Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study.

BACKGROUND: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. METHODS: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. RESULTS: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). CONCLUSIONS: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02650531.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial.

BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. OBJECTIVE: The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). METHODS AND ANALYSIS: Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. CONCLUSIONS: The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

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.

Stroke unit demand in Norway - present and future estimates.

BACKGROUND: All stroke patients should receive timely admission to a stroke unit (SU). Consequently, most patients with suspected strokes - including stroke mimics (SM) are admitted. The aim of this study was to estimate the current total demand for SU bed capacity today and give estimates for future (2020-2040) demand. METHODS: Time trend estimates for stroke incidence and time constant estimates for length of stay (LOS) were estimated from the Norwegian Patient Registry (2010-2015). Incidence and LOS models for SMs were based on data from Haukeland University Hospital (2008-2017) and Akershus University Hospital (2020), respectively. The incidence and LOS models were combined with scenarios from Statistic Norway's population predictions to estimate SU demands for each health region. A telephone survey collected data on the number of currently available SU beds. RESULTS: In 2020, 361 SU beds are available, while demand was estimated to 302. The models predict a reduction in stroke incidence, which offsets projected demographic shifts. Still, the estimated demand for 2040 rose to 316, due to an increase in SMs. A variation of this reference scenario, where stroke incidence was frozen at the 2020-level, gave a 2040-demand of 480 beds. CONCLUSIONS: While the stroke incidence is likely to continue to fall, this appears to be balanced by an increase in SMs. An important uncertainty is how long the trend of decreasing stroke incidence can be expected to continue. Since the most important uncertainty factors point toward a potential increase, which may be as large as 50%, we would recommend that the health authorities plan for a potential increase in the demand for SU bed capacity.

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.

BACKGROUND: Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population. METHODS: Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated. RESULTS: Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR. CONCLUSIONS: The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke.

BACKGROUND: Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population. METHODS: Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018. RESULTS: The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months. CONCLUSION: Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.

Stroke Mimics on the Stroke Unit - Temporal trends 2008-2017 at a large Norwegian university hospital.

OBJECTIVES: The objective was to quantify temporal trends in stroke mimics (SM) admissions relative to cerebrovascular accidents (CVA), incidence of hospitalized SMs and characterize the SM case-mix at a general hospital's stroke unit (SU). MATERIALS & METHODS: All SU admissions (n = 11240) of patients aged 15 or older to Haukeland University Hospital between 2008-2017 were prospectively included and categorized as CVA or SM. Logistic regression was used to estimate time trends in the proportion of SMs among the admissions. Poisson regression was used to estimate time trends in age- and sex-dependent SM incidence. RESULTS: SMs were on average younger thaan CVA patients (68.3 vs. 71.4 years) and had a higher proportion of females (53.6% vs. 44.5%). The total proportion of SM admissions was 51.0%. There was an increasing time trend in the proportion of SM admissions, odds ratio 1.150 per year (p < 0.001), but this trend appears flattening, represented by a significant quadratic time-term, odds ratio 1.009 (p < 0.001). A higher SM proportion was also associated with the time period of a Mass Media Intervention (FAST campaign) in 2014. There was also an increasing trend in SM incidence, that remains after adjusting for age, sex, and population; also, for incidence the trend appears to be flattening. CONCLUSIONS: SMs account for approximately half of the SU admissions, and the proportion has been increasing. A FAST campaign appears to have temporarily increased the SM proportion. The age- and sex-dependent incidence of SM has been increasing but appears to flatten out.

Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study.

BACKGROUND: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. METHODS: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. RESULTS: Patients' (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). CONCLUSIONS: Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. TRIAL REGISTRATION: NCT02650531 , date of registration: 08.01.2016.

Associations between post-stroke motor and cognitive function: a cross-sectional study.

BACKGROUND: Motor and cognitive impairments are frequently observed following stroke, but are often managed as distinct entities, and there is little evidence regarding how they are related. The aim of this study was to describe the prevalence of concurrent motor and cognitive impairments 3 months after stroke and to examine how motor performance was associated with memory, executive function and global cognition. METHODS: The Norwegian Cognitive Impairment After Stroke (Nor-COAST) study is a prospective multicentre cohort study including patients hospitalized with acute stroke between May 2015 and March 2017. The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission. Level of disability was assessed by the Modified Rankin Scale (mRS). Motor and cognitive functions were assessed 3 months post-stroke using the Montreal Cognitive Assessment (MoCA), Trail Making Test Part B (TMT-B), 10-Word List Recall (10WLR), Short Physical Performance Battery (SPPB), dual-task cost (DTC) and grip strength (Jamar®). Cut-offs were set according to current recommendations. Associations were examined using linear regression with cognitive tests as dependent variables and motor domains as covariates, adjusted for age, sex, education and stroke severity. RESULTS: Of 567 participants included, 242 (43%) were women, mean (SD) age was 72.2 (11.7) years, 416 (75%) had an NIHSS score ≤ 4 and 475 (84%) had an mRS score of ≤2. Prevalence of concurrent motor and cognitive impairment ranged from 9.5% for DTC and 10WLR to 22.9% for grip strength and TMT-B. SPPB was associated with MoCA (regression coefficient B = 0.465, 95%CI [0.352, 0.578]), TMT-B (B = -9.494, 95%CI [- 11.726, - 7.925]) and 10WLR (B = 0.132, 95%CI [0.054, 0.211]). Grip strength was associated with MoCA (B = 0.075, 95%CI [0.039, 0.112]), TMT-B (B = -1.972, 95%CI [- 2.672, - 1.272]) and 10WLR (B = 0.041, 95%CI [0.016, 0.066]). Higher DTC was associated with more time needed to complete TMT-B (B = 0.475, 95%CI [0.075, 0.875]) but not with MoCA or 10WLR. CONCLUSION: Three months after suffering mainly minor strokes, 30-40% of participants had motor or cognitive impairments, while 20% had concurrent impairments. Motor performance was associated with memory, executive function and global cognition. The identification of concurrent impairments could be relevant for preventing functional decline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

