Neuroradiological features of contrast-induced neurotoxicity: A systematic review and pooled analysis.

BACKGROUND: Contrast-induced neurotoxicity (CIN), is an increasingly recognised complication of endovascular procedures, presenting as a spectrum of neurological symptoms that mimic ischaemic stroke. The diagnosis of CIN remains a clinical challenge, and stereotypical imaging findings are not established. This study was conducted to characterise the neuroimaging findings in patients with CIN, to raise diagnostic awareness and improve decision making. METHODS: We performed a systematic review of PubMed and Embase databases from inception (1946/1947) to June 2023 for reports of CIN following administration of iodinated contrast media. Studies with a final diagnosis of CIN, which provided details of neuroimaging were included. All included cases were pooled and descriptive analysis was conducted. RESULTS: A total of 84 patients were included, with a median age of 64 years. A large proportion of patients had normal imaging (CT 40.8 %, MRI 53.1 %). CT abnormalities included cortical/subarachnoid hyperattenuation (42.1 %), cerebral oedema/sulcal effacement (26.3 %), and loss of grey-white differentiation (7.9 %). Frequently reported MRI abnormalities included brain parenchymal MRI signal change (40.8 %) and cerebral oedema (12.2 %), most commonly observed on FLAIR sequences (26.5 %). Characterisation of imaging findings according to anatomical location and clinical symptoms has been conducted. CONCLUSIONS: Neuroimaging is an essential part of the diagnostic workup of CIN. Analysis of the anatomical location and laterality of imaging abnormalities may suggest relationship between radiological features and actual clinical symptoms, although this remains to be confirmed with dedicated study. Radiological abnormalities, particularly CT, appear to be transient and reversible in most patients.

Risk of adjacent level fracture after percutaneous vertebroplasty and kyphoplasty vs natural history for the management of osteoporotic vertebral compression fractures: a network meta-analysis of randomized controlled trials.

OBJECTIVES: Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. MATERIALS AND METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. RESULTS: Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. CONCLUSION: There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. CLINICAL RELEVANCE STATEMENT: The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. KEY POINTS: RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.

The Clinical and Radiological Outcomes of the Multimodal Use of the Woven EndoBridge Device: A Large Multicenter Study.

BACKGROUND: The Woven EndoBridge (WEB) is a device used for intrasaccular flow diversion, designed for the elimination of wide-necked bifurcation aneurysms from the circulation. In this study, we aim to assess the safety and efficacy of the WEB and its uses in treating aneurysms of different morphologies and locations. METHODS: In a retrospective analysis, we compiled a comprehensive dataset from patients treated with the WEB device across three major Australian neurovascular centers from May 2017 to September 2023. The case series encompassed a spectrum of aneurysm types, including wide-necked bifurcation, sidewall, and irregularly shaped aneurysms, as well as cases previously managed with alternative therapeutic strategies. This study additionally encompasses cases where aneurysms were managed using the WEB device in combination with supplementary endovascular devices. RESULTS: The study included 169 aneurysms in 161 patients. The rate of satisfactory aneurysm occlusion was 85.6%, with 86.7% of patients maintaining good functional status at their most recent follow-up. The procedure exhibited a low mortality rate of 0.6% and a thromboembolic complication rate of 7.1% (n = 12/161). There were no instances of postoperative re-rupture and the procedure-related hemorrhage rate was low (1.2%, n = 2/169), aligning with the literature regarding the safety and efficacy of the WEB device. CONCLUSIONS: Our multicenter trial reinforces the WEB device's role as an effective and safe modality for intracranial aneurysm management, supporting its expanded application beyond wide-necked bifurcation aneurysms. Further prospective studies are required to delineate its evolving role fully.

Preoperative coil localization for spinal surgery is accurate, safe and effective: a single-centre initial experience.

OBJECTIVE AND STUDY DESIGN: This is a retrospective, descriptive study of consecutive patients undergoing novel preoperative pushable coil localization for spinal surgery, in order to evaluate its feasibility, safety and accuracy. METHODS: Consecutive patients who underwent pre-operative coil marking for spinal surgery at our institution from May 2018 to July 2021 were included. Data were collected for coil placement, accuracy, complications and fluoroscopy usage. Patient demographic and relevant perioperative and procedural data were also collected. RESULTS: A total of 34 patients were identified of which 32 (94%) had complete data and imaging at last clinical follow up, with a mean duration of 13.9 months. There were no incorrect level surgeries performed. There were no coil-related complications found in our cohort. CONCLUSIONS: Preoperative coil placement is an accurate, safe and well-tolerated method for level localization in spinal surgeries.

