Prolonged and Repeated Microemboli Detection in Acute Ischemic Stroke - The Norwegian Microemboli in Acute Stroke Study (NOR-MASS).

OBJECTIVES: Cerebral microemboli can be detected by transcranial Doppler monitoring (TCDM) and may elucidate stroke etiology, the effect of preventive therapy, and the risk of stroke recurrence. Microemboli detection is usually performed for up to 60 minutes, but due to temporal variability, microembolization may be missed if the monitoring time is too short. We aimed to assess the time course of microembolization in acute ischemic stroke and explore the utility of prolonged and repeated microemboli detection. MATERIALS AND METHODS: Patients with suspected ischemic stroke and symptom onset within 24 hours were examined with bilateral, stationary TCDM for one hour followed by unilateral, ambulatory TCDM for two hours. Unilateral TCDM was repeated for the following two days and after three months. RESULTS: We included 47 patients, of which 41 had ischemic stroke, five had transient ischemic attack, and one had amaurosis fugax. Microemboli were detected in 60% of patients. The occurrence was highest within 24 hours after onset and significantly lower at three months. Prolonged and repeated microemboli detection yielded only one additional microemboli-positive patient. Hence, patients who initially were microemboli negative tended to remain negative. We could not demonstrate an association between microemboli occurrence and clinical outcome or stroke recurrence. CONCLUSIONS: Microembolic signals are frequent within 24 hours after ischemic stroke onset, but prolonged and repeated microemboli detection did not increase the yield of MES positive patients. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT03543319.

Characteristics and predictors of stroke mimics in young patients in the norwegian tenecteplase stroke trial (NOR-TEST).

BACKGROUND: Several studies have shown that stroke mimics occur more often among young patients. Our aims were to identify the common mimics in young patients under the age of 60 years who received thrombolysis, to analyze the risk of hemorrhage after treatment with thrombolysis, and to identify risk factors and clinical parameters that might identify mimics in this group. METHODS: Norwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with acute ischemic stroke. Patients diagnosed with either acute cerebral ischemia or transient ischemic attack were categorized as stroke group, and patients with any diagnosis other than ischemic stroke or transient ischemic attack as mimics group. Patients were grouped post-hoc into young (< 60 years) and old (≥ 60 years). Logistic regression analyses were performed with mimics vs. stroke as dependent variable to identify predictors of mimics. RESULTS: Of the 1091 patients included in the trial, 211 patients (19.3%) were under the age of 60 years. Out of the 1091 patients, 434 (39.8%) were female, median age 77 years (18-99 years), and median NIHSS was 4. Sixty-nine patients (32.7%) out of the 211 patients under the age of 60 were diagnosed as mimic. Mimics were significantly more frequent among the young (OR = 3.3, 32.7% vs. 12.8%, p = < 0.001). The most frequent mimics diagnoses among patients under 60 years of age were migraine (11.8%), no definite diagnosis (11.4%) and peripheral vertigo (3.3%). Mimics were independently associated with age < 50 years (OR = 4.97, p = < 0.001), not currently working/studying (OR = 3.38, p = 0.002) and not having aphasia on admission (OR = 2.95, p = 0.025). None of the mimics under the age of 60 years had symptomatic or asymptomatic intracerebral hemorrhage as a complication to thrombolysis. CONCLUSION: We found significantly more mimics in the young, of which migraine was the most predominant diagnosis. Thrombolysis with alteplase or tenecteplase did not cause ICH in any mimics under 60 years.

Tenecteplase, 0.4 mg/kg, in Moderate and Severe Acute Ischemic Stroke: A Pooled Analysis of NOR-TEST and NOR-TEST 2A.

