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Stroke is a leading cause of death and disability. Some patients may present with atypical symptoms. One of the very rare presentations of stroke is initial neurogenic pain. Rare painful presentations include, amongst others, acute trigeminal neuralgia, atypical facial pain, hemi-sensory pain, and episodic pain. Based on the available literature, the pain at presentation may be episodic, transient, or persistent, and it may herald other debilitating stroke symptoms such as hemiparesis. Pain quality is often described as burning; less often as sharp. Patients often have accompanying focal symptoms and findings on neurological examination. However, in several of the reviewed cases, these were discrete or non-existent. In patients with pain located in the trunk and/or extremities, lesions may involve the thalamus, lateral medulla oblongata, insula, or parietal lobe. In patients with atypical facial or orbital pain (including the burning “salt and pepper” sensation), the stroke lesions are typically located in the pons. In this narrative review, we included studies/case series of patients who had pain at the time of onset, shortly before or within 24 h of stroke symptoms (on the day of admission). Cases with pain related to aortic or cervical vessel dissection, cerebral venous sinus thrombosis, subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, and CNS vasculitis were excluded. With this review, we aim to summarize the current knowledge on stroke presenting with acute pain.

BACKGROUND: The risk of thrombosis increases in infectious diseases, yet observational studies from single centers have shown a decrease in admission of acute ischemic stroke patients during the COVID-19 pandemic. To investigate unselected stroke admission rates we performed a nationwide study in Denmark.METHODS: We extracted information from Danish national health registries. The following mutually exclusive time periods were compared to the year before the lockdown: (1) first national lockdown, (2) gradual reopening, (3) few restrictions, (4) regional lockdown, and (5) second national lockdown.RESULTS: Generally, admission rates were unchanged during the pandemic. In the unadjusted data, we observed a small decrease in the admission rate for all strokes under the first lockdown (incidence rate ratio: 0.93, confidence interval [CI]: 0.87-0.99) and a slight increase during the periods with gradual reopening, few restrictions, and the regional lockdown driven by ischemic strokes. We found no change in the rate of severe strokes, mild strokes, or 30-day mortality. An exception was the higher mortality for all strokes during the first lockdown (risk ratio: crude 1.30 [CI: 1.03-1.59]; adjusted 1.17 [CI: 0.93-1.47]). The quality of care remained unchanged.CONCLUSION: Stroke admission rates remained largely unchanged during the pandemic, while an increased short-term mortality rate in patients admitted with stroke observed during the first lockdown was seen, probably reflecting that the more frail patients constituted a higher proportion of admitted patients at the beginning of the pandemic.

Introduction: Evidence-based early stroke care as reflected by fulfillment of process performance measures, is strongly related to better patient outcomes after stroke and transient ischemic attack (TIA). Detailed data on the resilience of stroke care services during the COVID-19 pandemic are limited. We aimed to examine the quality of early stroke care at Danish hospitals during the early phases of the COVID-19 pandemic. Materials and methods: We extracted data from Danish national health registries in five time periods (11 March, 2020–27 January, 2021) and compared these to a baseline pre-pandemic period (13 March, 2019–10 March, 2020). Quality of early stroke care was assessed as fulfilment of individual process performance measures and as a composite measure (opportunity-based score). Results: A total of 23,054 patients were admitted with stroke and 8153 with a TIA diagnosis in the entire period. On a national level, the opportunity-based score (95% confidence interval [CI]) at baseline for ischemic patients was 81.1% (80.8–81.4), for intracerebral hemorrhage (ICH) 85.5% (84.3–86.6), and for TIA 96.0% (95.3–96.1). An increase of 1.1% (0.1–2.2) and 1.5% (0.3–2.7) in the opportunity-based score was observed during the first national lockdown period for AIS and TIA followed by a decline of −1.3% (−2.2 to −0.4) in the gradual reopening phase for AIS indicators. We found a significant negative association between regional incidence rates and quality-of-care in ischemic stroke patients implying that quality decreases when admission rates increase. Conclusion: The quality of acute stroke/TIA care in Denmark remained high during the early phases of the pandemic and only minor fluctuations occurred.

