Prehospital computed tomography in a rural district for rapid diagnosis and treatment of stroke.

BACKGROUND: Early diagnosis and triage of patients with ischemic stroke is essential for rapid reperfusion therapy. The prehospital delay may be substantial and patients from rural districts often arrive at their local hospital too late for disability-preventing thrombolytic therapy due to prolonged transport times. METHODS: Hallingdal District Medical Centre (HDMC) is located in a rural area of Norway and is equipped with a computed tomography (CT) scanner. We established emergency pathways of CT imaging and thrombolytic treatment of patients with acute ischemic stroke at HDMC. During office hours these pathways were managed by a radiographer and a general physician supported by videoconference from the Primary Stroke Centre. Outside office hours we remotely controlled the CT exam and supported telestroke guided paramedics handling and examining the patients. With a primary aim of demonstrating the feasibility of this de novo concept we enrolled patients in the period 2017-2021 into a comparative cohort observational study. We compared patients treated at HDMC (the Rural CT group) to patients from two other rural regions in Norway with similar distances to their local hospital but without access to a rural CT scanner (the Reference group). RESULTS: A total of 86 patients were included in the Rural CT group (mean age 74, 52% male, 43% stroke mimics), and 69 patients were included in the Reference group (mean age 70, 42% male, 28% stroke mimics). Median time from onset of symptoms to completed CT examination was 93 min in the Rural CT group as compared to 240 min in the Reference group (p < 0.05). In patients receiving intravenous thrombolysis time from onset of symptoms to treatment was median 124 min in the Rural CT group and 213 min in the Reference group, p < 0.05. The frequency of thrombolysis for ischemic stroke did not significantly differ between the two groups. CONCLUSION: Combining prehospital rural CT examination with telestroke guided diagnosis and thrombolytic treatment by paramedics may facilitate earlier initiation of thrombolysis for patients with ischemic stroke.

Exploring the Impact of Age and Pre-Stroke Modified Rankin Scale in Elderly Thrombectomy: A 15-Year Single-Center Experience.

INTRODUCTION: The selection of endovascular thrombectomy (EVT) for acute ischemic stroke in the elderly remains challenging due to the underrepresentation of these patients in landmark randomized trials. The aim of this study was to assess the association between age and the pre-stroke modified Rankin scale score with functional outcomes after EVT in elderly patients aged ≥80 years. METHODS: We prospectively collected data from consecutive elderly patients who underwent EVT of the anterior or posterior circulation at our institution between 2007 and 2022. Clinical and radiological parameters were analyzed using a fair outcome (mRS ≤3 or retained pre-stroke mRS score of 4) as the primary outcome. RESULTS: In total, 307 elderly patients were included in the analysis. Fair functional outcomes were achieved in 162 (53%) patients. Eighty-four (27.4%) patients were deceased at 3-month follow-up and the mortality rate increased to 37.1% (114 deceased) at 1-year follow-up. The likelihood of achieving a fair functional outcome decreased by 8% for every 1-year age increase (OR 0.81, 95% CI 0.73-0.90). Lower National Institutes of Health Stroke Scale (OR 0.89, 95% CI 0.85-0.93, p < 0.001) and pre-stroke mRS (OR 0.67, 95% CI 0.53-0.84, p < 0.001) were associated with fair outcomes. CONCLUSIONS: EVT in elderly patients with stroke is beneficial in selected cases. Increasing age was associated with an increased risk of an mRS change to 4 or worse and death within 1 year. The pre-stroke mRS may aid clinicians in the selection of elderly patients for EVT.

External validation of clinical risk prediction score for elderly treated with endovascular thrombectomy.

BACKGROUND AND AIM: The thrombectomy in the elderly prediction score (TERPS) for functional outcome after anterior circulation endovascular therapy (EVT) in patients ≥ 80 years was recently developed. The aim of this study was to assess predictors of functional outcome in the elderly and validate the prediction model. METHODS: Consecutive patients treated with EVT from the Oslo Acute Reperfusion Stroke Study were evaluated for inclusion. Clinical and radiological parameters were used to calculate the TERPS, and functional outcome were assessed at 3-month follow-up. RESULTS: Out of 1028 patients who underwent EVT for acute ischemic stroke from January 2017 to July 2022, 218 (21.2%) patients ≥ 80 years with anterior ischemic stroke were included. Fair outcome, defined as modified Rankin scale ≤ 3 (mRS), was achieved in 117 (53.7%). In bivariate analyses, male sex (p 0.035), age (p 0.025), baseline National Institute of Health Stroke Scale (NIHSS, p < 0.001), pre-stroke mRS (p 0.002) and Alberta Stroke Program Early Computed Tomography score (ASPECTS, p 0.001) were associated with fair outcome. Significant predictors for fair outcome in regression analyses were lower pre-stroke mRS, adjusted odd ratio, (aOR) 0.67 (95% CI 0.50-0.91, p 0.01), NIHSS, aOR 0.92 (95% CI 0.87-0.97, p 0.002), and higher ASPECTS, aOR 1.22 (95% CI 1.03-1.44, p 0.023). The area under the curve (AUC) using TERPS was 0.74 (95% CI 0.67-0.80). CONCLUSIONS: The risk prediction score TERPS showed moderate performance in this external validation. Other variables may still be included to improve the model and validation using other cohorts is recommended. TRIAL REGISTRATION: NCT06220981.

