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.

Factors associated with progression of arterial stiffness in ischemic stroke survivors: the Norwegian Stroke in the Young Study.

BACKGROUND: Progressive arterial stiffening may increase the risk of recurrent cardiovascular events in ischemic stroke survivors. Information about factors associated with progressive arterial stiffening during the follow-up of young patients with ischemic stroke is lacking. METHODS: Arterial stiffness by carotid-femoral pulse wave velocity (cf-PWV) and ambulatory 24-hour blood pressure (24hBP) were assessed in 81 women and 190 men ≤60 years of age included in the Norwegian Stroke in the Young (NOR-SYS) study 3 months and 5.5 years after the incident ischemic stroke, representing baseline and follow-up. Covariables of change in cf-PWV were identified using linear regression analysis. RESULTS: At baseline, women had less prevalent hypertension (53% vs. 69%, p < 0.05), and lower clinic and 24hBP than men, whereas age, obesity, and prevalence of smoking and antihypertensive drug treatment did not differ. During follow-up, systolic 24hBP remained unchanged, while diastolic 24hBP fell significantly (p < 0.01). Cf-PWV was lower in women both at baseline (7.3 m/s vs. 8.1 m/s) and at follow-up (7.3 m/s vs. 8.0 m/s, both p < 0.001), but the average change during follow-up did not differ between genders. In linear regression analysis, an increase in cf-PWV at the 5-year follow-up was associated with the presence of hypertension and lower cf-PWV at baseline, and higher systolic 24hBP and lack of use of antihypertensive treatment at follow-up (all p < 0.05). CONCLUSION: In ischemic stroke survivors participating in the NOR-SYS study, the 5-year increase in cf-PWV did not differ between genders and was associated with higher systolic 24hBP and lack of antihypertensive treatment.

Progressive arterial stiffening increases the risk of recurrent stroke. More information about factors associated with progression of arterial stiffness in young ischemic stroke survivors is needed. This study followed 81 women and 190 men for 5 years and examined changes in arterial stiffness in relation to blood pressure levels and other factors.Arterial stiffness was measured using the carotid-femoral pulse wave velocity. We also measured blood pressure at study visits and over a 24-hour period while the study participants led their daily life. Measurements were performed 3 months after the index ischemic stroke (baseline) and repeated after an average of 5.5 years of follow-up.Our main finding was that hypertension is very common and is important for arterial health in young ischemic stroke survivors. An increase in arterial stiffness during follow-up was associated with hypertension, higher 24-hour blood pressure, and lack of use of blood pressure-lowering drugs in participants with hypertension. There were no differences between women and men.This study shows the importance of proper blood pressure management in young ischemic stroke survivors to avoid progressive stiffening of the arteries. The results also demonstrated the value of using 24-hour measurements rather than office measurements in the evaluation of blood pressure control during treatment.

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.

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.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

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.

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.

Short-Term Outcome and In-Hospital Complications After Acute Cerebral Infarcts in Multiple Arterial Territories.

Background and Purpose- Patients with acute cerebral infarcts in multiple arterial territories (MACI) represent a substantial portion of the stroke population. There are no data on short-term outcome and in-hospital complications in patients with MACI. We compared patients with MACI with patients having acute cerebral infarct(s) in a single arterial territory. Methods- We analyzed 3343 patients with diffusion-weighted imaging-confirmed acute cerebral infarcts. MACI was defined as at least 2 acute cerebral ischemic lesions in at least 2 arterial cerebral territories. Patients with MACI were compared with patients with acute cerebral infarct(s) in a single arterial territory for relevant in-hospital complications and short-term outcome, namely National Institutes of Health Stroke Scale and modified Rankin Scale at day 7 after admission or at discharge when earlier. Results- A total of 311 patients (9.3%) met the definition of MACI. Both median National Institutes of Health Stroke Scale (2 [1-7] versus 1 [0-4]) and modified Rankin Scale (3 [1-4] versus 2 [1-3]) were higher in patients with MACI. MACI was independently associated with higher National Institutes of Health Stroke Scale and modified Rankin Scale. Deep venous thrombosis, myocardial infarction, and any complications were more frequent in patients with MACI. Conclusions- In-hospital complications were more frequent in patients with MACI, which may adversely affect short-term clinical and functional outcome. Closer follow-up of patients with MACI during hospitalization may prevent such events and negative progression.

