR = 0.50, 95% CI = 0.28-0.89, p = 0.018), but not with in-hospital mortality (aOR = 0.69, 95% CI = 0.38-1.26, p = 0.227). CONCLUSION: SAH patients with THRT show lower burden of ischemia-relevant cerebrovascular events and more favorable outcome. Further experimental and clinical studies are required to confirm our results and elaborate the mechanistic background of the effect of THRT on course and outcome of SAH.

Pharmacological Prevention of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH) include early brain injury and delayed neurologic deterioration, which may result from delayed cerebral ischemia (DCI). Complex pathophysiological mechanisms underlie DCI, which often includes angiographic vasospasm (aVSP) of cerebral arteries. METHODS: Despite the study of many pharmacological therapies for the prevention of DCI in aSAH, nimodipine-a dihydropyridine calcium channel blocker-remains the only drug recommended universally in this patient population. A common theme in the research of preventative therapies is the use of promising drugs that have been shown to reduce the occurrence of aVSP but ultimately did not improve functional outcomes in large, randomized studies. An example of this is the endothelin antagonist clazosentan, although this agent was recently approved in Japan. RESULTS: The use of the only approved drug, nimodipine, is limited in practice by hypotension. The administration of nimodipine and its counterpart nicardipine by alternative routes, such as intrathecally or formulated as prolonged release implants, continues to be a rational area of study. Additional agents approved in other parts of the world include fasudil and tirilazad. CONCLUSIONS: We provide a brief overview of agents currently being studied for prevention of aVSP and DCI after aSAH. Future studies may need to identify subpopulations of patients who can benefit from these drugs and perhaps redefine acceptable outcomes to demonstrate impact.

Stellate Ganglion Block in Subarachnoid Hemorrhage: A Promising Protective Measure Against Vasospasm?

BACKGROUND: Stellate ganglion block (SGB) may have protective effects in patients at risk of vasospasm following subarachnoid hemorrhage (SAH) due to reduced sympathetic activity. However, the safety and clinical outcomes of SGB in this scenario are not definitively known. The objective was to evaluate the safety, clinical outcomes, and cerebral blood flow velocity in patients submitted to SGB or cervical sympathectomy with SAH. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review and meta-analysis of studies investigating SGB or cervical sympathectomy use in SAH were conducted. PubMed, Cochrane Library, and Embase were evaluated. Patients with mRS from 0 to 2, GOS from 4 to 5, or symptom resolution were considered favorable clinical outcomes. Related mortality was defined as death by vasospasm or delayed cerebral ischemia. RESULTS: The analysis included 8 studies comprising 182 patients. Only 2 studies employed SGB prophylactically. The results revealed favorable outcomes in 52% of patients (95% CI: 37%-65%). The overall incidence of complications was 2% (95% CI: 0% -26%). The mortality rate was 13% (95% CI: 7%-21%), with a vasospasm-related mortality rate of 11% (95% CI: 2%-20%). A decrease of cerebral blood flow velocity was reported in 4 studies. CONCLUSIONS: The notable reduction in cerebral blood flow velocity following SGB, alongside positive outcomes and a low occurrence of mortality and complications, highlights its significance as a therapeutic intervention for vasospasm following SAH. While the number of studies evaluating SGB as a preventive measure is limited, the promising results emphasize the importance of future research.

Effect of Intrathecal Urokinase Infusion on Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Vasospasm following an aneurysmal subarachnoid hemorrhage (SAH) causes serious neurological complications, despite surgical clipping of the aneurysm. Intrathecal urokinase (UK) infusion has been shown to effectively prevent symptomatic vasospasm in patients who have undergone endovascular obliteration of the ruptured aneurysms. OBJECTIVE: To investigate whether intrathecal UK infusion can prevent symptomatic vasospasm in patients undergoing surgical or endovascular treatment. METHODS: A total of 90 patients with severe aneurysmal SAH were enrolled and assigned to a surgical neck clipping (n = 56) or an endovascular coil embolization (n = 34) groups. After treatment, UK infusion from the lumbar drain was repeated in 32 patients in the surgical neck clipping group (group B) and all in the endovascular coil embolization group (group C) until complete resolution of the SAH was observed on computed tomography. The remaining 24 of the surgical neck clipping group, without UK infusion, were assigned to group A. RESULTS: Symptomatic vasospasm occurred in 7 (29.2%) patients in group A, 2 (6.3%) in group B, and none in group C (group A vs. group B [P = 0.02]; group B vs. group C [P = 0.14]). Excellent clinical outcomes (modified Rankin score, 0 or 1) were observed in 37.5%, 59.4%, and 76.5% of patients in group A, B, and C, respectively (group A vs. group B [P = 0.11]). CONCLUSION: Clearance of SAH via intrathecal UK infusion significantly reduced symptomatic vasospasm in patients in both UK groups, resulting in better clinical outcomes.