Clinical outcome after thrombectomy in patients with MeVO stroke: importance of clinical and technical factors.

BACKGROUND AND AIMS: Whereas high-level evidence has been proven for safety and efficacy of endovascular treatment (EVT) in large vessel occlusion (LVO) stroke, the evidence for EVT in medium vessel occlusion (MeVO) in both sexes and different age groupremains to be answered. The aim of this study was to evaluate the importance of clinical and technical parameters, focusing on sex, age and EVT procedural factors, on functional outcome in primary MeVO (pMeVO) strokes. METHODS: 144 patients with pMeVO in the MCA territory from the Oslo Acute Reperfusion Stroke Study (OSCAR) were included. Clinical and radiological data were collected including 90-day mRS follow-up. RESULTS: Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 123 patients (84%). Good functional outcome (mRS ≤ 2) at 90-day follow-up was achieved in 84 patients (61.8%). Two or more passes with stent retriever was associated with increased risk of SAH, poor mTICI and poor functional outcome. In average, women had 62 min longer ictus to recanalization time compared to men. Age over 80 years was significantly associated with poor outcome and death. CONCLUSION: In pMeVO patients, TICI score and number of passes with stent retriever were the main technical factors predicting mRS ≤ 2. Good clinical outcome occurred almost twice as often in patients under 80 years of age compared to patients over 80 years. Women with MeVO strokes had significant longer time from ictus to recanalization; however, this did not affect the clinical outcome.

Predictors of outcome after endovascular treatment for tandem occlusions: a single center retrospective analysis.

BACKGROUND: The endovascular treatment procedure in tandem occlusions (TO) is complex compared to single occlusion (SO) and optimal management remains uncertain. The aim of this study was to identify clinical and procedural factors that may be associated to efficacy and safety in the management of TO and compare functional outcome in TO and SO stroke patients. METHODS: This is a retrospective single center study of medium (MeVO) and large vessel occlusion (LVO) of the anterior circulation. Clinical, imaging, and interventional data were analyzed to identify predictive factors for symptomatic intracranial hemorrhage (sICH) and functional outcome after endovascular treatment (EVT) in TO. Functional outcome in TO and SO patients was compared. RESULTS: Of 662 anterior circulation stroke patients with MeVO and LVO stroke, 90 (14%) had TO. Stenting was performed in 73 (81%) of TO patients. Stent thromboses occurred in 8 (11%) patients. Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 82 (91%). SICH occurred in seven (8%). The strongest predictors for sICH were diabetes mellitus and number of stent retriever passes. Good functional clinical outcome (mRS ≤ 2) at 90-day follow up was similar in TO and SO patients (58% vs 59% respectively). General anesthesia (GA) was associated with good functional outcome whereas hemorrhage in the infarcted tissue, lower mTICI score and history of smoking were associated with poor outcome. CONCLUSIONS: The risk of sICH was increased in patients with diabetes mellitus and those with extra stent-retriever attempts. Functional clinical outcomes in patients with TO were comparable to patients with SO.

We need mobile stroke units. / Vi trenger slagambulanser.

Mobile stroke units save time from symptom onset to treatment in cases of acute ischaemic stroke, have a sustainable cost-benefit profile and are now recommended in European guidelines. We should investigate the use of mobile stroke units in the pre-hospital healthcare service in Norway as well.

Barriers to and facilitators for making emergency calls - a qualitative interview study of stroke patients and witnesses.

