What Do We Really Know About the Effect of Prolonged Heart Rhythm Monitoring After Stroke?

The bulk of the current knowledge on atrial fibrillation (AF)-associated stroke risk and benefit of oral anticoagulation derives from studies on patients with clinically diagnosed AF. Subclinical AF (SCAF), defined as AF discovered during the interrogation of prolonged heart monitoring, is often asymptomatic and short-lasting, is associated with increased stroke risk compared with sinus rhythm, and may progress to clinical AF. Despite the extensive screening for and treatment of SCAF, especially in secondary stroke prevention, the net benefit of this practice is not established. Recent studies of SCAF have provided new insights: (1) SCAF is extremely common and may sometimes indicate physiological findings, (2) the stroke risk associated with SCAF is lower than that of clinically detected AF, and (3) any benefit on stroke risk may be countered by increased bleeding risk (no net benefit). How should we interpret the latest knowledge in the setting of poststroke AF screening and prevention?

Iatrogenic botulism. / Iatrogen botulisme.

This case study describes severe iatrogenic botulism following treatment with a botulinum toxin injection at a private clinic abroad.

Stroke After SARS-CoV-2 mRNA Vaccine: A Nationwide Registry Study.

BACKGROUND: Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain. METHODS: In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident. RESULTS: The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85-1.00) and 0.89 (0.73-1.08) for ischemic stroke, 0.81 (0.67-0.98) and 1.05 (0.64-1.71) for intracerebral hemorrhage, and 0.64 (0.46-0.87) and 1.12 (0.57-2.19) for subarachnoid hemorrhage, respectively. CONCLUSIONS: We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

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.

Is Frailty Index a better predictor than pre-stroke modified Rankin Scale for neurocognitive outcomes 3-months post-stroke?

BACKGROUND: The prognostic value of frailty measures for post-stroke neurocognitive disorder (NCD) remains to be evaluated. AIMS: The aim of this study was to compare the predictive value of pre-stroke FI with pre-stroke modified Rankin Scale (mRS) for post-stroke cognitive impairment. Further, we explored the added value of including FI in prediction models for cognitive prognosis post-stroke. METHODS: We generated a 36-item Frailty Index (FI), based on the Rockwood FI, to measure frailty based on pre-stroke medical conditions recorded in the Nor-COAST multicentre prospective study baseline assessments. Consecutive participants with a FI score and completed cognitive test battery at three months were included. We generated Odds Ratio (OR) with NCD as the dependent variable. The predictors of primary interest were pre-stroke frailty and mRS. We also measured the predictive values of mRS and FI by the area (AUC) under the receiver operating characteristic curve. RESULTS: 598 participants (43.0% women, mean/SD age = 71.6/11.9, mean/SD education = 12.5/3.8, mean/SD pre-stroke mRS = 0.8/1.0, mean/SD GDS pre-stroke = 1.4/0.8, mean/SD NIHSS day 1 3/4), had a FI mean/SD score = 0.14/0.10. The logistic regression analyses showed that FI (OR 3.09), as well as the mRS (OR 2.21), were strong predictors of major NCD. When FI and mRS were entered as predictors simultaneously, the OR for mRS decreased relatively more than that for FI. AUC for NCD post-stroke was higher for FI than for mRS, both for major NCD (0.762 vs 0.677) and for any NCD (0.681 vs 0.638). CONCLUSIONS: FI is a stronger predictor of post-stroke NCD than pre-stroke mRS and could be a part of the prediction models for cognitive prognosis post-stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

Carotid Atherosclerosis and Longitudinal Changes of MRI Visual Rating Measures in Stroke Survivors: A Seven-Year Follow-Up Study.