Impact of ventriculo-cisternal irrigation on prevention of delayed cerebral infarction in aneurysmal subarachnoid hemorrhage: a single-center retrospective study and literature review.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and delayed cerebral infarction (DCI) by washing out subarachnoid clots earlier after aneurysm surgery. METHODS: We retrospectively identified 340 subarachnoid hemorrhage (SAH) patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. As VCI therapy, a ventricular drain/cisternal drain was placed during aneurysm surgery, and lactated Ringer's solution was used for irrigation until day 4 of SAH, followed by intracranial pressure control at 5-10 cmH2O until day 14. RESULTS: The median age was 65 years (interquartile range 52-75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: grade I or II, 175 patients (51%); grade III or IV, 84 (25%); and grade V, 81 (24%). With VCI management in all patients, total vasospasm occurred in 162 patients (48%), although the DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventive factor against DCI occurrence (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.07-0.67; P = 0.008), while additional surgery (4.76, 1.62-13.98; P = 0.005) and dyslipidemia (3.27, 1.24-8.63; P = 0.017) were associated with DCI occurrence. CONCLUSION: Managing vasospasms with VCI after SAH is considered a safe and effective method to prevent DCI. Early surgery after SAH may be associated with a decreased risk of DCI with VCI therapy.

Efficacy and Safety of Clazosentan After Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. METHODS: Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. RESULTS: Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). CONCLUSION: Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.

Isoflurane Conditioning-Induced Delayed Cerebral Ischemia Protection in Subarachnoid Hemorrhage-Role of Inducible Nitric Oxide Synthase.

Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH. Our current study aims to define the role of iNOS in isoflurane conditioning-induced protection against delayed cerebral ischemia in a mouse model of SAH. Methods and Results The experiments used 10- to 14-week-old male wild-type (C57BL/6) and iNOS global knockout mice. Anesthetic conditioning was initiated 1 hour after SAH with isoflurane 2% for 1 hour. Isoflurane-induced changes in iNOS expression were measured. N-(3-(aminomethyl) benzyl) acetamidine, a highly selective iNOS inhibitor, was injected intraperitoneally immediately after SAH and then daily. Vasospasm, microvessel thrombosis, and neurological assessment was performed. Data were analyzed by 1-way ANOVA and 2-way repeated measures ANOVA followed by Student Newman Keuls comparison test. Statistical significance was set at P<0.05. Isoflurane conditioning downregulated iNOS expression in naïve and SAH mice. N-(3-(aminomethyl) benzyl) acetamidine attenuated large artery vasospasm and microvessel thrombosis and improved neurological deficits in wild-type animals. iNOS knockout mice were significantly resistant to vasospasm, microvessel thrombosis, and neurological deficits induced by SAH. Combining isoflurane with N-(3-(aminomethyl) benzyl) acetamidine did not offer extra protection, nor did treating iNOS knockout mice with isoflurane. Conclusions Isoflurane conditioning-induced delayed cerebral ischemia protection appears to be mediated by downregulating iNOS. iNOS is a potential therapeutic target to improve outcomes after SAH.

Management of neurological complications related to aneurysmal subarachnoid hemorrhage: A comparison of the bedside therapeutic algorithms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is of the most serious emergencies in neurosurgical practice and continues to be associated with high morbidity and mortality. Beyond securing the ruptured aneurysm to prevent a rebleed, physicians continue to be concerned about potential complications such as cerebral vasospasm-delayed cerebral ischemia (DCI), an area where management remains highly variable. This study aimed at reviewing the most recent literature and assessing any up-to-date schemes for treating the most common aSAH neurological complications in adults that can be applied in daily clinical practice towards optimising outcomes. METHODS: A systematic review was performed according to PRISMA guidelines on the management of aSAH neurological complications in adults. The literature surveyed was between 2016 and 2022 inclusive, using the Pubmed search engine. Comparisons between the methods suggested by existing therapeutic algorithms were discussed. RESULTS: Six stepwise algorithms assisting the decision-making for treating cerebral vasospasm-DCI were recognised and compared. No algorithm was found for the management of any other neurological complications of aSAH. Despite differences in the algorithms, induced hypertension and endovascular therapy were common treatments in all approaches. Controversy in the therapeutic process of these complications surrounds not only the variability of methods but also their optimal application towards clinical outcome optimisation. CONCLUSIONS: A universal approach to managing aSAH complications is lacking. Despite advances in the techniques to secure a ruptured aneurysm, there persist a high rate of neurological deficit and mortality, and several unanswered questions. More research is required towards stratification of current treatment algorithms as per the quality of their evidence.