OBJECTIVES: The main aim of the study is to investigate the performance of a two-part stroke scale for screening and subsequent severity assessment combined with a telephone conference (teleconference).MATERIALS AND METHODS: During a 6-month period, we prospectively tested the Prehospital Stroke Score (PreSS). PreSS part 1 is designed to identify stroke or TIA in a prehospital setting. PreSS part 2 is a stroke severity scale designed to identify large-vessel occlusion (LVO). PreSS was performed by emergency medical service (EMS) providers prior to a teleconference with a stroke neurologist.RESULTS: Combined teleconference and PreSS part 1 were performed on 79.3% of all patients diagnosed with stroke/TIA, and 99.1% of the patients with positive scores were subsequently PreSS part 2 scored. PreSS part 1 and teleconference had a sensitivity to identify stroke/TIA of 89.3% (95% CI 85.7-92.2), specificity of 64.5% (95% CI 59.3-69.5), and an area under the curve (AUC) of 0.80 (95% CI 0.77-0.83). Regarding LVO, PreSS part 1 with teleconference recognized 96.7% (95% CI 88.7-99.6) of all cases as stroke. PreSS part 2 had a sensitivity of 55.7% (95% CI 42.4-68.5), specificity of 91.5% (95% CI 89.0-93.6), and AUC of 0.86 (95% CI 0.82-0.90) for identification of LVO.CONCLUSIONS: PreSS was feasible and the sensitivity for stroke/TIA and LVO was high to moderate providing an overall high precision. Almost all LVO cases were ensured acute stroke admission. The high specificity for LVO could be useful for determining transfers strategies.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence when evaluating PreSS combined with teleconference.

BackgroundDespite effective treatments, many patients are still not offered reperfusion therapy for acute ischemic stroke.MethodsWe present a single-center observational study on acute ischemic stroke patients, who presented as candidates for reperfusion therapy but were deemed ineligible after work-up. Reasons for non-treatment were obtained by studying patient files and subsequently grouped into “too risky” (e.g., anticoagulant use, comorbidities), “too large” (large infarct), “too late” (late presentation of stroke and wake-up strokes), or “too mild” (clinically mild/remitting symptoms). Modified Rankin scale (mRS) score was prospectively collected in all patients by a structured telephone interview. All non-treated patients with a National Institute of Health Stroke Scale (NIHSS) score of 0–5 were compared with a similar cohort that was treated.ResultsOf 529 patients with acute ischemic stroke arriving as reperfusion therapy candidates, 198 (37.4%) were not treated. The majority (42%) were not treated due to admission outside the treatment window (too late) and 24% had absolute contraindications (too risky). Only 8% was excluded because their infarct was too large [median Alberta Stroke Program Early CT score 3 (2–4)]. In the “too mild” group (14%) the percentage of patients not being independent at 90 days was 30%. The adjusted odds ratio for a better outcome (lower mRS) among treated patients with NIHSS 0–5 compared with non-treated was 1.93 (95% confidence interval 1.15–3.23).ConclusionPresenting outside the treatment window is still the most common reason for not receiving therapy. Our study suggests a benefit of thrombolysis for patients with mild symptoms.

