Angiographic Vasospasm Research Articles

Systematic Review of Intrathecal Nicardipine for the Treatment of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Intrathecal nicardipine has been shown to have some efficacy for the treatment of symptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). We performed a PRISMA-based systematic review of intrathecal nicardipine for the treatment of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. A total of 825 articles were reviewed. After duplicates were removed and the search criteria was applied, 9 articles remained that were eligible for inclusion and analysis. 377 patients received a total of 6,596 injections of intrathecal nicardipine for aSAH-related cerebral vasospasm. The cumulative ventriculostomy-associated infection risk was 6%. Intrathecal nicardipine injections for aSAH-related cerebral vasospasm appears efficacious and safe. Administration of 4 mg of nicardipine every 12 hours was the most commonly reported dosing regimen. Intrathecal nicardipine decreases mean flow velocities on transcranial Doppler and reduces angiographic and clinical vasospasm. The infection risk appears to be in-line with studies in which rates of EVD-related infections have been reported.

A Pilot Study of Facial Nerve Stimulation on Cerebral Artery Vasospasm in Subarachnoid Hemorrhage Patients.

Background: The objective of this pilot study was to assess the safety and efficacy of VitalFlow stimulation in aneurysmal subarachnoid hemorrhage (aSAH) patients with vasospasm for the purpose of guiding the design of larger, controlled studies in vasospasm patients, a largely untreated condition [1]. Methods: Six patients with angiographic vasospasm developing post-aSAH were treated with VitalFlow stimulation. Digital subtraction angiograms were obtained at the time of diagnosis (baseline) and then 30 minutes post-stimulation. A single 2-minute period of stimulation was delivered to the patients using parameters previously shown to be safe, tolerable, and effective at increasing cerebral blood flow (CBF) in healthy volunteers. Results: VitalFlow stimulation improved tissue perfusion as assessed by parenchymography and reversed the constriction of vasospastic arteries. Two patients had only partial improvement and so were treated with intraarterial nimodipine after VitalFlow stimulation, whereas four patients had complete resolution of the vasospasm after VitalFlow stimulation per the treating neuroendovascular surgeon’s evaluation. Clinical examination showed improvement in Hunt and Hess Scale scores assessed post-stimulation. Conclusions: Non-invasive magnetic stimulation of the facial nerve with the VitalFlow stimulator appears to be a safe and effective means to reverse angiographic vasospasm in aSAH patients. Clinical Impact: This study provides Class IV evidence that non-invasive magnetic stimulation of the facial nerves reduce angiographic vasospasm in aSAH patients.

Outcome of Oral and Intra-arterial Nimodipine Administration After Aneurysmal Subarachnoid Haemorrhage - A Single-centre Study.

Oral nimodipine is administered to improve clinical outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, clinical outcome in patients with and without oral nimodipine administration was assessed. A total of 105 patients did not receive oral nimodipine but did receive intra-arterial nimodipine in the occurrence of hemodynamically relevant vasospasm after aSAH, whereas 74 patients received applications of both. Demographic/radiological details and clinical presentation were abstracted from the case records. Patient baseline characteristics were comparable, a predominance of endovascular coiling was shown in cohort 2 (p=0.0135). Severity of initial aSAH and clinical status at admission (Hunt and Hess) was significantly higher in those receiving oral nimodipine. Incidence of angiographic vasospasm was significantly higher in patients not treated with oral nimodipine (p=0.0305); a significantly better outcome measured by the National Institute of Health Stroke Scale (p=0.0213), was noted in those receiving oral nimodipine. Oral nimodipine administration improved clinical outcome of patients after aSAH and should be administered routinely for such patients.

Ozagrel for Postoperative Management of Aneurysmal Subarachnoid Hemorrhages.