Background The optimal dose of tenecteplase in acute ischemic stroke remains to be defined. We present a pooled analysis of the 2 NOR-TESTs (Norwegian Tenecteplase Stroke Trials) exploring the efficacy and safety of tenecteplase, 0.4 mg/kg. Methods and Results We retrospectively reviewed 2 PROBE (Prospective Randomized Open, Blinded End-point) trials, NOR-TEST and NOR-TEST 2A. Patients were randomized to either tenecteplase, 0.4 mg/kg, or alteplase, 0.9 mg/kg. The primary end point was favorable functional outcome at 3 months (modified Rankin Scale score, 0-1) or return to baseline if prestroke modified Rankin Scale score was 2. Secondary end points included favorable functional and clinical outcome and safety data. The pooled analysis includes patients with National Institutes of Health Stroke Scale score ≥6 from both trials and an additional post hoc analysis of patients with National Institutes of Health Stroke Scale score ≤5 from NOR-TEST. The per-protocol analysis contains 483 patients, of whom 235 were assigned to tenecteplase and 248 were assigned to alteplase. In per-protocol analysis, functional outcome was better in the alteplase arm with cutoff modified Rankin Scale score of 2 (odds ratio [OR], 0.52 [95% CI, 0.33-0.80]; P=0.003) and expressed by ordinal shift analysis (OR, 1.64 [95% CI, 1.17-2.28]; P=0.004). Mortality at 3 months was higher in the tenecteplase arm (OR, 2.48 [95% CI, 1.20-5.10]; P=0.01). Mortality and intracranial hemorrhage rates were higher in the severe stroke group randomized to tenecteplase, whereas these rates were similar for alteplase and tenecteplase in moderate and mild stroke. Conclusions Tenecteplase, 0.4 mg/kg, is unsafe in moderate and severe stroke, and the risk of death and intracranial hemorrhage probably increases with stroke severity. A lower tenecteplase dose should be tested in future trials. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01949948, NCT03854500.

Comparison of diffusion weighted imaging b0 with T2*-weighted gradient echo or susceptibility weighted imaging for intracranial hemorrhage detection after reperfusion therapy for ischemic stroke.

PURPOSE: Diffusion-weighted imaging (DWI) b0 may be able to substitute T2*-weighted gradient echo (GRE) or susceptibility-weighted imaging (SWI) in case of comparable detection of intracranial hemorrhage (ICH), thereby reducing MRI examination time. We evaluated the diagnostic accuracy of DWI b0 compared to T2*GRE or SWI for detection of ICH after reperfusion therapy for ischemic stroke. METHODS: We pooled 300 follow-up MRI scans acquired within 1 week after reperfusion therapy. Six neuroradiologists each rated DWI images (b0 and b1000; b0 as index test) of 100 patients and, after a minimum of 4 weeks, T2*GRE or SWI images (reference standard) paired with DWI images of the same patients. Readers assessed the presence of ICH (yes/no) and type of ICH according to the Heidelberg Bleeding Classification. We determined the sensitivity and specificity of DWI b0 for detection of any ICH, and the sensitivity for detection of hemorrhagic infarction (HI1 & HI2) and parenchymal hematoma (PH1 & PH2). RESULTS: We analyzed 277 scans of ischemic stroke patients with complete image series and sufficient image quality (median age 65 years [interquartile range, 54-75], 158 [57%] men). For detection of any ICH on DWI b0, the sensitivity was 62% (95% CI: 50-76) and specificity 96% (95% CI: 93-99). The sensitivity of DWI b0 was 52% (95% CI: 28-68) for detection of hemorrhagic infarction and 84% (95% CI: 70-92) for parenchymal hematoma. CONCLUSION: DWI b0 is inferior for detection of ICH compared to T2*GRE/SWI, especially for smaller and more subtle hemorrhages. Follow-up MRI protocols should include T2*GRE/SWI for detection of ICH after reperfusion therapy.

Interobserver Agreement on Intracranial Hemorrhage on Magnetic Resonance Imaging in Patients With Ischemic Stroke.