Clinical management of contrast-induced neurotoxicity: a systematic review.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures utilising contrast. It remains poorly understood with heterogenous clinical management strategies. The aim of this review was to identify commonly employed treatments for CIN to enhance clinical decision making. METHODS: A systematic search of Embase (1947-2022) and Medline (1946-2022) was conducted. Articles describing (i) patients with a clinical diagnosis of CIN, (ii) with radiological exclusion of other pathologies, (iii) detailed report of treatments, and (iv) discharge outcomes, were included. Data relating to demographics, procedure, symptoms, treatment and outcomes were extracted. RESULTS: A total of 73 patients were included, with a median age of 64 years. The most common procedures were cerebral angiography (42.5%) and coronary angiography (42.5%), and the median volume of contrast administered was 150 ml. The most common symptoms were cortical blindness (38.4%) and reduced consciousness (28.8%), and 84.9% of patients experienced complete resolution at the time of discharge. Management included intravenous fluids to dilute contrast in the cerebrovasculature (54.8%), corticosteroids to reduce blood-brain barrier damage (47.9%), antiseizure (16.4%) and sedative (16.4%) medications. Mannitol (13.7%) was also utilised to reduce cerebral oedema. Intensive care admission was required for 19.2% of patients. No statistically significant differences were observed between treatment and discharge outcomes. CONCLUSIONS: The clinical management of CIN should be considered on a patient-by-patient basis, but may consist of aggressive fluid therapy alongside corticosteroids, as well as other supportive therapy as required. Further examination of CIN management is required to define best practice.

Pathophysiology of Contrast-Induced Neurotoxicity: A Narrative Review of Possible Mechanisms.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly observed event following the administration of iodinated contrast. It presents as a spectrum of neurological symptoms that closely mimic ischaemic stroke, however, CIN remains a poorly understood clinical phenomenon. An appreciation of the underlying pathophysiological mechanisms is essential to improve clinical understanding and enhance decision-making. METHODS: A broad literature search of Medline (1946 to December 2022) and Embase (1947 to December 2022) was conducted. Articles discussing the pathophysiology of CIN were reviewed. SUMMARY: The pathogenesis of CIN appears to be multifactorial. A key step is likely blood-brain barrier (BBB) breakdown due to factors including ischaemic stroke, uncontrolled hypertension, and possibly contrast agents themselves, among others. This is followed by passage of contrast agents across the BBB, leading to chemotoxic sequelae on neural tissue. KEY MESSAGES: This review provides a clinically oriented review on the pathophysiology of CIN to enhance knowledge and improve decision-making among clinicians.

Current knowledge and perspectives of contrast-induced neurotoxicity: A survey of Australian clinicians.

BACKGROUND: Contrast-induced Neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures. It remains a relatively unexplored clinical entity, and we sought to characterise clinician perspectives towards CIN, as well as identify gaps in knowledge and provide directions for future research. METHODS: An online survey was distributed to members of the Australian and New Zealand Society of Neuroradiology, as well as several Australian tertiary hospitals. Questions related to clinical exposure to CIN, diagnosis, management and pathophysiology were explored. Descriptive analysis was conducted on survey responses, and statistical analysis was performed using Chi-square and Fisher's exact test as appropriate. RESULTS: A total of 95 survey responses were recorded (26.8% response rate). Only 28.4% of respondents were comfortable in diagnosing CIN, and even fewer (24.2%) were comfortable in independently managing CIN patients. Based on clinician opinion, symptoms including impaired consciousness and cortical blindness were thought to be most associated with CIN, whilst the radiological findings of parenchymal oedema and cortical enhancement were considered to be most indicative of CIN. Most clinicians agreed that further investigation is required related to pathophysiology (86.3%), diagnosis (83.2%), and treatment (82.1%). CONCLUSION: CIN is a poorly understood complication following endovascular procedures. Significant gaps in clinical understanding are evident, and further investigation is vital to improve diagnosis and management.

Tranexamic acid as a novel adjunct in the management of vessel perforation complicating Endovascular Clot Retrieval.

