To Örebro University

INTRODUCTION: Stroke cases among older people will increase due to demographic changes, necessitating an optimization of care strategies for this population. We aimed to examine clinical characteristics, prognostic factors, and the impact of frailty in an older stroke cohort.

PATIENTS AND METHODS: We consecutively included 120 patients aged ≥85 years with acute ischemic or hemorrhagic stroke at a regional hospital in Sweden. Baseline characteristics, etiological subclassification, National Institutes of Health Stroke Scale (NIHSS) on admission, pre- and post-stroke functional level and frailty, measured by the modified Rankin Scale (mRS), the Barthel ADL Index (BI), and the Clinical Frailty Scale (CFS), were recorded. Regression analyses were conducted to evaluate predictors of death or poor functional outcome, defined as an mRS of ≥4, at 3 months.

RESULTS: The mean age was 89.1 years and 57.5% were women. Ischemic strokes accounted for 90.8% and atrial fibrillation was diagnosed in 55.8%. Overall, 26.6% received reperfusion therapy. At 3 months, the mortality and poor functional outcomes were 35.8 and 54.2%, respectively. A multivariate regression analysis identified age ≥89 years, BI ≤70, CFS ≥ 7 prior to stroke, total anterior circulation infarction, NIHSS ≥15 on admission, and post-stroke dysphagia as independent predictors of death or poor outcome.

DISCUSSION AND CONCLUSION: We found a high prevalence of cardioembolic disease in older people with stroke, emphasizing the importance of diagnosing atrial fibrillation and optimizing anticoagulant treatment. In addition to well-known predictors, severe frailty prior to stroke and post-stroke dysphagia predicted poor outcome. In the growing older stroke population, assessment of frailty may be beneficial in decision-making regarding interventions and direction of care.

Background: Body temperature and peripheral blood inflammatory markers are often elevated in acute stroke. Whether the increase in inflammatory markers is caused by the stroke itself or is attributable to a complication, is incompletely understood. This uncertainty may hamper the diagnosis and treatment of infections. We aimed to describe the dynamics of inflammatory parameters in a cohort of stroke patients free from complications.

Methods: Acute stroke patients were prospectively included within 48 h of symptom onset and monitored through daily questions of symptoms and clinical examinations to detect complications. Inflammatory parameters in blood and body temperature were measured daily for up to ten days and the 97.5th percentile calculated. Values were compared with paired t-test to measurements at a 90-day follow up.

Results: 70 stroke patients were included. 51 of them were considered complication-free and sampled for a total of 282 days. Body temperature, CRP and WBC were all significantly elevated the first days after stroke, compared to 90-days post stroke. Mean body temperature was highest at 24-48h at 37.1 degrees C, mean WBC was highest at 0-24h at 8.1 x 10<^>9/L, compared to 36.7 degrees C and 6.0 x 10<^>9/L at the 90-day follow-up (p-values < 0.01). Median CRP peaked at 7.0 mg/L 120-144 h after stroke, compared to 0.9 mg/L at follow-up (p-value < 0.01).

Conclusions: Acute stroke may cause mildly elevated levels of CRP, WBC and body temperature. Except for WBC during the first 24h, higher levels (such as CRP > 50mg/L, WBC > 11 x 10<^>9/L or body temp > 38 degrees C) are very uncommon (< 2.5%) and are likely to reflect a complication.

OBJECTIVE: To determine the temporal profiles of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (t-tau), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in plasma the first week after acute ischemic stroke, and identify the optimal time points for assessing infarct volume by these biomarkers.

PATIENTS & METHODS: In this cohort study, biomarker plasma concentrations were determined daily over the first week and at 90 days after symptom onset in patients with acute ischemic stroke. A brain MRI was performed on day three. Temporal variations in biomarker levels were analyzed using linear mixed-effects models, and optimal time points for infarct volume correlation were identified with continuous Pearson analysis.