Evaluation of External Trigeminal Nerve Stimulation to Prevent Cerebral Vasospasm after Subarachnoid Hemorrhage Due to Aneurysmal Rupture: A Randomized, Double-Blind Proof-of-Concept Pilot Trial (TRIVASOSTIM Study).

Cerebral vasospasm remains the most frequent and devastating complication after subarachnoid aneurysmal hemorrhage because of secondary cerebral ischemia and its sequelae. The underlying pathophysiology involves vasodilator peptide release (such as CGRP) and nitric oxide depletion at the level of the precapillary sphincters of the cerebral (internal carotid artery network) and dural (external carotid artery network) arteries, which are both innervated by craniofacial autonomic afferents and tightly connected to the trigeminal nerve and trigemino-cervical nucleus complex. We hypothesized that trigeminal nerve modulation could influence the cerebral flow of this vascular network through a sympatholytic effect and decrease the occurrence of vasospasm and its consequences. We conducted a prospective double-blind, randomized controlled pilot trial to compare the effect of 10 days of transcutaneous electrical trigeminal nerve stimulation vs. sham stimulation on cerebral infarction occurrence at 3 months. Sixty patients treated for aneurysmal SAH (World Federation of Neurosurgical Societies scale between 1 and 4) were included. We compared the radiological incidence of delayed cerebral ischemia (DCI) on magnetic resonance imaging (MRI) at 3 months in moderate and severe vasospasm patients receiving trigeminal nerve stimulation (TNS group) vs. sham stimulation (sham group). Our primary endpoint (the infarction rate at the 3-month follow-up) did not significantly differ between the two groups (p = 0.99). Vasospasm-related infarctions were present in seven patients (23%) in the TNS group and eight patients (27%) in the sham group. Ultimately, we were not able to show that TNS can decrease the rate of cerebral infarction secondary to vasospasm occurrence. As a result, it would be premature to promote trigeminal system neurostimulation in this context. This concept should be the subject of further research.

Cervical sympathectomy to treat cerebral vasospasm: a scoping review.

BACKGROUND/IMPORTANCE: Delayed cerebral ischemia (DCI) is the second-leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (aSAH), and is associated with cerebral arterial vasospasm (CAV). Current treatments for CAV are expensive, invasive, and have limited efficacy. Cervical sympathetic block (CSB) is an underappreciated, but potentially highly effective therapy for CAV. OBJECTIVE: To provide a comprehensive review of the preclinical and human literature pertinent to CSB in the context of CAV. EVIDENCE REVIEW: This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. We conducted a literature search using Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus and Web of Science until February 2022, to identify abstracts, conference proceedings, and full-text papers pertinent to cervical sympathectomy and CAV in animal/adult patients. FINDINGS: We included six human and six experimental studies. Human studies were mostly prospective observational, except one retrospective and one randomized clinical trial, and used various imaging modalities to measure changes in arterial diameter after the block. Studies that used digital subtraction angiography showed an improvement in cerebral perfusion without change in vessel diameter. Transcranial Doppler studies found an approximately 15% statistically significant decrease in velocities consistent with arterial vasodilatation. Overall, the results suggest an increase in cerebral arterial diameter and neurological improvement in patients receiving a CSB. Animal studies demonstrate that sympathetic system ablation vasodilates cerebral vasculature and decreases the incidence of symptomatic vasospasm. CONCLUSIONS: This scoping review suggests that CSB may be a viable option for treatment and prevention of CAV/DCI in patients with aSAH, although the included studies were heterogeneous, mostly observational, and with a small sample size. Further research is needed to standardize the technique and prove its effectiveness to treat patients suffering of CAV/DCI after aSAH.

Cerebral Vasospasm: Practical Review of Diagnosis and Management.

