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Teratomas account for 18–20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar teratomas described in the literature. Here, we present a case of a child with an intracranial mature teratoma with pancreatic features causing vasospasm and subsequent stroke, found to be positive for CDKN2A—an independent variant associated with malignancy and small vessel disease leading to stroke. [ABSTRACT FROM AUTHOR]

The Circle of Willis (CoW) is a ring-like network of blood vessels that perfuses the brain. Flow in the collateral pathways that connect major arterial inputs in the CoW change dynamically in response to vessel narrowing or occlusion. Vasospasm is an involuntary constriction of blood vessels following subarachnoid hemorrhage (SAH), which can lead to stroke. This study investigated interactions between localization of vasospasm in the CoW, vasospasm severity, anatomical variations, and changes in collateral flow directions. Patient-specific computational fluid dynamics (CFD) simulations were created for 25 vasospasm patients. Computed tomographic angiography scans were segmented capturing the anatomical variation and stenosis due to vasospasm. Transcranial Doppler ultrasound measurements of velocity were used to define boundary conditions. Digital subtraction angiography was analyzed to determine the directions and magnitudes of collateral flows as well as vasospasm severity in each vessel. Percent changes in resistance and viscous dissipation were analyzed to quantify vasospasm severity and localization of vasospasm in a specific region of the CoW. Angiographic severity correlated well with percent changes in resistance and viscous dissipation across all cerebral vessels. Changes in flow direction were observed in collateral pathways of some patients with localized vasospasm, while no significant changes in flow direction were observed in others. CFD simulations can be leveraged to quantify the localization and severity of vasospasm in SAH patients. These factors as well as anatomical variation may lead to changes in collateral flow directions. Future work could relate localization and vasospasm severity to clinical outcomes like the development of infarct. [ABSTRACT FROM AUTHOR]

Re-rupture of untreated intracranial aneurysm is a potentially life-threatening condition. Despite tremendous advances in the diagnosis and treatment of intracranial aneurysms, such events are not rare and continue to pose a management dilemma. In this study, we examined the clinical, radiological and treatment details of patients who underwent microsurgical clipping for re-rupture of previously untreated intracranial aneurysms. Re ruptures were categorized as early and late re ruptures (< or > 7 days of inter ictus interval respectively). Modified Rankin Score (mRS) was used for functional outcome assessment and logistic regression analysis was used to test the predictors of long-term outcome. Re-ruptured intracranial aneurysms comprised 5% (n = 32/637) of the aneurysm clippings done at our center in this time span. The mean mRS score at discharge and at last follow-up were 3 and 3.04 respectively. Twenty-four (75%) patients were alive at a mean follow-up of 36 months. Early re-ruptures were associated with worse mean mRS scores at discharge (3.9 vs 2.5, p = 0.03) including the perioperative deaths (n = 4, 12.5%). The functional status at discharge and a poor preoperative clinical grade predicted a poor long-term outcome. Therefore, the long-term outcomes are primarily dependent on the short-term outcomes and to a lesser extent, the clinical grade at presentation. Those presenting with poor preoperative clinical grade, especially in the setting of an early re rupture, have a very poor prognosis and do not benefit from surgery. [ABSTRACT FROM AUTHOR]

Background: Patients with aneurysmal subarachnoid hemorrhage (aSAH) who survive the rupture are at risk for delayed neurologic deficits and cerebral infarction. The ideal method(s) of surveillance for cerebral vasospasm, and the link between radiographic vasospasm and delayed neurologic deficits, remain controversial. We instituted a postbleed day 7 angiography protocol with the stated goals of identification of vasospasm, improving neurologic outcomes, and possibly lowering cost of care. Methods: We conducted a quality improvement project in which we retrospectively analyzed consecutive cases of aSAH from a single institution over a 5-year period. Patients were excluded if they did not receive treatment for their aneurysm or were < 18 years of age. We analyzed demographic and outcome information for patients managed by protocolled angiography versus those who were managed by as-needed endovascular rescue therapy. Statistical tests were performed comparing means and proportions in both cohorts, as appropriate. Results: In total, 223 patients were identified who met inclusion criteria. In total, 157 patients were identified in the protocolled day 7 angiography group, and 66 were in the nonprotocolled angiography group. Demographics were similar between the day 7 angiogram and medical management cohorts, except for a higher mean age among the latter group (p = 0.016). The protocolled angiography group underwent a significantly greater number of angiograms (p < 0.001) and had a significantly higher cost of hospitalization ($240,327 vs. $205,719, p = 0.03), with no significant difference in rate of cerebral infarction, length of intensive care unit stay, length of hospital stay, discharge location, or discharge modified Rankin Score. Conclusions: This cohort comparison analysis draws into question the practice of protocolized cerebral angiography in patients with aSAH. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and haemodynamic monitoring, as derangements in these systems can precipitate secondary brain damage. Challenges persist in treating aSAH patients, exacerbated by a paucity of robust clinical evidence, with many interventions showing no benefit when tested in rigorous clinical trials. Given the growing body of literature in this field and the issuance of contemporary guidelines, our objective is to furnish an updated review of essential principles of ICU management for this patient population. Our review will discuss the epidemiology, initial stabilization, treatment strategies, long-term prognostic factors, the identification and management of post-aSAH complications. We aim to offer practical clinical guidance to intensivists, grounded in current evidence and expert clinical experience, while adhering to a concise format. [ABSTRACT FROM AUTHOR]

Background: Delayed cerebral ischaemia (DCI) is a major cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage (aSAH). Chemical angioplasty (CA) and transluminal balloon angioplasty (TBA) are used to treat patients with refractory vasospasm causing DCI. Multi-modal monitoring including brain tissue oxygenation (PbtO2) is routinely used at this centre for early detection and management of DCI following aSAH. In this single-centre pilot study, we are comparing these two treatment modalities and their effects on PbtO2. Methods: Retrospective case series of patients with DCI who had PbtO2 monitoring as part of their multimodality monitoring and underwent either CA or TBA combined with CA. PbtO2 values were recorded from intra-parenchymal Raumedic NEUROVENT-PTO® probes. Data were continuously collected and downloaded as second-by-second data. Comparisons were made between pre-angioplasty PbtO2 and post-angioplasty PbtO2 median values (4 h before angioplasty, 4 h after and 12 h after). Results: There were immediate significant improvements in PbtO2 at the start of intervention in both groups. PbtO2 then increased by 13 mmHg in the CA group and 15 mmHg in the TBA plus CA group in the first 4 h post-intervention. This improvement in PbtO2 was sustained for the TBA plus CA group but not the CA group. Conclusion: Combined balloon plus chemical angioplasty results in more sustained improvement in brain tissue oxygenation compared with chemical angioplasty alone. Our findings suggest that PbtO2 is a useful tool for monitoring the response to angioplasty in vasospasm. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment. [ABSTRACT FROM AUTHOR]

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague–Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm. [ABSTRACT FROM AUTHOR]