The aging process leads to subtle decline in cognitive function, and in some overt dementia. Like physical activity Remote Ischemic Conditioning (RIC) may ameliorate these changes on cognitive impairment in humans. The purpose of this study was to compared the effects of single, repeated short-term and long-term treatment RIC, and analyze its effect registered as immediate vs. long-term on cognitive performance in humans. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with PROSPERO, number (CRD42021285668). A systematic review was conducted to identify relevant studies through six healthcare science databases (Cochrane, PubMed, EMBASE, EBSCO, Scopus, and Web of Science) up to December 2021. Eligibility criteria included (1) a study sample of participants aged ≥18 years, (2) post-intervention changes on cognitive performance in humans, and (3) this systematic review included only randomized controlled trials of RIC in humans. The quality of the included studies was assessed by GRADEpro tool. A total of 118 articles were initially identified, 35 of which met the inclusion criteria. Based on title/abstract, age and RIC protocol, 14 articles were included in this review: 5 studies investigated the immediate and long-term effect of a single RIC (n = 370 patients), 4 studies examined intermittent short-term RIC (n = 174 patients) and 5 studies evaluated repeated long-term RIC (n = 228 patients). A single pre-operative RIC treatment had an immediate effect that disappeared at one week. Short-term RIC showed either a positive or no effects on cognitive function. The majority of studies examining long-term RIC treatment showed improvements in cognitive performance, particularly in very old adults and older patients with cognitive impairments. Single RIC treatment did not show any persisting effect on cognition. However, repeated short term RIC showed some improvement and long-term RIC may improve cognitive performance after stroke or enhance neuropsychological tests in patients diagnosed with vascular dementia. The mixed results might be explained by different RIC treatment protocols and populations investigated.

We describe the first Danish case of presumed inflammatory and thrombotic response to vaccination with an adenoviral (ChAdOx1) vector based COVID-19 vaccine (AZD1222). The case describes a 60-year old woman, who was admitted with intractable abdominal pain seven days after receiving the vaccine. Computer Tomography (CT) of the abdomen revealed bilateral adrenal hemorrhages. On the following day she developed a massive right sided ischemic stroke and Magnetic Resonance Imaging (MRI) angiography showed occlusion of the right internal carotid artery. The ischemic area was deemed too large to offer reperfusion therapy. During admission, blood tests showed a remarkable drop in platelet counts from 118,000 to 5,000 per µL and a substantial increase in D-dimer. The patient died on the 6th day of hospitalization. Blood test revealed platelet factor 4 (PF-4) reactive antibodies, imitating what is seen in heparin-induced thrombocytopenia. This may be a novel immune mediated response to the vaccine.

Bladder dysfunction may occur in acute stroke patients and as a consequence the risk of urinary retention, incontinence and urinary tract infections increases. The literature is sparse regarding occurrence of bladder dysfunction in acute stroke and if catheterization should be performed to prevent bladder overdistension in acute stroke thrombolysis. The aim of this study was to investigate the safety of implementing a new selective and “watchful waiting strategy” for intermittent catheterization during acute stroke thrombolysis. From November 2018 to June 2019, we conducted a prospective cohort study before and after implementing (in March 2019) a selective and watchful waiting strategy for intermittent catheterization. Data were collected on nurse-administered registration forms for ischemic stroke patients treated with thrombolysis. In both periods urogenital complications were registered. We found no significant differences between period 1 (before) and 2 (after) in the occurrence of urinary tract infections and/or macroscopic urogenital bleeding episodes. However, for developing blood in the 24hour urine analysis we found a significant reduction in period 2 compared to period 1, 8 (23%) vs 3 (7%) respectively. Applying a selective and watchful waiting strategy towards urinary catheterization in acute ischemic stroke patients treated with intravenous thrombolysis did not increase the risk of urogenital complications, and the discomfort associated with catheterization was limited to fewer patients.

OBJECTIVES: Prehospital delay is the main reason why only a limited number of stroke patients receive reperfusion therapy. We aimed to investigate help-seeking behaviour in patients and bystanders after onset of stroke and subsequent patient and system delay.MATERIALS & METHODS: We conducted a cross-sectional study of 332 patients with stroke. We performed structured interviews and used data from the medical records and the Danish Stroke Registry. Primary outcomes were patient delay and system delay.RESULTS: The median patient delay was 280 min, and the median system delay was 97 min. For a patient delay of CONCLUSIONS: Patient delay remains the main reason for delayed arrival at the stroke centre. Appropriate help-seeking behaviour and efficient pre-hospital triage are essential for reducing the prehospital delay and increasing the proportion of patients receiving reperfusion therapy.