BACKGROUND: Cerebral vasospasm is one of the frequent complications that can occur following subarachnoid hemorrhage (SAH). With new protocols in the management of SAH, the combined risk of death and long-term disability have been reduced by about 10% compared with the past. OBJECTIVE: This work aims to report the latest updates on the vasospasm developing after the SAH in patients in the ICU department. In this short review, we reviewed the latest scientific findings on the mechanisms of vasospasm, and in addition, we considered it necessary to review the literature to report the tools for early diagnosis of vasospasm and the best treatment strategies to prevent the negative outcome in patients admitted to ICU. AIM: The aim of this narrative review is to report the main characteristics of vasospasm, new diagnostic methods, and, especially, more effective treatment of vasospasm. MATERIALS AND METHODS: The peer-reviewed articles analyzed were selected from PubMed, Google scholar, Embase, and Scopus databases published in the previous 20 years using the keywords "vasospasm", "vasospasm diagnosis", "vasospasm and SAH", "vasospasm treatment", and nontraumatic brain injury. Among the 78 papers identified, 43 articles were selected; after the title - abstract examination and removing the duplicates, only 31 articles were examined. RESULTS: Vasospasm can be classified according to clinical (asymptomatic vs. symptomatic) and diagnostic (angiographic vs. ultrasound) methods. Various procedures such as TCD and CT perfusion are used for early diagnosis and close monitoring of this condition. The treatment of vasospasm consists of both prevention (nimodipine, statitis, and magnesium sulphate) and active treatment (mainly endovascular). CONCLUSION: As the review shows, vasospasm is a complication of SAH, a complication that is difficult to recognize early and treat with the best outcome. However, with the equipment we have, it has been possible to improve the outcome, even if it is still not ideal, in patients who develop vasospasm. Several studies are in the final stages to improve the outcome of this unfortunately frequent condition.

Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial.

RATIONALE: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. AIM: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. METHODS AND DESIGN: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. SAMPLE SIZE ESTIMATES: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21. STUDY OUTCOME: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6). DISCUSSION: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.

[Pharmacological Profile and Clinical Study Results of endothelin receptor antagonist, Clazosentan Sodium (PIVLAZ® I.V. Infusion liquid 150†mg)].

Cerebral vasospasm occurs within 4 to 14 days from the onset of aneurysmal subarachnoid hemorrhage (aSAH) in 40 to 70% of patients. Of patients with cerebral vasospasm, 17 to 40% experience delayed ischemic neurological deficits and about half of them develop cerebral infarction. Although the mechanism of the onset of cerebral vasospasm has not been fully elucidated, one of mechanisms is considered that after the onset of aSAH, the level of endothelin, a potent and sustained vasoconstriction substance, increases by production induced by oxyhemoglobin and release from erythrocytes and thus cerebral vasospasm develops via endothelin (ET)A receptor. PIVLAZ I.V. Infusion liquid 150 mg (clazosentan sodium) is an endothelin receptor antagonist with a binding affinity for ETA receptor approximately 1,000 times higher than that for ETB receptor. In the clinical study, the incidence of cerebral vasospasm-related morbidity and all-cause mortality was significantly decreased by clazosentan compared with the placebo. The marketing approval was obtained for the indication of "Prevention of cerebral vasospasm, and vasospasm-related cerebral infarction and cerebral ischemic symptoms after aSAH securing" in January 2022. It is expected to contribute to reducing the risk of sequela and improving quality of life in patients with aSAH.

Effect of early stellate ganglion block in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (BLOCK-CVS): study protocol for a randomized controlled trial.

INTRODUCTION: Stellate ganglion block has been reported to expand cerebral vessels and alleviate vasospasm after aneurysmal subarachnoid hemorrhage. However, the causal relationship between early stellate ganglion block and cerebral vasospasm prevention has not yet been established. The purpose of this study was to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment for cerebral vasospasm and delayed cerebral ischemia. METHODS/DESIGN: This is a single-center, prospective, randomized, controlled, blinded endpoint assessment superiority trial. A total of 228 patients will be randomized within 48 h of aneurysmal subarachnoid hemorrhage onset in a 1:1 ratio into two groups, one group receiving an additional e-SGB and the other group receiving only a camouflaging action before anesthesia induction in the operating room. The primary outcome is the incidence of symptomatic vasospasm within 14 days after aSAH. Further safety and efficacy parameters include the incidence of radiographic vasospasm, new cerebral infarction, postoperative delirium, and complications up to 90 days after surgery; postoperative cerebral hemodynamics; Mini-Mental State Examination score; modified Rankin scale score; and all-cause mortality up to 90 days after surgery. DISCUSSION: This is a randomized controlled trial to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment to reduce cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. If the results are positive, it may provide a new direction for the prevention and treatment of cerebral vasospasm and delayed cerebral ischemia. TRIAL REGISTRATION: The study was registered on Clincaltrials.gov on December 13, 2020 (NCT04691271).