OBJECTIVES: We aimed to assess longitudinal changes in MRI measures of brain atrophy and white matter lesions in stroke and transient ischemic attack (TIA) survivors, and explore whether carotid stenosis predicts progression of these changes, assessed by visual rating scales. MATERIALS AND METHODS: All patients with a first-ever stroke or TIA admitted to Bærum Hospital, Norway, in 2007/2008, were invited in the acute phase and followed for seven years. Carotid ultrasound was performed during the hospital stay. Carotid stenosis was defined as ≥50% narrowing of lumen. MRI was performed one and seven years after the index event and analyzed according to the visual rating scales Fazekas scale (0-3), Medial Temporal Lobe Atrophy (MTLA) (0-4) score, and Global Cortical Atrophy (GCA) scale (0-3). Patients with MRI scans at both time points were included in this sub-study. RESULTS: Of 227 patients recruited, 76 had both MRI examinations. Mean age 73.9±10.6, 41% women, and 9% had ≥50% carotid stenosis. Mean Fazekas scale was 1.7±0.9 and 1.8±1.0, mean MTLA score 1.0 ±1.0 and 1.7±1.0, and mean GCA scale score 1.4±0.7 and 1.4±0.6 after one and seven years, respectively. 71% retained the same Fazekas scale score, while 21% showed progression. Deterioration in GCA scale was seen in 20% and increasing MTLA score in 57%. Carotid stenosis was not associated with progression on Fazekas score, MTLA score or GCA scale. CONCLUSIONS: Three out of five showed progression on the MTLA score. Carotid stenosis was not associated with longitudinal change of visual rating scales.

Anticoagulant reversal in intracerebral haemorrhage. / Reversering av antikoagulerende legemidler ved hjerneblødning.

Anticoagulant drugs are effective in preventing and treating blood clots, but they also increase the risk of intracerebral haemorrhage. When intracerebral haemorrhage occurs, rapid reversal of the anticoagulant effect is recommended. However, reversal treatment must be selected on the basis of the anticoagulants' various mechanisms of action, and a specific antidote is preferred where available.

No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study.

BACKGROUND: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-ß peptide (Aß42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke. METHODS: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aß42 levels were assessed using linear regression. RESULTS: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aß42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort. CONCLUSIONS: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

Predictors for Favorable Cognitive Outcome Post-Stroke: A-Seven-Year Follow-Up Study.

BACKGROUND AND PURPOSE: Knowledge of the burden and development of post-stroke cognitive impairments (CIs) in the long-term after the first event is limited. We aimed to assess the prevalence of mild CI (MCI) and dementia 7 years after first-ever stroke or transient ischemic attack (TIA), to subclassify the impairments, and to identify predictors for a favorable cognitive outcome. MATERIALS AND METHODS: During 2007 and 2008, 208 patients with first-ever stroke or TIA without preexisting CI were included. After 1 and 7 years, survivors were invited to a follow-up. Transitions of cognitive status from 1 to 7 years were recorded based on the 3 categories dementia, MCI, or none. Etiologic subclassification was based on clinical cognitive profile, magnetic resonance imaging (MRI) findings, and biomarkers at both time points. Favorable outcome was defined as normal cognitive function or MCI after 7 years with exclusion of those who had progression from normal to MCI. RESULTS: Eighty patients died during follow-up, 12 patients refused further participation. After 7 years, 109 completed follow-up of whom 40 (37%) were diagnosed with MCI and 24 (22%) with dementia. Of the 64 patients diagnosed with CI, 9 were subclassified with degenerative cognitive disease, 13 with vascular disease, and 42 had mixed cognitive disease. In all, 65 patients (60%) had a favorable outcome. In multivariable logistic regression analysis, lower age and lower medial temporal lobe atrophy (MTLA) grade on MRI at 12 months were independently associated with a favorable outcome, adjusted OR (95% CI), 0.94 (0.86-0.92), and 0.55 (0.35-0.85), respectively. CONCLUSIONS: Sixty percent of stroke survivors have a favorable cognitive outcome. Lower age and lower MTLA grade on MRI were associated with favorable outcome.

Post-stroke dementia - a comprehensive review.

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

Association between total-Tau and brain atrophy one year after first-ever stroke.

BACKGROUND: Although the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural MRI and pathological cerebrospinal fluid (CSF) concentrations of microtubule-associated protein tau (T-tau) and phosphorylated microtubule-associated protein tau indicate neurofibrillary degeneration. We aimed to explore the association between CSF T-tau and brain atrophy 1 year post-stroke. METHODS: We included 210 patients with first-ever ischemic stroke or transitory ischemic attack without pre-existing cognitive impairment. After 12 months, subjects underwent MRI, and CSF biomarkers were assessed. Using SIENAX (part of FSL), ventricular CSF volume and total brain volume were estimated and normalized for subject head size. The association between T-tau as explanatory variable and ventricular and total brain volume as outcome variables were studied using linear regression. RESULTS: One hundred eighty-two patients completed the follow-up. Forty-four had a lumbar puncture. Of these, 31 had their MRI with identical scan parameters. Mean age was 70.2 years (SD 11.7). Ventricular volume on MRI was significantly associated with age, but not with gender. In the multiple regression model, there was a significant association between T-tau and both ventricular (beta 0.44, 95% CI 376.3, 394.9, p = 0.021) and global brain volume (beta -0.50, 95% CI -565.9, -78.3, p = 0.011). There was no significant association between CSF T-tau 1 year post-stroke and baseline volumes. CONCLUSION: T-tau measured 1 year post-stroke is associated with measures of brain atrophy. The findings indicate that acute stroke may enhance or trigger tau-linked neurodegeneration with loss of neurons. TRIAL REGISTRATION: Clinicaltrials.gov NCT00506818 , July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