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler is being increasingly used as an essential diagnostic and monitoring tool at the bedside of critically ill neonates and children. Brain ultrasound has already established as a cornerstone of daily practice in the management of the critically ill newborn for diagnosis and follow-up of the most common brain diseases, considering the easiness to insonate the brain through transfontanellar window. In critically ill children, doppler based techniques are used to assess cerebral hemodynamics in acute brain injury and recommended for screening patients suffering from sickle cell disease at risk for stroke. However, more evidence is needed regarding the accuracy of doppler based techniques for non-invasive estimation of cerebral perfusion pressure and intracranial pressure, as well as regarding the accuracy of brain ultrasound for diagnosis and monitoring of acute brain parenchyma alterations in children. This review is aimed at providing a comprehensive overview for clinicians of the technical, anatomical, and physiological basics for brain ultrasonography and transcranial doppler or color-coded doppler, and of the current status and future perspectives of their clinical applications in critically ill neonates and children. Conclusion: In critically ill neonates, brain ultrasound for diagnosis and follow-up of the most common cerebral pathologies of the neonatal period may be considered the standard of care. Data are needed about the possible role of doppler techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles. In pediatric critical care, doppler based techniques should be routinely adopted to assess and monitor cerebral hemodynamics. New technologies and more evidence are needed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. What is Known: • In critically ill neonates, brain ultrasound for early diagnosis and follow-up of the most common cerebral and neurovascular pathologies of the neonatal period is a cornerstone of daily practice. In critically ill children, doppler-based techniques are more routinely used to assess cerebral hemodynamics and autoregulation after acute brain injury and to screen patients at risk for vasospasm or stroke (e.g., sickle cell diseases, right-to-left shunts). What is New: • In critically ill neonates, research is currently focusing on the use of novel high frequency probes, even higher than 10 MHz, especially for extremely preterm babies. Furthermore, data are needed about the role of doppler based techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles, also integrated with a non-invasive assessment of brain oxygenation. In pediatric critical care, new technologies should be developed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. Furthermore, large multicenter studies are needed to clarify role and accuracy of doppler-based techniques to assess cerebral perfusion pressure and its changes after treatment interventions. [ABSTRACT FROM AUTHOR]

Background: Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption. Methods: A cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption. Results: Forty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index. Conclusions: Dysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Delayed Cerebral Ischaemia (DCI) remains an important preventable driver of poor outcome in aneurysmal subarachnoid haemorrhage (aSAH). Our ability to predict DCI is based on historical patient cohorts, which use inconsistent definitions for DCI. In 2010, a definition of DCI was agreed upon and published by a group of aSAH experts. The aim of this study was to identify predictors using this agreed definition of DCI. Methods: We conducted a literature search of Medline (PubMed) to identify articles published since the publication of the 2010 consensus definition. Risk factors and prediction models for DCI were included if they: (1) adjusted for confounding factors or were derived from randomised trials, (2) were derived from prospectively collected data and (3) included adults with aSAH. The strength of studies was assessed based on quality, risk of bias and applicability of studies using PROBAST. Results: Eight studies totalling 4,542 patients were included from 105 relevant articles from 4,982 records. The most common reason for not including studies was failure to use the consensus definition of DCI (75%). No prediction models were identified in the eligible studies. Significant risk factors for DCI included the presence of onsite neuro-interventional services, high Neuropeptide Y, admission leucocytosis, neutrophil:lymphocyte >5.9 and Fisher Grade > 2. All studies had a high or unclear risk of bias. Conclusions: Only a few studies with high risk of bias have investigated the predictors using consensus-defined DCI. Further studies are warranted to clarify risk factors of DCI in the modern era. [ABSTRACT FROM AUTHOR]

Background: Pleiotropic effects of statins may be beneficial in alleviating cerebral vasospasm (VS) and improving outcome after aneurysmal subarachnoid hemorrhage (aSAH). Initiation of statin treatment at aSAH is not recommended; however, the effect of pre-ictal and continued statin use is not fully investigated. Methods: Retrospective study comparing aSAH patients admitted in 2012 to 2021 with pre-ictal statin use versus those not using statins. Patient entry variables, radiological/sonological VS, symptomatic VS, and radiologically documented delayed cerebral ischemia (DCI) were registered. Outcome was scored in terms of mortality, modified Rankin score, Glasgow outcome score extended, and levels of fatigue. Patients were compared on group level and in a case–control design. Results: We included 961 patients, with 204 (21.2%) statin users. Statin users were older and had more often hypertension. Severe radiological/sonological VS, symptomatic VS, and DCI were less frequent in statin users, and their length of stay was shorter. Mortality, functional outcome, and levels of fatigue were similar in both groups. When analyzing 89 pairs of statin users and non-statin users matched for age, aSAH severity, gender, and hypertension, we confirmed decreased radiological/sonological and symptomatic VS as well as shorter length of stay in statin users. They also had more often a favorable functional outcome and lower levels of fatigue. Conclusions: Patients with pre-ictal and continued use of statins have a reduced occurrence of radiological/sonological and symptomatic VS, shorter length of stay, and more often favorable functional outcome, whereas mortality is similar to non-statin users. Even though larger multicenter studies with common, strict protocols for prevention, diagnosis, and treatment of vasospasm are needed to finally establish the value of statins in aSAH, continuation of pre-ictal statin use seems worthwhile. [ABSTRACT FROM AUTHOR]

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Background: Non-aneurysmal subarachnoid hemorrhages (SAHs) are thought to have a benign clinical course compared to aneurysmal SAHs. The aim of this study is to report the clinical course and outcomes of non-aneurysmal SAHs in a large single-center study. Methods: The patients with non-aneurysmal SAHs were screened from Tampere University Hospital from 2005 to 2020. The clinical data were collected from the patient's medical records and from the imaging studies. The primary interest was the neurological outcome assessed by dichotomized GOS at 2 months. Multivariable logistic regression was used to study the factors associated with unfavorable outcome. Results: We found 216 non-aneurysmal SAHs in 214 patients (2 patients with > 1 bleed). Ninety-seven percent of patients with a typical perimesencephalic bleeding pattern SAH (PSAH) (75/77) had a favorable outcome, while 86% of patients with non-perimesencephalic SAH (NPSAH) had a favorable outcome (84/98). In a multivariable logistic regression analysis, loss of consciousness (LOC) (aOR 214.67, 95% CI 17.62–2615.89) and Fisher grade 4 bleeding pattern (aOR 23.32, 95% CI 1.40–387.98) were associated with increased risk for unfavorable outcome (GOS 1–3). Vasospasm was seen in 20% of non-aneurysmal SAH patients, hydrocephalus in 17%, and 13% needed ventriculostomy. Conclusions: Non-aneurysmal SAH seems to have a good prognosis for majority of patients, especially for patients with a PSAH. Non-aneurysmal SAH patients are however affected by vasospasm and hydrocephalus and have similar risk factors for poor outcome as patients with aneurysmal SAH. This suggests that it is the severity of the bleed rather than the etiology that associates with poor outcome. [ABSTRACT FROM AUTHOR]

Delayed cerebral infarction (DCI) is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). The benefits of magnesium sulfate as an alternative treatment are controversial, and most previous studies examined its benefits only as adjunctive treatment to traditional nimodipine. We retrospectively analyzed aSAH patients records with magnesium sulfate between 2010 and 2021. We aimed for a serum magnesium concentration of 2–2.5 mmol/l between post-hemorrhage days 3 and 12. The patients were separated in three groups based on average serum magnesium concentration (magnesium >2 mmol/l, reduced magnesium 1.1–1.9 mmol/l, and no magnesium). Additionally, we assessed delayed cerebral infarction (DCI) and clinical outcome at follow-up, using the modified Rankin Scale (mRS), categorized in favorable (0–3) and unfavorable outcome (4–5). In this analysis, 548 patients were included. Hereof, radiological evidence of DCI could be found in 23.0% (n = 126) of patients. DCI rates were lower if patients' average serum magnesium was higher than 2 mmol/l (magnesium 18.8%, n = 85; reduced magnesium 38.3%, n = 23; no magnesium 51.4%, n = 18; p < 0.001). Also, at the last follow-up, patients in the group with a higher serum magnesium concentration had better outcome (favorable outcome: magnesium 64.7%, n = 293; reduced magnesium 50.0%, n = 30; no magnesium 34.3%, n = 12; p < 0.001). This 12-year study reveals the value of serum concentration-guided magnesium administration in aSAH patients. Our findings demonstrate the safety and efficacy when titrated to a serum concentration of 2–2.5 mmol/l. We observed higher rates of delayed cerebral infarction and unfavorable outcomes in patients with serum concentrations below 2 mmol/l. [ABSTRACT FROM AUTHOR]