A number of pharmacological agents have been tried to circumvent the problem of delayed cerebral ischemia (DCI) with ozagrel sodium being one such agent aimed at the prevention of DCI. Ozagrel is an inhibitor of thromboxane synthetase. It has anti-platelet aggregation action and it dilates vessels. Ozagrel was not available outside Japan till recently. It is available now in India and we had the opportunity to use it among patients with aneurysmal subarachnoid hemorrhage (SAH). To analyse the results of ozagrel administration for patients with aneurysmal SAH. Tertiary care neurosurgical center. Retrospective analysis of the outcomes of patients who received ozagrel after microsurgical cllipping of aneurysm and comparison with a control grpup who received treatment as usual. The t-test (two-tailed), Chi-square test, and Mann-Whitney U-test asymptomatic significance (two-tailed), were used respectively for continuous, categorical, and ordinal variables. The significance was determined at P = 0.05 level. A total of 106 patients underwent surgical clipping of their ruptured intracranial aneurysms over a period of 22 months. Forty two (39.6%) patients received ozagrel, and 62 (60.4%) received the standard treatment. Ozagrel was started at a median of one [interquartile range (IQR) 0.75] day after the surgery, and was given for a median of five (IQR 5) days after the surgery. There was no difference in age, postictal days, World Federation Neurosurgical Society grade, Fisher grade, and the size of ruptured aneurysm in patients who received ozagrel compared to the patients who did not receive ozagrel. Of the 42 patients who received ozagrel, 30 patients (71.4%) had preoperative angiographic vasospasm which improved after the administration of ozagrel. Fifteen (35.5%) patients who received ozagrel developed delayed cerebral ischemia compared to only 11 (17.2%) patients who did not receive ozagrel. Thirty-six (85.7%) patients who received ozagrel had favorable outcome at discharge compared to 52 (81.3%) patients who did not receive ozagrel. No adverse event was observed with ozagrel therapy. At 3-month follow-up, 37 patients (88.1%) who received ozagrel had favorable outcomes against 53 patients (82.8%) who did not receive ozagrel. Ozagrel may be a useful drug in the armamentarium to treat vasospasm after aneurysmal SAH. A future multicenter large cohort study may validate the findings of our study.

Elucidating the novel biomarker and therapeutic potentials of High-mobility group box 1 in Subarachnoid hemorrhage: A review.

Subarachnoid hemorrhage (SAH) frequently arises after an aneurysm in a cerebral artery ruptures, resulting into bleeding as well as clot formation. High-mobility group box 1 (HMGB1) is an extremely preserved, universal protein secreted in the nuclei of all cell varieties. This review explores the biomarker as well as therapeutic potentials of HMBG1 in SAH especially during the occurrence of cerebral vasospasms. Plasma HMGB1 levels have proven to be very useful prognosticators of effective outcome as well as death after SAH. Correspondingly, higher HMGB1 levels in the cerebrospinal fluid (CSF) of SAH patients correlated well with poor outcome; signifying that, CSF level of HMGB1 is a novel predictor of outcome following SAH. Nonetheless, the degree of angiographic vasospasm does not always correlate with the degree of neurological deficits in SAH patients. HMGB1 stimulated cerebral vasospasm, augmented gene as well as protein secretory levels of receptor for advance glycation end product (RAGE) in neurons following SAH; which means that, silencing HMGB1 during SAH could be of therapeutic value. Compounds like resveratrol, glycyrrhizin, rhinacanthin, purpurogallin, 4′-O-β-D-Glucosyl-5-O-Methylvisamminol (4OGOMV) as well as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) gene are capable of interacting with HMGB1 resulting in therapeutic benefits following SAH.

A case report of delayed cortical infarction adjacent to sulcal clots after traumatic subarachnoid hemorrhage in the absence of proximal vasospasm

BackgroundCortical ischemic lesions represent the predominant pathomorphological pattern of focal lesions after aneurysmal subarachnoid hemorrhage (aSAH). Autopsy studies suggest that they occur adjacent to subarachnoid blood and are related to spasm of small cortical rather than proximal arteries. Recent clinical monitoring studies showed that cortical spreading depolarizations, which induce cortical arterial spasms, are involved in lesion development. If subarachnoid blood induces adjacent cortical lesions, it would be expected that (i) they also develop after traumatic subarachnoid hemorrhage (tSAH), and (ii) lesions after tSAH can occur in absence of angiographic vasospasm, as was found for aSAH.Case presentationAn 86-year-old woman was admitted to our hospital with fluctuating consciousness after hitting her head during a fall. The initial computed tomography (CT) was significant for tSAH in cortical sulci. On day 8, the patient experienced a secondary neurological deterioration with reduced consciousness and global aphasia. Whereas the CT scan on day 9 was still unremarkable, magnetic resonance imaging (MRI) on day 10 revealed new cortical laminar infarcts adjacent to sulcal blood clots. Proximal vasospasm was ruled out using MR and CT angiography and Doppler sonography. CT on day 14 confirmed the delayed infarcts.ConclusionsWe describe a case of delayed cortical infarcts around sulcal blood clots after tSAH in the absence of proximal vasospasm, similar to results found previously for aSAH. As for aSAH, this case suggests that assessment of angiographic vasospasm is not sufficient to screen for risk of delayed infarcts after tSAH. Electrocorticography is suggested as a complementary method to monitor the hypothesized mechanism of spreading depolarizations.

Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage.

Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs. Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD-induced perfusion deficits (spreading ischemia) was assessed in an aSAH-mimicking model. There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059-1.192, p = 0.084). However, the total SD-induced depression duration per recording day (22.2 vs 30.2 minutes, β = -251.905, 95% CI = -488.458 to -15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, β = -0.916, 95% CI = -1.746 to -0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD-induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3-55.1, p = 0.020). Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH-mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873-885.

An Update on the Efficacy and Safety Profile of Clazosentan in Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis

The present meta-analysis was conducted to provide an update on the efficacy and safety profile of clazosentan with different doses in aneurysmal subarachnoid hemorrhage (aSAH). We performed a comprehensive and electronic search updated to September 2018 of The Cochrane Library, Embase, and PubMed to identify relevant clinical trials. Trials of the effectiveness of clazosentan in treating cerebral vasospasm after aSAH were studied. The main outcomes included new cerebral infarction (NCI), delayed ischemic neurologic deficit (DIND), vasospasm associated with morbidity/mortality, angiographic vasospasm, rescue therapy, and adverse events. We applied RevMan 5.3 software for this meta-analysis to analyze the combined pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed- or random-effects model on the basis of heterogeneity. A total of 5 randomized placebo-controlled trials were included in this meta-analysis. Beneficial outcome was found in patients who received higher doses of clazosentan (>5 mg/h) after aSAH based on decreased incidence of DINDs (OR, 1.76; 95% CI, 1.16-2.69; P= 0.008), NCIs (OR, 2.31; 95% CI, 1.34-3.95; P= 0.002), and angiographic vasospasms (OR, 1.85; 95% CI, 1.19-2.89; P= 0.007). Meanwhile, other parameters, such as vasospasm-related morbidity/mortality, rescue therapy, and adverse events, showed no statistical significance (P > 0.05) between high and low doses of clazosentan. The significant beneficial outcomes of high-dose clazosentan have been proven in preventing cerebral vasospasm and subsequent cerebral infarction compared with low-dose clazosentan, with a manageable safety profile. However, high doses of clazosentan had no significant effect on rescue therapy and vasospasm-related morbidity/mortality.

Evolution of neurological recovery during the first year after subarachnoid haemorrhage in a French university centre

IntroductionThe evolution of neurological recovery during the first year after aneurysmal Subarachnoid Haemorrhage (SAH) is poorly described. PatientsPatients with SAH in one university hospital from March the 1st 2010, to December 31st 2012, with a one-year follow-up. MethodEvaluation was performed via phone call at 3, 6 and 12 months. Primary endpoint was poor neurological recovery (modified Rankin Scale 3–4–5–6), one year after SAH. Secondary endpoints were the incidence of lack of self-perceived previous health status recovery and incidence of cognitive disorders, one year after SAH. Risk factors of poor neurological recovery were retrieved with multivariable logistic regression. ResultsTwo hundred and eleven patients were included and 208 had a complete follow-up. One hundred and twenty (57.7%) patients were female, 112 (53.8%) had a WFNS grade I–II–III. Seventy (33.6%) patients displayed one-year poor neurological outcome and risk factors of poor outcome were age, baseline Glasgow Coma Score ≤ 8, external ventricular drainage, intra-cranial hypertension and angiographic vasospasm. We observed an improvement in good outcome at 3 months [112 (53.8%) patients], 6 months [127 (61.1%) patients] and one-year [138 (66.3%) patients]. Fifty-nine (35.3%) patients recovered previous health status, 96 (57.5%) had persistent behaviour disorders, and 71 (42.5%) suffered from memory losses at one year. DiscussionNeurological recovery seems to improve over time. The same key complications should be targeted worldwide in SAH patients. ConclusionNeurological complications in the following of SAH should be actively treated in order to improve outcome. The early neuro-ICU phase remains a key determinant of long-term recovery.

Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage: Predictors and Long-Term Functional Outcomes.

Although chronic hydrocephalus requiring shunt placement is a known sequela of aneurysmal subarachnoid hemorrhage (aSAH), its effect on long-term functional outcomes is incompletely understood. To identify predictors of shunt-dependent hydrocephalus and shunt complications after aSAH and determine the effect of shunt dependence on functional outcomes in aSAH patients. We evaluated a database of patients treated for aSAH at a single center from 2000 to 2015. Favorable and unfavorable outcomes were defined as modified Rankin Scale grades 0 to 2 and 3 to 6, respectively. We performed statistical analyses to identify variables associated with shunt-dependent hydrocephalus, unfavorable outcome, and shunt complication. Of the 888 aSAH patients, 116 had shunt-dependent hydrocephalus (13%). Older age (P= .001), intraventricular hemorrhage (IVH) (P= .004), higher World Federation of Neurological Surgeons (WFNS) grade (P< .001), surgical aneurysm treatment (P= .002), and angiographic vasospasm (P= .005) were independent predictors of shunt-dependent hydrocephalus in multivariable analysis. Functional outcome was evaluable in 527 aSAH patients (mean follow-up 18.6 mo), with an unfavorable outcome rate of 17%. Shunt placement (P< .001), shunt infection (P= .041), older age (P< .001), and higher WFNS grade (P= .043) were independently associated with an unfavorable outcome in multivariable analysis. Of the shunt-dependent patients, 18% had a shunt-related complication. Higher WFNS grade (P= .011), posterior circulation aneurysm (P= .018), and angiographic vasospasm (P= .008) were independent predictors of shunt complications in multivariable analysis. aSAH patients with shunt-dependent hydrocephalus have significantly poorer long-term functional outcomes. Patients with risk factors for post-aSAH shunt dependence may benefit from increased surveillance, although the effect of such measures is not defined in this study.

Intra-Arterial Papaverine-Hydrochloride and Transluminal Balloon Angioplasty for Neurointerventional Management of Delayed-Onset Post-Aneurysmal Subarachnoid Hemorrhage Vasospasm

After subarachnoid hemorrhage, delayed onset vasospasm can result in devastating ischemic stroke. The phenomenon of delayed cerebral ischemia (DCI) is not yet fully understood, and the correlation of angiographic vasospasm and cerebral infarction is still unclear. Therefore, we investigated the effect of endovascular treatment on the angiographic response and occurrence of DCI. Eighty patients with subarachnoid hemorrhage and serious cerebral vasospasm underwent endovascular treatment using intra-arterial papaverine-hydrochloride (IAP) or transluminal balloon angioplasty (TBA). The angiographic response and infarction rate were classified using the pre- and postinterventional angiographic images and computed tomography scans. In 90% of patients, vasospasm could be improved. In most cases (78.8%), IAP was used. Retreatment after IAP was necessary in 32.9% of patients but never after TBA. A total of 233 vascular territories were treated in 128 procedures. Angiographic improvement was observed in 66.5% of territories, which was significantly associated with early intervention (P= 0.02), the use of TBA (P= 0.01), and the dose of papaverine-hydrochloride (P= 0.01). DCI occurred in 47.5% of the patients. Territorial infarction was associated with a poor Hunt and Hess grade (P= 0.03), day of aneurysm treatment (P= 0.01), severe vasospasm before (P= 0.02) and after (P= 0.03) treatment, and number of interventions (P= 0.01). However, the infarction rate was independent of the angiographic response. The discrepancy of excellent angiographic results and the high incidence of DCI might stem from an inaccurate or a delayed diagnosis of impending ischemia. In view of the limited time window, optimized peri-interventional management and continuous cerebral multimodality neuromonitoring might be crucial for the ideal timing of endovascular procedures to prevent cerebral infarctions.

