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.

Hemodynamic Stroke: Emerging Concepts, Risk Estimation, and Treatment.

Ischemic stroke can arise from the sudden occlusion of a brain-feeding artery by a clot (embolic), or local thrombosis. Hemodynamic stroke occurs when blood flow does not sufficiently meet the metabolic demand of a brain region at a certain time. This discrepancy between demand and supply can occur with cerebropetal arterial occlusion or high-grade stenosis but also arises with systemic conditions reducing blood pressure. Treatment of hemodynamic stroke is targeted toward increasing blood flow to the affected area by either systemically or locally enhancing perfusion. Thus, blood pressure is often maintained above normal values, and extra-intracranial flow augmentation bypass surgery is increasingly considered. Still, current evidence supporting the superiority of pressure or flow increase over conservative measures is limited. However, methods assessing hemodynamic impairment and identifying patients at risk of hemodynamic stroke are rapidly evolving. Sophisticated models incorporating clinical and imaging factors have been suggested to aid patient selection. In this narrative review, we provide current state-of-the-art knowledge about hemodynamic stroke, tools for assessment, and treatment options.

Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Prehospital identification of acute ischaemic stroke with large vessel occlusion: a retrospective study from western Norway.

BACKGROUND: In 2019, the emergency medical services (EMS) covering the western Norway Regional Health Authority area implemented its version of the prehospital clinical criteria G-FAST (Gaze deviation, Facial palsy, Arm weakness, Visual loss, Speech disturbance) to detect acute ischaemic stroke (AIS) with large vessel occlusion (LVO). For patients with gaze deviation and at least one other G-FAST symptom, a primary stroke centre (PSC) may be bypassed and the patient taken directly to a comprehensive stroke centre (CSC) for rapid endovascular treatment (EVT) evaluation. The study aim was to investigate the efficacy of the G-FAST criteria for LVO patient selection and direct transfer to a CSC. METHODS: This retrospective study included patients with code-red emergency medical communication centre (EMCC) stroke suspicion ambulance dispatch between August to December 2020. Stroke suspicion was defined as having at least one G-FAST symptom at EMS arrival. We obtained patient data from dispatches from EMCCs, EMS records and local EVT registries. Clinical features, CT images, and reperfusion treatment were recorded. The test characteristics for gaze deviation plus one other G-FAST symptom in detecting LVO were determined. RESULTS: Among 643 patients, 59 were diagnosed with LVO at hospital arrival. In this group, seven fulfilled the G-FAST criteria for direct transport to a CSC at EMS arrival on scene, resulting in a sensitivity of 12% (95% CI 5% to 23%). The specificity was 99.66% (95% CI 98.77% to 99.96%), the positive predictive value 78%, and the negative predictive value 92%. EVT was performed in 64% (38/59) of LVO cases. Median time from PSC arrival to start of EVT at a CSC was 163 min. CONCLUSION: The use of local G-FAST prehospital criteria by EMS personnel to identify patients with AIS with LVO is not suitable for selection of patients with LVO for direct transfer to a CSC.

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 Between First-Ever Ischemic Stroke in Young Adults in 1988-1997 and 2008-2017.

Aim: To compare incidence of first-ever acute cerebral infarction, etiology and traditional risk factors in young adults 15-49 years in 1988-1997 and 2008-2017 in Hordaland County, Norway. Methods: Case-finding of young adults with acute cerebral infarction in 1988-1997 was done retrospectively by computer research from hospital registries in Hordaland County. Young adults with acute cerebral infarction living in the Bergen region in 2008-2017 were prospectively included in a database at Haukeland University Hospital. Traditional risk factors, etiology and modified Rankin scale score on discharge were registered. Results: Crude average incidence of acute cerebral infarction was 11.4 per 100.000 per year in 1988-1997 and 13.2 per 100.000 per year in 2008-2017 (P=0.04). The prevalence of prior myocardial infarction, angina pectoris, and dyslipidemia were lower in the 2008-2017 cohort (all P<0.05). Atherosclerosis was less common in the 2008-2017 cohort (P<0.001). Conclusion: The observed incidence of acute cerebral infarction in young adults increased from 1988-1997 to 2008-2017 in Hordaland County. Atherosclerosis was less common in the 2008-2017 cohort.

