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.

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.

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.

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.

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.

Dyslipidemia and rupture risk of intracranial aneurysms-a systematic review.

Dyslipidemia is a well-established risk factor for coronary artery disease. However, the effect on cerebral artery disease, and more specifically the rupture risk of intracranial aneurysms, is unclear and has not yet been reviewed. We therefore performed a systematic review to investigate associations between different types of dyslipidemia and incidence of aneurysmal subarachnoid hemorrhage (aSAH). We used the MEDLINE, Embase, and Web of Science databases to identify clinical trials that compared the rupture risk among SAH patients with or without dyslipidemia. The risk of bias in each included study was evaluated using the Critical Appraisal Skills Program (CASP). Of 149 unique citations from the initial literature search, five clinical trials with a case-control design met our eligibility criteria. These studies compared aSAH patients to patients with unruptured aneurysms and found an overall inverse relationship between hypercholesterolemia and rupture risk of intracranial aneurysms. The quality assessment classified all included studies as high risk of bias. The evidence indicates that hypercholesterolemia is associated with a reduced rupture risk of intracranial aneurysms. However, it is not clear whether this relation is due to the dyslipidemic condition itself or the use of antihyperlipidemic medication.

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.

Discontinuation of External Ventricular Drainage in Patients with Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage - a Scandinavian Multi-institutional Survey.

BACKGROUND: Hydrocephalus requiring external ventricular drainage is common following aneurysmal subarachnoid hemorrhage (aSAH). Timing and strategy for the discontinuation of the external ventricular drain (EVD) are, however, controversial as guidelines are based on limited scientific evidence. A recent similar survey showed that guidelines and recommendations are not being followed. We conducted a questionnaire survey regarding the management of EVD treatment in patients with aSAH and investigated current treatment practice, consensus, and adherence to guidelines within the neurosurgical departments in Scandinavia. METHODS: A questionnaire concerning the management of EVD discontinuation in patients with hydrocephalus following aSAH was distributed to all 14 neurosurgical departments in Scandinavia (Norway, Sweden, and Denmark). Neurosurgeons and neurosurgical trainees at all levels were asked to complete the questionnaire individually. A total of 175 completed questionnaires were received between May 2018 and April 2019, resulting in a response rate of 64 %. RESULTS: Eighty-five percent of respondents reported no knowledge of international guidelines regarding EVD discontinuation in patients with hydrocephalus following aSAH. Within every department, respondents disagreed on whether a common discontinuation strategy was followed or not. Seventy-four percent decided upon the EVD discontinuation strategy mainly determined by patients' clinical condition and drainage volume. Forty-five percent considered Glasgow Coma Score (GCS) the most important clinical variable when assessing the timing of EVD discontinuation. There was general agreement towards the initiation of EVD discontinuation 4-7 days after ictus of aSAH in a stable patient with a drainage volume of < 150 ml/day and intracranial pressure (ICP) < 15 mmHg. CONCLUSION: Awareness of and adherence to international guidelines regarding EVD discontinuation in patients with hydrocephalus following aSAH were limited in Scandinavia. Internal consensus at department level was absent. Initiation of the discontinuation process appeared to be case dependent and mainly influenced by the patients' clinical condition and drainage volume. GCS was the clinical variable considered most important when deciding on the initiation of EVD discontinuation.

Incidence and Etiologies of Stroke Mimics After Incident Stroke or Transient Ischemic Attack.

Background and Purpose- Stroke mimics (SM) pose a common clinical challenge, but the burden of SM in patients with previous ischemic stroke (IS) or transient ischemic attack is unknown. The objective of this study was to calculate the incidence of SM in IS survivors, compare it with the incidence of recurrent stroke in the same population, and explore the time-dependent patterns of SM etiologies. Methods- This prospective cohort study registered SM events and etiologies among 1872 IS and transient ischemic attack survivors diagnosed with index stroke at Haukeland University Hospital stroke unit from 2007 to 2013 by review of medical records. Cumulative incidences of SM were estimated with a competing risks Cox model and compared with incidence of recurrent stroke in the same population. Results- During 8172 person-years of follow-up, 339 patients had 480 SM events. The cumulative incidence rate of SM during follow-up was 58.7 per 1.000 person-years (95% CI, 53.7-64.2) compared with 34.0 per 1.000 person-years (95% CI, 30.2-38.2) for recurrent stroke in the same time period. The risks of SM and recurrent stroke were highest the first year after index IS or transient ischemic attack. The most frequent SM diagnoses were sequelae of cerebral infarction (19.8%), medical observation, and evaluation for suspected cerebrovascular disease (15.6%) and infections (14.0%). The 2 most frequent and unspecific diagnoses (sequelae of cerebral infarction and medical observation) were clustered in the first months after index stroke. Conclusions- SM after IS or transient ischemic attack are more frequent than recurrent stroke and the risk is especially high in the early period. SMs are multietiological and unspecific diagnoses are most frequent early after index stroke.