Acute ischemic stroke and measurement of apixaban and rivaroxaban: an observational cohort implementation study.

Background: Treatment with intravenous thrombolysis for acute ischemic stroke is contraindicated with intake of apixaban/rivaroxaban in the last 48 hours. Recent European Stroke Organization guidelines suggest that thrombolysis can be considered if anti-factor Xa activity (AFXa) is <0.5 × 103 IU/L with low-molecular-weight (LMWH) or unfractionated heparin (UFH) calibrated assays. Some centers also use apixaban/rivaroxaban-calibrated AFXa assays to identify patients with low drug concentrations. Objectives: To prospectively evaluate the first year of implementation of drug-calibrated AFXa assays at our center with 2500 yearly admittances with suspected stroke. Methods: Samples were analyzed on Sysmex CS-5100 instruments with Innovance anti-Xa reagents. Thrombolysis could be considered with drug concentrations <25 µg/L. Patients were registered in an institutionally approved quality register. Outcomes included (1) the number of patients receiving thrombolysis after drug measurement, (2) turn-around time for drug concentration measurements, and (3) sensitivity of LMWH/UFH AFXa to apixaban and rivaroxaban. Results: Apixaban or rivaroxaban was measured in 148 samples, and 4 patients who previously would have been ineligible for thrombolysis were treated with thrombolysis. In total, thrombolysis was administered in 123 patient episodes in the study period. The median turn-around time for the drug measurements was 38 minutes. Apixaban concentrations of 25 µg/L and 50 µg/L corresponded to LMWH/UFH AFXa of 0.13 and 0.27 × 103 IU/L, respectively. There were too few rivaroxaban results for regression analysis. Conclusion: Implementation of apixaban and rivaroxaban measurements led to a small increase in the number of patients receiving thrombolysis. Excluding significant concentrations of apixaban or rivaroxaban using LMWH/UFH AFXa may be feasible.

The precision by the Face Arm Speech Time (FAST) algorithm in stroke capture, sex and age differences: a stroke registry study.

Background: The shift towards milder strokes and studies suggesting that stroke symptoms vary by age and sex may challenge the Face-Arm-Speech Time (FAST) coverage. We aimed to study the proportion of stroke cases admitted with FAST symptoms, sex and age differences in FAST presentation and explore any additional advantage of including new item(s) from the National Institute of Health Stroke Scale (NIHSS) to the FAST algorithm. Methods: This registry-based study included patients admitted with acute stroke to Sahlgrenska University Hospital (November 2014 to June 2019) with NIHSS items at admission. FAST symptoms were extracted from the NIHSS at admission, and sex and age differences were explored using descriptive statistics. Results: Of 5022 patients, 46% were women. Median NIHSS at admission for women was (2 (8-0) and for men 2 (7-0)). In total, 2972 (59%) had at least one FAST symptom, with no sex difference (p=0.22). No sex or age differences were found in FAST coverage when stratifying for stroke severity. 52% suffered mild strokes, whereas 30% had FAST symptoms. The most frequent focal NIHSS items not included in FAST were sensory (29%) and visual field (25%) and adding these or both in modified FAST algorithms led to a slight increase in strokes captured by the algorithms (59%-67%), without providing enhanced prognostic information. Conclusions: 60% had at least one FAST symptom at admission, only 30% in mild strokes, with no sex or age difference. Adding new items from the NIHSS to the FAST algorithm led only to a slight increase in strokes captured.

Prognostic value of acute National Institutes of Health Stroke Scale Items on disability: a registry study of first-ever stroke in the western part of Sweden.