Safety and Outcomes of Tenecteplase in Moderate and Severe Ischemic Stroke.

Background and Purpose- Tenecteplase represents a promising alternative to alteplase as thrombolytic treatment in acute ischemic stroke. There are limited data on tenecteplase 0.4 mg/kg in patients with increased stroke severity. We aimed to assess safety and efficacy of tenecteplase 0.4 mg/kg in patients with moderate and severe ischemic stroke. Methods- NOR-TEST (Norwegian Tenecteplase Stroke Trial) was a phase III trial designed to investigate the safety and efficacy of tenecteplase 0.4 mg/kg versus alteplase 0.9 mg/kg in ischemic stroke. In this post hoc analysis, moderate stroke was defined as admission National Institutes of Health Stroke Scale; 6 to 14 and severe stroke as National Institutes of Health Stroke Scale; ≥15. Rates of favorable outcome at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality after 7 and 90 days were assessed. Results- In patients with moderate stroke (n=261), there were no differences in rates of favorable outcome, sICH, or mortality between tenecteplase and alteplase. In patients with severe stroke (n=87), there were no differences in outcome, frequency of sICH, or mortality at 7 days, but all-cause mortality at 90 days was increased in patients treated with tenecteplase (10 [26.3%] versus 4 [9.1%]; P=0.045). One patient died of sICH in the tenecteplase group, and 2 patients died of sICH in the alteplase group. Conclusions- Rates of favorable outcome and sICH were similar between treatment groups in patients with moderate and severe stroke. Mortality after 90 days was increased in patients with severe stroke receiving tenecteplase. Future studies assessing tenecteplase 0.4 mg/kg should monitor safety parameters closely in patients with severe stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale.

Background and Purpose- Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods- The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing tenecteplase with alteplase. Results- The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2-6). In the intention-to-treat analysis, 57% of patients that received tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0-1) at 3 months (odds ratio, 1.19; 95% CI, 0.68-2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26-2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65-2.37). Conclusions- Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

One-year versus five-year hospital readmission after ischemic stroke and TIA.

BACKGROUND: The burden of hospital readmission after stroke is substantial, but little knowledge exists on factors associated with long-term readmission after stroke. In a cohort comprising patients with ischemic stroke and transient ischemic attack (TIA), we examined and compared factors associated with readmission within 1 year and first readmission during year 2-5. METHODS: Patients with ischemic stroke or TIA who were discharged alive between July 2007 and October 2012, were followed for 5 years by review of medical charts. The timing and primary cause of the first unplanned readmission were registered. Cox regression was used to identify independent risk factors for readmission within 1 year and first readmission during year 2-5 after discharge. RESULTS: The cohort included 1453 patients, of whom 568 (39.1%) were readmitted within 1 year. Of the 830 patients that were alive and without readmission 1 year after discharge, 439 (52.9%) were readmitted within 5 years. Patients readmitted within 1 year were older, had more severe strokes, poorer functional outcome, and a higher occurrence of complications during index admission than patients readmitted during year 2-5. Cardiovascular comorbidity and secondary preventive treatment did not differ between the two groups of readmitted patients. Higher age, poorer functional outcome, coronary artery disease and hypertension were independently associated with readmission within both 1 year and during year 2-5. Peripheral artery disease was independently associated with readmission within 1 year, and atrial fibrillation was associated with readmission during year 2-5. CONCLUSIONS: More than half of all patients who survived the first year after stroke without any readmissions were readmitted within 5 years. Patients readmitted within 1 year and between years 2-5 shared many risk factors for readmission, but they differed in age, functional outcome and occurrence of complications during the index admission.

U-shaped relationship between hemoglobin level and severity of ischemic stroke.