Dose-Dependent Inhibitory Effects of Cilostazol on Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Cilostazol is a selective inhibitor of phosphodiesterase type III that downregulates tenascin-C (TNC), a matricellular protein, which may cause delayed cerebral infarction after aneurysmal subarachnoid hemorrhage (SAH). The authors increased the dosage and evaluated the dose-dependent effects of cilostazol on delayed cerebral infarction and outcomes in SAH patients. This was a retrospective cohort study in a single center. One hundred fifty-six consecutive SAH patients including 67 patients of admission World Federation of Neurological Surgeons grades IV-V who underwent aneurysmal obliteration within 48h post-SAH from 2007 to 2017 were analyzed. Cilostazol (0 to 300mg/day) was administered from 1-day post-clipping or post-coiling to day 14 or later. Cilostazol treatment dose-dependently decreased delayed cerebral infarction and tended to improve outcomes, although cilostazol did not affect other outcome measures including angiographic vasospasm. On multivariate analyses, 300mg/day (100mg three times) cilostazol independently decreased delayed cerebral infarction and improved 3-month outcomes, but other regimens including 200mg/day (100mg twice) cilostazol were not independent prognostic factors. Propensity score-matched analyses showed that the 300mg/day cilostazol cohort had lower plasma TNC levels and a lower incidence of delayed cerebral infarction associated with better outcomes compared with the non-cilostazol cohort. The 300mg/day cilostazol may improve post-SAH outcomes by reducing plasma TNC levels and delayed cerebral infarction, but not vasospasm. Further studies are warranted to investigate if 300mg/day cilostazol is more beneficial to post-SAH outcomes than a usual dose of 200mg/day cilostazol that was demonstrated to be effective in randomized controlled trials.

Prediction of Delayed Cerebral Ischemia with Cerebral Angiography: A Meta-Analysis.

Cerebral catheter angiography is the gold standard for diagnosing cerebral artery vasospasm (vasospasm) in aneurysmal subarachnoid hemorrhage (SAH). We have previously published a meta-analysis of prediction of delayed cerebral ischemia (DCI) from transcranial Doppler (TCD) evidence of vasospasm. Analogous data relating to prediction of DCI have not been previously collated for cerebral angiography nor reconciled against TCD. We searched PUBMED, the Cochrane database, and clinicaltrials.gov for studies that used cerebral angiography for diagnosis of vasospasm and evaluated DCI in patients with SAH. We performed a random-effects meta-analysis of prediction of DCI with cerebral angiography, reconciling its accuracy against that of TCD. We also report quality of evidence for the value of cerebral angiography and TCD in SAH based on pooled data from our meta-analyses. A total of 15 studies (n = 5463) were included in the meta-analysis. Sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of cerebral angiography for prediction of DCI are 57, 68, 32, and 90%. These metrics for TCD, based on our previous meta-analysis, are 90, 71, 57, and 92%. We report that test accuracy estimates are "moderate" for TCD and "low" for angiography based on pooled data from our meta-analyses. TCD evidence of vasospasm is a better predictor of DCI than angiographic vasospasm. Future comparative effectiveness studies can better define the value of these diagnostic tools in patients with SAH.

Study of Correlation Between Hp α1 Expression of Haptoglobin 2-1 and Clinical Course in Aneurysmal Subarachnoid Hemorrhage

