The weekend effect in aneurysmal subarachnoid haemorrhage: a single centre experience and review.

Clinical outcomes for patients admitted to hospital during weekend hours have been reported to be poorer than for those admitted during the week. Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of haemorrhagic stroke, with a mortality rate greater than 30%. A number of studies have reported higher mortality for patients with aSAH who are admitted during weekend hours. This study evaluates the effect of weekend admission on patients in our unit with aSAH in terms of time to treatment, treatment type, rebleeding rates, functional outcome, and mortality. We analysed a retrospective database of all patients admitted to our tertiary referral centre with aneurysmal subarachnoid haemorrhage between February 2016 and February 2020. Chi-square tests and t-tests were used to compare weekday and weekend demographic and clinical variables. Univariate and multivariate logistic regression analyses were performed to assess for any association between admission during weekend hours and increased neurological morbidity (assessed via Glasgow Outcome Scale at 3 months) and mortality. Of the 571 patients included in this study, 191 were admitted during on-call weekend hours. There were no significant differences found in time to treatment, type of treatment, rebleeding rates, neurological morbidity, or mortality rates between patients admitted during the week and those admitted during weekend hours. Weekend admission was not associated with worsened functional outcome or increased mortality in this cohort. These results suggest that provision of 7-day cover by vascular neurosurgeons and interventional neuroradiologists in high-volume centres could mitigate the weekend effect sometimes reported in the aSAH cohort.

Outcomes following poor-grade aneurysmal subarachnoid haemorrhage: a prospective observational study.

BACKGROUND: Up to 35% of aneurysmal subarachnoid haemorrhage (aSAH) cases may present as poor grade, defined as World Federation of Neurosurgical Societies (WFNS) grades IV and V. In this study, we evaluate functional outcomes and prognostic factors. METHODS: This prospective study included all patients referred to a national, centralized neurosurgical service with a diagnosis of poor-grade aSAH between 01/01/2016 and 31/12/2019. Multivariable logistic regression models were used to estimate probability of poor functional outcomes, defined as a Glasgow Outcome Scale (GOS) of 1-3 at 3 months. RESULTS: Two hundred fifty-seven patients were referred, of whom 116/257 (45.1%) underwent treatment of an aneurysm, with 97/116 (84%) treated within 48 h of referral. Median age was 62 years (IQR 51-69) with a female predominance (167/257, 65%). Untreated patients tended to be older; 123/141 (87%) had WFNS V, 60/141 (45%) unreactive pupils and 21/141 (16%) circulatory arrest. Of all referred patients, poor outcome occurred in 169/230 (73.5%). Unreactive pupils or circulatory arrest conferred a universally poor prognosis, with mortality in 55/56 (98%) and 19/19 (100%), respectively. The risk of a poor outcome was 14.1% (95% CI 4.5-23.6) higher in WFNS V compared with WFNS IV. Age was important in patients without circulatory arrest or unreactive pupils, with risk of a poor outcome increasing by 1.8% per year (95% CI 1-2.7). In patients undergoing aneurysm securement, 48/101 (47.5%) had a poor outcome, with age, rebleeding, vasospasm and cerebrospinal fluid (CSF) diversion being important prognosticators. The addition of serum markers did not add significant discrimination beyond the clinical presentation. CONCLUSIONS: The overall outcomes of WFNS IV and V aSAH remain poor, mainly due to the devastating effects of the original haemorrhage. However, in patients selected for aneurysm securement, good outcomes can be achieved in more than half of patients. Age, pre-intervention rebleeding, vasospasm, and CSF diversion are important prognostic factors.

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

BACKGROUND AND PURPOSE: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. METHODS: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. RESULTS: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]). CONCLUSIONS: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

OBJECTIVES: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. MATERIALS AND METHODS: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. RESULTS: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. CONCLUSIONS: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.

OBJECTIVES: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. MATERIALS AND METHODS: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. RESULTS: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. CONCLUSION: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.

