Early and late onset post-stroke cognitive impairment (PCI) contributes substantially to disability following stroke, and is a high priority within stroke research. The aetiology for PCI is complex ...and related to the stroke itself, brain resilience, comorbid brain diseases, prestroke vulnerability and complications during the hospital stay. The aim of the Norwegian Cognitive Impairment After Stroke study (Nor-COAST) is to quantify and measure levels of cognitive impairments in a general Norwegian stroke population and to identify biological and clinical markers associated with prognosis for cognitive disorders following incident stroke. The study will be organised within five work packages: 1) Incidence and trajectories 2) Pathological mechanisms 3) Development of a risk score 4) Impact of physical activity and 5) Adherence to secondary prevention.
Nor-COAST is an ongoing multicentre (five participating hospitals), prospective, cohort study with consecutive inclusion during the acute phase and with follow-up at three and 18 months, and at three years. Inclusion criteria are stroke defined according to the WHO criteria. During the recruitment period from 18.05.2015 to 31.03.2017, 816 participants have been included. Cognitive impairment will be classified according to the DSM-5 criteria using a consensus group. Cognitive function is assessed by a standardised neuropsychological test battery, the Montreal Cognitive Assessment, Trail making A and B, ten-word immediate and delayed recall test, the Controlled Oral Word Association, Global Deterioration Scale and proxy based information by and the Ascertain Dementia 8 item informant questionnaire. Biomarkers include magnetic resonance imaging, routine blood samples and bio-banking. Clinical assessments include characteristics of the stroke, comorbidity, delirium, frailty and tests for cognitive and physical function, sensor based activity monitoring and adherence to secondary prophylaxis.
Nor-COAST is the first Norwegian multicentre study to quantify burden of PCI that will provide reliable estimates in a general stroke population. A multidisciplinary approach aiming to identify biomarkers and clinical markers of overall prognosis will add new knowledge about risk profiles, including pre-stroke vulnerability and modifiable factors such as physical activity and secondary prophylaxis of relevance for clinical practice and later intervention studies.
ClinicalTrials.gov: NCT02650531 . Retrospectively registered January 8, 2016. First participant included May 18, 2015.
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.
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.
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 (
<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 (
<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (
<0.01).
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.
URL: https://www.
gov; Unique identifier: NCT02650531.
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.
To compare incidence of first-ever acute cerebral infarction, etiology and traditional risk factors in young adults 15-49 years in 1988-1997 and 2008-2017 in Hordaland County, Norway.
Case-finding of ...young adults with acute cerebral infarction in 1988-1997 was done retrospectively by computer research from hospital registries in Hordaland County. Young adults with acute cerebral infarction living in the Bergen region in 2008-2017 were prospectively included in a database at Haukeland University Hospital. Traditional risk factors, etiology and modified Rankin scale score on discharge were registered.
Crude average incidence of acute cerebral infarction was 11.4 per 100.000 per year in 1988-1997 and 13.2 per 100.000 per year in 2008-2017 (P=0.04). The prevalence of prior myocardial infarction, angina pectoris, and dyslipidemia were lower in the 2008-2017 cohort (all P<0.05). Atherosclerosis was less common in the 2008-2017 cohort (P<0.001).
The observed incidence of acute cerebral infarction in young adults increased from 1988-1997 to 2008-2017 in Hordaland County. Atherosclerosis was less common in the 2008-2017 cohort.
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.
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.
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.
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.
Background:
Carotid artery atherosclerosis is a major risk factor for ischemic stroke. This risk is related to plaque vulnerability and is characterized by plaque morphology, intraplaque ...neovascularization, and cerebral microembolization. Advanced neurosonology can identify vulnerable plaques and aid in preventing subsequent stroke. We aimed to assess the time course of cerebral microembolization and intraplaque neovascularization during 6 months of follow-up and to explore the utility of advanced neurosonology in patients with acute cerebral ischemia.