Antiplatelet therapy (AT) may serve to reduce the effects of aneurysmal subarachnoid hemorrhage (aSAH)-induced pro-coagulant state in the cerebral circulation. Several studies, however, have delivered conflicting conclusions on the efficacy of AT post aSAH. Systematic searches of Medline, Embase, and Cochrane Central were undertaken on 27th March 2023. The primary outcome was delayed cerebral ischaemia (DCI). Secondary outcomes were symptomatic and angiographic vasospasm, good functional outcome (modified Rankin Scale [mRS] with scores 0–2), hemorrhagic events, and in-hospital mortality. Twenty-two studies reporting 4378 patients with aSAH were included in the meta-analysis. AT was associated with lower rates of DCI (RR=0.62, 95% CI: 0.43; 0.89), symptomatic vasospasm (RR=0.63, 95% CI: 0.46; 0.86), and moderate/severe angiographic vasospasm (RR=0.74, 95% CI: 0.65; 0.84), with no effect on hemorrhagic complications (RR=1.36, 95% CI: 0.77; 2.41). When analyzing only post-ictal use of AT, AT additionally favored rates of good functional outcomes (RR=1.18, 95% CI: 1.10; 1.26) and in-hospital mortality (RR=0.56, 95% CI: 0.39; 0.80). In the subgroup treated with cilostazol, AT was associated with lower rates of DCI (RR=0.40, 95% CI: 0.32), symptomatic vasospasm (RR=0.47, 95% CI: 0.33; 0.65), moderate/severe angiographic vasospasm (RR=0.75, 95% CI: 0.57; 0.98) and good functional outcome (RR=1.24, 95% CI: 1.08; 1.43). In the surgically treated aSAH subgroup, AT favored rates of symptomatic vasospasm (RR=0.55, 95% CI: 0.30; 0.98), moderate/severe angiographic vasospasm (RR=0.70, 95% CI: 0.54; 0.90) and good functional outcome (RR=1.23, 95% CI: 1.09; 1.41). In the endovascularly treated aSAH subgroup, AT was associated with lower rates of in-hospital mortality (RR=0.60, 95% CI: 0.41; 0.88). In aSAH patients, post-ictal AT is associated with benefits in terms of rates of DCI, vasospasm, good functional outcomes, and in-hospital mortality without an increased risk of hemorrhagic events. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0–6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge. [ABSTRACT FROM AUTHOR]

Background: Delayed cerebral ischemia (DCI) occurs in around 30% of patients suffering from nontraumatic subarachnoid hemorrhage (SAH) and is associated with poor neurological outcome. Whether the Neurological Pupil index (NPi) derived from the automated pupillometry could help to diagnose the occurrence of DCI remains unknown. The aim of this study was to investigate the association of NPi with the occurrence of DCI in patients with SAH. Methods: This was a multicenter, retrospective cohort study of consecutive patients with SAH admitted to the intensive care units of five hospitals between January 2018 and December 2020 who underwent daily NPi recordings (every 8 h) during the first 10 days of admission. DCI was diagnosed according to standard definitions (in awake patients) or based on neuroimaging and neuromonitoring (in sedated or unconscious patients). An NPi < 3 was defined as abnormal. The primary outcome of the study was to assess the time course of daily NPi between patients with DCI and patients without DCI. Secondary outcome included the number of patients who had an NPi < 3 before DCI. Results: A total of 210 patients were eligible for the final analysis; DCI occurred in 85 (41%) patients. Patients who developed DCI had similar values of mean and worst daily NPi over time when compared with patients without DCI. Patients with DCI had a higher proportion of at least one NPi < 3 at any moment before DCI when compared with others (39/85, 46% vs. 35/125, 38%, p = 0.009). Similarly, the worst NPi before DCI diagnosis was lower in the DCI group when compared with others (3.1 [2.5–3.8] vs. 3.7 [2.7–4.1], p = 0.05). In the multivariable logistic regression analysis, the presence of NPi < 3 was not independently associated with the development of DCI (odds ratio 1.52 [95% confidence interval 0.80–2.88]). Conclusions: In this study, NPi measured three times a day and derived from the automated pupillometry had a limited value for the diagnosis of DCI in patients with SAH. [ABSTRACT FROM AUTHOR]

Paediatric intracranial aneurysms are rare entities accounting for less than 5% of all age intracranial aneurysms. Traumatic aneurysms are more common in children and have an association with anatomical variations such as arterial fenestrations. Here, we present a case of a child initially presenting with traumatic subarachnoid haemorrhage who returned to baseline and was discharged home only to return within 2 weeks with diffuse subarachnoid and intraventricular re-haemorrhage. A dissecting aneurysm of a duplicated (fenestrated) V4 vertebral artery segment was identified as a rare cause of rebleeding. We describe a course complicated by severe vasospasm delaying aneurysm detection and treatment. Dissecting aneurysms in children should be considered in all cases of delayed post-traumatic cranial rebleeding, particularly where there is anomalous arterial anatomy. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a major health burden that accounts for approximately 5% of all strokes. The most common cause of a non-traumatic SAH is the rupture of a cerebral aneurysm. The most common symptom associated with SAH is a headache, often described as "the worst headache of my life." Delayed cerebral ischemia (DCI) is a major factor associated with patient mortality following SAH and is often associated with SAH-induced cerebral vasospasm (CV). Cannabidiol (CBD) is emerging as a potential drug for many therapeutic purposes, including epilepsy, anxiety, and pain relief. We aim to review the potential use of CBD as a treatment option for post-SAH critically ill patients. Through a literature review, we evaluated the known pharmacology and physiological effects of CBD and correlated those with the pathophysiological outcomes associated with cerebral vasospasm following subarachnoid hemorrhage. Although overlap exists, data were formatted into three major categories: anti-inflammatory, vascular, and neuroprotective effects. Based on the amount of information known about the actions of CBD, we hypothesize the anti-inflammatory effects are likely to be the most promising therapeutic mechanism. However, its cardiovascular effects through calcium regulation and its neuroprotective effects against cell death, excitotoxicity, and oxidative stress are all plausible mechanisms by which post-SAH critically ill patients may benefit from both early and late intervention with CBD. More research is needed to better understand if and how CBD might affect neurological and vascular functions in the brain following injury such as subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is an uncommon and severe subtype of stroke leading to the loss of many years of productive life. We analyzed NLRP3 activity as well as key components of the inflammasome cascade in monocytes and plasma from 28 patients with aSAH and 14 normal controls using flow cytometry, western blot, ELISA, and qPCR technologies. Our data reveal that monocytes from patients with aSAH present an overactivation of the NLRP3 inflammasome, which results in the presence of high plasma levels of interleukin (IL)-1β, IL-18, gasdermin D, and tissue factor. Although further research is needed, we propose that serum tissue factor concentration might be a useful prognosis biomarker for clinical outcome, and for Tako-Tsubo cardiomyopathy and cerebral vasospasm prediction. Remarkably, MCC-950 inhibitor effectively blocks NLRP3 activation in aSAH monocyte culture and supresses tissue factor release to the extracellular space. Finally, our findings suggest that NLRP3 activation could be due to the release of erythrocyte breakdown products to the subarachnoid space during aSAH event. These data define NLRP3 activation in monocytes from aSAH patients, indicating systemic inflammation that results in serum TF upregulation which in turns correlates with aSAH severity and might serve as a prognosis biomarker for aSAH clinical outcome and for cerebral vasospasm and Tako-Tsubo cardiomyopathy prediction. [ABSTRACT FROM AUTHOR]