Haptoglobin (Hp) comprising 2 light (α) and 2 heavy (β) chains has an antioxidant effect following free hemoglobin binding. Among 3 phenotypes-Hp1-1 (two α1), Hp2-1 (α1 and α2), and Hp2-2 (two α2)-a greater protective effect for toxic-free hemoglobin was reported for Hp2-2 compared with Hp1-1. However, few studies have focused on the association of Hp2-1 with outcomes. This study examined α1 and α2 expression, and evaluated thecorrelation of Hp2-1 with outcomes of subarachnoid hemorrhage (SAH). Eighty-seven patients were enrolled prospectively, including 12 in the Hp1-1 group (13.8%), 36 in the Hp2-1 group (41.4%), and 39 in the Hp2-2 group (44.8%). Phenotypes were confirmed by Western blot analysis. The relative band intensities were measured as α subunit intensities normalized to albumin intensities and expressed as median (interquartile range). The differences in α intensities according to delayed cerebral ischemia (DCI), angiographic vasospasm (AV), and outcome were analyzed. DCI and AV were more frequently associated with Hp2-2 than with Hp1-1 (DCI: 21 [53.8%] vs. 3 [25.0%]; AV: 22 [56.4%] vs. 3 [25.0%]). The α1 intensities of Hp2-1 without DCI and AV were significantly higher than those with DCI and AV (without DCI: 0.70 [interquartile range (IQR), 0.54-0.89]; with DCI: 0.24 [IQR, 0.14-0.32]; P < 0.001; without AV: 0.65 [IQR, 0.32-0.88]; with AV: 0.32 [IQR, 0.17-0.67]; P= 0.046). No significant difference was noted with α2 intensities. The α1 (P= 0.359) and α2 (P= 0.233) intensities did not differ significantly according to outcome. Higher α1 intensities in Hp2-1 are associated with a lower risk of DCI and AV. The degree of α1 intensity may provide additional information about the individual risk of secondary injury following SAH in patients with Hp2-1.

Predictors of cerebral infarction in patients with ruptured anterior communicating artery aneurysms

Objective To investigate the incidence and predictors of cerebral infarction in patients with ruptured ACoA aneurysms, and to provide diagnostic and therapeutic information. Methods A total of 319 patients with ruptured ACoA aneurysms in our hospital from January 2009 to February 2015 were reviewed in this study. The author collected data regarding clinical characteristics, and measured the aneurysm morphologies on CTA images. Age, flow angle, vessel angle were analyzed by independent-samples t tests in patients with or without cerebral infarction. Mann-Whitney U tests were used for aneurysm size, aneurysm height, perpendicular height, neck size, size ratio, aspect ratio, aneurysm angle, World Federation of Neurosurgical Societies (WFNS) grade at admission and Fisher grade. Chi-square tests and Fisher's exact tests were used for sex, histories of hypertension, smoking and stroke, treatment modalities, anterior cerebral A1 segment configuration and angiographic vasospasm on CTA images. The multivariate logistic regression analyses were used to determine the independent risk factors of cerebral infarction using the stepwise regression method. Results Of the 319 patients, there were 253 without and 66 patients with cerebral infarction. Differences of age (53±11 vs 57±12,respectively;t=-2.415, P=0.016) , Fisher grade [Ⅰ 23(9.1%), Ⅱ 27(10.7%), Ⅲ 74(29.2%), Ⅳ 129(51.0%) vs Ⅰ 1(1.5%), Ⅱ 7(10.6%), Ⅲ 13(19.7%), Ⅳ 45(68.2%), respectively;Z=-2.541, P=0.035] and treatment modalities[endovascular coil embolization 155(61.3%), neurosurgical clipping 98(38.7%) vs endovascular coil embolization 23(34.8%), neurosurgical clipping 43(65.2%), respectively; χ2=14.810, P<0.001] reached statistical significance. Multivariate analysis showed that Fisher grade Ⅳ (OR=10.36, 95% CI 1.34-80.29, P=0.025) and neurosurgical clipping (OR=3.28, 95% CI 1.84-5.86, P<0.001)still had statistical significance. Conclusions Cerebral infarction in patients with ruptured ACoA aneurysms may be associated with Fisher grade and treatment modalities. Although there is difference between the two groups in age, it is not a predictor of the occurrence of cerebral infarction. Key words: Aneurysm; Subarachnoid hemorrhage; Cerebral infarction; Tomography, X-ray computed