European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke.

Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of <4.5 h duration who are eligible for IVT, tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS of <4.5 h duration who are eligible for IVT, we recommend against using tenecteplase at a dose of 0.40 mg/kg (low evidence, strong recommendation). For patients with AIS of <4.5 h duration with prehospital management with a mobile stroke unit who are eligible for IVT, we suggest tenecteplase 0.25 mg/kg over alteplase 0.90 mg/kg (low evidence, weak recommendation). For patients with large vessel occlusion (LVO) AIS of <4.5 h duration who are eligible for IVT, we recommend tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS on awakening from sleep or AIS of unknown onset who are selected with non-contrast CT, we recommend against IVT with tenecteplase 0.25 mg/kg (low evidence, strong recommendation). Expert consensus statements are also provided. Tenecteplase 0.25 mg/kg may be favoured over alteplase 0.9 mg/kg for patients with AIS of <4.5 h duration in view of comparable safety and efficacy data and easier administration. For patients with LVO AIS of <4.5 h duration who are IVT-eligible, IVT with tenecteplase 0.25 mg/kg is preferable over skipping IVT before MT, even in the setting of a direct admission to a thrombectomy-capable centre. IVT with tenecteplase 0.25 mg/kg may be a reasonable alternative to alteplase 0.9 mg/kg for patients with AIS on awakening from sleep or AIS of unknown onset and who are IVT-eligible after selection with advanced imaging.

Monitoring following acute stroke should be improved. / Overvåkning etter akutt hjerneslag bør bli bedre.

Many serious complications following acute stroke can be prevented and treated. This requires close and systematic monitoring following stroke.

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.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative.

BACKGROUND AND OBJECTIVES: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression. RESULTS: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

The impact of age and 24-h blood pressure on arterial health in acute ischemic stroke patients: The Norwegian stroke in the young study.

The impact of age and 24-h ambulatory blood pressure (ABPM) on arterial stiffness and carotid intima-media thickness (cIMT) in ischemic stroke patients younger than 60 years of age is poorly explored. A total of 385 acute ischemic stroke patients (aged 49.6±9.7 years, 68% men) were prospectively included and grouped in younger (15-44 years, n = 93) and middle-aged (45-60 years, n = 292). Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV), and cIMT by carotid ultrasound. 24-h ABPM was recorded. The middle-aged stroke patients had higher prevalence of smoking, hypertension, diabetes mellitus, metabolic syndrome and hypercholesterolemia, and had higher PWV and cIMT (all p < .05). In multivariable linear regression analyses adjusted for sex, BMI, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, triglycerides, eGFR, systolic BP and concomitant antihypertensive treatment, 1SD (4.4 years) higher age was associated with higher PWV (ß = 0.44,R2  = 0.46, p < .001) in the younger group, and with higher mean cIMT (ß = 0.16, R2  = 0.21, p = .01) in the middle-aged group. In the middle-aged group, 24-h pulse pressure had a significant association with PWV (ß = 0.18, R2  = 0.19, p = .009), while the association with cIMT was attenuated (ß = 0.13, R2  = 0.16, p = .065). 24-h diastolic BP was associated with higher cIMT in the middle-aged group (ß = 0.24, p < .001, R2  = 0.23), but not with PWV in either age groups. Among ischemic stroke patients < 60 years, higher age was associated with increased arterial stiffness for patients up to age 44 years, and with cIMT in middle-aged patients. 24-h pulse pressure was associated with arterial stiffness, and 24-h diastolic BP was associated with cIMT only in middle-aged patients.

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.

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.

SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women.

RATIONALE: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn. AIMS: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome. METHODS AND DESIGN: This is an observational, prospective, multicentre, international case-control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant. SUMMARY: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management.

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.