Methods:
Fifteen patients with acute cerebral ischemia and carotid artery plaques underwent comprehensive extra- and intracranial ultrasound examinations, including microemboli detection and contrast-enhanced ultrasound. The examinations were repeated after 3 and 6 months.
Results:
We examined 28 plaques in 15 patients. The ultrasonographic features of plaque vulnerability were frequent in symptomatic and asymptomatic plaques. There were no significant differences in stenosis degree, plaque composition, plaque surface, neovascularization, or cerebral microembolization between symptomatic and asymptomatic plaques, but symptomatic plaques had a higher number of vulnerable features. None of the patients had recurrent clinical stroke or transient ischemic attack during the follow-up period. We observed a decrease in cerebral microembolization at 6 months, but no significant change in intraplaque neovascularization.
Conclusions:
In patients with acute cerebral ischemia and carotid artery plaques, cerebral microembolization decreased during 6 months of follow-up, indicating plaque stabilization.
Clinical Trial Registration:
ClinicalTrial.gov
, identifier NCT02759653.
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.
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).
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.
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.
Objectives
To study the development of cognitive and emotional symptoms between 3 and 12 months after a minor stroke.
Material and Methods
We included patients from stroke units at hospitals in the ...Central Norway Health Authority and from Haukeland University Hospital. We administered a selection of cognitive tests, and the patients completed a questionnaire 3 and 12 months post‐stroke. Cognitive impairment was defined as impairment of ≥2 cognitive tests.
Results
A total of 324 patients completed the 3‐month testing, whereas 37 patients were lost to follow‐up at 12 months. The results showed significant improvement of cognitive function defined as impairment of ≥2 cognitive tests (P = .03) from months 3 to 12. However, most patients still showed cognitive impairment at 12 months with a prevalence of 35.4%. There is significant association between several of the cognitive tests and hypertension and smoking (P = .002 and .05). The prevalence of depression, but not anxiety, increased from 3 to 12 months (P = .04). The prevalence of fatigue did not change and was thus still high with 29.5% after 12 months.
Conclusions
This study shows that an improvement of cognitive function still occurs between 3 and 12 months. Despite this, the prevalence of mostly minor cognitive impairment still remains high 12 months after the stroke. The increasing prevalence of depressive symptoms highlights the importance of being vigilant of depressive symptoms throughout the rehabilitation period. Furthermore, high prevalence of fatigue persisted.
The aim of the present study was to investigate the associations stroke severity, aphasia severity, lesion location and lesion size in acute stroke, and aphasia severity in the subacute and chronic ...stages post stroke. We hypothesized that initial stroke severity and aphasia severity were associated with the patient's aphasia severity in the subacute and chronic stages of stroke. We expected to find that lesions within the left frontotemporal regions of the brain were associated with aphasia severity post-stroke.
Thirty-three patients with aphasia were included in the study. They were assessed with a standardized aphasia test at admission to the hospital (T1), after 3 months (T2) and finally after 12 months (T3). Stroke severity, initial physical impairment, and initial functional independence were also assessed at T1. Diffusion-weighted magnetic resonance imaging was performed as clinical-routine at admission. Voxel-based lesion symptom mapping and a region of interest analysis (ROI) was performed to analyze MRI-findings.
Initial lesion size and aphasia severity were associated with aphasia severity at T2. Initial stroke severity, aphasia severity, and lesion size were not associated with aphasia severity at T3, but the patients' aphasia severity at T2 predicted aphasia severity at T3. Lesion analysis showed that lesions within the left postcentral gyrus and the left inferior parietal gyrus were significantly associated with aphasia severity at T3. The ROI-analysis did not yield any significant regions of interest to explain the total variance of the patients' change in scores on the aphasia test from T1 to T3.
Lesions within the postcentral gyrus and the inferior parietal gyrus are associated with aphasia severity at T3. Lesion size in the acute stages of stroke is associated with aphasia severity at T1 and T2, but not T3. However, neither initial aphasia severity nor stroke severity was associated with aphasia severity at T3. Aphasia severity in T2 is however strongly associated with aphasia severity in T3.
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.
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.
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.
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.
The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.
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