Background: Vasospasm is a grave complication of aneurysmal subarachnoid hemorrhage (SAH) with a significant rate of morbidity and mortality. Endovascular intra-arterial injection of Ca channel blocker agent (Nimodipine) may offer a promising solution in refractory vasospasm. Results: During the period between April 2017 and May 2019, 120 patients who presented with SAH due to a ruptured intracranial aneurysm were admitted to the neurosurgery department at Alexandria University Hospitals. Among them, 30 patients developed refractory vasospasm and were subjected to endovascular super selective intraarterial injection of nimodipine. The angiographic improvement was excellent in three (10%), good in 14 (46%) and poor in the remaining 13 procedures (43%). Clinical improvement was achieved in 15 cases while 15 cases showed no improvement on Modified Rankin Scale. No cases deteriorated following the injection. Conclusions: Endovascular chemical angioplasty using a ca channel blocker agent (Nimodipine) is a safe and efficient method for the treatment of refractory post aneurysmal SAH vasospasm. The quest is still needed for developing a better efficient agent to overcome the vasospasm dilemma. [ABSTRACT FROM AUTHOR]

Pelvic fractures are common in cases of blunt trauma, which is strongly associated with mortality. Transcatheter arterial embolization is a fundamental treatment strategy for fatal arterial injuries caused by blunt pelvic trauma. However, vascular injuries due to blunt pelvic trauma can show various imaging findings other than arterial hemorrhage. We present a pictorial review of common and uncommon vascular injuries, including active arterial bleeding, pseudoaneurysm, arteriovenous fistula, arterial occlusion, vasospasm, and active venous bleeding. Knowledge of these vascular injuries can help clinicians select the appropriate therapeutic strategy and thus save lives. [ABSTRACT FROM AUTHOR]

Vasospastic angina (VSA), or variant angina, is an under-recognized cause of chest pain and myocardial infarction, especially in Western countries. VSA leads to a declined quality of life and is associated with increased morbidity and mortality. Currently, the diagnosis of VSA relies on invasive testing that requires the direct intracoronary administration of ergonovine or acetylcholine. However, invasive vasoreactivity testing is underutilized. Several non-invasive imaging alternatives have been proposed to screen for VSA. This review aims to discuss the strengths and limitations of available non-invasive imaging tests for vasospastic angina. [ABSTRACT FROM AUTHOR]

This critique examines a 12-year retrospective study on serum magnesium concentration-guided administration of magnesium sulfate in 548 patients with aneurysmal subarachnoid hemorrhage (aSAH). The study reported that maintaining serum magnesium levels between 2 and 2.5 mmol/L reduced rates of delayed cerebral infarction and improved clinical outcomes. However, limitations due to its retrospective nature, single-center design, and unequal treatment group sizes may affect generalizability. Future multicentric randomized controlled trials are recommended to validate these findings and refine magnesium dosing strategies for aSAH treatment. [ABSTRACT FROM AUTHOR]

Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 — 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15–49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are: Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarction Application of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transition Application of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patterns Application of innovative screening programmes which adequately consider the needs of young populations Stroke is a severe brain disease which has reached an epidemic scale worldwide: in 2019, the global stroke prevalence was 101.5 million people. The World Stroke Organisation predicted that globally, 1 in 4 adults over the age of 25 will get a stroke in their lifetime. Not only old people but also teenagers and young adults are affected. Current global costs of stroke are estimated at 721 billion US dollars. Due to undiagnosed so-called "silent" brain infarction, the number of affected individuals is about 14 times greater in the population than clinically recorded. If it remains untreated, silent brain infarction may cause many severe and fatal disorders such as dementia, depression and even suicide. In this position paper, the consortium describes how the rudimental approach to treating severely diseased people could be replaced by an innovative predictive and preventive one to protect people against the health-to-disease transition. [ABSTRACT FROM AUTHOR]

Background: The appropriate management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. We aimed to evaluate the effect of implementing a standardized protocol for detection and management of DCI after aSAH on cerebral infarction and functional outcome. Methods: We studied two cohorts of aSAH patients, one before (pre-implementation cohort: January 2012 to August 2014) and one after (post-implementation cohort: January 2016 to July 2018) implementation of a multidisciplinary approach, with standardized neurological and radiological assessment and risk-based medical treatment of DCI. We assessed the presence of new hypodensities on CT within 6 weeks after aSAH and categorized cerebral infarction into overall and DCI-related infarctions (hypodensities not within 48 h after IA repair and not attributable to aneurysm occlusion or intraparenchymal hematoma). Functional outcome was assessed at 3 months using the extended Glasgow outcome scale (eGOS), dichotomized into unfavorable (eGOS: 1–5) and favorable (eGOS: 6–8). We calculated odds ratios (OR) with corresponding 95% confidence intervals (CI's), and adjusted for age, WFNS grade, Fisher score, and treatment modality (aOR). Results: In the post-implementation (n = 158) versus the pre-implementation (n = 143) cohort the rates for overall cerebral infarction were 29.1% vs 46.9% (aOR: 0.41 [0.24–0.69]), for DCI-related cerebral infarction 17.7% vs. 31.5% (aOR: 0.41 [0.23–0.76]), and for unfavorable functional outcome at 3 months 37.3% vs. 53.8% (aOR: 0.30 [0.17–0.54]). For patients with DCI, the rates for unfavorable functional outcomes at 3 months in the post-implementation versus the pre-implementation cohort were 42.3% vs. 77.8% (aOR: 0.1 [0.03–0.27]). Conclusions: A multidisciplinary approach with more frequent and standardized neurological assessment, standardized CT and CT perfusion monitoring, as well as tailored application of induced hypertension and invasive rescue therapy strategies, is associated with a significant reduction of cerebral infarction and unfavorable functional outcome after aneurysmal aSAH. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) continues to be a sequela of aneurysmal subarachnoid hemorrhage (aSAH) that carries significant morbidity and mortality. Aside from nimodipine, no therapeutic agents are available to reduce the incidence of DCI. Pathophysiologic mechanisms contributing to DCI are poorly understood, but accumulating evidence over the years implicates several factors. Those have included microvessel vasoconstriction, microthrombosis, oxidative tissue damage, and cortical spreading depolarization as well as large vessel vasospasm. Common to these processes is red blood cell leakage into the cerebrospinal fluids (CSF) and subsequent lysis which releases hemoglobin, a central instigator in these events. This has led to the hypothesis that early blood removal may improve clinical outcome and reduce DCI. This paper will provide a narrative review of the evidence of hemoglobin as an instigator of DCI. It will also elaborate on available human data that discuss blood clearance and CSF drainage as a treatment of DCI. Finally, we will address a recent novel device that is currently being tested, the Neurapheresis CSF Management System™. This is an automated dual-lumen lumbar drainage system that has an option to filter CSF and return it to the patient. [ABSTRACT FROM AUTHOR]

