Ticagrelor use in ruptured aneurysms: A retrospective cohort study.

Subarachnoid hemorrhage (SAH) is a common and frequently devastating condition, accounting for ≈5% of all strokes and affecting as many as 30 000 Americans each year.1,2 The American Heart Association (AHA) previously published “Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage.”3 Since then, considerable advances have been made in endovascular techniques, diagnostic methods, and surgical and perioperative management paradigms. Nevertheless, outcome for patients with SAH remains poor, with population-based mortality rates as high as 45% and significant morbidity among survivors.4–9 Several multicenter, prospective, randomized trials and prospective cohort analyses have influenced treatment protocols for SAH. However, rapid evolution of newer treatment modalities, as well as other practical and ethical considerations, has meant that rigorous clinical scientific assessment of the treatment protocols has not been feasible in several important areas. To address these issues, the Stroke Council of the AHA formed a writing group to reevaluate the recommendations for management of aneurysmal SAH. A consensus committee reviewed existing data in this field and prepared the recommendations in 1994.3 In an effort to update those recommendations, a systematic literature review was conducted based on a search of MEDLINE to identify all relevant randomized clinical trials published between June 30, 1994, and November 1, 2006 (search terms: subarachnoid hemorrhage , cerebral aneurysm , trial ; Table 1). Each identified article was reviewed by at least 2 members of the writing group. Selected articles had to meet one of the following criteria to be included: randomized trial or nonrandomized concurrent cohort study. Case series and nonrandomized historical cohort studies were reviewed if no studies with a higher level of evidence were available for a particular topic covered in the initial guidelines. These were chosen on the basis of sample size and the relevance of the particular studies to subjects that …

To the Editor: The use of statins after aneurysmal subarachnoid hemorrhage (SAH) has a strong scientific rationale and appears promising in preliminary clinical studies.1–2 However, the assertion by Sillberg et al that their meta-analysis “supports the routine use of statins” is too strong.3 This conclusion was based on the cumulative experience from three small single-center clinical trials involving a total of only 158 patients. The purported reduction in mortality (reported in only 2/3 trials) was based on 11 deaths among control patients compared with 2 deaths among statin-treated patients. Because of the small numbers, this finding is not particularly robust—if there had been, for example, one less death in the …

Intracranial stenting and flow diversion require the use of dual antiplatelet therapy (DAPT) to prevent in-stent thrombosis. DAPT may significantly increase the risk of hemorrhagic complications in patients who require subsequent surgical interventions. In this study, the authors sought to investigate whether DAPT is a risk factor for hemorrhagic complications associated with ventriculoperitoneal (VP) shunt placement in patients with aneurysmal subarachnoid hemorrhage (aSAH). Moreover, the authors sought to compare VP shunt complication rates with respect to the shunt's location from the initial external ventricular drain (EVD) site. Patients with aSAH who presented to the authors' institution from July 2009 through November 2016 and required VP shunt placement for persistent hydrocephalus were included. The rates of hemorrhagic complications associated with VP shunt placement were compared between patients who were on a regimen of DAPT (aspirin and clopidogrel) for use of a stent or flow diverter, and patients who underwent microsurgical clipping or coiling only and were not on DAPT using a backward stepwise multivariate analysis. Rates of radiographic hemorrhage and infection-related VP shunt revision were compared between patients who underwent VP shunt placement along the same track and those who underwent VP shunt placement at a different site (contralateral or posterior) from the initial EVD. A total of 443 patients were admitted for the management of aSAH. Eighty of these patients eventually required VP shunt placement. Thirty-two patients (40%) had been treated with stent-assisted coiling or flow diverters and required DAPT, whereas 48 patients (60%) had been treated with coiling without stents or surgical clipping and were not on DAPT at the time of VP shunt placement. A total of 8 cases (10%) of new hemorrhage were observed along the intracranial proximal catheter of the VP shunt. Seven of these hemorrhages were observed in patients on DAPT, and 1 occurred in a patient not on DAPT. After multivariate analysis, only DAPT was significantly associated with hemorrhage (OR 31.23, 95% CI 2.98-327.32; p = 0.0001). One patient (3%) on DAPT who experienced hemorrhage required shunt revision for hemorrhage-associated proximal catheter blockage. The remaining 7 hemorrhages were clinically insignificant. The difference in rates of hemorrhage between shunt placement along the same track and placement at a different site of 0.07 was not significant (6/47 vs 2/32, p = 0.46). The difference in infection-related VP shunt revision rate was not significantly different (1/47 vs 3/32, p = 0.2978). This clinical series confirms that, in patients with ruptured aneurysms who are candidates for stent-assisted coiling or flow diversion, the risk of clinically significant VP shunt-associated hemorrhage with DAPT is low. In an era of evolving endovascular therapeutics, stenting or flow diversion is a viable option in select aSAH patients.