OBJECTIVES: We aimed to study how the individual items of the National Institutes of Health Stroke Scale (NIHSS) at admission predict functional independence 3 months post-stroke in patients with first-ever stroke. SETTING: This registry-based study used data from two Swedish stroke registers (Riksstroke, the mandatory national quality register for stroke care in Sweden, and Väststroke, a local quality stroke register in Gothenburg). PARTICIPANTS: This study included patients with first-ever acute stroke admitted from November 2014 to August 2018, with available NIHSS at admission and modified Rankin Scale (mRS) at 3-month follow-up. PRIMARY OUTCOME: The primary outcome variable was mRS≤1 (defined as an excellent outcome) at 3-month follow-up. RESULTS: We included 1471 patients, mean age was 72 (± 14.5) years, 48% were female, and 66% had mild strokes (NIHSS≤3). In adjusted binary logistic regression analysis, the NIHSS items impaired right motor arm and leg, and impairment in visual field, reduced the odds of an excellent outcome at 3 months ((OR 0.60 (95% CI 0.37 to 0.98), OR 0.60 (95% CI 0.37 to 0.97), and OR 0.65 (95% CI 0.45 to 0.94)). When exploring the effect size of associations between NIHSS items and mRS≤1 p, orientation, language and right leg motor had the largest yet small association. CONCLUSIONS: Stroke patients with scores on the NIHSS items right motor symptoms or visual field at admission are less likely to have an excellent outcome at 3 months. Clinicians should consider the NIHSS items affected, not only the total NIHSS score, both in treatment guidance and prognostics.

Delirium screening in a stroke unit by nurses using 4AT: Results from a quality improvement project.

AIM: To assess the feasibility of delirium screening with the screening tool 4AT conducted by stroke unit nurses. DESIGN: Observational. METHODS: Patients with confirmed acute stroke admitted to the stroke unit at Baerum Hospital, Norway, from March to October 2020, were consecutively recruited. Nurses performed delirium screening using the rapid screening tool 4AT within 24 h of admission, at discharge and when delirium was suspected, and filled out a questionnaire assessing their experiences with the delirium screening. A geriatrician validated the delirium diagnosis. RESULTS: In all, 62 patients were included, mean age 73.3 years. 4AT was performed according to protocol in 49 (79.0%) and 39 (62.9%) patients at admission and discharge respectively. Lack of time (40%) was reported as the most common reason for not performing delirium screening. The nurses reported that the felt competent to carry out the 4AT screening, and did not experience it as significant extra workload. Five patients (8%) were diagnosed with delirium. Delirium screening performed by stroke unit nurses seemed feasible and the nurses experienced that 4AT was a useful tool for this purpose.

Carotid Plaque Score for Stroke and Cardiovascular Risk Prediction in a Middle-Aged Cohort From the General Population.

Background We aimed to explore the predictive value of the carotid plaque score, compared with the Systematic Coronary Risk Evaluation 2 (SCORE2) risk prediction algorithm, on incident ischemic stroke and major adverse cardiovascular events and establish a prognostic cutoff of the carotid plaque score. Methods and Results In the prospective ACE 1950 (Akershus Cardiac Examination 1950 study), carotid plaque score was calculated with ultrasonography at inclusion in 2012 to 2015. The largest plaque diameter in each extracranial segment of the carotid artery on both sides was scored from 0 to 3 points. The sum of points in all segments provided the carotid plaque score. The cohort was followed up by linkage to national registries for incident ischemic stroke and major adverse cardiovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, and cardiovascular death) throughout 2020. Carotid plaque score was available in 3650 (98.5%) participants, with mean±SD age of 63.9±0.64 years at inclusion. Only 462 (12.7%) participants were free of plaque, and and 970 (26.6%) had a carotid plaque score of >3. Carotid plaque score predicted ischemic stroke (hazard ratio [HR], 1.25 [95% CI, 1.15-1.36]) and major adverse cardiovascular events (HR, 1.21 [95% CI, 1.14-1.27]) after adjustment for SCORE2 and provided strong incremental prognostic information to SCORE2. The best cutoff value of carotid plaque score for ischemic stroke was >3, with positive predictive value of 2.5% and negative predictive value of 99.3%. Conclusions The carotid plaque score is a strong predictor of ischemic stroke and major adverse cardiovascular events, and it provides incremental prognostic information to SCORE2 for risk prediction. A cutoff score of >3 seems to be suitable to discriminate high-risk subjects. Registration Information clinicaltrials.gov. Identifier: NCT01555411.