Background: Delayed cerebral infarction (DCIn) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of morbi-mortality; yet, the causes for DCIn remain incompletely understood. Objective: We tested the hypothesis that acute hydrocephalus could be related to the occurrence of DCIn, independently of the occurrence and severity of vasospasm. Methods: Radiological and clinical data of patients treated at a single large volume academic center for aSAH between 2017 and 2019 were retrospectively analyzed. DCIn was defined as imaging stigma of cerebral infarction visible on 6-week imaging follow-up after aSAH. Hydrocephalus was defined on baseline imaging as a relative bicaudate index above 1. Cerebral vasospasm was defined by reduction of artery diameter in comparison with initial diameter. We used uni- and multivariable models to test the associations between these variables, hydrocephalus and DCIn. Results: Of 164 included patients, vasospasm occurred in 58 patients (35.4%), and DCIn in 47 (28.7%). Acute hydrocephalus was present in 85 patients (51.8%) on baseline CT. No relation was found between acute hydrocephalus and delayed cerebral infarction in our multivariate analysis (adjusted OR: 1.20 95% CI [0.43–3.37]; p = 0.732). Only vasospasm occurrence was independently associated with DCIn (adjusted OR: 10.97 95% CI [4.60–26.01]). Conclusion: Our study did not show an association between acute hydrocephalus and DCIn after aSAH, after adjustment for the presence and severity of cerebral vasospasm. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm is a highly investigated phenomenon in neurovascular research. Experimental vasospasm models are irreplaceable for the evaluation of new antivasospastic drugs. In this study, we assessed the reliability of in vivo vasospasm induction by ultrasound application in the chicken chorioallantoic membrane (CAM) model. After incubation of fertilized chicken eggs for four days, a fenestration was performed to enable examination of the CAM vessels. On the thirteenth day, continuous-wave ultrasound (3 MHz, 1 W/cm2) was applied on the CAM vessels for 60 s. The ultrasound effect on the vessels was recorded by life imaging (5-MP HD-microscope camera, Leica®). The induced vessel diameter changes were evaluated in a defined time interval of 20 min using a Fiji macro. The vessel diameter before and after sonication was measured and the relative diameter reduction was determined. A first reduction of vessel diameter was observed after three minutes with an average vessel-diameter decrease to 77%. The maximum reduction in vessel diameter was reached eight minutes after sonication with an average vessel diameter decrease to 57% (mean relative diameter reduction of 43%, range 44–61%), ANOVA, p = 0.0002. The vasospasm persisted for all 20 recorded minutes post induction. Vasospasm can be reliably induced by short application of 3 MHz-ultrasound to the CAM vessels. This might be a suitable in vivo model for the evaluation of drug effects on vasospasm in an experimental setting as intermediary in the transition process from in vitro to in vivo assessment using animal models. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review most recent literature on management of blood pressure in acute aneurysmal subarachnoid hemorrhage (SAH) and provide practice recommendations for the emergency clinician. Recent Findings: There is increased risk of aneurysmal rebleeding with systolic blood pressure (SBP) greater than 160 mmHg in the acute setting. Avoiding large degrees of blood pressure variability improves clinical outcomes in aneurysmal SAH. Summary: Acute lowering of SBP to a range of 140–160 mmHg decreases risk of rebleeding while also maintaining cerebral perfusion pressure (CPP) after aneurysmal rupture. Treatment with a short acting antihypertensive agent allows for rapid titration of blood pressure (BP) and reduces BP variability. Elevations in intracranial pressure occur commonly after SAH due to increased intracranial blood volume, cerebral edema, or development of hydrocephalus. Clinicians should be familiar with changes in cerebral autoregulation and effects on CPP when treating elevated BP, in order to mitigate the risk of secondary neurological injury. [ABSTRACT FROM AUTHOR]

Purpose of Review: Fluoropyrimidine (FDP) chemotherapy regimens used in the treatment of solid tumors such as breast, gastrointestinal, and hepatobiliary malignancies have led to significant survival benefits. However, FDP cardiotoxicity can lead to premature termination of FDP-based chemotherapy treatments. Resuming these crucial therapies after initial FDP cardiotoxicity can be challenging for patients and healthcare providers. Recent Findings: Symptomatic cardiotoxicity occurs in up to 35% of patients treated with FDP-based chemotherapy. The most common symptom is chest pain, but palpitations, dyspnea, myocardial infarction, cardiogenic shock, and cardiac arrest can also occur. Several large studies have attempted to discern clinical and genetic risk factors in those who develop FDP cardiotoxicity. With cardiac risk factor optimization and aggressive pre-treatment with anti-anginal agents, rechallenging with FDP is possible and allows patients to resume optimal cancer-directed treatment. Summary: FDP cardiotoxicity remains a poorly understood identity. We highlight several recent publications attempting to define the risk factors associated with developing FDP cardiotoxicity. The management of FDP cardiotoxicity and consideration of rechallenge of FDP-based regimens highlights the importance of a multidisciplinary partnership between oncologists and cardiologists/cardio-oncologists. [ABSTRACT FROM AUTHOR]

Background: Epoxyeicosatrienoates (EETs) are endogenous regulators of neuroinflammation and cerebral blood flow. Their metabolism to dihydroxyeicosatrienoates (DHETs) is catalyzed by soluble epoxide hydrolase (sEH). After subarachnoid hemorrhage (SAH), EETs' pathway amplification may be a therapeutic target for the prevention of delayed cerebral ischemia (DCI). We conducted a double-blind, placebo-controlled, phase Ib randomized trial of GSK2256294, a pharmacologic inhibitor of sEH, to evaluate the safety profile and to assess biomarkers of neurovascular inflammation in patients with aneurysmal SAH. Methods: Patients were randomly assigned to receive 10 mg of GSK2256294 or a placebo treatment once daily for 10 days, beginning within 72 hours after aneurysm rupture. The primary study end point was safety. Secondary end points included serum and cerebrospinal fluid (CSF) EETs-to-DHETs ratio, cytokine levels, and serum endothelial injury biomarkers, measured at day 7 and day 10 after SAH. Tertiary end points included neurologic status, disposition, length of stay, incidence of DCI, and mortality; these were assessed at hospital discharge and at 90 days. Results: Ten patients received GSK2256294 and nine patients received a placebo. There were no adverse events related to the study drug. GSK2256294 administration resulted in a significant increase in the EET/DHET ratio at day 7 and day 10 in serum, but not in the CSF. There was a trend for decreased CSF inflammatory cytokines following GSK2256294 administration, but this did not reach statistical significance. Conclusions: GSK2256294 administration was safe and well tolerated in critically ill patients with SAH, producing an increase in serum EETs and the EET-to-DHET ratio. Our findings support future studies in a larger population to evaluate the role of sEH inhibition in the prevention of DCI after SAH and other forms of brain injury and inflammatory conditions. Clinical trial registration: ClinicalTrials.gov: NCT03318783. [ABSTRACT FROM AUTHOR]

Background: Patients with aneurysmal subarachnoid hemorrhage (aSAH) may develop refractory arterial cerebral vasospasm requiring multiple endovascular interventions. The aim of our study is to evaluate variables associated with need for repeat endovascular treatments in refractory vasospasm and to identify differences in outcomes following one versus multiple treatments. Methods: We retrospectively reviewed patients treated for aSAH between 2017 and 2020 at two tertiary care centers. We included patients who underwent treatment (intraarterial infusion of vasodilatory agents or mechanical angioplasty) for radiographically diagnosed vasospasm in our analysis. Patients were divided into those who underwent single treatment versus those who underwent multiple endovascular treatments for vasospasm. Results: Of the total 418 patients with aSAH, 151 (45.9%) underwent endovascular intervention for vasospasm. Of 151 patients, 95 (62.9%) underwent a single treatment and 56 (37.1%) underwent two or more treatments. Patients were more likely to undergo multiple endovascular treatments if they had a Hunt–Hess score > 2 (odds ratio [OR] 5.10 [95% confidence interval (CI) 1.82–15.84]; p = 0.003), a neutrophil-to-lymphocyte ratio > 8.0 (OR 3.19 [95% CI 1.40–7.62]; p = 0.028), and more than two fevers within the first 5 days of admission (OR 7.03 [95% CI 2.68–20.94]; p < 0.001). Patients with multiple treatments had poorer outcomes, including increased length of stay, delayed cerebral ischemia, in-hospital complications, and higher modified Rankin scores at discharge. Conclusions: A Hunt–Hess score > 2, a neutrophil-to-lymphocyte ratio > 8.0, and early fevers may be predictive of need for multiple endovascular interventions in refractory cerebral vasospasm after aSAH. These patients have poorer functional outcomes at discharge and higher rates of in-hospital complications. [ABSTRACT FROM AUTHOR]