AIM: To assess the safety and utility of tranexamic acid (TXA) as an adjunct salvage therapy in iatrogenic vessel perforation complicating endovascular clot retrieval. Iatrogenic vessel perforation and extravasation are known and potentially fatal complications of endovascular clot retrieval (ECR). Various methods of establishing haemostasis post perforation have been reported. TXA is widely utilised intraoperatively to reduce bleeding in various surgical specialities. The use of TXA in endovascular procedures has not been previously described in the literature. METHODS: Retrospective case control study of all cases that underwent ECR. Cases where arterial rupture occurred were identified. Details of management and functional status at 3 months were recorded. Modified Rankin score (mRS) 0-2 was considered a good functional outcome. Comparison of proportions analysis was performed. RESULTS: Of 1378 cases of ECR, rupture complicated 36 (2.6%). TXA was administered in addition to standard care in 11 cases (31%). At 3 months, 4 of 11 cases (36%) where TXA was administered had a good functional outcome compared to 3 of 22 (12%) in the standard care group (P=0.09). Mortality at 3 months occurred in 4 of 11 cases (41.7%) where TXA was administered compared to 16 of 25 (64%) where it was not (P=0.13). CONCLUSION: Tranexamic acid administration in iatrogenic vessel rupture was associated with a lower mortality rate and a larger proportion of patients achieving a good functional outcome at 3 months. This effect trended towards but was not statistically significant. TXA administration was not associated with adverse effects.

Evaluation of techniques to improve a deep learning algorithm for the automatic detection of intracranial haemorrhage on CT head imaging.

BACKGROUND: Deep learning (DL) algorithms are playing an increasing role in automatic medical image analysis. PURPOSE: To evaluate the performance of a DL model for the automatic detection of intracranial haemorrhage and its subtypes on non-contrast CT (NCCT) head studies and to compare the effects of various preprocessing and model design implementations. METHODS: The DL algorithm was trained and externally validated on open-source, multi-centre retrospective data containing radiologist-annotated NCCT head studies. The training dataset was sourced from four research institutions across Canada, the USA and Brazil. The test dataset was sourced from a research centre in India. A convolutional neural network (CNN) was used, with its performance compared against similar models with additional implementations: (1) a recurrent neural network (RNN) attached to the CNN, (2) preprocessed CT image-windowed inputs and (3) preprocessed CT image-concatenated inputs. The area under the receiver operating characteristic curve (AUC-ROC) and microaveraged precision (mAP) score were used to evaluate and compare model performances. RESULTS: The training and test datasets contained 21,744 and 491 NCCT head studies, respectively, with 8,882 (40.8%) and 205 (41.8%) positive for intracranial haemorrhage. Implementation of preprocessing techniques and the CNN-RNN framework increased mAP from 0.77 to 0.93 and increased AUC-ROC [95% confidence intervals] from 0.854 [0.816-0.889] to 0.966 [0.951-0.980] (p-value = 3.91 × 10-12). CONCLUSIONS: The deep learning model accurately detected intracranial haemorrhage and improved in performance following specific implementation techniques, demonstrating clinical potential as a decision support tool and an automated system to improve radiologist workflow efficiency. KEY POINTS: • The deep learning model detected intracranial haemorrhages on computed tomography with high accuracy. • Image preprocessing, such as windowing, plays a large role in improving deep learning model performance. • Implementations which enable an analysis of interslice dependencies can improve deep learning model performance. • Visual saliency maps can facilitate explainable artificial intelligence systems. • Deep learning within a triage system may expedite earlier intracranial haemorrhage detection.

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials.

BACKGROUND AND OBJECTIVES: The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs. METHODS: We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK. RESULTS: Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed. DISCUSSION: Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.

Safety and effectiveness of spinal dural defect repair in the management of superficial siderosis: A systematic review and patient-level analysis.

OBJECTIVE: Superficial siderosis (SS) is a disabling neurodegenerative condition that may be caused by spinal dural defects. Surgical repair is increasingly performed, however clinical outcomes remain unclear. METHODS: A systematic search of PubMed, MEDLINE, and EMBASE was conducted (inception to February 2020). Studies reporting cases of (i) superficial siderosis, (ii) spinal dural defect, (iii) and surgical closure of the defect were included. Demographic characteristics, clinical presentation, operative technique and clinical outcome were extracted for patient-level analysis. RESULTS: A total of 26 publications were included, which reported 38 patients with a median age of 58 years, and a male predominance (78.9 %). Ataxia (85.7 %) and hearing loss (80.0 %) were the most common presenting symptoms. The causative dural defect was most commonly ventral in location (91.7 %) and most commonly identified by CT myelography (48.6 %). Operative technique was highly variable and included primary suture, fibrin glue, dural substitute, or tissue (fat or muscle) graft. Clinical improvement was reported in 21 %, with stabilisation of symptoms in the majority (66 %) and clinical deterioration in 13.2 %. Surgical complications were observed in 7.9 %. CONCLUSION: In patients with superficial siderosis and spinal dural defect, operative closure leads to improvement or stabilisation of symptoms in the vast majority (87%) of patients.