BACKGROUND AND OBJECTIVES: Early access to hospital for diagnosis and treatment is strongly recommended for patients with acute stroke. Unfortunately, prehospital delay frequently occurs. The aim of the current study was to gain in-depth insight into patient experience and behavior in the prehospital phase of a stroke. METHODS: We conducted qualitative interviews with a purposive sample of 11 patients and six witnesses within four weeks post stroke. The interviews were audio recorded, transcribed, and analyzed utilizing Systematic Text Condensation. RESULTS: The material was classified according to two main categories each containing three subgroups. The first category contained the diversity of sudden changes that all participants noticed. The subgroups were confusing functional changes, distinct bodily changes and witnesses' observations of abnormal behavior or signs. The second category was delaying and facilitating factors. To trivialize or deny stroke symptoms, or having a high threshold for contacting emergency services, led to time delay. Factors facilitating early contact were severe stroke symptoms, awareness of the consequences of stroke or a witness standing by when the stroke occurred. CONCLUSIONS: Prehospital delays involved interrelated elements: (1) Difficulties in recognition of a stroke when symptoms were mild, odd and/or puzzling; (2) Recognition of a stroke or need for medical assistance were facilitated by interaction/communication; (3) High threshold for calling emergency medical services, except when symptoms were severe. The findings may be helpful in planning future public stroke campaigns and in education and training programs for health personnel.

Mechanical thrombectomy in acute ischaemic stroke. / Mekanisk trombektomi ved akutt hjerneinfarkt.

Mechanical thrombectomy is now the standard treatment for acute ischaemic stroke with occlusion of a carotid or intercranial artery. With occlusions of this type, thrombolytic treatment often has limited effect. The therapeutic outcome with the use of thrombectomy is time-dependent, and a personalised approach to indication is always necessary. To achieve the best possible results, the main prerequisites are good clinical procedures, an optimal patient pathway, high neuroradiological competence and coordinated, interdisciplinary teams.

Streamlining Acute Stroke Care by Introducing National Institutes of Health Stroke Scale in the Emergency Medical Services: A Prospective Cohort Study.

BACKGROUND: National Institutes of Health Stroke Scale (NIHSS) is the most validated clinical scale for stroke recognition, severity grading, and symptom monitoring in acute care and hospital settings. Numerous modified prehospital stroke scales exist, but these scales contain less clinical information and lack compatibility with in-hospital stroke scales. In this real-life study, we aimed to investigate if NIHSS conducted by paramedics in the field is a feasible and accurate prehospital diagnostic tool. METHODS: This prospective cohort study is part of Treat-NASPP (Treat-Norwegian Acute Stroke Prehospital Project) conducted at a single medical center in Østfold, Norway. Sixty-three paramedics were trained and certified in NIHSS, and the prehospital NIHSS scores were compared with the scores obtained by in-hospital stroke physicians. Interrater agreement was assessed using a Bland-Altman plot with 95% limits of agreement. In secondary analysis, Cohen κ was used for the clinical categories NIHSS score of 0 to 5 and ≥6. As a safety measure, prehospital time was compared between paramedics conducting NIHSS and conventional paramedics. RESULTS: We included 274 patients. The mean difference in NIHSS scores between the paramedics and the stroke physicians was 0.92 with limits of agreement from -5.74 to 7.59. Interrater agreement for the 2 clinical categories was moderate with a κ of 0.58. The prehospital NIHSS scoring was performed mean (SD) 42 (14) minutes earlier than the in-hospital scoring. Prehospital time was not significantly increased in the NIHSS-trained paramedic group compared with conventional paramedics (median [interquartile range] on-scene-time 18 [13-25] minutes versus 16 [11-23] minutes, P=0.064 and onset-to-hospital time 86 [65-128] minutes versus 84 [56-140] minutes, P=0.535). CONCLUSIONS: Paramedics can use NIHSS as an accurate and time efficient prehospital stroke severity quantification tool. Introducing NIHSS in the emergency medical services will enable prehospital evaluation of stroke progression and provide a common language for stroke assessment between paramedics and stroke physicians. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03158259.

Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series.

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1-2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.

Ultraearly thrombolysis by an anesthesiologist in a mobile stroke unit: A prospective, controlled intervention study.