Background: Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI) and worsened neurological outcome. Transcranial Doppler (TCD) measurements of cerebral blood flow velocity are commonly used after aSAH to screen for vasospasm; however, their association with cerebral infarction is not well characterized. We sought to determine whether time-varying TCD-measured vasospasm severity is associated with cerebral infarction and investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction. Methods: We conducted a retrospective single-center cohort study of consecutive adult patients with aSAH with at least one TCD study between 2011 and 2020. The primary outcome was radiological DCI, defined as a cerebral infarction developing at least 2 days after any surgical or endovascular intervention without an alternative cause. Cox proportional hazards models were used to examine associations between time-varying vasospasm severity and radiological DCI. Optimal TCD-based time/severity thresholds for predicting radiological DCI were then determined. Results: Of 262 patients with aSAH who underwent TCD studies, 27 (10%) developed radiological DCI. Patients with radiological DCI had higher modified Fisher scale scores and trended toward earlier onset of vasospasm. Adjusted for age, Hunt and Hess scores, and modified Fisher scale scores, the worst-vessel vasospasm severity was associated with radiological DCI (adjusted hazard ratio 1.7 [95% confidence interval 1.1–2.4]). Vasospasm severity within a specific vessel was associated with risk of delayed infarction in the territory supplied by that vessel. Optimal discrimination of patients with radiological DCI was achieved with thresholds of mild vasospasm on days 4–5 or moderate vasospasm on days 6–9, with negative predictive values greater than 90% and positive predictive values near 20%. Conclusions: TCD-measured vasospasm severity is associated with radiological DCI after aSAH. An early, mild TCD-based vasospasm severity threshold had a high negative predictive value, supporting its role as a screening tool to identify at-risk patients. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral vasospasm (VSP) is the leading risk factor of neurological deterioration (i.e., delayed cerebral ischemia [DCI] and cerebral infarction) after aneurysmal subarachnoid hemorrhage (aSAH) and a cause of morbidity and mortality. The objective of this systematic literature review is to summarize the economic and humanistic burden of VSP and its related complications after aSAH. Methods: A predefined protocol was designed, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Systematic searches were conducted in MEDLINE, Embase, and Cochrane (in January 2021) to identify studies reporting economic and/or humanistic (i.e., health-related quality of life [HRQoL]) outcomes for patients with asymptomatic and symptomatic VSP after aSAH. Related conferences and additional sources were searched manually. Dual screening, data extraction, and qualitative analysis were conducted. Results: Of 3818 abstracts identified for review, 43 full-text articles representing 42 single studies met the inclusion criteria and were included. Most studies (33) were observational; nine were randomized clinical trials (RCTs). Economic outcomes were reported in 31 studies, and alongside HRQoL outcomes in 4 studies; 7 studies reported HRQoL outcomes only. Forty studies were conducted in single countries, while only 2 RCTs were conducted in multiple countries. Patients diagnosed with VSP or DCI spent between 2.1 and 7.4 days longer in intensive care and between 4.7 and 17 days longer in hospital (total) compared with patients without VSP or DCI. A significantly higher cost burden of US$33,945 (2021 £26,712) was identified for patients with VSP and £9370 (2021 £13,733) for patients with DCI compared with patients without. Patients with DCI were also disadvantaged by being employed for 62 fewer days (during 24-month follow-up), with an estimated mean cost of £3821 (2021 £5600) for days off work. Poor HRQoL was associated with ≥ 1 days with VSP symptoms (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.4–5.3), symptomatic VSP (OR: 1.9, 95% CI: 1.0–3.6), and DCI (OR: 2.3, 95% CI: 1.3–4.2), although this was not consistent across all studies. Symptomatic VSP and DCI were identified as significant risk factors for depressed mood (OR: 2.2, 95% CI: 1.0–4.9) and global cognitive impairment (OR: 2.3) at 12 months, respectively. The severity of VSP was a critical predictor of post-aSAH economic and humanistic burden. Similar trends in economic and humanistic burden were identified in the general aSAH patient population. Study design and patient heterogeneity precluded direct metaanalysis of the results. Conclusion: A substantial direct and indirect economic burden is linked to VSP and its related complications after aSAH. Although limited evidence was identified for humanistic burden, these patients seem to suffer from poor HRQoL with long-lasting burden. Overall, there is an urgent need to understand better the concept of "burden of illness" of VSP and its related complications after aSAH. Plain Language Summary: Aneurysmal subarachnoid hemorrhage is a sudden, life-threatening emergency caused by bleeding in the subarachnoid space between the brain and skull. Vasospasm of the arteries surrounding the hemorrhage occurs in most patients and may lead to permanent brain damage. This study summarizes the published literature to describe the burden that patients may experience due to vasospasm and its related complications after aneurysmal subarachnoid hemorrhage, focusing on financial and life quality aspects. We show that the burden of vasospasm, and its related complications, is huge. Patients often experience reduced quality of life due to their poor health and are more likely to suffer from depression and intellectual impairment. There is also a substantial financial burden linked to vasospasm and its related complications, driven by the need for more intensive care, hospitalization, and higher investigative costs associated with the treatment and management of these patients. In addition, days off work and unemployment can cause a substantial indirect financial burden. Our study highlights the need for additional research to understand further the "burden of illness" of vasospasm and its related complications after aneurysmal subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

We hypothesized that the enzyme arginase-1 is released into the cerebrospinal fluid (CSF) during red blood cell lysis and contributes to dysregulated metabolism of the nitric oxide (NO) precursor L-arginine during aneurysmal subarachnoid hemorrhage (SAH). This prospective case–control study included 43 patients with aneurysmal SAH and ventricular drainage for clinical reasons. Longitudinal CSF samples (99) were obtained in the course of SAH. Patients were dichotomized regarding the occurrence of cerebral vasospasm syndrome (CVS) (N = 19). Arginase-1 and the amino acids L-arginine and L-ornithine were quantified in CSF. Outcome assessments included delayed cerebral ischemia (DCI) and functional status after 3 months using the modified Rankin Scale (mRS). Arginase-1 was released into the CSF of SAH patients whereas this enzyme was undetectable in controls. Compared to patients without CVS, arginase-1 levels were higher in CVS patients until day 14 after clinical event. The well-known surrogate parameter for arginase acitivity, the L-arginine to L-ornithine ratio (Arg/Orn), correlated with CSF arginase-1 levels. Arg/Orn was reduced in patients with CVS from disease onset (days 1–3, p = 0.0009) until day 14. Logistic regression analysis of early Arg/Orn was predictive for CVS (p = 0.008) and DCI (p = 0.035), independent of age, Hunt and Hess grade, and intraventricular blood. Arg/Orn < 2.71 at disease onset predicted CVS with a sensitivity of 86.7% and specificity of 72.2%. Arg/Orn ≥ 2.71 predicted excellent functional outcome. We propose a novel mechanism contributing to NO deprivation during SAH: arginase-1 is released from erythrocytes into the CSF, leading to L-arginine consumption and reduced NO bioavailability. Furthermore, Arg/Orn is a robust predictor for occurrence of CVS, DCI, and functional outcome 3 months after aneurysmal SAH. Our data provide a novel prognostic biomarker and may contribute to the development of novel therapeutic strategies in SAH. Clinical Trial Registration-URL: http://www.drks.de. Unique identifier: DRKS00015293, date of registration: 13.09.2018. [ABSTRACT FROM AUTHOR]