BACKGROUND: The Heidelberg Bleeding Classification, developed for computed tomography, is also frequently used to classify intracranial hemorrhage (ICH) on magnetic resonance imaging. Additionally, the presence of any ICH is frequently used as (safety) outcome measure in clinical stroke trials that evaluate acute interventions. We assessed the interobserver agreement on the presence of any ICH and the type of ICH according to the Heidelberg Bleeding Classification on magnetic resonance imaging in patients treated with reperfusion therapy. METHODS: We used 300 magnetic resonance imaging scans including susceptibility-weighted imaging or T2*-weighted gradient echo imaging of ischemic stroke patients within 1 week after reperfusion therapy. Six observers, blinded to clinical characteristics except for suspected location of the infarction, independently rated ICH according to the Heidelberg Bleeding Classification in random pairs. Percent agreement and Cohen's kappa (κ) were estimated for the presence of any ICH (yes/no), and for agreement on the Heidelberg Bleeding Classification class 1 and 2. For the Heidelberg Bleeding Classification class 1 and 2, weighted κ was estimated to take the degree of disagreement into account. RESULTS: In 297 of 300 scans, the quality of scans was sufficient to score ICH. Observers agreed on the presence or absence of any ICH in 264 of 297 scans (88.9%; κ 0.78 [95% CI, 0.71-0.85]). There was agreement on the Heidelberg Bleeding Classification class 1 and 2 and no ICH in class 1 and 2 in 226 of 297 scans (76.1%; κ 0.63 [95% CI, 0.56-0.69]; weighted κ 0.90 [95% CI, 0.87-0.93]). CONCLUSIONS: The presence of any ICH can be reliably scored on magnetic resonance imaging and can, therefore, be used as (safety) outcome measure in clinical stroke trials that evaluate acute interventions. Agreement of ICH types according to the Heidelberg Bleeding Classification is substantial and disagreements are small.

Vascular risk factors and staging of atherosclerosis in patients and controls: The Norwegian Stroke in the Young Study.

Objectives: We studied the prevalence of vascular risk factors (RFs) among 385 ischaemic stroke patients ⩽60 years and 260 controls, and their association with atherosclerosis in seven vascular areas. Methods: History of cardiovascular events (CVE), hypertension, diabetes mellitus (DM), dyslipidaemia, pack-years of smoking (PYS), alcohol, and physical inactivity were noted. Blood pressure, body mass index (BMI), waist-hip ratio (WHR), lipid profile, epicardial adipose tissue (EAT), visceral abdominal adipose tissue (VAT), and subcutaneous abdominal adipose tissue were measured. Numeric staging of atherosclerosis was done by standardized examination of seven vascular areas by right and left carotid and femoral intima-media thickness, electrocardiogram, abdominal aorta plaques, and the ankle-arm index. All results were age and sex-adjusted. Poisson regression analysis was applied. Results: At age ⩽49 years at least one RF was present in 95.6% patients versus 90.0% controls. Compared to controls, male patients and middle-aged female patients showed no significant differences. Young female patients compared to young female controls had a higher burden of RFs (94.3% vs 88.6%, p = 0.049). Poisson regression analysis combined for patients and controls, adjusted for age and sex, showed numeric staging of atherosclerosis associated with age, prior CVE, hypertension, DM, dyslipidaemia, PYS, alcohol, BMI, WHR, EAT, VAT, and an increased number of risk factors. Adjusted for all risk factors, numeric staging of atherosclerosis was associated with increasing age, hypertension, DM, PYS, and BMI. Conclusion: Vascular risk factors are highly prevalent in young- and middle-aged patients and controls, and are predictors of established atherosclerosis at study inclusion. Focus on main modifiable vascular RFs in primary prevention, and early and aggressive secondary treatment of patients are necessary to reduce further progression of atherosclerosis.

Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial.

