Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

Sex differences in outcomes after endovascular treatment in posterior circulation stroke: results from the MR CLEAN Registry.

BACKGROUND: Women with anterior circulation large vessel occlusion (LVO) have been reported to have worse outcomes after endovascular treatment (EVT) than men. Whether these disparities also exist in LVO of the posterior circulation is yet uncertain. We assessed sex differences in clinical, technical, and safety outcomes of EVT in posterior circulation LVO. METHODS: We used data of patients with posterior circulation LVO included in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2018). Primary outcome was the modified Rankin Scale (mRS) score at 90 days assessed with multivariable ordinal regression analysis. Secondary outcomes included favorable functional outcome (mRS ≤3), functional independence (mRS ≤2), death within 90 days, National Institutes of Health Stroke Scale (NIHSS) score 24-48 hours postintervention, complications, successful reperfusion (extended Thrombolysis in Cerebral Ischemia 2B-3), and procedure duration analyzed with multivariable logistic and linear regression analyses. RESULTS: We included 264 patients (42% women). Compared with men, women were older (median age 68 vs 63 years), more often had prestroke disability (mRS ≥1: 37% vs 30%), and received intravenous thrombolytics less often (45% vs 56%). Clinical outcomes were similar between sexes (adjusted (common) OR (aOR) 0.82, 95% CI 0.51 to 1.34; favorable functional outcome 50% vs 43%, aOR 1.31, 95% CI 0.77 to 2.25; death 32% vs 29%, aOR 0.98, 95% CI 0.52 to 1.84). In addition, NIHSS score after 24-48 hours (median 7 vs 9), successful reperfusion (77% vs 73%), and complications did not differ between men and women. CONCLUSIONS: Outcomes in women treated with EVT for posterior circulation LVO were similar compared with men despite less favorable baseline characteristics in women. Therefore men and women may benefit equally from EVT.

Influence of time metrics on the treatment effect of intravenous alteplase prior to endovascular treatment in MR CLEAN-NO IV.

BACKGROUND: We assessed whether the treatment effect of intravenous alteplase (IVT) prior to endovascular treatment (EVT) on functional outcome is modified by time metrics. METHODS: We used data from all patients included in MR CLEAN-NO IV, a randomized trial of IVT followed by EVT versus EVT alone in patients who presented directly to EVT-capable hospitals. The primary outcome was the modified Rankin Scale score at 90 days. We used ordinal regression with a multiplicative interaction term to assess if the effect of IVT is modified by onset-to-randomization (OTR), onset-to-IV-needle (OTN), door-to-groin (DTG) or needle-to-groin (NTG) times. Secondary outcomes included successful reperfusion (extended Thrombolysis In Cerebral Infarction Scale 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: In 539 included patients (266 allocated to IVT+EVT and 273 to EVT alone), median workflow times were OTR: 93 (IQR 71-145) min; OTN: 98 (IQR 75-156) min; DTG: 64 (IQR 51-78) min; and NTG: 28 (IQR 20-41) min. There was a significant association between worse outcomes and longer time intervals for all metrics except NTG. We found no interaction between any of the time metrics and IVT for the effect on functional outcome (p values for interaction: OTR=0.40, OTN=0.39, DTG=0.61, NTG=0.56). We also did not observe any significant interaction for successful reperfusion or sICH. CONCLUSION: In MR CLEAN-NO IV, the effect of IVT prior to EVT was not modified by OTR, OTN, DTG or NTG times. Our results do not support the use of these metrics to guide IVT treatment decisions prior to EVT in comprehensive stroke centres. TRIAL REGISTRATION NUMBER: ISRCTN80619088.

Influence of the interventionist's experience on outcomes of endovascular thrombectomy in acute ischemic stroke: results from the MR CLEAN Registry.