Objective To study the management of aneurysmal subarachnoid haemorrhage and compare neurological outcomes in different elderly age groups. Design Retrospective cohort study Methods Patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to Royal Victoria Hospital Belfast between 2015 to 2019 were separated into different age groups, all patients above age of 70 were enrolled to this study. Study population was further divided into 3 sub-groups, age 70 – 74, age 75 – 79 and age >80. Patient characteristics and clinical courses were compared, including underlying co-morbidities, WFNS grade of aSAH, intervention received, complications and long-term neurological outcomes in follow up clinics. Results A total of 54 patients were included, with 29 in group I (age 70 – 74), 20 in group II (age 75 – 79) and 5 in group III (age >80). Despite patients in group III presented with only WFNS grade 1 & 2 aSAH, mortality increased exponentially with age, from 10.3% to 15% to 40% across 3 sub-groups. There was also a linear increase in average length of stay from 21 days to 24 days. 23 patients (79.3%) developed complications in group I and 15 patients (75%) in group II. 3 patients (60%) in group III developed complications and the other 2 patients within same sub-group did not survive. Most common complications were hydrocephalus and hospital acquired infections, 44.4% of patients developed each condition respectively. Conclusion Our study suggests patients with age >80 had less favourable neurological outcomes despite having good grade aSAH at presentation and received similar intervention, when compared to other age groups. Average length of stay in hospital also increased with age. Similar complication rates were noticed in all age groups. Comparing our data with other neurosurgical units in the United Kingdom and Ireland will provide further information in managing elderly aSAH patients and facilitate risk stratification when considering those patients for intervention. Disclosures P. Cheng: None. H. Simms: None. A. Abouharb: None.

Prognostic Value and Determinants of Ultraearly Angiographic Vasospasm after Aneurysmal Subarachnoid Hemorrhage