BACKGROUND: Tenecteplase is a modified tissue plasminogen activator with pharmacological and practical advantages over alteplase-which is currently the only approved thrombolytic drug for ischaemic stroke. The NOR-TEST trial showed that 0·4 mg/kg tenecteplase had an efficacy and safety profile similar to that of a standard dose (0·9 mg/kg) of alteplase, albeit in a patient population with a high prevalence of minor stroke. The aim of NOR-TEST 2 was to establish the non-inferiority of tenecteplase 0·4 mg/kg to alteplase 0·9 mg/kg for patients with moderate or severe ischaemic stroke. METHODS: This phase 3, randomised, open-label, blinded endpoint, non-inferiority trial was performed at 11 hospitals with stroke units in Norway. Patients with suspected acute ischaemic stroke with a National Institutes of Health Stroke Scale score of 6 or more who were eligible for thrombolysis and admitted within 4·5 h of symptom onset were consecutively included. Random assignment, done by a computer with a block size of 4 and with allocations placed into opaque envelopes to be opened consecutively, was 1:1 between intravenous tenecteplase (0·4 mg/kg) or standard dose alteplase (0·9 mg/kg). Doctors and nurses providing acute care were not masked to treatment, but primary outcome assessment at 3 months was masked. The primary outcome was favourable functional outcome defined as a modified Rankin Scale score of 0-1 at 3 months, assessed in the modified intention-to-treat analysis (excluding patients who did not qualify for thrombolysis after randomisation or who withdrew informed consent). The non-inferiority margin was 3%. This trial (NOR-TEST 2) is registered with EudraCT (number 2018-003090-95) and ClinicalTrials.gov (NCT03854500). The trial was stopped early for safety reasons and is designated part A for analysis. Part B is ongoing with a lower dose of tenecteplase (0·25 mg/kg). FINDINGS: Between Oct 28, 2019, and Sept 26, 2021, 216 patients were enrolled. Patient enrolment was stopped after a per-protocol safety review showed an imbalance in the rates of symptomatic intracranial haemorrhage between the treatment groups, which surpassed the prespecified criteria for stopping the trial. Of 204 patients entering the modified intention-to-treat analysis, 100 were randomly allocated tenecteplase and 104 were allocated alteplase. All patients were followed up within 14 days of the end of the 3-months' follow-up period. A favourable functional outcome was reported less frequently in patients receiving tenecteplase (31 [32%] of 96 patients) compared with alteplase (52 [51%] of 101 patients; unadjusted OR 0·45 [95% CI 0·25-0·80]; p=0·0064). Any intracranial haemorrhage was significantly more frequent with tenecteplase (21 [21%] of 100 patients) than with alteplase (seven [7%] of 104 patients; unadjusted OR 3·68 [95% CI 1·49-9·11]; p=0·0031). Mortality at 3 months was also significantly higher with tenecteplase (15 [16%] of 96 patients) than with alteplase (five [5%] of 101 patients; unadjusted OR 3·56 [95% CI 1·24-10·21]; p=0·013). Numerically more cases of symptomatic intracranial haemorrhage were reported with tenecteplase (six [6%] of 100 patients) than with alteplase (one [1%] of 104 patients; unadjusted OR 6·57 [95% CI 0·78-55·62]; p=0·061). INTERPRETATION: In this prematurely terminated study (terminated to fulfil the prespecified safety criteria), tenecteplase at a dose of 0·4 mg/kg yielded worse safety and functional outcomes compared with alteplase. Our study consequently could not show that 0·4 mg/kg tenecteplase is non-inferior to alteplase in moderate and severe ischaemic stroke. Future stroke trials should assess a lower dose of tenecteplase versus alteplase in patients with moderate or severe stroke. FUNDING: The Norwegian National Programme for Clinical Therapy Research.

Sex differences in the Norwegian Tenecteplase Trial (NOR-TEST).

BACKGROUND AND PURPOSE: Sex differences in acute ischemic stroke is of increasing interest in the era of precision medicine. We aimed to explore sex disparities in baseline characteristics, management and outcomes in patients treated with intravenous thrombolysis included in the Norwegian Tenecteplase trial (NOR-TEST). METHODS: NOR-TEST was an open-label, randomized, blinded endpoint trial, performed from 2012 to 2016, comparing treatment with tenecteplase to treatment with alteplase within 4.5 h after acute ischemic stroke symptom onset. Sex differences at baseline, treatment and outcomes were compared using multivariable logistic regression models. Heterogeneity in treatment was evaluated by including an interaction term in the model. RESULTS: Of 1100 patients enrolled, 40% were women, and in patients aged >80 years, the proportion of women was greater than men (19% vs. 14%; p = 0.02). Women had a lower burden of cardiovascular risk factors, such as diabetes mellitus (11% vs. 15%; p = 0.05) and a higher mean high-density lipoprotein cholesterol level (1.7 ± 0.6 mmol/L vs. 1.3 ± 0.4 mmol/L; p < 0.001), and a higher proportion of women had never smoked (45% vs. 33%; p < 0.001) compared with men. While there was no sex difference in time from onset of symptoms to admission, door to needle time or in-hospital workup, women were admitted with more severe stroke (National Institutes of Health Stroke Scale [NIHSS] score 6.2 ± 5.6 vs. 5.3 ± 5.1; p = 0.01). Stroke mimic diagnosis was more common in women (21% vs. 15%; p = 0.01). There were no significant sex differences in clinical outcome, measured by the NIHSS, the modified Rankin Scale, intracranial hemorrhage and mortality. CONCLUSION: Women were underrepresented in number in NOR-TEST. The included women had a lower cardiovascular risk factor burden and more severe strokes.