Clinical prediction of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

The aim of this study was to derive a clinically applicable decision rule using clinical, radiological, and laboratory data to predict the development of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. Patients presenting over a consecutive 9-year period with subarachnoid hemorrhage (SAH) and at least 1 angiographically evident aneurysm were included. Variables significantly associated with DCI in univariate analysis underwent multivariable logistic regression. Using the beta coefficients, points were assigned to each predictor to establish a scoring system with estimated risks. DCI was defined as neurological deterioration attributable to arterial narrowing detected by transcranial Doppler ultrasonography, CT angiography, MR angiography, or catheter angiography, after exclusion of competing diagnoses. Of 463 patients, 58% experienced angiographic vasospasm with an overall DCI incidence of 21%. Age, modified Fisher grade, and ruptured aneurysm location were significantly associated with DCI. This combination of predictors had a greater area under the receiver operating characteristic curve than the modified Fisher grade alone (0.73 [95% CI 0.67-0.78] vs 0.66 [95% CI 0.60-0.71]). Patients 70 years or older with modified Fisher grade 0 or 1 SAH and a posterior circulation aneurysm had the lowest risk of DCI at 1.2% (0 points). The highest estimated risk was 38% (17 points) in patients 40-59 years old with modified Fisher grade 4 SAH following rupture of an anterior circulation aneurysm. Among patients presenting with aSAH, this score-based clinical prediction tool exhibits increased accuracy over the modified Fisher grade alone and may serve as a useful tool to individualize DCI risk.

Neuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a sub-type of hemorrhagic stroke associated with the highest rates of mortality and long-term neurological disabilities. Despite the improvement in the management of SAH patients and the reduction in case fatality in the last decades, disability and mortality remain high in this population. Brain injury can occur immediately and in the first days after SAH. This early brain injury can be due to physical effects on the brain such as increased intracranial pressure, herniations, intracerebral, intraventricular hemorrhage, and hydrocephalus. After the first 3 days, angiographic cerebral vasospasm (ACV) is a common neurological complication that in severe cases can lead to delayed cerebral ischemia and cerebral infarction. Consequently, the prevention and treatment of ACV continue to be a major goal. However, most treatments for ACV are vasodilators since ACV is due to arterial vasoconstriction. Other targets also have included those directed at the underlying biochemical mechanisms of brain injury such as inflammation and either independently or as a consequence, cerebral microthrombosis, cortical spreading ischemia, blood–brain barrier breakdown, and cerebral ischemia. Unfortunately, no pharmacologic treatment directed at these processes has yet shown efficacy in SAH. Enteral nimodipine and the endovascular treatment of the culprit aneurysm, remain the only treatment options supported by evidence from randomized clinical trials to improve patients’ outcome. Currently, there is no intervention directly developed and approved to target neuroinflammation after SAH. The goal of this review is to provide an overview on anti-inflammatory drugs tested after aneurysmal SAH.

STELLATE GANGLION BLOCK FOR TREATMENT OF ISCHEMIA AND PAIN ASSOCIATED WITH AUTOIMMUNE ASSOCIATED RAYNAUD’S SYNDROME

The etiology of Raynaud’s syndrome is characterized by inappropriate vascular constriction of digits and extremities from a complex interaction between the sympathetic nervous system, vascular endothelium, and the paracrine/endocrine system. Secondary Raynaud’s, complicated by autoimmunity, is generally more severe and was not expected to respond to sympathetic blocks. Our report demonstrates profound improvement of angiographically confirmed severe secondary Raynaud’s following stellate ganglion block, with resolution of multiple nonhealing digital ulcers. A 53-year-old woman with mixed connective tissue disease and idiopathic thrombocytopenic purpura (ITP) presented with right hand pain, severe ischemic changes, and several areas of nonhealing digital ulcerations. Maximal medical management had provided transient symptomatic improvement. When angiographic findings of diffuse vasospasm on the right suggested increased sympathetic tone, we performed a trial of stellate ganglion blocks. The first block immediately improved vasoconstriction and pain. Over 7 months she underwent three series of weekly injections (11 total injections). Slow healing of her ulcerations occurred. At 6-month follow-up, her ulcerations remained healed. Prior reports had indicated stellate ganglion or sympathetic blocks are ineffective or contraindicated in secondary Raynaud’s. The resolution of dry gangrene resulting in digit salvage after serial stellate ganglion blocks suggests that increased sympathetic tone may be a mechanism of disease in secondary Raynaud’s. Despite prior reports to the contrary, some patients may benefit from a trial of sympathetic blocks before undergoing surgical sympathectomy. Key words: Raynaud’s syndrome, mixed connective tissue disorder, stellate ganglion block, peripheral ischemia, secondary Raynaud’s, sympathectomy