BACKGROUND AND AIM: We aimed to explore the relation between hemoglobin level and ischemic stroke severity and short-term improvement in patients admitted to hospital within 3 hours of stroke onset. METHODS: The relation between stroke severity and hemoglobin was explored by locally weighted scatterplot smoothing (lowess smoother) curves. The effect of hemoglobin on short-term outcome was determined by means of linear regression analyses with NIHSS score day 7 as dependent variable after adjusting for confounders including NIHSS score on admission. Analyses were performed to disclose clinical factor associated with hemoglobin level. RESULTS: This study includes 905 ischemic stroke patients admitted within 3 hours of stroke onset. Lowess smoother curves showed a U-shaped relation between NIHSS score on admission and mRS score day 7 and hemoglobin level. Regression analysis showed low hemoglobin to be independently associated with females, high age, severe stroke, low systolic blood pressure, prior cerebral infarction, not smoking, not atrial fibrillation, and unknown etiology (all P < 0.05). Another regression analysis showed that high NIHSS score day 7 was independently associated with low hemoglobin after adjusting for confounders including NIHSS score on admission. CONCLUSIONS: We found a U-shaped relationship between hemoglobin level on admission and stroke severity. There was no U-shaped relationship between improvement and hemoglobin level. Poor short-term improvement was associated with low hemoglobin levels.

High risk of early neurological worsening of lacunar infarction.

BACKGROUND AND PURPOSE: We aimed to evaluate factors associated with neurological worsening among patients with lacunar or non-lacunar infarction admitted within 3 hours and between 3 and 24 hours after stroke onset. METHODS: All patients admitted to Haukeland university hospital between 2006 and 2016 with acute cerebral infarction on MRI and admission within 24 hours were included. Repeated National Institute of Health Stroke Scale (NIHSS) scoring was performed in all patients whenever possible. Neurological worsening during the hospital stay was defined as NIHSS score increase ≥3 compared to NIHSS score on admission. RESULTS: In patients with lacunar infarction admitted within 3 hours of onset, neurological worsening was associated with low NIHSS score on admission, low body temperature, and leukoaraiosis, whereas only internal carotid artery stenosis or occlusion was associated with neurological worsening in non-lacunar infraction. For patients admitted 3-24 hours after onset, neurological worsening was associated with low body temperature, high systolic blood pressure, and short time from onset to admission in patients with lacunar infarction, whereas high systolic blood pressure, high NIHSS score on admission, middle cerebral artery occlusion, and high blood glucose were associated with neurological worsening in patients with non-lacunar infarction (all P < 0.05). CONCLUSIONS: Lacunar infarctions with minor neurological deficits within 3 hours of stroke onset are at high risk of neurological worsening especially if concomitant low body temperature and leukoaraiosis.

When to Screen Ischaemic Stroke Patients for Cancer.

BACKGROUND AND PURPOSE: Ischemic stroke can be the first manifestation of cancer and it is therefore important to ascertain which stroke patients should be considered for cancer-diagnostic investigations. We aimed to determine the frequency of active cancer in patients with acute ischemic stroke and to compare clinical findings in stroke patients with active cancer to ischemic stroke patients with no history of cancer. Finally, we aimed to develop a predictive and feasible score for clinical use to uncover underlying malignancy. METHODS: All ischemic stroke patients admitted to the stroke unit in the Department of Neurology, Haukeland University Hospital were consecutively included in the Norwegian Stroke Research Registry (NORSTROKE). Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Data on cancer diagnoses was obtained from patients' medical records and the Cancer Registry of Norway. Active cancer was defined as cancer diagnosis, metastasis of known cancer, recurrent cancer or receiving cancer treatment, all within 12 months before or after the index stroke. Based on variables independently associated with active cancer, a predictive score was developed using the area under the receiver operating characteristic (AUC-ROC) curves. Bayes' theorem was used to calculate post-test probabilities of active cancer. RESULTS: Of the 1,646 ischemic stroke patients included, 82 (5.0%) had active cancer. Increased D-dimer (OR = 1.1, 95% CI: 1.1-1.2, p = <0.001), lower Hb (OR = 0.6, 95% CI: 0.5-0.7, p = <0.001), smoking (OR = 2.2, 95% CI: 1.2-4.3, p = 0.02) and suffering a stroke of undetermined etiology (OR = 1.9, 95% CI: 1.1-3.3, p = 0.03) were factors independently associated with active cancer. These were included in the final predictive score which gave an AUC of 0.73 (95% CI: 0.65-0.81) in patients younger than 75 years of age. Assuming the prevalence of cancer to be 5%, the score shows that if a patient fulfills all 3 score points, the probability of active cancer is 53%. CONCLUSIONS: Active cancer was found in 5% of our ischemic stroke patients. We found that a clinical score comprising elevated D-dimer ≥3 mg/L, lower Hb ≤12.0 g/dL and previous or current smoking is feasible for predicting active cancer in ischemic stroke patients.