Marked Reduction of Cerebral Vasospasm with Intrathecal Urokinase Infusion Therapy after Endovascular Coil Embolization of the Aneurysmal Subarachnoid Hemorrhage: A Case Series.

Delayed cerebral vasospasms after subarachnoid hemorrhage (SAH) are a risk factor for poor prognosis after successful treatment of ruptured intracranial aneurysms. Different strategies to remove clots from the subarachnoid space and prevent vasospasms have different outcomes. Intrathecal urokinase infusion therapy combined with endovascular treatment (EVT) can reduce the incidence of symptomatic vasospasms. To analyze the relationship between symptomatic vasospasms and residual SAHs after urokinase infusion therapy, we retrospectively reviewed the records of 348 consecutive patients managed with EVT and intrathecal urokinase infusion therapy for aneurysmal SAH at our institution between 2010 and 2021. Among them, 163 patients met the study criteria and were classified into two groups according to the presence of residual SAH in the cisterns, Sylvian fissures, and frontal interhemispheric fissure. The incidence of symptomatic vasospasms and the clinical outcomes were assessed. In total, eight (5.0%) patients developed symptomatic vasospasms. Patients with symptomatic vasospasms had a significantly higher incidence of residual SAH in the Sylvian or frontal interhemispheric fissures than those without (P <.0001). No patient with SAHs resolved by urokinase infusion therapy developed symptomatic vasospasms. However, the two groups did not differ significantly in terms of modified Rankin scale scores at discharge. Treatment with intrathecal urokinase infusion after EVT for aneurysmal SAH can substantially reduce the risk of clinically evident vasospasms.

Cervical spinal cord stimulation for prevention and treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: clinical and radiographic outcomes of a prospective single-center clinical pilot study.

BACKGROUND: Cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of high morbidity and mortality, for which there is no consistently effective treatment. Cervical spinal cord stimulation (cSCS) has been shown to induce vasodilatation and improve peripheral and cerebral blood flow in both animal and human studies. This pilot study was performed to assess the clinical effect and long-term results of cSCS treatment in aSAH patients. METHODS: This was the first IRB- and US FDA-approved prospective non-randomized non-controlled study comprising of 12 aSAH patients (8 women, 4 men, age range 34-62 years) treated between May and November 2008. All patients underwent up to 2 weeks of cSCS with a single percutaneously implanted 8-contact electrode. Neurological outcomes at discharge and follow-up of up to 13 years and mortality/complications rates were analyzed. RESULTS: All 12 aSAH patients underwent cSCS electrode implantation immediately after securing the aneurysm. Patients were stimulated for 10-14 consecutive days starting within 3 days of aneurysm rupture. Angiographic vasospasm occurred in six patients; two patients developed new vasospasm-related neurological symptoms; both recovered completely by discharge time. One patient died from unrelated multi-system failure; the rest were followed up clinically (average, 7.5 years; range, 12-151 months) and angiographically (average, 6.5 years; range, 36-125 months). No delayed ischemic neurological deficits/strokes and no cSCS-related adverse effects were observed. CONCLUSIONS: Our short- and long-term data suggest that cSCS is feasible and safe for patients in the acute aSAH settings. Small size of the patient cohort and lack of control do not allow us to conclude whether cSCS is able to prevent cerebral vasospasm, decrease its severity, and improve clinical outcomes in aSAH patients. However, our findings support further clinical trials and development of cSCS as a new concept to prevent and treat cerebral vasospasm. CLINICALTRIALS: gov NCT00766844, posted on 10/06/2008.

Angiographic Treatment of Asymptomatic Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage for the Prevention of Delayed Cerebral Ischemia.