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.

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.

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.

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.

Recurrent ischemic stroke: Incidence, predictors, and impact on mortality.

BACKGROUND AND PURPOSE: Recurrent ischemic stroke (IS) or TIA is frequent with a considerable variation in incidence and mortality across populations. Current data on stroke recurrence and mortality are useful to examine trends, risk factors, and treatment effects. In this study, we calculated the incidence of recurrent IS or TIA in a hospital-based stroke population in Western Norway, investigated recurrence factors, and estimated the effect of recurrence on all-cause mortality. METHODS: This prospective cohort study registered recurrence and mortality among 1872 IS and TIA survivors admitted to the stroke unit at Haukeland University Hospital between July 2007 and December 2013. Recurrence and death until September 1, 2016, were identified by medical chart review. Cumulative incidences of recurrence were estimated with a competing risks Cox model. Multivariate Cox models were used to examine recurrence factors and mortality. RESULTS: During follow-up, 220 patients had 277 recurrent IS or TIAs. The cumulative recurrence rate was 5.4% at 1 year, 11.3% at 5 years, and 14.2% at the end of follow-up. Hypertension (HR = 1.65, 95% CI 1.21-2.25), prior symptomatic stroke (HR = 1.63, 95% CI 1.18-2.24), chronic infarcts on MRI (HR = 1.48, 95% CI 1.10-1.99), and age (HR 1.02/year, 95% CI 1.00-1.03) were independently associated with recurrence. A total of 668 (35.7%) patients died during follow-up. Recurrence significantly increased the all-cause mortality (HR = 2.55, 95% CI 2.04-3.18). CONCLUSIONS: The risk of recurrent IS stroke or TIA was modest in our population and was associated with previously established risk factors. Recurrence more than doubled the all-cause mortality.

Short-Term Outcome of Spontaneous Intracerebral Hemorrhage in Algarve, Portugal: Retrospective Hospital-Based Study.

BACKGROUND: The short-term outcome from spontaneous intracerebral hemorrhage (SICH) is influenced by local quality of care and population specificities. There are no studies about the SICH mortality in southern Portugal. The objective of this study was to describe the predictors of 30-day in-hospital SICH mortality in Algarve, the southernmost region of Portugal. METHODS: Logistic regression was used to identify predictors of in-hospital death. Kaplan-Meier analysis was used to estimate survival over time based on SICH severity. RESULTS: Of the 549 cases, 349 (63.6%) were men; the mean age was 71.4 years. Two hundred seventeen patients (39.5%) did not receive stroke unit (SU) care. The 30-day mortality was 34.4%. Independent predictors of death were older age (odds ratio [OR] = 1.096, 95% confidence interval [CI] = 1.031-2.062, P = .022) per additional year, vitamin K antagonists use (OR = 5.464, 95% CI = 2.088-25.714, P = .043), admission Glasgow Coma Scale (GCS) score of 8 or lower (OR = 20.511, 95% CI = 7.862-62.168, P < .0001) or GCS score of 9-12 (OR = 12.709, 95% CI = 3.078-44.113, P < .0001), hematoma volume (OR = 1.037, 95% CI = 1.004-1.071, P = .028) per additional milliliter, intraventricular dissection (OR = 1.916, 95% CI = 1.105-4.566, P = .046), and pneumonia (OR 12.918, 95% CI = 4.603-24.683, P < .0001). SU care was independently associated with reduction of death (OR .395, 95% CI = .126-.635, P = .004). Severity correlated with short time to death (P < .0001). Sixty-five of the patients (39.2%) died after the seventh day of SICH ("non-neurological deaths"). CONCLUSIONS: The in-hospital 30-day mortality is high in the region. Admitting more patients to the SU and implementation of preventive strategies of complications can reduce mortality.

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.