Door-in-door-out times for patients with large vessel occlusion ischaemic stroke being transferred for endovascular thrombectomy: a Victorian state-wide study.

Background: Time to reperfusion is an important predictor of outcome in ischaemic stroke from large vessel occlusion (LVO). For patients requiring endovascular thrombectomy (EVT), the transfer times from peripheral hospitals in metropolitan and regional Victoria, Australia to comprehensive stroke centres (CSCs) have not been studied. Aims: To determine transfer and journey times for patients with LVO stroke being transferred for consideration of EVT. Methods: All patients transferred for consideration of EVT to three Victorian CSCs from January 2017 to December 2018 were included. Travel times were obtained from records matched to Ambulance Victoria and the referring centre via Victorian Stroke Telemedicine or hospital medical records. Metrics of interest included door-in-door-out time (DIDO), inbound journey time and outbound journey time. Results: Data for 455 transferred patients were obtained, of which 395 (86.8%) underwent EVT. The median DIDO was 107 min (IQR 84-145) for metropolitan sites and 132 min (IQR 108-167) for regional sites. At metropolitan referring hospitals, faster DIDO was associated with use of the same ambulance crew to transport between hospitals (75 (63-90) vs 124 (99-156) min, p<0.001) and the administration of thrombolysis prior to transfer (101 (79-133) vs 115 (91-155) min, p<0.001). At regional centres, DIDO was consistently longer when patients were transported by air (160 (127-195) vs 116 (100-144) min, p<0.001). The overall door-to-door time by air was shorter than by road for sites located more than 250 km away from the CSC. Conclusion: Transfer times differ significantly for regional and metropolitan patients. A state-wide database to prospectively collect data on all interhospital transfers for EVT would be helpful for future study of optimal transport mode at regional sites and benchmarking of DIDO across the state.

Coccygeoplasty: preliminary experience with this new alternative treatment of refractory coccydynia in patients with coccyx hypermobility.

BACKGROUND: Coccydynia has many causes, including fracture, subluxation, and hypermobility of sacrococcygeal segments. Existing treatments are limited in their effectiveness. Coccygeoplasty (CP) is a relatively new, minimally invasive treatment that appears to address this difficult clinical challenge. OBJECTIVE: To describe clinical results at the time of the procedure and at 3- and 12-months' follow-up of patients with coccydynia related to subluxation and coccyx hypermobility treated with the CP technique. Additionally, to determine if there is any correlation between the final imaging and clinical results at 3- and 12-months' follow-up. METHODS: A prospectively maintained database was used, and all patients who underwent CP for chronic coccydynia between January 2005 and October 2018 were retrospectively reviewed. All the patients had painful hypermobility (greater than 25°) with anterior flexion confirmed on radiological imaging. Alternative causes of coccydynia were excluded using CT and MRI. Procedures were performed under local anesthesia with combined fluoroscopic and CT guidance. Clinical follow-up was performed at two time points: 3 and 12 months after treatment using the Visual Analogue Scale (VAS). RESULTS: Twelve patients were treated in a single center. No procedural complications occurred. At 3- and 12-months' follow-up, the majority (75%) of patients had significantly lower VAS scores than at baseline, with mean changes of 3.5 and 4.9, respectively. There was no pain recurrence at 12 months and just one patient had no improvement of the pain. Follow-up CT images confirmed fixation of the sacrococcygeal bone segments in nine patients; however, no correlation was found between final imaging results and clinical outcome (p=0.1). CONCLUSIONS: Patients with refractory painful coccyx subluxation and hypermobility undergoing CP have a favorable clinical response at 3- and 12-months' follow-up. Further studies are required to validate this technique and to identify predictors of treatment response. Coccygeoplasty may be considered a reasonable alternative to coccygectomy.

Is sex a predictor for delayed cerebral ischaemia (DCI) and hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH)? A systematic review and meta-analysis.