Prevalence and covariates of uncontrolled hypertension in ischemic stroke survivors: the Norwegian stroke in the young study.

PURPOSE: Hypertension is the most important modifiable risk factor for stroke. Few data are available on control of hypertension in younger ischemic stroke survivors. MATERIAL AND METHODS: We assessed clinic and ambulatory blood pressure (BP) measurements in 320 patients aged 15-60 years (mean 48 ± 10) included in the Norwegian Stroke in the Young Study during 3-months follow-up after the index stroke. Controlled hypertension was defined as ambulatory BP <130/80 mmHg. Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry. Carotid plaque was considered present if focal intima-media thickness >1.5 mm. RESULTS: At hospital discharge, 58% of the patients were treated for hypertension. Another 9% of the total study population was diagnosed with new-onset hypertension during follow-up. At the 3-months follow-up visit, 56% of patients with treated hypertension were uncontrolled. Patients with uncontrolled treated hypertension were older, had higher body mass index (BMI) and PWV, and were more likely to have diabetes and carotid plaques compared to patients with normotension (p < .01). Compared to controlled treated hypertension, patients with uncontrolled treated hypertension had higher prevalence of carotid plaque (p < .01). In a multivariate logistic regression, uncontrolled treated hypertension was associated with higher PWV and BMI, and presence of carotid plaque, independent of the more intensified use of antihypertensive treatment (all p < .05). CONCLUSION: Uncontrolled hypertension was highly prevalent in ischemic stroke survivors <60 years and associated with co-presence of obesity and functional and structural arterial damage. Our results highlight the unmet potential and challenge of optimization of hypertension diagnosis and management in order to prevent recurrent vascular events in ischemic stroke survivors.

NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population.

BACKGROUND AND PURPOSE: The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population. METHODS: Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1. RESULTS: A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis. CONCLUSIONS: CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01949961.

C-reactive protein in the detection of post-stroke infections: systematic review and individual participant data analysis.

We conducted a systematic review and individual participant data meta-analysis to explore the role of C-reactive protein (CRP) in early detection or prediction of post-stroke infections. CRP, an acute-phase reactant binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria, thereby activating complement and promoting phagocytosis by macrophages. We searched PubMed up to May-2015 for studies measuring CRP in stroke and evaluating post-stroke infections. Individual participants' data were merged into a single database. CRP levels were standardized and divided into quartiles. Factors independently associated with post-stroke infections were determined by logistic regression analysis and the additional predictive value of CRP was assessed by comparing areas under receiver operating characteristic curves and integrated discrimination improvement index. Data from seven studies including 699 patients were obtained. Standardized CRP levels were higher in patients with post-stroke infections beyond 24 h. Standardized CRP levels in the fourth quartile were independently associated with infection in two different logistic regression models, model 1 [stroke severity and dysphagia, odds ratio = 9.70 (3.10-30.41)] and model 2 [age, sex, and stroke severity, odds ratio = 3.21 (1.93-5.32)]. Addition of CRP improved discrimination in both models [integrated discrimination improvement = 9.83% (0.89-18.77) and 5.31% (2.83-7.79), respectively], but accuracy was only improved for model 1 (area under the curve 0.806-0.874, p = 0.036). In this study, CRP was independently associated with development of post-stroke infections, with the optimal time-window for measurement at 24-48 h. However, its additional predictive value is moderate over clinical information. Combination with other biomarkers in a panel seems a promising strategy for future studies.

Covariates of non-dipping and elevated night-time blood pressure in ischemic stroke patients: the Norwegian Stroke in the Young Study.