Remote ischemic conditioning (RIC) is a promising safe, feasible, and inexpensive treatment for acute stroke, both ischemic and hemorrhagic. It is applied with a blood pressure cuff on the limbs and is ideal for the prehospital setting. RIC is a form of preconditioning with similarities to physical exercise. Its mechanisms of action are multiple and include improvement of collateral cerebral blood flow (CBF) and RIC acts as a “collateral therapeutic”. The increased CBF is likely related to nitric oxide synthase 3 in the endothelium and more importantly in circulating blood cells like the red blood cell. The RESIST clinical trial is a 1500 subject multicenter, randomized, sham-controlled trial of RIC in the prehospital setting in Denmark and should address the questions of whether RIC is safe and effective in acute stroke and whether the effect is mediated by an effect on nitric oxide/nitrite metabolism.

IMPORTANCE: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. OBJECTIVE: To assess the efficacy of RIC for acute moderate ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, blinded–end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. INTERVENTIONS: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). MAIN OUTCOMES AND MEASURES: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. RESULTS: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. CONCLUSIONS AND RELEVANCE: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03740971

Stroke is a leading cause of death and disability. Intravenous thrombolysis and mechanical thrombectomy have greatly improved outcomes in acute ischemic stroke (AIS). However, only a minority of patients receive reperfusion therapies, highlighting the need for novel neuroprotective therapies. Remote ischemic conditioning (RIC), consisting of brief, intermittent extremity occlusion and reperfusion induced with an inflatable cuff, is a potential neuroprotective therapy in acute stroke. The objective of this narrative review is to describe the effect of RIC on endogenous fibrinolysis and, from this perspective, investigate the potential of RIC in the prevention and treatment of stroke. A systematic literature search was performed in PubMed, and human studies in English were included. Seven studies had investigated the effect of RIC on fibrinolysis in humans. Long-term daily administration of RIC increased endogenous fibrinolysis, whereas a single RIC treatment did not acutely influence endogenous fibrinolysis. Fifteen studies had investigated the effect of RIC as a neuroprotective therapy in the prevention and treatment of stroke. Long-term RIC administration proved effective in reducing new cerebral vascular lesions in patients with established cerebrovascular disease. In patients with acute stroke, RIC was safe and feasible, though its clinical efficacy as a neuroprotectant is yet unproven. In conclusion, a single RIC treatment does not affect fibrinolysis in the acute phase, whereas long-term RIC administration may increase endogenous fibrinolysis. Increased endogenous fibrinolysis is unlikely to be the mediator of the acute neuroprotective effect of RIC in stroke patients, whereas it may partly explain the reduced stroke recurrence associated with long-term RIC treatment.

Introduction Only a minority of patients with acute ischaemic stroke receive reperfusion treatment, primarily due to prehospital delay. We aimed to investigate predictors of a primary contact to the emergency medical services, arrival at stroke centre within 3 h of symptom onset and initiation of reperfusion therapy in patients with acute stroke. Patients and methods We conducted a cross-sectional study of consecutive patients with acute ischaemic stroke, intracerebral haemorrhage or transient ischaemic attack. Structured interviews of patients and bystanders were performed and combined with clinical information from the Danish Stroke Registry. Eligible patients were aged ≥18 years and were independent in activities of daily living before the stroke. Results We included 435 patients. Presence of a bystander at symptom onset and knowledge of ≥2 core symptoms of stroke were associated with a primary emergency medical services contact. Higher stroke severity and patients or bystanders perceiving the situation as very serious were associated with a primary emergency medical services contact (ORpatients 2.10; 95% CI 1.12–3.95 and ORbystanders 22.60; 95% CI 4.98–102.67), patients 3.01; 95% CI 1.46–6.21 and ORbystanders 4.44; 95% CI 1.37–14.39) and initiation of reperfusion therapy (ORpatients 3.08; 95% CI 1.23–7.75 and ORbystanders 4.70; 95% CI 1.14–19.5). Conclusion: Having a bystander, knowledge of ≥2 core symptoms and understanding that stroke is a serious event are associated with appropriate help-seeking behaviour, shorter prehospital delay and higher chance of reperfusion therapy in acute stroke patients.