The increased use of stent-assisted coiling, and more recently, flow diverters and the need for dual antiplatelet therapy have introduced an additional layer of complexity to the management of intracranial aneurysms. Because of the pitfalls of dual antiplatelet therapy in patients with freshly ruptured aneurysms, acute subarachnoid hemorrhage (SAH) was long considered a relative contraindication to the use of these devices. In the setting of acute SAH, dual antiplatelet therapy exposes the patient to higher risks of hemorrhagic complications, especially if invasive procedures, such as placement of an external ventricular drain (EVD) or a ventriculoperitoneal (VP) shunt, are required. As the use of stents has expanded, several centers have reported their experience with stentassisted coiling in patients with acute SAH.1 In the current issue, Mahaney and coworkers3 describe their recent experience with 37 patients who underwent VP shunting after aneurysmal SAH. Twelve of the 37 patients had undergone stent-assisted coiling of the aneurysm and were on dual antiplatelet therapy at the time of VP shunt insertion. Four patients suffered an intracranial hemorrhage related to the VP shunt procedure, and, not surprisingly, all of these 4 patients were on dual antiplatelet therapy. Despite the relatively small number of patients in this report, the difference was statistically significant. Each hemorrhage was minor, along the catheter tract, and only 1 resulted in clinical consequences as the patient required shunt revision because of catheter obstruction. The same authors have previously reported a rate of hemorrhage as high as 32% after EVD placement in patients treated with stent-assisted coiling and on dual antiplatelet therapy.2 This and other studies1 confirm that dual antiplatelet therapy exposes patients with aneurysmal SAH to a higher risk of hemorrhagic complications. In such cases, it is important to consider and devise strategies to minimize these untoward events. Over the years at our institution we have limited to only a few selected cases stent-assisted coiling in the acute phase after aneurysm rupture. Instead, for complex wide-necked and large ruptured aneurysms, we prefer a staged approach and perform only coiling first (usually leaving a residual neck), followed, after 4–6 weeks, by a more aggressive and definitive endovascular treatment with stenting or, increasingly, with flow diverters. In this manner, patients are protected from the risk of early rebleeding (even with partial coiling, the dome is usually adequately covered) while definitive treatment is carried out in an elective fashion when dual antiplatelet therapy does not pose particular risks. If a complex treatment with stent assistance cannot be staged, then there are strategies that can minimize the risk of hemorrhagic complications after EVD or shunt placement. For example, in patients receiving antiplatelet therapy, we try to avoid placing an EVD and, instead, use a lumbar drain, which usually works quite as well. If an EVD is at all necessary, such as in patients with a large intraventricular hemorrhage or very high intracranial pressure, then we try to place the EVD before the endovascular procedure so that patients can be safely loaded with antiplatelet agents after the EVD has been inserted. If permanent CSF diversion is needed, there are strategies to minimize hemorrhagic complications in patients on dual antiplatelet therapy. One is to utilize a lumboperitoneal shunt instead of a VP shunt, and I am surprised that the authors of the present study did not even consider this possibility. The other strategy is to use the same tract of a preexisting EVD and “soft” pass a new ventricular catheter without the stylet immediately after removal of the EVD. This strategy is very safe and associated with a very low complication rate.4 (http://thejns.org/doi/abs/10.3171/2013.4.JNS13372)

Ventricular Assist Devices as Rescue Therapy in Cardiogenic Shock After Subarachnoid Hemorrhage

The cerebral angiography result is negative for an underlying vascular lesion in 15-20% of patients with nontraumatic subarachnoid hemorrhage (SAH). Patients with angiogram-negative SAH include those with perimesencephalic SAH and diffuse SAH. Consensus suggests that perimesencephalic SAH confers a more favorable prognosis than diffuse SAH. Limited data exist to contextualize the clinical course and prognosis of diffuse SAH in relation to aneurysmal SAH in terms of critical care complications, neurologic complications, and functional outcomes. Here we compare the clinical course and functional outcomes of patients with perimesencephalic SAH, diffuse SAH, and aneurysmal SAH to better characterize the prognostic implications of each SAH subtype. We conducted a retrospective cohort study that included all patients with nontraumatic SAH admitted to a tertiary care referral center between January 1, 2012, and December 31, 2017. Bleed patterns were radiographically adjudicated, and patients were assigned to three groups: perimesencephalic SAH, diffuse SAH, and aneurysmal SAH. Patient demographics, complications, and clinical outcomes were reported and compared. Eighty-six patients with perimesencephalic SAH, 174 with diffuse SAH, and 998 with aneurysmal SAH presented during the study period. Patients with aneurysmal SAH were significantly more likely to be female, White, and active smokers. There were no significant differences between patients with diffuse SAH and perimesencephalic SAH patterns. Critical care complications were compared across all three groups, with significant between-group differences in hypotension and shock (3.5% vs. 16.1% vs. 38.4% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01) and endotracheal intubation (0% vs. 26.4% vs. 48.8% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01). Similar trends were noted with long-term supportive care with tracheostomy and gastrostomy tubes and length of stay. Cerebrospinal fluid diversion was increasingly required across bleed types (9.3% vs. 54.6% vs. 76.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively, p < 0.001). Vasospasm and delayed cerebral ischemia were comparable between perimesencephalic SAH and diffuse SAH but significantly lower than aneurysmal SAH. Patients with diffuse SAH had intermediate functional outcomes, with significant rates of nonhome discharge (23.0%) and poor functional status on discharge (26.4%), significantly higher than patients with perimesencephalic SAH and lower than patients with aneurysmal SAH. Diffuse SAH similarly conferred an intermediate rate of good functional outcomes at 1-6months post discharge (92.3% vs. 78.6% vs. 47.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.016). We confirm the consensus data that perimesencephalic SAH is associated with a more benign clinical course but demonstrate that diffuse SAH confers an intermediate prognosis, more malignant than perimesencephalic SAH but not as morbid as aneurysmal SAH. These results highlight the significant morbidity associated with diffuse SAH and emphasize need for vigilance in the acute care of these patients. These patients will likely benefit from continued high-acuity observation and potential support to avert significant risk of morbidity and neurologic compromise.