Per-Pass Analysis of Thrombus Composition in Patients With Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

Background and Purpose- Mechanical thrombectomy may involve multiple attempts to retrieve the occluding thrombus. This study examined the composition of thrombus fragments retrieved with each pass of a device during the thrombectomy procedure. Second, the per-pass composition was compared with procedural and clinical data including angiographic outcome and stroke etiology. Methods- Thrombi were retrieved from 60 patients with acute ischemic stroke, where thrombus fragments retrieved in each pass were segregated as individual samples and maintained throughout the histological analysis as independent samples. All samples were stained with hematoxylin and eosin and Martius Scarlet Blue. The relative composition of red blood cells, fibrin, and white blood cells in thrombus fragments from each pass was quantified. Results- Over the 60 cases, thrombus material was retrieved in 106 of 138 passes. The number of passes required to complete the cases ranged from 1 to 6 passes. The analysis of thrombus fragments retrieved in each pass provided a greater insight into the thrombectomy procedure progression than the overall thrombus composition; the red blood cell content of thrombus fragments retrieved in passes 1 and 2 was significantly higher than that retrieved in passes 3 to 6. The removal of thrombus material in a total of 1, 2, or 3 passes was associated with the highest percentage of final modified Thrombolysis in Cerebral Infarction score of 2c-3. There was no association between modified Thrombolysis in Cerebral Infarction score and per-pass thrombus composition. Conclusions- The differentiation achieved through the per-pass analysis of acute ischemic stroke thrombi provides a greater insight into the thrombectomy procedure progression than the combined per-case thrombus analysis. Insights gained may be a useful consideration in determining the treatment strategy as a case evolves and may be useful for the development of new devices to increase rates of 1-pass recanalization.

Outcomes of endovascular thrombectomy with and without bridging thrombolysis for acute large vessel occlusion ischaemic stroke.

BACKGROUND: Endovascular thrombectomy (EVT) for management of large vessel occlusion (LVO) acute ischaemic stroke is now current best practice. AIM: To determine if bridging intravenous (i.v.) alteplase therapy confers any clinical benefit. METHODS: A retrospective study of patients treated with EVT for LVO was performed. Outcomes were compared between patients receiving thrombolysis and EVT with EVT alone. Primary end-points were reperfusion rate, 90-day functional outcome and mortality using the modified Rankin Scale (mRS) and symptomatic intracranial haemorrhage (sICH). RESULTS: A total of 355 patients who underwent EVT was included: 210 with thrombolysis (59%) and 145 without (41%). The reperfusion rate was higher in the group receiving i.v. tissue plasminogen activator (tPA) (unadjusted odds ratio (OR) 2.2, 95% confidence interval (CI): 1.29-3.73, P = 0.004), although this effect was attenuated when all variables were considered (adjusted OR (AOR) 1.22, 95% CI: 0.60-2.5, P = 0.580). The percentage achieving functional independence (mRS 0-2) at 90 days was higher in patients who received bridging i.v. tPA (AOR 2.17, 95% CI: 1.06-4.44, P = 0.033). There was no significant difference in major complications, including sICH (AOR 1.4, 95% CI: 0.51-3.83, P = 0.512). There was lower 90-day mortality in the bridging i.v. tPA group (AOR 0.79, 95% CI: 0.36-1.74, P = 0.551). Fewer thrombectomy passes (2 versus 3, P = 0.012) were required to achieve successful reperfusion in the i.v. tPA group. Successful reperfusion (modified thrombolysis in cerebral infarction ≥2b) was the strongest predictor for 90-day functional independence (AOR 10.4, 95% CI:3.6-29.7, P < 0.001). CONCLUSION: Our study supports the current practice of administering i.v. alteplase before endovascular therapy.

White blood cell subtypes and neutrophil extracellular traps content as biomarkers for stroke etiology in acute ischemic stroke clots retrieved by mechanical thrombectomy.

BACKGROUND: Lymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS. METHODS: AIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots. Martius Scarlet Blue stain was used to identify the main histological components of the clots. Immunohistochemical staining was used to identify neutrophils, lymphocytes, macrophages, and NETs patterns. The cellular and histological components were quantified using Orbit Image Analysis software. RESULTS: AT clots were larger, with more red blood cells and fewer WBCs than CE clots. AT clots had more lymphocytes and cryptogenic clots had fewer macrophages than other etiologies. Most significantly, CE clots showed higher expression of neutrophils and extracellular web-like NETs compared to AT and cryptogenic clots. There was also a significantly higher distribution of web-like NETs around the periphery of the CE clots while a mixed distribution was observed in AT clots. CONCLUSION: The difference in neutrophil and NETs expression in clots from different etiologies may provide insight into the mechanism of clot formation.

Standardised aspiration first approach reduces materials used and cost of thrombectomy procedure in anterior circulation large vessel occlusion stoke.