There is a large unmet need for fast and reliable diagnostics in several diseases. One such disease is stroke, where the efficacy of modern reperfusion therapies is highly time-dependent. Diagnosis of stroke and treatment initiation should be performed as soon as possible, and preferably before arrival at the stroke center. In recent years, several potential blood biomarkers for stroke have been evaluated, but without success. In this review, we will go into detail on the possibility of utilizing extracellular vesicles (EVs) released into the blood as novel biomarkers for stroke diagnostics. EVs are known to reflect the immediate state of the secreting cells and to be able to cross the blood–brain barrier, thus making them attractive as diagnostic biomarkers of brain diseases. Indeed, several studies have reported EV markers that enable differentiation between stroke patients and controls and, to a lesser extent, the ability to correctly classify the different stroke types. Most of the studies rely on the use of sophisticated and time-consuming methods to quantify specific subpopulations of the nanosized EVs. As these methods cannot be easily implemented in a rapid point of care (POC) test, technical developments followed by prospective clinical studies are needed.

Background and Purpose: Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This effect is lost in NOS3-KO mice. We wanted to determine if the beneficial effect of C-RIC can be restored by bone marrow cell-derived NOS3. Methods: We prepared BM chimera from adult WT (B6.SJL-Ptprc a ; CD45.1) to adult NOS3-KO (B6.129; CD45.2) & vice versa in male mice (5-6 months) following confirmation for BM engrafting with flow cytometry at 2 weeks. Microcoil (0.18 mm) induced BCAS model was used to induce chronic hypoperfusion. Mice were randomly assigned to 3-groups: (1) Sham (2) BCAS and (3) BCAS+RIC. RIC was started 7d post-surgery daily for 3-4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. We measured whole blood P-NOS3, P-AMPK and VEGFR2/CD31 by flow cytometry. Results: C-RIC-therapy for 3-4 weeks improves CBF in engrafted BM of WT into NOS3-KO in the BCAS+RIC groups at both 2 weeks and 4 weeks compared to BCAS (Sham RIC groups).No effect of C-RIC was shown in engrafted BM of NOS3 into WT. There was significant change between the BCAS and BCAS+RIC groups in the functional outcomes and histopathological evidences also reflects major changing in the groups in the BM of WT into NOS3-KO mice. Whole blood P-NOS3, P-AMPK and VEGFR2/CD31 was increased by C-RIC. However, no effect was shown in the NOS3-KO into WT chimera. Conclusions: The Beneficial effect of C-RIC is dependent upon bone marrow derived NOS3.Further studies are needed to determine if the red blood cell is the key cell carrying NOS3

Introduction: Physical activity (PA) is associated with a lower risk of stroke and stroke mortality as well as a favorable stroke outcome. PA may also prevent general cognitive decline. Poststroke cognitive impairment is both common and disabling, and focusing on all possible preventive measures is important. Studies on the effect of PA on poststroke cognitive performance are sparse, however. We therefore aimed to examine the association between prestroke PA and poststroke cognitive performance. Methods: We studied the correlation between prestroke PA and poststroke cognitive performance in a prespecified analysis in The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS) trial. We used the Physical Activity Scale for the Elderly (PASE) to collect information on PA during the 7-day period before stroke. PA was quantified, and patients were stratified into quartiles based on their PASE score. Cognitive performance was measured using the Symbol Digit Modalities Test (SDMT) at 1 and 6 months and the Mini-Mental State Examination (MMSE) at 6 months. The functional outcome was assessed using the modified Rankin Scale (mRS). Results: In total, 625 of 642 patients (97%) completed the PASE questionnaire. The median age was 69 (interquartile range [IQR]: 60–77), and the median PASE score was 137 (82–205). Higher prestroke PASE quartiles (2nd, 3rd, and 4th, each compared to the 1st) were independently associated with a higher SDMT score at 1 month in the both the univariable and multivariable analyses (2nd: 3.99 points, 95% confidence interval [CI]: 1.01–6.97; 3rd: 3.6, CI: 0.6–6.61; 4th: 4.1, CI: 0.95–7.24). This association remained at 6 months. PA was not statistically associated with the MMSE score or mRS. Conclusion: Higher prestroke PA was associated with a better cognitive performance as measured by the SDMT at 1 and 6 months poststroke. We found no significant association between prestroke PA and functional outcome. Our results are encouraging and support further investigations of PA as a protective measure against poststroke cognitive impairment.