BACKGROUND: The relationship between the interventionist's experience and outcomes of endovascular thrombectomy (EVT) for acute ischemic stroke of the anterior circulation, is unclear. OBJECTIVE: To assess the effect of the interventionist's level of experience on clinical, imaging, and workflow outcomes. Secondly, to determine which of the three experience definitions is most strongly associated with these outcome measures. METHODS: We analysed data from 2700 patients, included in the MR CLEAN Registry. We defined interventionist's experience as the number of procedures performed in the year preceding the intervention (EXPfreq), total number of procedures performed (EXPno), and years of experience (EXPyears). Our outcomes were the baseline-adjusted National Institutes of Health Stroke Scale (NIHSS) score at 24-48 hours post-EVT, recanalization (extended Thrombolysis in Cerebral Infarction (eTICI) score ≥2B), and procedural duration. We used multilevel regression models with interventionists as random intercept. For EXPfreq and EXPno results were expressed per 10 procedures. RESULTS: Increased EXPfreq was associated with lower 24-48 hour NIHSS scores (adjusted (a)ß:-0.46, 95% CI -0.70 to -0.21). EXPno and EXPyears were not associated with short-term neurological outcomes. Increased EXPfreq and EXPno were both associated with recanalization (aOR=1.20, 95% CI 1.11 to 1.31 and aOR=1.08, 95% CI 1.04 to 1.12, respectively), and increased EXPfreq, EXPno, and EXPyears were all associated with shorter procedure times (aß:-3.08, 95% CI-4.32 to -1.84; aß:-1.34, 95% CI-1.84 to -0.85; and aß:-0.79, 95% CI-1.45 to -0.13, respectively). CONCLUSIONS: Higher levels of interventionist's experience are associated with better outcomes after EVT, in particular when experience is defined as the number of patients treated in the preceding year. Every 20 procedures more per year is associated with approximately one NIHSS score point decrease, an increased probability for recanalization (aOR=1.44), and a 6-minute shorter procedure time.

Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Early Thromboembolic Stroke Risk of Postoperative Atrial Fibrillation Following Cardiac Surgery.

OBJECTIVE: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery. DESIGN: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed. PARTICIPANTS: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit. SETTING: Academic tertiary care medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke. CONCLUSIONS: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery.

Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms: An Individual Patient Data Meta-analysis.

BACKGROUND AND OBJECTIVES: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. METHODS: For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. RESULTS: We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40). DISCUSSION: The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account.

Interexaminer Agreement and Reliability of an Internationally Endorsed Screening Framework for Cervical Vascular Risks Following Manual Therapy and Exercise: The Go4Safe Project.

OBJECTIVE: Clinicians are recommended to use the clinical reasoning framework developed by the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) to provide guidance regarding assessment of the cervical spine and potential for cervical artery dysfunction prior to manual therapy and exercise. However, the interexaminer agreement and reliability of this framework is unknown. This study aimed to estimate the interexaminer agreement and reliability of the IFOMPT framework among physical therapists in primary care. METHODS: Ninety-six patients who consulted a physical therapist for neck pain or headache were included in the study. Each patient was tested independently by 2 physical therapists, from a group of 17 physical therapists (10 pairs) across The Netherlands. Patients and examiners were blinded to the test results. The overall interexaminer agreement, specific agreement per risk category (high-, intermediate-, and low-risk), and interexaminer reliability (weighted κ) were calculated. RESULTS: Overall agreement was 71% (specific agreement in high-risk category = 63%; specific agreement in intermediate-risk category = 38%; specific agreement in low-risk category = 84%). Overall reliability was moderate (weighted κ = 0.39; 95% CI = 0.21-0.57) and varied considerably between pairs of physical therapists (κ = 0.14-1.00). CONCLUSION: The IFOMPT framework showed an insufficient interexaminer agreement and fair interexaminer reliability among physical therapists when screening the increased risks for vascular complications following manual therapy and exercise prior to treatment. IMPACT: The IFOMPT framework contributes to the safety of manual therapy and exercise. It is widely adopted in clinical practice and educational programs, but the measurement properties are unknown. This project describes the agreement and reliability of the IFOMPT framework.

Distribution of Cardioembolic Stroke: A Cohort Study.