PURPOSE: The aim of this study is to compare the volume of equipment and equipment costs in a cohort of consecutive patients with anterior circulation large vessel occlusion treated with a standardised aspiration first approach to those treated with a stent retriever first approach. METHODS: The equipment used in each case was recorded from a prospectively maintained equipment log. We then compared the volume of equipment used in each group. The cost of this equipment was calculated for each group based on local prices. Estimated equipment costs were then compared. RESULTS: Our patient cohort consisted of 127 consecutive patients who were treated with a non-standardised stent retriever first technique (group A), 127 consecutive patients who underwent a new standardised aspiration first technique (group B), and 126 consecutive patients reflecting more recent practise where an aspiration first approach has been an established practise in our department (group C).Standardised aspiration first approach results in reduced equipment usage in thrombectomy procedures. The total equipment cost per case in the stent retriever first group (group A) was significantly higher at €4726.4 ($4818.3) versus €3093.1 ($3153.2) in the aspiration first group (group B), a reduction of 34.6% and €2798.5 ($2852.9) in the current practise group (group C), a reduction of 40.8%. There was no statistically significant difference in cost between groups B and C (p = 0.57). CONCLUSION: The standardised aspiration first technique utilised a reduced volume of equipment and confers a 40.8% reduced cost per procedure compared to a stent retriever first approach.

The impact of the COVID-19 pandemic on the provision of endovascular thrombectomy for stroke: an Irish perspective.

BACKGROUND: The COVID-19 pandemic produced unprecedented challenges to healthcare systems. These challenges were amplified in the setting of endovascular thrombectomy (EVT) for large vessel occlusion strokes given the time-sensitive nature of the procedure. AIMS: To assess the impact of the COVID-19 pandemic on service provision at the primary endovascular stroke centre in Ireland. METHODS: A retrospective review of the National Thrombectomy Service database was performed. All patients undergoing EVT from 1 January to 31 December inclusive of 2019 to 2021 were included. Patient demographics, functional outcomes and endovascular treatment time metrics were recorded. RESULTS: Data from 2019, 2020 and 2021 were extracted. Three hundred seven thrombectomies were performed in 2019 and 2020; this number increased to 327 in 2021. Median time from arrival to groin puncture for thrombectomy was 64 min in 2019, increasing to 65 min in 2020. In 2021, this decreased to 52 min. Median time taken from groin puncture to first perfusion remained stable from 2019 to 2021 years at 20 min. Total duration of emergency thrombectomies reduced from 32 min in 2019 to 27 min in 2020. This increased to 29 min in 2021. CONCLUSIONS: Despite the myriad of challenges presented by the pandemic, service provision at the primary Irish ESC, and the referring hospitals, has proven to be robust. Procedural time metrics were maintained whilst the expected reduction in number of EVTs performed did not materialise, there actually being a significant increase in number of EVTs performed in the pandemic's second year.

Timing of treatment of aneurysmal subarachnoid haemorrhage: are the goals set in international guidelines achievable?

BACKGROUND AND AIMS: International guidelines emphasise the importance of securing ruptured cerebral aneurysms within 48-72 h of ictus. We assessed the timing of treatment of patients with aneurysmal subarachnoid haemorrhage (aSAH) referred to a national neurosurgical centre. MATERIALS AND METHODS: Analysis of a prospective database of patients with aSAH admitted between 1st of February 2016 and 29th of February 2020 was performed. The timing to treatment was expressed in days and analysed in three ways: ictus to treatment, ictus to referral and referral to treatment. ORs with 95% CI were calculated for aneurysm treatment within 24, 48 and 72 h for good grade (WFSN 1-3) and poor grade (WFNS 4-5) cohorts separately. RESULTS: Of a total of 538 patients with aSAH, the aneurysm was secured in 312 (58%) within 24 h and in 398 (74%) within 48 h of ictus. Securing the aneurysm within 48 h of ictus was achieved in 89% (395/444) of patients who were referred within 24 h of ictus, but in only 3.2% (3/94) who were referred > 24 h after ictus. Poor grade patients (WFNS 4-5) were more likely than good grade patients (WFNS 1-3) to be referred to neurosurgery within 48 h of ictus (OR 22.87, 95% CI 3.14-166.49, p = 0.0020) and for their aneurysm to be secured within 48 h (OR 1.78, 95% CI 1.06-2.98, p = 0.0297) of ictus. Ictus to referral delay was highest in WFNS grade 1 patients. CONCLUSIONS: In centres with 7 day per week provision of interventional neuroradiology and vascular neurosurgery, the majority of patients with aSAH can be treated within the timeframes recommended by international guidelines and this applies to all grades of aSAH. However, delays still occur in a significant proportion of patients and this particularly applies to delays in presentation and diagnosis in good grade patients.