The Course of Carotid Plaque Vulnerability Assessed by Advanced Neurosonology.

Background: Carotid artery atherosclerosis is a major risk factor for ischemic stroke. This risk is related to plaque vulnerability and is characterized by plaque morphology, intraplaque neovascularization, and cerebral microembolization. Advanced neurosonology can identify vulnerable plaques and aid in preventing subsequent stroke. We aimed to assess the time course of cerebral microembolization and intraplaque neovascularization during 6 months of follow-up and to explore the utility of advanced neurosonology in patients with acute cerebral ischemia. Methods: Fifteen patients with acute cerebral ischemia and carotid artery plaques underwent comprehensive extra- and intracranial ultrasound examinations, including microemboli detection and contrast-enhanced ultrasound. The examinations were repeated after 3 and 6 months. Results: We examined 28 plaques in 15 patients. The ultrasonographic features of plaque vulnerability were frequent in symptomatic and asymptomatic plaques. There were no significant differences in stenosis degree, plaque composition, plaque surface, neovascularization, or cerebral microembolization between symptomatic and asymptomatic plaques, but symptomatic plaques had a higher number of vulnerable features. None of the patients had recurrent clinical stroke or transient ischemic attack during the follow-up period. We observed a decrease in cerebral microembolization at 6 months, but no significant change in intraplaque neovascularization. Conclusions: In patients with acute cerebral ischemia and carotid artery plaques, cerebral microembolization decreased during 6 months of follow-up, indicating plaque stabilization. Clinical Trial Registration:ClinicalTrial.gov, identifier NCT02759653.

Clinical manifestation of acute cerebral infarcts in multiple arterial territories.

OBJECTIVES: We aimed to assess frequencies and radiological aspects of single- and multiterritory clinical manifestation among patients with acute cerebral infarcts in multiple arterial territories (MACI). MATERIALS & METHODS: We retrospectively reviewed admission records and diffusion-weighted magnetic resonance imaging of patients with MACI admitted to our stroke unit between 2006 and 2017. MACI was defined as acute cerebral ischemic lesions in at least two out of three arterial cerebral territories, that is, the left anterior, right anterior and the bilateral posterior territory. Patients with single- and multiterritory clinical manifestation were then compared for topographical distribution of the ischemic lesions, the number of ischemic lesions, and The Oxfordshire Community Stroke Project classification. RESULTS: Out of 311 patients with MACI, 222 (71.4%) presented with single-territory clinical manifestation. Involvement of the left hemisphere (OR = 0.37, 95% CI 0.16-0.82), less than five ischemic lesions (OR = 0.58, 95% CI 0.35-0.97), and partial anterior circulation infarct clinical stroke syndrome (OR = 0.57, 95% CI 0.34-0.97) were associated with single-territory clinical manifestation. Involvement of all three territories (OR = 2.58, 95% = 1.48-4.50), more than 10 ischemic lesions (OR = 2.30, 95% CI 1.32-4.01) and total anterior circulation infarct clinical stroke syndrome (OR = 3.31, 95% CI 1.39-7.86) were associated with multiterritory clinical manifestation. CONCLUSION: Most patients with MACI present with single-territory clinical manifestation on admission. Diffusion-weighted magnetic resonance imaging is therefore necessary for a definite diagnosis.

Sonothrombolysis in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-controlled clinical trials. METHODS: We included all available randomized-controlled clinical trials comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in patients with AIS with large vessel occlusion. The primary outcome measure was the rate of complete recanalization at 1 to 36 hours following intravenous thrombolysis initiation. We present crude odds ratios (ORs) and ORs adjusted for the predefined variables of age, sex, baseline stroke severity, systolic blood pressure, and onset-to-treatment time. RESULTS: We included 7 randomized controlled clinical trials that enrolled 1102 patients with AIS. A total of 138 and 134 confirmed large vessel occlusion patients were randomized to treatment and control groups respectively. Patients randomized to sonothrombolysis had increased odds of complete recanalization compared with patients receiving intravenous thrombolysis alone (40.3% versus 22.4%; OR, 2.17 [95% CI, 1.03-4.54]; adjusted OR, 2.33 [95% CI, 1.02-5.34]). The likelihood of symptomatic intracranial hemorrhage was not significantly different between the 2 groups (7.3% versus 3.7%; OR, 2.03 [95% CI, 0.68-6.11]; adjusted OR, 2.55 [95% CI, 0.76-8.52]). No differences in the likelihood of asymptomatic intracranial hemorrhage, 3-month favorable functional and 3-month functional independence were documented. CONCLUSIONS: Sonothrombolysis was associated with a nearly 2-fold increase in the odds of complete recanalization compared with intravenous thrombolysis alone in patients with AIS with large vessel occlusions. Further study of the safety and efficacy of sonothrombolysis is warranted.