Rationale For patients with acute ischemic stroke and large vessel occlusions, intravenous thrombolysis and endovascular therapy are standard of care, but the effect of endovascular therapy is superior to intravenous thrombolysis. If a severe stroke with symptoms indicating large vessel occlusions occurs in the catchment area of a primary stroke center, there is equipoise regarding optimal transport strategy. Aim For patients presenting with suspected large vessel occlusions (PASS ≥ 2) and a final diagnosis of acute ischemic stroke, we hypothesize that bypassing the primary stroke center will result in an improved 90-day functional outcome. Sample size We aim to randomize 600 patients, 1:1. Design A national investigator-driven, multi-center, randomized assessor-blinded clinical trial. The Prehospital Acute Stroke Severity Scale has been developed. It identifies most patients with large vessel occlusions in the pre-hospital setting. Patients without a contraindication for intravenous thrombolysis are randomized to either transport directly to a comprehensive stroke centers for intravenous thrombolysis and of endovascular therapy or to a primary stroke center for intravenous thrombolysis and subsequent transport to a comprehensive stroke centers for of endovascular therapy, if needed. Outcomes The primary outcome will be the 90-day modified Rankin Scale score (mRS) for all patients with acute ischemic stroke. Secondary outcomes include 90-day mRS for all randomized patients, all patients with ischemic stroke but without large vessel occlusions, and patients with hemorrhagic stroke. The safety outcomes include severe dependency or death and time to intravenous thrombolysis for ischemic stroke patients. Discussion Study results will influence decision making regarding transport strategy for patients with suspected large vessel occlusions.

Rationale: Remote ischaemic conditioning, applied in the prehospital setting and continued in-hospital, may improve functional outcome in patients with acute ischaemic stroke and intracerebral haemorrhage. Aims: To evaluate whether combined remote ischaemic per- and postconditioning can improve long-term functional outcome in acute ischaemic stroke and intracerebral haemorrhage patients. Methods and design: Danish multicentre, prospective, randomised, patient-assessor blinded, sham-controlled study. Adult patients with a putative stroke identified prehospital with symptom duration

Background: Prehospital delay has several causes, most of them being patient-dependent. Knowledge of how patients and bystanders actually experience and react to symptoms at onset are essential. Purpose: Our aim is to characterize symptoms described by patients and bystanders at onset, perceived symptom seriousness, and whether this was associated with calling EMS directly. Methods: A cross-sectional study of consecutive acute stroke and TIA patients admitted at two stroke centres in the Central Denmark Region, in a three months period in 2018. Structured interviews of pre-stroke independent patients and bystanders were performed separately. Questions were open-ended. Symptoms identified as indicating stroke were classified as being focal or non-focal and perceived seriousness as mild or moderate/severe. Analysis were performed using logistic regression analysis. Results: A total of 1210 patients had a stroke/TIA in the period, of these 469 were included. We performed 654 interviews of patients and/or bystanders in median 1 day after stroke admission. Most frequent recognized symptoms by patients were limb palsy (31%), speech difficulties (26%) and dizziness (21 %). For bystanders: speech difficulties (47%), limb palsy (39%) and facial palsy (26%). Of patients and bystanders, 29 % and 23 % could not describe at least one focal symptom at onset. Focal symptoms were perceived as more serious in both patients and bystanders, OR (95% CI) 2.2 (1.29-3.76) and 2.61 (1.32-5.14). Patients who perceived symptoms as serious were more likely to make a direct EMS call, OR 2.10 (1.23-3.61). For bystanders, symptoms perceived as serious, were strongly associated with a direct EMS call: OR 22.7 (3.05-169.61). In patients being alone at stroke onset (98 (21%)) only 16% were able to call EMS directly and median (IQR) stroke severity (Scandinavian Stroke Scale) was lower among those calling EMS directly 57(52-58) vs 51(43-52), p Conclusion: Approximately 1 in 3 patients did not recognize focal stroke symptoms, but when focal symptoms were recognized and perceived as serious, this was associated with direct EMS call. The role of a bystander is pivotal and bystanders role to step in of importance.