BACKGROUND: Acute stroke treatment in mobile stroke units (MSU) is feasible and reduces time-to-treatment, but the optimal staffing model is unknown. We wanted to explore if integrating thrombolysis of acute ischemic stroke (AIS) in an anesthesiologist-based emergency medical services (EMS) reduces time-to-treatment and is safe. METHODS: A nonrandomized, prospective, controlled intervention study. INCLUSION CRITERIA: age ≥18 years, nonpregnant, stroke symptoms with onset ≤4 h. The MSU staffing is inspired by the Norwegian Helicopter Emergency Medical Services crew with an anesthesiologist, a paramedic-nurse and a paramedic. Controls were included by conventional ambulances in the same catchment area. Primary outcome was onset-to-treatment time. Secondary outcomes were alarm-to-treatment time, thrombolytic rate and functional outcome. Safety outcomes were symptomatic intracranial hemorrhage and mortality. RESULTS: We included 440 patients. MSU median (IQR) onset-to-treatment time was 101 (71-155) minutes versus 118 (90-176) minutes in controls, p = 0.007. MSU median (IQR) alarm-to-treatment time was 53 (44-65) minutes versus 74 (63-95) minutes in controls, p < 0.001. Golden hour treatment was achieved in 15.2% of the MSU patients versus 3.7% in the controls, p = 0.005. The thrombolytic rate was higher in the MSU (81% vs 59%, p = 0.001). MSU patients were more often discharged home (adjusted OR [95% CI]: 2.36 [1.11-5.03]). There were no other significant differences in outcomes. CONCLUSIONS: Integrating thrombolysis of AIS in the anesthesiologist-based EMS reduces time-to-treatment without negatively affecting outcomes. An MSU based on the EMS enables prehospital assessment of acute stroke in addition to other medical and traumatic emergencies and may facilitate future implementation.

Pectin Synthesis and Pollen Tube Growth in Arabidopsis Involves Three GAUT1 Golgi-Anchoring Proteins: GAUT5, GAUT6, and GAUT7.

The major cell wall pectic glycan homogalacturonan (HG) is crucial for plant growth, development, and reproduction. HG synthesis occurs in the Golgi and is catalyzed by members of the galacturonosyltransferase (GAUT) family with GAUT1 being the archetypal and best studied family member. In Arabidopsis suspension culture cells and tobacco leaves, the Golgi localization of Arabidopsis GAUT1 has been shown to require protein-protein interactions with its homolog GAUT7. Here we show that in pollen tubes GAUT5 and GAUT6, homologs of GAUT7, also target GAUT1 to the Golgi apparatus. Pollen tube germination and elongation in double homozygous knock-out mutants (gaut5 gaut6, gaut5 gaut7, and gaut6 gaut7) are moderately impaired, whereas gaut5 -/- gaut6 -/- gaut7 +/- triple mutant is severely impaired and male infertile. Amounts and distributions of methylesterified HG in the pollen tube tip were severely distorted in the double and heterozygous triple mutants. A chimeric protein comprising GAUT1 and a non-cleavable membrane anchor domain was able to partially restore pollen tube germination and elongation and to reverse male sterility in the triple mutant. These results indicate that GAUT5, GAUT6, and GAUT7 are required for synthesis of native HG in growing pollen tubes and have critical roles in pollen tube growth and male fertility in Arabidopsis.

Low prevalence of end plate junction failure in danish patients with lumbar disc herniation.

The present study was undertaken to determine the prevalence of endplate junction failure in a smaller cohort of Danish patients with lumbar disk herniation and compare this to the previously published data from India. Consecutive patients seen in a large regional hospital spine-care unit, with a clinical presentation suggesting a lumbar disk herniation with concomitant radiculopathy and confirmatory recent MRI were included. Additional imaging by CT was performed as part of the study and these were analyzed with specific attention to endplate junction failures. For ethical reasons, the number of participants was kept to a minimum and a total of 26 patients were included. The prevalence (n = 5) of endplate junction failure was found to be statistically significantly lower than that previously reported. Our findings do not echo those previously reported in an Indian population: Endplate junction failure was indeed observed, but at a significantly lower rate. We discuss potential reasons for the difference in findings with due attention to the weaknesses of the current study.

Stroke severity quantification by critical care physicians in a mobile stroke unit.

BACKGROUND: Cerebral revascularization in acute stroke requires robust diagnostic tools close to symptom onset. The quantitative National Institute of Health Stroke Scale (NIHSS) is widely used in-hospital, whereas shorter and less specific stroke scales are used in the prehospital field. This study explored the accuracy and potential clinical benefit of using NIHSS prehospitally. PATIENTS AND METHODS: Thirteen anesthesiologists trained in prehospital critical care enrolled patients with suspected acute stroke in a mobile stroke unit. NIHSS was completed twice in the acute phase: first prehospitally and then by an on-call resident neurologist at the receiving hospital. The agreement between prehospital and in-hospital NIHSS scores was assessed by a Bland-Altman plot, and inter-rater agreement for predefined clinical categories was tested using Cohen's κ. RESULTS: This Norwegian Acute Stroke Prehospital Project study included 40 patients for analyses. The mean numerical difference between prehospital and in-hospital NIHSS scores was 0.85, with corresponding limits of agreement from - 5.94 to 7.64. Inter-rater agreement (κ) for the corresponding clinical categories was 0.38. A prehospital diagnostic workup (NIHSS and computed tomographic examination) was completed in median (quartiles) 10 min (range: 7-14 min). Time between the prehospital and in-hospital NIHSS scores was median (quartiles) 40 min (32-48 min). CONCLUSION: Critical care physicians in a mobile stroke unit may use the NIHSS as a clinical tool in the assessment of patients experiencing acute stroke. The disagreement in NIHSS scores was mainly for very low values and would not have changed the handling of the patients.