OBJECTIVE: Angiographic treatment of asymptomatic cerebral vasospasm (CVS) in aneurysmal subarachnoid hemorrhage remains controversial. We sought to investigate its relationship with the development of delayed cerebral ischemia. METHODS: Consecutive patients admitted between July 2017 and June 2019, with a diagnosis of aneurysmal subarachnoid hemorrhage, were retrospectively analyzed. The rate of development of delayed cerebral ischemia was compared between a group of patients who underwent cerebral angiography for asymptomatic CVS and those who did not. The Mann-Whitney U test or χ2 test was used to compare the 2 groups. RESULTS: Thirty-seven of the 94 patients with aneurysmal subarachnoid hemorrhage were screened for CVS, of whom 16 (43%) had moderate-severe vasospasm. When patients who underwent therapeutic cerebral angiography were compared with those who did not and after adjusting for sex, age, and grade of subarachnoid hemorrhage, treatment was not found to be significantly associated with delayed cerebral ischemia (hazard ratio = 0.82, 95% confidence interval: 0.19-3.52, P = 0.79). We found that the median length of stay in the intensive care unit and hospital increased significantly with the severity of CVS (P < 0.001). CONCLUSIONS: Cerebral angiography has a low rate of detecting moderate-severe CVS in asymptomatic patients. Moreover, there was no statistically significant difference in the rate of delayed cerebral ischemia between asymptomatic patients treated versus those not treated for CVS. There was significant association between the severity of CVS and the intensive care unit and hospital length of stay. More studies are needed to evaluate the utility of treating asymptomatic CVS in high-grade aneurysmal subarachnoid hemorrhage.

Protective Felix Culpa Effect of Superior Sympathetic Cervical Ganglion Degenerations on Prevention of Basilar Artery Spasm After Subarachnoid Hemorrhage: A Preliminary Experimental Study.

BACKGROUND: Posterior cerebral blood flow is regulated by the basilar arteries (BAs). Vasospasm of BAs can occur after subarachnoid hemorrhage (SAH). Superior cervical sympathetic ganglia (SCG) fibers have a vasoconstrictor effect on the BA. We aimed to investigate the relationship between the degenerated neuron density of the SCG and the severity of BA vasospasm after experimental SAH. METHODS: Twenty-four rabbits were used. Five were used as the control group, and 5 were used as the sham group. Experimental SAHs were performed in the remaining 14 animals (study group) by injecting homologous blood into the cisterna magna. After 3 weeks of injection, neuron densities of SCG and the severity of BA vasospasm index values (VSI) were examined histopathologically and compared statistically. RESULTS: The mean VSI was 0.669 ± 0.1129 in the control group, 0.981 ± 0.159 in the sham group, and 1.512 ± 0.298 in the study group. The mean degenerated neuronal density of SCG was 436 ± 79/mm3 in severe vasospasm (n = 3), 841 ± 101/mm3 in moderate vasospasm (n = 4), and 1.921 ± 849/mm3 in the less vasospasm detected animals (n = 6). CONCLUSIONS: This study shows an inverse relationship between the degenerated neuronal density in the SCG and VSI values. This finding indicates a diminished sympathetic input from the SCG, resulting in a beneficial effect (the felix culpa) by dilating the lumen diameter of the BA, so SCG degeneration after SAH protects the BA spasm.

Comparing Protection of Remote Limb with Resveratrol Preconditioning following Rodent Subarachnoid Hemorrhage.

BACKGROUND: Preventing delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) remains an important therapeutic target. Preconditioning stimulates multiple endogenous protective mechanisms and may be a suitable treatment for DCI following SAH. We here compare remote limb conditioning with resveratrol conditioning in a clinically relevant SAH model. METHODS: We produced a SAH in 39 male Sprague Dawley rats using a single injection model. Animals were randomized to four groups: repetitive limb conditioning with a blood pressure cuff, sham conditioning, intraperitoneal resveratrol (10 mg/kg) or intraperitoneal vehicle administered at 24, 48 and 72 h after SAH. On day 4 neurological and behavioral scores were obtained, and animals were euthanized. The cross-sectional area of the basilar artery was measured at the vertebrobasilar junction, and at the mid and distal segments. Hippocampal cells were counted in both hemispheres and normalized per mm length. We compared true limb preconditioning with sham conditioning and resveratrol with vehicle preconditioning. RESULTS: The cross-sectional area of the mid-basilar artery in the true limb preconditioning group was significantly larger by 43% (p = 0.03) when compared with the sham preconditioning group. No differences in the cross-sectional area were found in the resveratrol-treated group when compared to the vehicle-treated group. We found no differences in the neuro score, behavioral score, and in mean hippocampal neuron counts between the groups. CONCLUSION: We found beneficial vascular effects of remote limb preconditioning on SAH-induced basilar artery vasoconstriction. Our findings support further studies of limb preconditioning as a potential treatment after SAH.