BACKGROUND: A cardiac origin in ischemic stroke is more frequent than previously assumed, but it is not clear which patients benefit from cardiac work-up if obvious cardiac pathology is absent. We hypothesized that thromboembolic stroke with a cardiac source occurs more frequently in the posterior circulation compared with thromboembolic stroke of another etiology. METHODS: We performed a multicenter observational study in 3,311 consecutive patients with ischemic stroke who were enrolled in an ongoing prospective stroke registry of 8 University hospitals between September 2009 and November 2014 in The Netherlands. In this initiative, the so-called Parelsnoer Institute-Cerebrovascular Accident Study Group, clinical data, imaging, and biomaterials of patients with stroke are prospectively and uniformly collected. We compared the proportions of posterior stroke location in patients with a cardiac stroke source with those with another stroke etiology and calculated risk ratios (RR) with corresponding 95% CI with Poisson regression analyses. To assess which patient or disease characteristics were most strongly associated with a cardiac etiology in patients with ischemic stroke, we performed a stepwise backward regression analysis. RESULTS: For the primary aim, 1,428 patients were eligible for analyses. The proportion of patients with a posterior stroke location among patients with a cardiac origin of their stroke (28%) did not differ statistically significant to those with another origin (25%), age and sex adjusted RR 1.16; 95% CI 0.96-1.41. For the secondary aim, 1,955 patients were eligible for analyses. No recent history of smoking, no hyperlipidemia, coronary artery disease, a higher age, and a higher National Institutes of Health Stroke Scale (NIHSS) score were associated with a cardiac etiology of ischemic stroke. CONCLUSIONS: We could not confirm our hypothesis that thromboembolic stroke localized in the posterior circulation is associated with a cardioembolic source of ischemic stroke, and therefore posterior stroke localization on itself does not necessitate additional cardiac examination. The lack of determinants of atherosclerosis, for example, no recent history of smoking and no hyperlipidemia, coronary artery disease, a higher age, and a higher NIHSS score are stronger risk factors for a cardiac source of ischemic stroke.

Equal performance of aspiration and stent retriever thrombectomy in daily stroke treatment.

BACKGROUND: Mechanical thrombectomy with stent retrievers has proved to be safe and effective in endovascular treatment of acute ischemic stroke. Direct aspiration has shown revascularization rates comparable to those of stent retrievers in the recent ASTER and COMPASS trials. However, the efficacy of aspiration in routine clinical practice has not yet been shown. OBJECTIVE: To show that aspiration has clinical and technical outcomes equal to those of stent retriever thrombectomy in daily clinical practice. METHODS: We analysed data of patients with a large vessel occlusion of the anterior circulation registered in the Dutch MR CLEAN Registry between March 2014 and June 2016. Primary outcome was functional outcome measured with the modified Rankin Scale (mRS) score. Secondary outcomes were reperfusion grade, periprocedural complication rate, and procedure duration. Association of treatment technique with functional outcome was estimated with univariable and multivariable ordinal logistic regression analysis and expressed as a common OR (cOR) for a shift towards better outcome on the mRS. RESULTS: As first-line treatment, 207 of 1175 patients (17.6%) were treated with direct aspiration, and 968 (82.4%) by a stent retriever. We observed no differences in functional outcome (adjusted cOR=1.020 (95% CI 0.68 to 1.52)) and periprocedural complications. Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b) was similar. Duration of the procedure was shorter with aspiration (57 min (IQR 35-73) vs 70 min (IQR 47-95), p<0.0001). CONCLUSION: Direct aspiration shows clinical outcomes equal to those of stent retriever thrombectomy in our large multicenter real-life cohort. We found no difference in complication rates and shorter procedure times for aspiration.

Recurrence Rates After Surgical or Endovascular Treatment of Spinal Dural Arteriovenous Fistulas: A Meta-analysis.

BACKGROUND: There is an increasing tendency to treat spinal dural arteriovenous fistulas (SDAVFs) endovascularly despite the lack of clear evidence favoring embolization over surgery. OBJECTIVE: To compare the initial failure and recurrence rates of primary treatment of SDAVFs by surgery and endovascular techniques. METHODS: A meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was performed. All the English literature from 2004 onward was evaluated. From each article that compared the 2 treatment modalities, the odds ratio (OR) was calculated. Combined ORs were calculated with Review Manager 5.3 of The Cochrane Collaboration. RESULTS: A total of 35 studies harboring 1112 patients were assessed. Initial definitive fistula occlusion was observed in 588 of 609 surgical patients (96.6%; 95% confidence interval [CI], 94.8-97.8) vs 363 of 503 endovascularly treated patients (72.2%; 95% CI, 68.1-75.9; P < .001). The combined OR from 18 studies that assessed both treatment modalities (730 patients) was 6.15 (95% CI, 3.45-11.0) in favor of surgical treatment. Late recurrence (13 studies, 480 patients) revealed an OR of 3.15 (95% CI, 1.66-5.96; P < .001) in favor of surgery. In a subgroup, recurrence was reported in 10 of 22 patients (45%) treated with Onyx vs 8 of 35 (23%) treated with n-butyle-2-cyanoacrylate (OR, 2.51; 95% CI, 0.75-8.37; P = .13). CONCLUSION: Although hampered by inclusion of poor quality studies, this meta-analysis shows a definite advantage of primary surgical treatment of SDAVF over endovascular treatment in initial failure rate and late recurrences. The often-used argument that endovascular techniques have improved and therefore outweigh surgery is not supported by this meta-analysis.