Cerebral Vasospasm: New Strategies in Research and Treatment

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235.

With the evolution of neuroendovascular treatments, there is a great trend to treat acutely ruptured wide-necked aneurysms with stent-assisted coiling (SAC) and flow diverters (FDs), which inevitably requires dual antiplatelet therapy (DAPT). This therapy can increase the rate of hemorrhagic complications following other neurosurgical maneuvers, such as external ventricular drain (EVD) placement or removal. In this study, the authors aimed to evaluate the safety of DAPT in patients with aneurysmal subarachnoid hemorrhage (SAH) treated with SAC or FDs and the therapy's potential benefit in reducing cerebral ischemia and cerebral vasospasm. In this retrospective study, the authors reviewed the records of patients who had been admitted to their hospital with acute aneurysmal SAH and treated with SAC, FDs, and/or coiling between 2012 and 2022. Patients were classified into two groups: a DAPT group, including patients who had received DAPT for SAC or FDs, and a non-DAPT group, including patients who had not received any antiplatelet regimen and had been treated with coiling. Perioperative hemorrhagic and ischemic complications and clinical outcomes were compared between the two groups. From among 938 cases of acute ruptured aneurysms treated during 10 years of study, 192 patients were included in this analysis, with 96 patients in each treatment group, after propensity score matching. All basic clinical and imaging characteristics were equivalent between the two groups except for the neck size of aneurysms (p < 0.001). EVD-related hemorrhage was significantly higher in the DAPT group than in the non-DAPT group (p = 0.035). In most patients, however, the EVD-related hemorrhage was insignificant. Parent artery or stent-induced thrombosis was higher in the DAPT group than in the non-DAPT group (p = 0.003). The rate of cerebral ischemia was slightly lower in the DAPT group than in the non-DAPT group (11.5% vs 15.6%, p = 0.399). In the multivariate analysis, cerebral ischemia, rebleeding before securing the aneurysm, extracranial hemorrhage, and cerebral vasospasm were the predictive factors of a poor clinical outcome (p < 0.001, p < 0.001, p = 0.038, and p = 0.038, respectively). The DAPT regimen may be safe in the setting of acute aneurysmal SAH. Although EVD-related hemorrhage is more common in the DAPT group than the non-DAPT group, it is usually insignificant without any neurological deficit.

Perioperative management of aneurysmal subarachnoid hemorrhage: Part 2. Postoperative management.