Introduction: We investigated the association between pre-stroke core symptom knowledge and recognition of core symptoms at stroke onset, with prehospital delay and receiving reperfusion therapies. Core symptoms are defined as facial palsy, palsy of extremities and aphasia/dysarthria. Methods: A cross-sectional study of consecutive patients with acute stroke and TIA admitted at two stroke centres in the Central Denmark Region, between January 28 th 2018 and May 10 th 2018. Structured interviews of patients and bystanders (separately), combined with clinical information from the Danish stroke registry were obtained. Eligible patient were > 18 years, independent in daily activities (mRS Results: We included 469 of 1210 stroke/TIA patients in the period with a median (IQR) age of 71 (61-80). Median (IQR) admission-to-interview time was 1 (1-1) day. Pre-stroke knowledge of ≥ 1 core symptom was 46 % for patients and 71 % for bystanders. Knowledge of ≥ 2 core symptoms was 22 % and 52 % respectively. Pre-stroke knowledge in patients was not significantly associated to EMS contact, onset-to admission < 3 hours or reperfusions therapy, but in bystanders pre-stroke knowledge of ≥ 2 core symptoms was associated with increased EMS contact OR (95% CI) 2,35 (1,24-4.45) and receiving reperfusion therapy 1,94 (1,04-3.61). Help-seeking based on ≥ 1 observed core symptom at onset by bystanders and ≥ 2 core symptoms experienced by patients were significantly associated with a direct EMS contact, onset-to admission < 3 hours and receiving reperfusions therapy. Conclusions: Pre-stroke knowledge and help-seeking based on observed core symptoms at onset is essential reducing prehospital delay and increasing reperfusion rates. The pivotal role of bystanders “to act” should be a target for future stroke awareness campaigns.

Background: A high prestroke physical activity (PA) level is associated with reduced stroke rate, stroke mortality, better functional outcome, and possible neuroprotective abilities. The aim of the present study was to examine the possible neuroprotective effect of prestroke PA on 24-h cerebral infarct growth in a cohort of acute ischemic stroke patients treated with intravenous tPA and randomized to remote ischemic perconditioning. Methods: In this predefined subanalysis, data from a randomized clinical trial investigating the effect of remote ischemic perconditioning (RIPerC) on AIS was used. Prestroke (7 days before admission) PA was quantified using the PA Scale for the Elderly (PASE) questionnaire at baseline. Infarct growth was evaluated using MRI (acute, 24-h, and 1-month). Results: PASE scores were obtained from 102 of 153 (67%) patients with a median (interquartile range) age of 66 (58-73) years. A high prestroke PA level correlated significantly with reduced acute infarct growth (24 h) in the linear regression model (4th quartile prestroke PA level compared with the 1st quartile), β4th quartile = -0.82 (95% CI -1.54 to -0.10). However, the effect of prestroke PA was present mainly in patients randomized to RIPerC, β4th quartile = -1.14 (95% CI -2.04 to -0.25). In patients randomized to RIPerC, prestroke PA was a predictor of final infarct size (1-month infarct volume), β4th quartile = -1.78 (95% CI -3.15 to -0.41). Conclusion: In AIS patients treated with RIPerC, as add-on to intravenous thrombolysis, the level of PA the week before the stroke was associated with decreased 24-h infarct growth and final infarct size. These results are highly encouraging and stress the need for further exploration of the potentially protective effects of both PA and remote ischemic conditioning.