Risk factors for cerebral venous thrombosis and deep venous thrombosis in patients aged between 15 and 50 years.

Cerebral venous thrombosis (CVT) and deep vein thrombosis or pulmonary embolism (DVT/PE) are associated with many risk factors. It is unclear why CVT occurs less often than DVT/PE. Age dependent risk factors may play a role. The aim of our study was to compare risk factors in a uniform age group of CVT and DVT/PE patients aged between 15 and 50 years. Thrombophilic markers and clinical risk factors of 79 CVT patients and 173 DVT/PE patients aged 15-50 years were compared. Multivariable logistic regression analysis was performed to investigate if risk factors were independently associated with CVT or DVT/PE. Cerebral venous thrombosis patients were younger (median age 30 years vs. 42 years; p<0.001) and more often female (82% vs. 52%; p<0.001). There were no differences in thrombophilic markers. Cerebral venous thrombosis was less often associated with trauma, immobilisation or surgery than DVT/PE (6% vs. 21%; adjusted OR 0.29; 95%CI 0.10-0.82). In women, CVT was more frequently associated with oral contraceptive use, pregnancy or puerperium (82% vs. 53%; adjusted OR 2.34; 95%CI 1.03-5.32). This study demonstrated no differences in thrombophilic markers between CVT patients and DVT/PE patients aged between 15 and 50 years, while the frequency of some transient risk factors was different. Cerebral venous thrombosis was relatively more common in women and hormonal factors may predispose to CVT compared to DVT/PE, while trauma, immobilisation and surgery may be less important in the pathophysiology of CVT.

Cigarette smoking and progression in multiple sclerosis.

OBJECTIVE: To investigate the influence of cigarette smoking on progression and disability accumulation in multiple sclerosis (MS). METHODS: Information on past and present smoking of 364 patients with MS was obtained through a structured questionnaire survey. We used Kaplan-Meier analyses and Cox regression models to evaluate the influence of smoking on the development and age at onset of secondary progression, on the age at onset of progression in patients with primary progressive MS, and on the time from disease onset to Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0 in all patients. We also investigated the correlation between smoked pack-years and EDSS scores and the rate of progression as measured with the Multiple Sclerosis Severity Score. RESULTS: We found no significant associations between cigarette smoking and any of the used measures. CONCLUSION: Our data suggest that cigarette smoking has no influence on disease progression or accumulation of disability in multiple sclerosis.

Intravenous alteplase for stroke: beyond the guidelines and in particular clinical situations.

BACKGROUND AND PURPOSE: Because of the risk of hemorrhage, especially in the brain, thrombolytic therapy with intravenous alteplase is restricted by guidelines, and only a small number of selected patients are being treated. Findings from metaanalyses, post hoc analyses of the randomized trials, and postlicensing experience suggest that more subjects, who otherwise have a poor predicted outcome without treatment, might benefit from intravenous alteplase. Summary of Review- There is a strong indication that treatment may still be beneficial beyond 3 hours up until 4.5 hours. The risk of symptomatic intracerebral hemorrhage is not increased in patients aged 80 years or older. Excluding patients with severe stroke or with early ischemic changes in more than one third of the middle cerebral artery territory on baseline CT scan is probably not necessary when treatment is started <3 hours of symptom onset. Patients with minor or improving symptoms can also benefit. Intravenous thrombolysis appears appropriate as first line therapy for posterior circulation stroke. Alteplase can be given to patients with cervical artery dissection, seizure at onset and evidence of acute ischemia on brain imaging, and after carefully weighing risk and benefit in pregnancy and during menstruation. There are anecdotal reports on its use in children, patients with recent myocardial infarction, cardiac embolus, intracranial aneurysm or arteriovenous malformation, prior stroke and recent surgery. There appears to be a substantially increased risk of symptomatic cerebral hemorrhage in hyperglycemic stroke patients. The combined intravenous and intraarterial approach to recanalization appears safe and is currently under investigation in a randomized trial. CONCLUSIONS: This document does not intend to change the guidelines but reviews the literature on the use of intravenous alteplase for stroke beyond guidelines and in particular conditions.