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Purpose: High intracranial pressure variability (ICPV) is associated with favorable outcome in traumatic brain injury, by mechanisms likely involving better cerebral blood flow regulation. However, less is known about ICPV in aneurysmal subarachnoid hemorrhage (aSAH). In this study, we investigated the explanatory variables for ICPV in aSAH and its association with delayed cerebral ischemia (DCI) and clinical outcome. Methods: In this retrospective study, 242 aSAH patients, treated at the neurointensive care, Uppsala, Sweden, 2008–2018, with ICP monitoring the first ten days post-ictus were included. ICPV was evaluated on three time scales: (1) ICPV-1 m—ICP slow wave amplitude of wavelengths between 55 and 15 s, (2) ICPV-30 m—the deviation from the mean ICP averaged over 30 min, and (3) ICPV-4 h—the deviation from the mean ICP averaged over 4 h. The ICPV measures were analyzed in the early phase (day 1–3), in the early vasospasm phase (day 4–6.5), and the late vasospasm phase (day 6.5–10). Results: High ICPV was associated with younger age, reduced intracranial pressure/volume reserve (high RAP), and high blood pressure variability in multiple linear regression analyses for all ICPV measures. DCI was associated with reduced ICPV in both vasospasm phases. High ICPV-1 m in the post-ictal early phase and the early vasospasm phase predicted favorable outcome in multiple logistic regressions, whereas ICPV-30 m and ICPV-4 h in the late vasospasm phase had a similar association. Conclusions: Higher ICPV may reflect more optimal cerebral vessel activity, as reduced values are associated with an increased risk of DCI and unfavorable outcome after aSAH. [ABSTRACT FROM AUTHOR]

Objectives: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Methods: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Results: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Conclusions: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Clinical relevance statement: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Key Points: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study.A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score.Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74–0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25).Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction.Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct.The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients. [ABSTRACT FROM AUTHOR]

Purpose: Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and effect on brain perfusion is unknown. The aim of the actual analysis was to define cerebral hemodynamic effects and outcome of intravenous milrinone plus norepinephrine supplemented by intra-arterial nimodipine as a rescue strategy for DCI following aneurysmal SAH. Methods: Of 176 patients with aneurysmal SAH treated at our neurosurgical department between April 2016 and March 2021, 98 suffered from DCI and were submitted to rescue therapy. For the current analysis, characteristics of these patients and clinical response to rescue therapy were correlated with hemodynamic parameters, as assessed by CT angiography (CTA) and perfusion CT. Time to peak (TTP) delay in the ischemic focus and the volume with a TTP delay of more than 4 s (T4 volume) were used as hemodynamic parameters. Results: The median delay to neurological deterioration following SAH was 5 days. Perfusion CT at that time showed median T4 volumes of 40 cc and mean focal TTP delays of 2.5 ± 2.1 s in these patients. Following rescue therapy, median T4 volume decreased to 10 cc and mean focal TTP delay to 1.7 ± 1.9 s. Seventeen patients (17% of patients with DCI) underwent additional intra-arterial spasmolysis using nimodipine. Visible resolution of macroscopic vasospasm on CTA was observed in 43% patients with DCI and verified vasospasm on CTA, including those managed with additional intra-arterial spasmolysis. Initial WFNS grade, occurrence of secondary infarction, ischemic volumes and TTP delays at the time of decline, the time to clinical decline, and the necessity for additional intra-arterial spasmolysis were identified as the most important features determining neurological outcome at 6 months. Conclusion: The current analysis shows that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved by milrinone and norepinephrine–based hyperdynamic therapy. A long-term clinical benefit by the addition of milrinone appears likely. Separation of the direct effect of milrinone from the effect of induced hypertension is not possible based on the present dataset. [ABSTRACT FROM AUTHOR]

Background: In aneurysmal subarachnoid hemorrhage (aSAH), one of the main determinants of prognosis is delayed cerebral ischemia (DCI). Transcranial Doppler (TCD) is used to monitor vasospasm and DCI. We aimed to better understand cerebral hemodynamics response to hypertension induction (HI) with norepinephrine (NE) and inotropic therapy with milrinone so that TCD can be a bedside tool in helping to guide DCI therapies. Our primary objective was to determine TCD blood flow velocity (BFV) kinetics during HI and inotropic therapy for DCI treatment. Secondly, we performed an analysis by treatment subgroups and evaluated clinical response to therapies. Methods: We performed a prospective observational cohort study in a Brazilian high-volume center for aSAH. Patients with aSAH admitted between 2016 and 2018 who received NE or milrinone for DCI treatment were included. TCDs were performed before therapy initiation (t0) and 45 (t1) and 90 min (t2) from the onset of therapy. For each DCI event, we analyzed the highest mean flow velocity (MFV) and the mean MFV and compared their kinetics over time. The National Institutes of Health Stroke Scale was determined at t0, t1, and t2. Results: Ninety-eight patients with aSAH were admitted during the study period. Twenty-one (21.4%) developed DCI, of whom six had DCI twice, leading to a total of 27 analyzed DCI events (12 treated with HI and 15 with milrinone). Patients treated with NE had their mean arterial pressure raised (85 mm Hg in t0, 112 mm Hg in t2 [p < 0.001]), whereas those treated with milrinone had a significant decrease in mean arterial pressure over treatment (94 mm Hg in t0, 88 mm Hg in t2 [p = 0.004]). Among all treated patients, there was a significant drop from t0 to t2 but not to t1 in the highest MFV and in the highest mean MFV. Among those treated with HI, there were no significant changes from t0 to t1 or t2 (highest MFV in t0 163.2 cm/s, in t1 172.9 cm/s [p = 0.27], and in t2 164 cm/s [p = 0.936]). Conversely, in those treated with milrinone, there was a significant decrease from t0 to t1 and to t2 (highest MFV in t0 197.1 cm/s, in t1 172.8 cm/s [p = 0.012], in t2 159 cm/s [p = 0.002]). Regarding clinical outcomes, we observed a significant improvement in mean National Institutes of Health Stroke Scale scores from 17 to 16 in t1 (p < 0.001) and to 15 in t2 (p = 0.002). Conclusions: BFV analyzed by TCD in patients with aSAH who developed DCI and were treated with milrinone or NE significantly decreased in a time-dependent way. Milrinone effectively decrease cerebral BFV, whereas NE do not. Clinical improvement was achieved with both treatment strategies. [ABSTRACT FROM AUTHOR]

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients. [ABSTRACT FROM AUTHOR]