Prevalence of atherosclerosis and association with 5-year outcome: The Norwegian Stroke in the Young Study.

Objectives: We studied the prevalence of atherosclerosis among ischaemic stroke patients ≤60 years and controls at the time of the index stroke, and its association with occurrence of new cardiovascular events (CVEs) and mortality at a 5-year follow-up. Methods: Prevalent atherosclerosis was assessed for 385 patients and 260 controls in seven vascular areas by electrocardiogram (ECG), ankle-arm index (AAI) and measurement of right and left carotid and femoral intima-media thickness (cIMT and fIMT) and abdominal aorta plaques (AAP). Clinical end-points were any new CVE (stroke, angina, myocardial infarction or peripheral arterial disease) or death from any cause at 5-year follow-up. All results were sex- and age-adjusted; logistic regression and Cox proportional hazards models were applied. Results: Young patients ≤49 years had prevalent atherosclerosis in 1/2 of males and 1/3 of females. Compared with controls, young female patients showed significantly higher prevalent atherosclerosis, p = 0.024. Ischaemic ECG and mean cIMT were higher in young and middle-aged female patients (p = 0.044, p = 0.020, p = 0.023 and p <0.001, respectively). Mean fIMT was higher in middle-aged female patients (p <0.001). Cardiovascular events were associated with ischaemic ECG; AAI ≤0.9, fIMT ≥0.9 mm and increased number of areas with atherosclerosis (NAA) among patients, and with AAP, cIMT ≥0.9 mm, fIMT ≥0.9 mm and NAA among controls. Mortality was associated with higher age, ischaemic ECG and NAA among patients, and cIMT ≥0.9 mm among controls. Conclusion: Atherosclerosis is highly prevalent even in young stroke patients. Some areas and increasing NAA are associated with CVEs and death.

Tenecteplase versus alteplase after acute ischemic stroke at high age.

BACKGROUND: Stroke prevalence is increasing with age. Alteplase is the only agent approved for thrombolytic treatment for patients with ischemic stroke, including patients ≥80 years. In the present study, the aim was to compare efficacy and safety of tenecteplase and alteplase in patients ≥80 years. METHODS: Data from the Norwegian Tenecteplase Stroke Trial, a randomized controlled trial comparing alteplase and tenecteplase, were assessed. RESULTS: Of the 273 patients ≥80 years included, mean age was 85.5 years.In the intention-to-treat analyses, 43.1% receiving tenecteplase and 39.9% receiving alteplase reached excellent functional outcome (modified Rankin Scale score 0-1) after 3 months (odds ratio (OR) 1.14, 95% confidence interval (CI) 0.70-1.85, p=0.59). No significant differences among patients in the two treatment groups regarding frequency of symptomatic intracranial hemorrhage during the first 48 h were identified (11 (8.5%) in the tenecteplase group, 10 (7.0%) in the alteplase group, OR 1.23, 95% CI 0.50-3.00, p 0.65). Death within 3 months occurred in 18 patients (14.3%) in the tenecteplase group and in 21 (15.3%) in the alteplase group (p 0.84). After excluding stroke mimics, the proportion of patients with excellent functional outcome was 44.1% in the tenecteplase group and 34.4% in the alteplase group (OR 1.50 CI 0.90-2.52, p 0.12). CONCLUSION: No differences in the efficacy and safety of tenecteplase versus alteplase in patients ≥80 years were identified. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01949948).

Clinical outcomes and safety profile of Tenecteplase in wake-up stroke.

BACKGROUND: Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of tenecteplase in wake-up stroke (WUPS). AIMS: To investigate safety and efficacy of tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. METHODS: WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients 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). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. RESULTS: Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. CONCLUSIONS: In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.

Vision-related quality of life in patients with occipital stroke.