Marked morphologic change of cerebral vessel with coexistence of severe flow compromise during endovascular treatment for ruptured aneurysm

Abstract In the vasospasm periods, the optimal timing of treatment for ruptured intracranial aneurysms remains controversial. In generally, it was recommended that treatment for a ruptured aneurysm be delayed until its disappearance, but this might be associated with aneurysmal re-rupture resulting in a poor outcome. Endovascular technique has been developed for many years, early treatment after aneurysmal subarachnoid hemorrhage (SAH) seems to be technically feasible even in the period of severe vasospasm. The present cases report our experiences of endovascular treatment for ruptured aneurysm in the presence of severe angiographic vasospasm and discuss the pertinent controversy.

Expression of alpha 1 subunit in the Haptoglobin 2‐1 phenotype and its association with clinical course in aneurysmal subarachnoid hemorrhage

ObjectDelayed cerebral ischemia (DCI) due to vasospasm contribute to poor clinical outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). Free hemoglobin (Hb) following hemolysis within the subarachnoid space has been thought to trigger vasospasm through oxidative radical and local inflammatory reactions. Haptoglobin (Hp), tetrameric protein comprised of two light chains (α) and two heavy chains (β), provides anti‐oxidant neutralization by binding to free Hb and its subsequent clearance by macrophages. In human, differences of α chain results in three phenotypes: Hp1‐1 (two α1 chains), Hp2‐1 (α1 and α2 chains), and Hp2‐2 (two α2 chains). Although protective effect against for toxic free Hb has been reported in SAH patients with Hp 2‐2 than those with Hp 1‐1, significance of Hp 2‐1 focusing on the expression of α1 subunit has not been well investigated. The aims of this study was to determine the association between intensity of α1 subunit and clinical courses in SAH patients.MethodsThis study examined the plasma from 86 patients: Hp 1‐1, n=12 (14.0%); Hp 2‐1, n=35 (40.7%), and Hp 2‐2, n=39 (45.3%). α1 intensity was confirmed by western blotting and expressed as the median (25th–75th percentile) in patients with Hp 2‐1. The relative intensity was measured as the intensity of α1 divided by the intensity of albumin. The difference in α1 intensity according to DCI, angiographic vasospasm and good outcome (mRS 0–2) on 3 months were analyzed.ResultsFor three Hp phenotypes, DCI and angiographic vasospasm were more frequently observed in Hp 2‐2 (DCI, n=21 (53.8%) and angiographic vasospasm, n=24 (61.5%)) and Hp 2‐1 (DCI, n=12 (34.3%) and angiographic vasospasm, n=18 (51.4%)) and compared to Hp 1‐1 (DCI, n=3 (25.0%); and angiographic vasospasm, n=4 (33.3%)). Other variables such as clinical (sex, age, hypertension, diabetes mellitus, dyslipidemia, and smoking), treatment types (endovascular coiling and surgical clipping), and initial patients' condition (Hunt‐Hess grade and Fisher grade) did not reach any significance according to three Hp phenotypes. Regarding Hp 2‐1, significant higher levels of α1 intensities were noted in SAH patient without DCI (0.79 (0.42–0.92)) and angiographic vasospasm (0.86 (0.75–0.99)) compared to those with DCI (0.18 (0.15–0.23), p&lt;0.001) and angiographic vasospasm (0.22 (0.18–0.41), p&lt;0.001). Patients with good neurologic outcome (0.75 (0.38–0.91)) tended to exhibit elevated α1 intensities, but not statistically significant (0.20 (0.18–0.65), p=0.107).ConclusionsHp 2‐1 and Hp 2‐2 seem to have higher incidence of DCI and vasospasm than Hp 1‐1 in patients presenting with aneurysmal SAH. Higher α1 intensities in Hp 2‐1 type can be associated with lower incidence of DCI and angiographic vasospasm. The intensity degree may provide additional information on individual risk of secondary injury following SAH.Support or Funding InformationThis work was supported by National Research Foundation of Korea (NFR) grant funded by the Korea government (NRF‐2017M3A9E8033223, NRF‐2017R1C1B5016678)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.