Background: The use of self-expanding stents to treat post-hemorrhagic cerebral vasospasm was recently described. We sought to determine the clinical efficacy of the Cascade device to treat delayed cerebral vasospasm (DCV). We performed benchside tests to determine the chronic outward force exerted by the Cascade in comparison to the Solitaire. Methods: The chronic outward force (COF) of the Cascade M agile and Cascade L Agile was tested with equivalent tests of the Solitaire 4x20mm. Further tests to determine the forces generated in pre-formed tubes of 1.5–6 mm were performed using both fully and partially unsheathed Cascades. A retrospective review to identify all patients with aSAH and DCV treated with a Cascade device between January 2020 and July 2021. We recorded the treatment arterial vessel diameters and hemorrhagic or ischemic complications. Results: In vitro the Cascade generated greater radial force than the Solitaire. The force generated by the Cascade M Agile at 1.5 mm was approximately 64% higher than the Solitaire 6x40mm and approximately 350% higher than the Solitaire 4x20mm. 4 patients with DCV were identified all of whom were treated with a cascade device. In all cases there was a significant improvement in the diameter of the vasospastic vessels treated with an average diameter increase of approximately 300%. There were no complications from the Cascade. Delayed CT angiography showed persistent dilatation of the segments treated with the Cascade at 24 h. Conclusion: The Cascade is a safe and effective device when used to treat DCV secondary to aSAH. Larger studies are required to validate our initial results. [ABSTRACT FROM AUTHOR]

Small trials have demonstrated promising results utilising intravenous milrinone for the treatment of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). Here we summarise and contextualise the literature and discuss the future directions of intravenous milrinone for DCI. A systematic, pooled analysis of literature was performed in accordance with the PRISMA statement. Methodological rigour was analysed using the MINORS criteria. Extracted data included patient population; treatment protocol; and clinical, radiological, and functional outcome. The primary outcome was clinical resolution of DCI. Eight hundred eighteen patients from 10 single-centre, observational studies were identified. Half (n = 5) of the studies were prospective and all were at high risk of bias. Mean age was 52 years, and females (69%) outnumbered males. There was a similar proportion of low-grade (WFNS 1–2) (49.7%) and high-grade (WFNS 3–5) (50.3%) SAH. Intravenous milrinone was administered to 523/818 (63.9%) participants. Clinical resolution of DCI was achieved in 375/424 (88%), with similar rates demonstrated with intravenous (291/330, 88%) and combined intra-arterial-intravenous (84/94, 89%) therapy. Angiographic response was seen in 165/234 (71%) receiving intravenous milrinone. Hypotension (70/303, 23%) and hypokalaemia (31/287, 11%) were common drug effects. Four cases (0.5%) of drug intolerance occurred. Good functional outcome was achieved in 271/364 (74%) patients. Cerebral infarction attributable to DCI occurred in 47/250 (19%), with lower rates in asymptomatic spasm. Intravenous milrinone is a safe and feasible therapy for DCI. A signal for efficacy is demonstrated in small, low-quality trials. Future research should endeavour to establish the optimal protocol and dose, prior to a phase-3 study. [ABSTRACT FROM AUTHOR]

Background: Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable complications of this procedure. We retrospectively evaluated whether adjuvant systemic heparinization just before arterial manipulation could reduce early failure of primary AVF. Methods: Three hundred and fifty-six patients with end-stage renal failure who underwent primary AVF surgery from April 2009 to September 2020 were enrolled in this study. The patients were divided into two groups based on whether they received adjuvant heparinization or not. Patient backgrounds, frequency of early AVF failure, and bleeding events were compared between the two groups. Multivariate Cox regression analysis identified risk factors for early AVF failure. Results: Early failure of AVF was observed in only 2 of 157 patients (1.2%) in the adjuvant group, and the incident was significantly lower than observed in the non-adjuvant group, i.e., 17 of 199 patients (8.5%) (p = 0.002). Bleeding events were not significantly different between the two groups. Seven of 157 patients (4.5%) in the adjuvant group and 7 of 199 patients (3.5%) in the non-adjuvant group experienced bleeding events (p = 0.785). Female sex, use of steroids, hypoalbuminemia, venous stenosis in pre-surgical evaluation, arterial spasm in the perioperative period, new-onset venous stenosis after AVF anastomosis, technical failure of surgery, no early cannulation after surgery, and non-adjuvant heparinization were related to early AVF failure in the multivariate regression analysis. Conclusion: Adjuvant systemic heparinization therapy just before arterial manipulation reduced early failure of primary AVF without increasing bleeding events. [ABSTRACT FROM AUTHOR]

Purpose: Delayed cerebral ischemia (DCI) is a frequent cause of morbidity and mortality in patients with cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH). Refractory CV remains challenging to treat and often leads to permanent deficits and death despite aggressive therapy. We hereby report the feasibility and safety of stellate ganglion block (SGB) performed with a vascular roadmap-guided technique to minimize the risk of accidental vascular puncture and may be coupled to a diagnostic or therapeutic cerebral angiography. Methods: In addition to a detailed description of the technique, we performed a retrospective analysis of a series of consecutive patients with refractory CV after aSAH that were treated with adjuvant roadmap-guided SGB. Clinical outcomes at discharge are reported. Results: Nineteen SGB procedures were performed in 10 patients, after failure of traditional hemodynamic and endovascular treatments. Each patient received 1 to 3 SGB, usually interspaced by 24 h. In 4 patients, an indwelling microcatheter for continuous infusion was inserted. First SGB occurred on average 7.3 days after aSAH. SGB was coupled to intra-arterial nimodipine infusion or balloon angioplasty in 9 patients. SGB was technically successful in all patients. There were no technical or clinical complications. Conclusion: Adjuvant SGB may be coupled to endovascular therapy to treat refractory cerebral vasopasm within the same session. To guide needle placement, using a roadmap of the supra-aortic arteries may decrease the risk of complications. More prospective data is needed to evaluate the therapeutic efficacy, durability, and safety of SGB compared with the established standard of care. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the management of aSAH in pregnancy. We identified all available literature and compiled management decisions as well as reported outcomes through a systematic literature review without meta-analysis to provide recommendations for management of aSAH during pregnancy. We included a total of 23 articles containing 54 cases of pregnancy-related aSAH in our review. From these reports and other literature, we evaluated information on aSAH pathophysiology, diagnosis, and management with respect to pregnancy. Early transfer to an appropriate facility with neurocritical care, a high-risk obstetric service, and a neurosurgery team available is crucial for the management of aSAH in pregnancy. Intensive monitoring and a multidisciplinary approach remain fundamental to ensure maternal and fetal health. [ABSTRACT FROM AUTHOR]

Early brain injury (EBI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia (DCI) are common complications of subarachnoid hemorrhage (SAH). Inflammatory processes in the cerebrospinal fluid (CSF) are one of the causes for such complications. Our aim to study the effects of an IL-6 receptor antagonist (Tocilizumab) examines the occurrence of DCVS, neuronal cell death, and microclot formation in an acute SAH rabbit model. Twenty-nine New Zealand white rabbits were randomized into one of three groups as the SAH, SAH + Tocilizumab, and sham groups. In SAH groups, hemorrhage was induced by extracranial-intracranial arterial blood shunting from the subclavian artery into the cisterna magna under intracranial pressure (ICP) monitoring. In the second group, Tocilizumab was given once intravenously 1 h after SAH induction. Digital subtraction angiography was performed, and CSF and blood were sampled before and after (day 3) SAH induction. IL-6 plasma and CSF levels were measured. TUNEL, FJB, NeuN, and caspase-3 immunostaining were used to assess cell apoptosis, neurodegeneration, and neuronal cell death, respectively. Microclot formation was detected by fibrinogen immunostaining. Between baseline and follow-up, there was a significant reduction of angiographic DCVS (p < 0.0001) in the Tocilizumab compared with the SAH group. Tocilizumab treatment resulted in decreased neuronal cell death in the hippocampus (p = 0.006), basal cortex (p = 0.001), and decreased microclot formation (p = 0.02). Tocilizumab reduced DCVS, neuronal cell death, and microclot formation in a rabbit SAH model, and could be a potential treatment to prevent DCVS and DCI in SAH patients. [ABSTRACT FROM AUTHOR]