Prehospital Advanced Diagnostics and Treatment of Acute Stroke: Protocol for a Controlled Intervention Study.

BACKGROUND: Acute ischemic stroke (AIS) is a medical emergency. The outcome is closely linked to the time elapsing from symptom onset to treatment, and seemingly small delays can mean the difference between full recovery and physical and cognitive dysfunction. Recanalization to allow blood to reenter the affected area is most efficient immediately after symptoms occur, and intravenous thrombolysis must be initiated no later than 4.5 hours after the symptom onset. A liable diagnosis is mandatory to administer the appropriate treatment. Prehospital diagnosis and, in cases where contraindications are ruled out, prehospital initiation of intravenous thrombolysis have been shown to significantly decrease the time from alarm to the treatment. OBJECTIVE: The objective of this paper is to investigate the effectiveness of prehospital thrombolysis as measured by (1) time spent from symptom onset to treatment and (2) the number of patients treated within 4.5 hours. In addition, we want to conduct explorative studies. These will include (1) the use of biomarkers for diagnostic and prognostic use where we will collect blood samples from various time points, including the hyperacute phase and (2) the study of magnetic resonance imaging (MRI) images at day 1 to determine the infarct volume and if the time to thrombolysis has an influence on this. METHODS: This is a prospective controlled intervention study. The intervention will involve a computed tomography (CT) and thrombolysis in a physician-manned ambulance called a mobile stroke unit (MSU). The control will be the conventional pathway where the patient is transported to the hospital for CT, and thrombolysis as per current procedure. RESULTS: Patient inclusion has started and a total of 37 patients are enrolled (control and intervention combined). The estimated time to completed inclusion is 36 months, starting from May 2017. The results of this study will be analyzed and published at the end of the trial. CONCLUSIONS: This trial aims to document the feasibility of saving time for all stroke patients by providing prehospital diagnostics and treatment, as well as transport to appropriate level of care, in a safe environment provided by anesthesiologists trained in prehospital critical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03158259; https://clinicaltrials.gov/show/NCT03158259 (Archived by WebCite at http://www.webcitation.org/6wxNEUMUD).

Interpretation of Brain CT Scans in the Field by Critical Care Physicians in a Mobile Stroke Unit.

BACKGROUND AND PURPOSE: In acute stroke, thromboembolism or spontaneous hemorrhage abruptly reduces blood flow to a part of the brain. To limit necrosis, rapid radiological identification of the pathological mechanism must be conducted to allow the initiation of targeted treatment. The aim of the Norwegian Acute Stroke Prehospital Project is to determine if anesthesiologists, trained in prehospital critical care, may accurately assess cerebral computed tomography (CT) scans in a mobile stroke unit (MSU). METHODS: In this pilot study, 13 anesthesiologists assessed unselected acute stroke patients with a cerebral CT scan in an MSU. The scans were simultaneously available by teleradiology at the receiving hospital and the on-call radiologist. CT scan interpretation was focused on the radiological diagnosis of acute stroke and contraindications for thrombolysis. The aim of this study was to find inter-rater agreement between the pre- and in-hospital radiological assessments. A neuroradiologist evaluated all CT scans retrospectively. Statistical analysis of inter-rater agreement was analyzed with Cohen's kappa. RESULTS: Fifty-one cerebral CT scans from the MSU were included. Inter-rater agreement between prehospital anesthesiologists and the in-hospital on-call radiologists was excellent in finding radiological selection for thrombolysis (kappa .87). Prehospital CT scans were conducted in median 10 minutes (7 and 14 minutes) in the MSU, and median 39 minutes (31 and 48 minutes) before arrival at the receiving hospital. CONCLUSION: This pilot study shows that anesthesiologists trained in prehospital critical care may effectively assess cerebral CT scans in an MSU, and determine if there are radiological contraindications for thrombolysis.

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.

BACKGROUND: Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. METHODS: This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. FINDINGS: Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64-79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2-8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84-1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). INTERPRETATION: Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase. FUNDING: Research Council of Norway.