Abnormal night-time blood pressure (BP) reduction is associated with increased cardiovascular risk in hypertension. Little is known about the prevalence and covariates of night-time BP reduction in ischemic stroke patients. Clinic and ambulatory BP measurements were recorded in 268 stroke survivors aged 15-60 years. The degree of night-time dipping was calculated from the difference between day-time and night-time mean BP, and defined as non-dipping if < 10%. Aortic stiffness was derived from carotid-femoral pulse-wave velocity (PWV) by applanation tonometry and carotid intima-media thickness (cIMT) by ultrasound. A non-dipping pattern was found in 38%. Non-dippers had higher PWV, mean cIMT and night-time BP, and included more patients with history of hypertension, diabetes and high for age PWV compared to dippers (all p < 0.05). In multivariate logistic regression analyses, non-dipping was associated with high for age PWV [odds ratio (OR) = 2.28; 95% confidence interval (CI) 1.06-4.92, p < 0.05] independent of history of hypertension and other confounders, while elevated night-time BP was associated with increased cIMT (OR = 3.83; 95% CI 1.01-14.50, p < 0.05) independent of non-dipping status, male gender, obesity, antihypertensive treatment and high for age PWV. In conclusion, in the Norwegian Stroke in the Young Study, non-dipping BP pattern was common and associated with increased aortic stiffness.

Hospital Readmission after Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most severe form of stroke, but limited literature exists on readmission after ICH. We aimed to assess frequencies, causes, and predictors of early and late readmissions within 1 year after ICH. METHODS: All patients admitted to the Department of Neurology at Haukeland University Hospital with acute stroke were prospectively included in the Bergen Norwegian Stroke Research Registry (NORSTROKE) registry. Surviving patients diagnosed with ICH were followed by medical chart reviews for 1 year. The first unplanned readmission was used as final outcome, and readmitted patients were defined as early readmitted (≤90 days) and late readmitted (91-365 days). Logistic regression was performed to assess predictors for early and late readmission. RESULTS: Of 121 patients discharged alive, 27 were early readmitted, and 17 were late readmitted. Within 1 year, 40.6% had at least 1 unplanned readmission. The most frequent cause of early readmission was infection, and the most frequent causes for late readmission were recurrent stroke and cardiovascular disease. Nursing home discharge was the only independent predictor of early readmission. Diabetes mellitus and increased length of the index admission were independent predictors of late readmission. Early readmitted patients were older and had more severe stroke and lower levels of fibrinogen on index admission compared with patients who were readmitted late. CONCLUSIONS: Readmission after ICH is frequent, and many patients are early readmitted. Early and late readmissions differed in both causes and predictors for readmission, reflecting different underlying mechanisms for readmission.

Atherosclerosis in Trial of Org 10172 in Acute Stroke Treatment Subtypes among Young and Middle-Aged Stroke Patients: The Norwegian Stroke in the Young Study.

BACKGROUND: Ischemic stroke patients subtyped as of undetermined cause (SUC) usually outnumber those with determined cause subtypes. Etiological stroke classifications may lead to neglect of parallel, noncausative findings. Atherosclerosis progresses over decades and is associated with high morbidity and mortality in young stroke patients in long-term follow-up studies. We compared the prevalence of carotid atherosclerosis in all TOAST subtypes among young patients with acute ischemic stroke. METHODS: We investigated 150 patients aged 15-60 years with documented acute ischemic stroke, and 84 controls free of cardiovascular disease. Stroke etiology was classified according to TOAST criteria. Carotid intima-media thickness (cIMT) measurements were obtained from 12 standardized multiangle measurements in the common carotid artery, carotid bifurcation, and internal carotid artery. RESULTS: The causes of stroke were 5.3% large-artery atherosclerosis (LAA), 26.7% cardioembolism, 21.3% small-artery occlusion (SAO), 10% stroke of other determined cause, and 36.7% stroke of undetermined cause (SUC). cIMT was increased in patients with LAA (1.56 mm, P = .002), SAO (1.11 mm, P = .006), and SUC (1.10 mm, P = .004) compared to controls (cIMT 0.86 mm). Segmental cIMT distribution differed across stroke subtypes, age groups, and sexes. CONCLUSIONS: Atherosclerotic disease is prevalent in the majority of young and middle-aged ischemic stroke patients, requiring determined investigation and aggressive treatment of modifiable risk factors.