Aneurysmal subarachnoid hemorrhage (SAH) has a 30-day mortality rate of 45%, with approximately half the survivors sustaining irreversible brain damage.1 On the basis of an annual incidence of 6 per 100 000, ≈15 000 Americans will have an aneurysmal SAH each year. Population-based incidence rates vary considerably from 6 to 16 per 100 000, with the highest rates reported from Japan and Finland.2 3 4 5 Approximately 5% to 15% of stroke cases are secondary to ruptured saccular aneurysms. Although the prevention of hemorrhage has been advocated as the most effective strategy aimed at lowering mortality rates,6 the optimal management of patients with unruptured intracranial aneurysms (UIAs) remains controversial. Management decisions require an accurate assessment of the risks of various treatment options compared with the natural history of the condition. The natural history of UIAs and treatment outcomes are influenced by (1) patient factors, such as previous aneurysmal SAH, age, and coexisting medical conditions; (2) aneurysm characteristics, such as size, location, and morphology; and (3) factors in management, such as the experience of the surgical team and the treating hospital. These many influences have contributed to considerable variability in the reported risks for aneurysmal SAH and the treatment of UIAs. There are no prospective randomized trials of treatment interventions versus conservative management to date, and it is possible that no such studies will be carried out in the future. According to a classification system suggested by Cook et al,7 randomized clinical trials with low likelihoods of false-positive and false-negative errors provide the highest level of evidence (level I) that can be applied to a clinical recommendation. Randomized trials with high likelihoods of false-negative and positive errors provide level II evidence. Level III evidence is generated with nonrandomized concurrent cohort comparisons between contemporaneous patients who did and …

Objectives of the study. Our aim was to analyse different antithrombotic drug regimens and duration in intracranial stenting procedures (stent assisted coiling, flow diverter) for unruptured aneurysms and based on the literature review from 2017–2023 to implement dual antiplatelet therapy algorithm for neuro-interventional procedures in Lithuania. Research methods and methodology. A comprehensive literature search of PubMed, BioMed Central, BMJ Journals, EBSCO Publishing, SAGE Journals Online, ScienceDirect, SpringerLink was conducted by two independent readers (MP, GŠ) for studies published from January 2017 to April 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. 23 studies: 6 retrospective cohort, 11 retrospective case-control, 1 prospective cohort, 1 prospective randomized-control, 1 systemic literature review, 3 metanalysis observational studies were identified. Results and conclusions. We found widespread variation in practices even among the same country centres, lending credence to the importance of a future prospective studies of dual antiplatelet drug therapy (DAPT) regimens and duration for the purpose of deriving optimal methods and streamlining tactics. Our suggested algorithm for DAPT in neuro-interventional procedures in Lithuania is provided in Graph 1.

Aim To study the management of aneurysmal subarachnoid haemorrhage (aSAH) and compare neurological outcomes in different elderly age groups. Method A retrospective cohort study. aSAH patients with age 60 and above admitted to Royal Victoria Hospital Belfast between 2015 to 2019 were enrolled, and divided into 3 sub-groups, age 60 – 69 (Group I), age 70 – 79 (Group II) and age &amp;gt;80 (Group III). Patient characteristics and clinical courses were compared, including co-morbidities, WFNS grades, interventions, complications and neurological outcomes at follow up. Results 158 patients were included, with 104 in Group I, 49 in Group II and 5 in Group III. Despite Group III patients presented with only WFNS grade 1 &amp; 2, mortality increased exponentially with age from 9.6% to 12.2% to 40% across 3 sub-groups. There was also a linear increase in average length of stay (LOS) from 21 to 24 days. 81 Group I patients (77.9%) developed complications and 38 patients (77.6%) in Group II. In Group III, 3 patients (60%) developed complications when 2 other patients did not survive. Most common complications were hydrocephalus (46.2%) and hospital acquired infections 36.7%). Conclusions Our study suggests patients with age &amp;gt;80 had less favourable neurological outcomes despite having low grade aSAH at presentation and received similar intervention. Average LOS in hospital also increased with age. Similar complication rates were noticed in all groups. Comparing our data with other neurosurgical units in UK and Ireland will provide further information in managing elderly aSAH patients and facilitate risk stratification when considering those patients for intervention.