RESULTS: 38 patients with a median age of 78 (IQR 72-86) and mean infarct volume of 5.5 (IQR 1.6-17) cm3 were included. We identified three distinct temporal patterns: (1) a parabolic trajectory of GFAP, reaching zenith after three days, (2) a consistent increase in NFL throughout the week, and (3) an initial surge in t-tau and UCHL1 levels, stabilizing by day three. The optimal time point for infarct volume correlation occurred at 119 h for GFAP (r = 0.94, 95% CI: [0.84-0.98]), 144 h for NFL (r = 0.78, [0.47, 0.92]), 122 h for t-tau (r = 0.82, [0.56, 0.93]) and 113 h for UCHL1 (r = 0.83, [0.60, 0.93]).

INTERPRETATION: This high-resolution serial sampling of plasma GFAP, NFL, t-tau, and UCHL1 the first week after acute ischemic stroke identified three distinct temporal profiles. These biomarkers provided the most accurate infarct volume assessment 4-6 days after symptom onset.

CLINICALTRIALS: gov NCT03812666 (registration date 2019-01-23).

INTRODUCTION: Reversal treatment is commonly used for managing oral anticoagulant (OAC)-associated intracranial haemorrhages. Its effects on mortality are still understudied, particularly in various subtypes of intracranial haemorrhages. This systematic review and meta-analysis aims to synthesise the available data to study the impact of reversal therapies on mortality following various OAC-associated acute intracranial haemorrhages.

METHODS AND ANALYSIS: This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Protocols, and the final review will be reported in accordance with the PRISMA reporting guidelines. This systematic review and meta-analysis will include studies that assess contemporary reversal treatment in comparison to no reversal treatment, in cases of OAC-associated intracranial haemorrhage. Stratification will be performed for the types of bleeding as well as OAC at bleeding onset. Preliminary searches to determine search term inclusions were conducted in May-August 2024 in the electronic databases Embase, PubMed, Scopus and Web of Science without language and publication date restrictions. Randomised controlled studies, non-randomised controlled trials, and observational studies will be considered for the final meta-analysis. Three reviewers (MT, JOS and AB) will screen titles and abstracts, and one reviewer (MT) will subsequently conduct full-text screening. Risks of bias will be assessed by MT using tools such as Risk of Bias 2, Risk Of Bias In Non-randomised Studies - of Interventions and the Newcastle-Ottawa Scale. Heterogeneity among the study results will be assessed using the I² statistic. If appropriate, a random-effects meta-analysis model will be performed. Subgroup analyses and meta-regression (if applicable) will be performed to assess sources of heterogeneity among (1) intracranial haemorrhage types, (2) OAC drugs and (3) study types, with randomised controlled trials being the primary focus.

ETHICS AND DISSEMINATION: Ethical approval is not needed as this project involves previously published data. We intend to publish the results in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42024556420.

PURPOSE: To perform a meta-analysis on how the admissions of stroke and transient ischemic attack (TIA) changed during the Corona Virus infection-19 (COVID-19) pandemic and evaluate if the effect was depending on stroke severity.

METHODS: Observational cohort studies comparing the number of stroke and/or TIA admissions during a period of the pandemic compared to a period before the pandemic were identified in PubMed and Embase. After excluding studies with overlapping populations and studies without satisfactory case ascertainment, data was extracted and meta-analyzed.

FINDINGS: A total of 59 studies were included. During the pandemic, there was a decrease in admissions of ischemic stroke (admission rate ratio (ARR) = 0.77, 95% confidence interval (CI): 0.72, 0.82), intracerebral hemorrhage (ARR = 0.79, 95% CI: 0.70, 0.90) and TIA (ARR = 0.66, 95% CI: 0.58, 0.75). Albeit admission rates of both mild (ARR = 0.61, 95% CI: 0.49, 0.77) and severe (ARR = 0.82, 95% CI = 0.71, 0.95) strokes decreased, milder strokes decreased more (proportion ratio (PR) = 0.76, 95% CI: 0.65, 0.89).