OBJECTIVES: DCI and hydrocephalus are the most common complications that predict poor outcomes after aSAH. The relationship between sex, DCI and hydrocephalus are not well established; thus, we aimed to examine sex differences in DCI and hydrocephalus following aSAH in a systematic review and meta-analysis. METHODS: A systematic search was conducted using the PubMed, Scopus and Medline databases from inception to August 2022 to identify cohort, case control, case series and clinical studies reporting sex and DCI, acute and chronic shunt-dependent hydrocephalus (SDHC). Random-effects meta-analysis was used to pool estimates for available studies. RESULTS: There were 56 studies with crude estimates for DCI and meta-analysis showed that women had a greater risk for DCI than men (OR 1.24, 95% CI 1.11-1.39). The meta-analysis for adjusted estimates for 9 studies also showed an association between sex and DCI (OR 1.61, 95% CI 1.27-2.05). For acute hydrocephalus, only 9 studies were included, and meta-analysis of unadjusted estimates showed no association with sex (OR 0.95, 95%CI 0.78-1.16). For SDHC, a meta-analysis of crude estimates from 53 studies showed that women had a somewhat greater risk of developing chronic hydrocephalus compared to men (OR 1.14, 95% CI 0.99-1.31). In meta-analysis for adjusted estimates from 5 studies, no association of sex with SDHC was observed (OR 0.87, 95% CI 0.57-1.33). CONCLUSIONS: Female sex is associated with the development of DCI; however, an association between sex and hydrocephalus was not detected. Strategies to target females to reduce the development of DCI may decrease overall morbidity and mortality after aSAH.

Sustainability in interventional radiology: are we doing enough to save the environment?

BACKGROUND: Healthcare waste contributes substantially to the world's carbon footprint. Our aims are to review the current knowledge of Interventional Radiology (IR) waste generation and ways of reducing waste in practice, to quantify the environmental and financial impact of waste generated and address green initiatives to improve IR waste management. METHODS: A systematic literature search was conducted in July 2022 using the Medline and Embase literature databases. The scope of the search included the field of IR as well as operating theatre literature, where relevant to IR practice. RESULTS: One-hundred articles were reviewed and 68 studies met the inclusion criteria. Greening initiatives include reducing, reusing and recycling waste, as well as strict waste segregation. Interventional radiologists can engage with suppliers to reformulate procedure packs to minimize unnecessary items and packaging. Opened but unused equipment can be prevented if there is better communication within the team and increased staff awareness of wasted equipment cost. Incentives to use soon-to-expire equipment can be offered. Power consumption can be reduced by powering down operating room lights and workstations when not in use, changing to Light Emitting Diode (LED) and motion sensor lightings. Surgical hand wash can be replaced with alcohol-based hand rubs to reduce water usage. Common barriers to improving waste management include the lack of leadership, misconceptions regarding infectious risk, lack of data, concerns about increased workload, negative staff attitudes and resistance to change. Education remains a top priority to engage all staff in sustainable healthcare practices. CONCLUSION: Interventional radiologists have a crucial role to play in improving healthcare sustainability. By implementing small, iterative changes to our practice, financial savings, greater efficiency and improved environmental sustainability can be achieved.

Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial.

BACKGROUND: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). METHODS: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. FINDINGS: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84). INTERPRETATION: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. FUNDING: Australian National Health and Medical Research Council and Stryker USA.

Barriers and facilitators to more timely treatment of aneurysmal subarachnoid haemorrhage across two tertiary referral centres in Australia: A thematic analysis.

BACKGROUND: Delays in treatment of aSAH appear to be common but the causes are not well understood. We explored facilitators and barriers to timely treatment of aSAH. METHODS: We used a multiple case study with cases of aSAH surviving> 1 day identified prospectively. We conducted semi-structured interviews with the patient, their next-of-kin and health professionals involved in the case. Within-case analysis identified barriers and facilitators in 4 phases (pre-hospital, presentation, transfer, in-hospital) followed by thematic analysis across cases using a case-study matrix. RESULTS: Twenty-seven cases with 90 interviewees yielded five themes related to facilitators or barriers of timely treatment. "Early recognition" led to urgent response. "Accessibility to health care" depended on patient's location, transport, and environmental conditions. Good "Coordination" between and within health services was a key facilitator. "Complexity" of patient's condition affected time to treatment in multiple time periods. "Availability of resources" was identified most frequently during the diagnostic and treatment phases as both barrier and facilitator. CONCLUSIONS: The identified themes may be modifiable at the patient/health professional level and health system level and may improve timely treatment of aSAH through targeted interventions, subsequently contributing to improve morbidity and mortality of patients with aSAH.

The Woven EndoBridge Device for the Treatment of Intracranial Aneurysms: Initial Clinical Experience within an Australian Population.