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

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

Factors influencing employment after minor stroke and NSTEMI.

AIM: To study the effect of cognitive function, fatigue and emotional symptoms on employment after a minor ischemic stroke compared to non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS: We included 217 patients with minor ischemic stroke and 133 NSTEMI patients employed at baseline aged 18-70 years. Minor stroke was defined as modified Rankin scale (mRS) 0-2 at day seven or at discharge if before. Included NSTEMI patients had the same functional mRS. We applied a selection of cognitive tests and the patients completed questionnaires measuring symptoms of anxiety, depression and fatigue at follow up. Stroke patients were tested at three and 12 months and NSTEMI at 12 months. RESULTS: The patients still employed at 12 monthswere significantly younger than the unemployed patients and the NSTEMI patients employed were significantly older than the stroke patients (59 vs 55 years, p < .001). In total, 82 % of stroke patients and 90 % of the NSTEMI patients employed at baseline were still employed at 12 months (p = 06). Stroke patients at work after 12 months had higher education than unemployed patients. There were no difference between employed and unemployed patients in risk factors or location of cerebral ischemic lesions. Cognitive function did not change significantly in the stroke patients from three to 12 months. For stroke patients, we found a significant association between HADS-depression and unemployment at 12 months (p = 04), although this association was not present at three months. Lower age and higher educational level were associated with employment at 12 months for all patients. DISCUSSION AND CONCLUSION: Age and education are the main factors influencing the ability to stay in work after a minor stroke. Employed stroke patients were younger than the NSTEMI patients, but there was no difference in the frequencies in remaining employed. The employment rate at 12 months was high despite the relatively high prevalence of cognitive impairment in both groups.

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.

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.

The frequency and impact of admission hyperglycemia on short term outcome of acute stroke patients admitted to Tikur Anbessa Specialized hospital, Addis Ababa, Ethiopia: a cross-sectional study.

BACKGROUND: Admission hyperglycemia (HG) has been associated with worse outcomes among acute stroke patients. A better understanding and awareness of the potentially adverse influence of hyperglycemia on the clinical outcome of acute stroke patients would help to provide guidance for acute stroke management and prevention of its adverse outcomes. We aimed to assess the frequency of admission hyperglycemia and its impact on short term (30-days) morbidity and mortality outcomes of stroke in adult Ethiopian patients in an urban setting. METHODS: A prospective, cross-sectional study was conducted among acute stroke patients admitted to Tikur Anbessa Specialized Hospital (TASH), within 72 h of symptom onset, from July to December 2016. Socio-demographic data, neuroimaging findings and capillary blood glucose values were obtained on admission. Hyperglycemia was defined as > 140 mg/dl. National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were used to assess the baseline stroke severity and the 30-days post-stroke outcome, respectively. RESULTS: A total of 103 first-ever acute stroke patients were included (mean age = 55.5 + 15.3 years, 64.1% male and 65% under the age of 65 years) and 51 (49.5%) were hyperglycemic at time of admission. The median admission NIHSS score was worse in the hyperglycemic patients 14 (IQR 10-19) compared to normoglycemic patients 11 (IQR 8-15). Among stroke survivors, patients with hyperglycemia were 3.83 times (95% CI, 1.99-6.19) more likely to be functionally impaired (mRS = 3-5) at 30-days compared to normoglycemic patients (P = 0.041).Older age (≥ 65 years) (P = 0.017) and stroke severity (NIHSS > 14) (P = 0.006) at admission were both significantly associated with poor functional recovery at 30-day. Among patients who died at 30-day, two-third (66.7%) were hyperglycemic but they failed to show any significant association. CONCLUSIONS: Hyperglycemia is prevalent among Ethiopian stroke patients at the time of presentation and it is associated with significantly poor functional recovery at 30th-day of follow up. This finding provides a rationale for achieving normal blood glucose in the course of acute stroke management which could have a favorable impact on the neurological outcome and quality of life for patients.

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.