DISCUSSION: Potential causes for the admission reduction could be strict prioritizations within the health care, patients' fear of acquiring COVID-19, or decreased access to health care due to lockdowns.

CONCLUSION: During the COVID-19 pandemic, there was a reduction in admissions of stroke and TIA, possibly caused by reluctance to seek medical care.

BACKGROUND: Due to the rapid growth of the world´s oldest population, the number of older persons with stroke is expected to rise. Knowledge of stroke etiology is essential to offer personalized and equal health care across age groups. The present systematic review aimed to investigate the prevalence of etiological subtypes of ischemic and hemorrhagic stroke in older compared to younger people.

METHODS: MEDLINE, Embase, Cochrane, Epistemonikos, and Cinahl were systematically searched for studies regarding etiological classification in people ≥80 years compared to those <80 years with ischemic or hemorrhagic stroke.

RESULTS: Out of 28 441 identified articles, eight met the inclusion criteria. In total, 8223 individuals were included in meta-analyses, of whom 2997 were 80 years or older. We demonstrated a higher prevalence of cardioembolic stroke in people ≥80 years OR 1.68 (95% CI, 1.12-2.53). Small vessel disease was significantly less common in older people OR .64 (95% CI, .50-.81). Regarding large vessel disease, no statistically significant difference between the two groups was shown OR 1.05 (95% CI, .77-1.43).

CONCLUSION: In people ≥80 years, cardioembolic stroke is more common, and small vessel disease less common compared to people <80 years. Overall, the results have to be interpreted with caution due to few studies. Large studies using validated classification systems are needed.

PURPOSE: Testosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments.

METHODS: Testosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose.

RESULTS: The testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected.

CONCLUSION: The current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women.

INTRODUCTION: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity.

METHODS AND ANALYSIS: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72 hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3 months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up.

ETHICS AND DISSEMINATION: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice.

TRIAL REGISTRATION NUMBER: NCT05134454.

Testosterone is thought to be incorporated in growing hair strands so that specific hair segments reflect average free hormone concentrations from the corresponding time period. However, the exact mechanisms of hormone integration in scalp hair have not yet been established and it is not known how testosterone is stored in the hair segments over time. The aim of this study was to investigate the stability of testosterone concentrations in hair as it grows and to determine if segmental hair analysis can be used as a retrospective testosterone diary. Thirty men and 40 women provided two hair samples and 16 saliva samples during a period of three months. Hair growth between the two samplings was measured. Hair samples were cut into 10 mm segments resulting in three segments from the first sampling and six segments from the second sampling. Hair samples were pulverised and extracted with methanol. Hair testosterone concentrations were analysed using an in-house radioimmunoassay. Salivary testosterone was analysed using a commercial enzyme-linked immunosorbent assay (Demeditec). The results demonstrated that there is a degree of segmental hormone conservation over time (rho = 0.405-0.461, p < 0.001, n = 66-67), but also highlighted three potential confounders. Firstly, testosterone concentrations were higher in distal hair segments (mean concentration ratio most distal by most scalp-near was 1.55, SD 0.70), which may be due to continuous hormone integration from sebum and changes in hair matrix composition. Secondly, more frequent hair washing stunted the increase in testosterone concentrations in distal segments (rho = -0.404, p =  < 0.001, n = 66). And lastly, intra- and inter- individual variability in hair growth rate influenced the temporal resolution along the hair, although mean growth rate was indeed 30.0 mm for three months. In a multiple regression model the biological sex, natural hair colour, and relationship status were significant explanatory variables to hair testosterone concentrations. The current results indicate that repeated hair sampling near the hair roots during a study may be preferable to analysing concentration changes between proximal and distal segments within the same hair sample. Also, hair testosterone analysis needs to be adjusted for sex and the natural hair colour.