PURPOSE: Advances in endovascular technology have expanded the treatment options for intracranial aneurysms. Intrasaccular flow diversion is a relatively new technique that aims to disrupt blood inflow at the neck of the aneurysm, hence promoting intrasaccular thrombosis. The Woven EndoBridge device (WEB; MicroVention, Aliso Viejo, CA, USA) is an US Food and Drug Administration approved intrasaccular flow diverter for wide-necked aneurysms. We report the early interim clinical and radiological outcomes of patients with both ruptured and unruptured intracranial aneurysms (IAs) treated using the WEB device in an Australian population. MATERIALS AND METHODS: A retrospective analysis was done of patients with ruptured or unruptured IAs who received treatment with WEB across 5 Australian neuroendovascular referral centers between May 2017 and November 2020. Angiographic occlusion was assessed with time-of-flight magnetic resonance angiography. Complications were recorded and clinical outcomes were assessed using the modified Rankin scale at follow-up. RESULTS: In total, 66 aneurysms were treated in 63 patients, with successful deployment of the WEB device in 98.5% (n=65). Eighteen (26.9%) ruptured aneurysms were included. Failure of deployment occurred in a single case. Adjunct coiling and/or stenting was performed in 20.9% (n=14) cases. Sixty-two patients with 65 aneurysms using a WEB device were followed up (mean=9.1 months), and 89.4% of these had complete aneurysm occlusion while 1.5% remained patent. Functional independence was achieved in 93.5% of cases. CONCLUSION: Early results following the use of WEB devices in Australia demonstrate safety and adequate aneurysm occlusion comparable to international literature.

Association of Onset-to-Treatment Time With Discharge Destination, Mortality, and Complications Among Patients With Aneurysmal Subarachnoid Hemorrhage.

Importance: Rapid access to specialized care is recommended to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH), but understanding of the optimal onset-to-treatment time for aneurysmal SAH is limited. Objective: To assess the optimal onset-to-treatment time for aneurysmal SAH that maximized patient outcomes after surgery. Design, Setting, and Participants: This cohort study assessed 575 retrospectively identified cases of first-ever aneurysmal SAH occurring within the referral networks of 2 major tertiary Australian hospitals from January 1, 2010, to December 31, 2016. Individual factors, prehospital factors, and hospital factors were extracted from the digital medical records of eligible cases. Data analysis was performed from March 1, 2020, to August 31, 2021. Exposures: Main exposure was onset-to-treatment time (time between symptom onset and aneurysm surgical treatment in hours) derived from medical records. Main Outcomes and Measures: Clinical characteristics, complications, and discharge destination were extracted from medical records and 12-month survival obtained from data linkage. The associations of onset-to-treatment time (in hours) with (1) discharge destination of survivors (home vs rehabilitation), (2) 12-month survival, and (3) neurologic complications (rebleed, delayed cerebral ischemia, meningitis, seizure, hydrocephalus, and delayed cerebral injury) were investigated using natural cubic splines in multivariable Cox proportional hazards and logistic regression models. Results: Of the 575 patients with aneurysmal SAH, 482 patients (mean [SD] age, 55.0 [14.5] years; 337 [69.9%] female) who received endovascular coiling or neurosurgical clipping were studied. A nonlinear association of treatment delay was found with the odds of being discharged home vs rehabilitation (effective df = 3.83 in the generalized additive model, χ2 test P = .002 for the 4-df cubic spline), with a similar nonlinear association remaining significant after adjustment for sex, treatment modality, severity, Charlson Comorbidity Index, history of hypertension, and hospital transfer (likelihood ratio test: df = 3, deviance = 9.57, χ2 test P = .02). Both unadjusted and adjusted cox regression models showed a nonlinear association between time to treatment and 12-month mortality with the lowest hazard of death with receipt of treatment at 12.5 hours after symptom onset, although the nonlinear term became nonsignificant upon adjustment. The odds of being discharged home were higher with treatment before 20 hours after onset, with the probability of being discharged home compared with rehabilitation or other hospital increased by approximately 10% when treatment was received within the first 12.5 hours after symptom onset and increased by an additional 5% from 12.5 to 20 hours. Time to treatment was not associated with any complications. Conclusions and Relevance: This cohort study found evidence that more favorable outcomes (discharge home and survival at 12 months) were achieved when surgical treatment occurred at approximately 12.5 hours. These findings provide more clarity around optimal timelines of treatment with people with aneurysmal SAH; however, additional studies are needed to confirm the findings.