OBJECTIVES: The aim of this study was to detect visual field defects (VFDs) after occipital infarction, investigate the rate of recovery and the impact of VFD upon vision-related quality of life (QoL). MATERIALS AND METHODS: Multicenter, prospective study including patients with MRI verified acute occipital infarction (NOR-OCCIP project). Ophthalmological examination including perimetry was performed within 2 weeks and after 6 months. Vision-related QoL was assessed by the National Eye Institute Visual Function Questionnaire 25 (VFQ-25) at one and 6 months post-stroke. RESULTS: We included 76 patients, reliable perimetry results were obtained in 66 patients (87%) at a median of 8 days after admittance and VFD were found in 52 cases (79%). Evaluation of VFD after 6 months revealed improvement in 52%. Patients with VFD had significantly lower composite score in VFQ-25 at both test points (77 vs 96, P = .001 and 87 vs 97, P = .009), in nine out of eleven subscales of VFQ-25 at 1 month and seven subscales after 6 months, including mental health, dependency, near and distance activities. Milder VFD had better results on VFQ-25 modified composite score (95 vs 74, P = .002).VFD improvement was related to improved VFQ-25 modified composite score (9.6 vs 0.8, P = .018). About 10% of patients with VFD reported driving 1 month post-stroke and 38% after 6 months. CONCLUSION: VFD substantially reduces multiple aspects of vision-related QoL. Severity of VFD is related to QoL and VFD improvement results in better QoL. Neglecting visual impairment after stroke may result in deterioration of rehabilitation efforts. Driving post-stroke deserves particular attention.

Persistent Microembolic Signals in the Cerebral Circulation on Transcranial Doppler after Intravenous Sulfur Hexafluoride Microbubble Infusion.

BACKGROUND AND PURPOSE: Microembolic signals (MES) are detectable by transcranial Doppler monitoring and associated with increased risk of first or recurrent ischemic stroke. MES detection can also illuminate stroke etiology and the effect of prophylactic treatment. MES detection cannot accurately distinguish between stroke-related microemboli and ultrasound contrast agents. These agents contain microbubbles and are frequently used in neuro- and cardiovascular diagnostics. We aimed to assess how long after contrast infusion microbubbles are detectable by transcranial Doppler monitoring. METHODS: Ten healthy volunteers received an intravenous infusion of stabilized sulfur hexafluoride microbubbles (SonoVue®) for 30 minutes. The infusion was followed by continuous unilateral Doppler monitoring (TCD-X, Atys Medical, Soucieu-en-Jarrest, France) for 3.5 hours. RESULTS: MES persisted for 12 to 77 minutes (median 40.5 minutes), and the frequency tended to decrease gradually until cessation. CONCLUSIONS: None of the subjects had detectable MES for more than 77 minutes after ultrasound contrast infusion. MES detection with the intent to detect stroke-related microemboli should wait for at least this long after completed infusion.

Impaired cerebrovascular reactivity may predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a major cause of disability and death after aneurysmal subarachnoid hemorrhage. The literature suggests that impaired cerebrovascular reactivity (CVR) may be a predictor for DCI; still no CVR based prediction model has been developed. Increased knowledge about possible predictors of DCI can improve patient management in high-risk patients and allow for shorter hospital stay in low-risk patients. METHOD: CVR was examined in 42 patients with aneurysmal subarachnoid hemorrhage and 37 patients treated for unruptured intracranial aneurysm, using acetazolamide test with transcranial Doppler monitoring of blood flow velocities. Patients were followed for development of DCI, separated into clinical deterioration and radiographic infarction. RESULTS: For all patients, regardless of aneurysm rupture status, CVR was on average 5.5 percentage points lower on the ipsilateral side of aneurysm treatment. Patients with clinical deterioration due to DCI had lower CVR than patients without DCI, and the difference was larger on the contralateral side (33.9% vs. 49.2%). Two prediction models were constructed for clinical deterioration due to DCI. The area under the receiver operating characteristic curve was 0.82 in the model using established predictors, and 0.86 in the model that also included CVR. CONCLUSION: Our findings support the hypothesis that impaired CVR may be an independent predictor of clinical deterioration due to DCI, and may assist in identifying patients at risk after aneurysmal subarachnoid hemorrhage. Ipsilateral CVR reduction occurs in all patients after aneurysm treatment, regardless of DCI development, thus highlighting the need to evaluate ipsi- and contralateral CVR separately.