Objective. Alterations of the electroencephalogram (EEG) have been reported in patients with hepatic encephalopathy (HE). However, previous methods have not assessed transient phenomena in the EEG signal (dynamics) and associations to psychometric test performance have in general been poor. The aims were to quantify spectral and dynamic EEG abnormalities in patients with HE and to correlate putative findings to psychometric test performances. Methods. Multichannel EEG (64 electrodes) was recorded in 24 cirrhotic patients with various grades of HE and 26 healthy volunteers. Spectral and dynamic EEG indices were quantified by continues wavelet analysis. In addition, the psychometric hepatic encephalopathy score (PHES), continues reaction time, and biochemical profile were assessed. Results. Compared with healthy volunteers, patients had progressively slowing of the EEG (all p ≤ 0.004) (spectral EEG indices) and increased variability in the alpha [7.5-13.5 Hz] (p = 0.001) and beta bands [13.5-32 Hz] (p = 0.02) (dynamic EEG indices). In addition, anteriorization and dissociation of the basic posterior alpha rhythm, along with dissociation of frontal delta activities [1-3.5 Hz] were seen with worsening of HE. Spectral EEG indices (all frequency bands) as well as dynamic EEG indices (alpha and beta bands) were correlated to PHES scores (all p

Udgivelsesdato: 2010 BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a severe and frequent complication of liver cirrhosis characterized by abnormal cerebral function. Little is known about the underlying neural mechanisms in HE and human data are sparse. Electrophysiological methods such as evoked brain potentials after somatic stimuli can be combined with inverse modeling of the underlying brain activity. Thereby, information on neuronal dynamics and brain activity can be studied in vivo. The aim of this study was to investigate the sensory brain processing in patients with HE. PATIENTS AND METHODS: Twelve patients with minimal or overt HE and 26 healthy volunteers were included in the study. Cerebral sensory processing was investigated as (i) an auditory reaction time task; (ii) visual and somatosensory evoked brain potentials, and (iii) reconstruction of the underlying brain activity. RESULTS: Somatosensory evoked potentials were reproducible (all P>0.05), whereas flash evoked potentials were not reproducible (all P

Remote ischaemic conditioning (RIC) triggers endogenous protective pathways in distant organs such as the kidney, heart and brain, and represents an exciting new paradigm in neuroprotection. RIC involves repetitive inflation and deflation of a blood pressure cuff on the limb, and is safe and feasible. The exact mechanism of signal transmission from the periphery to the brain is not known, but both humoral factors and an intact nervous system seem to have critical roles. Early-phase clinical trials have already been conducted to test RIC in the prehospital setting in acute ischaemic stroke, and in subarachnoid haemorrhage for the prevention of delayed cerebral ischaemia. Furthermore, two small randomized clinical trials in patients with symptomatic intracranial atherosclerosis have shown that RIC can reduce recurrence of stroke and have neuroprotective activity. RIC represents a highly practical and translatable therapy for acute, subacute, and chronic neurological diseases with an ischaemic or inflammatory basis. In this Review, we consider the principles and mechanisms of RIC, evidence from preclinical models and clinical trials that RIC is beneficial in neurological disease, and how the procedure might be used in the future in disorders such as vascular cognitive impairment and traumatic brain injury.

Background and aims Autonomic neuropathy seems to play a central role in the development of gastrointestinal symptoms in diabetes. In order to explore the neuronal mechanisms behind the symptoms we evaluated the brain processing of painful visceral stimuli. Methods Evoked brain potentials were recorded to assess the response to painful oesophageal electrical stimuli in 15 healthy volunteers and 14 type-1 diabetes patients with autonomic neuropathy and related gastrointestinal symptoms. Source reconstruction analysis (fixed Multiple Signal Classification (MUSIC) algorithm) was applied to estimate the location of the evoked electrical activity in the brain. Results The patients had increased oesophageal sensory thresholds compared to the controls (P = 0.004). The latencies of the evoked brain potentials at vertex (Cz) were increased (P = 0.007) and amplitudes reduced (P = 0.011) in diabetics. Compared with controls the patients had a posterior shift of the electrical sources in the anterior cingulate cortex at 54 ms, and additional sources close to the posterior insula at 95 ms and in medial frontal gyrus at 184 ms. Conclusions There is evidence of altered central processing to visceral stimulation, and both peripheral and central mechanisms seem involved. Central neuronal reorganisation may contribute to our understanding of the gastrointestinal symptoms in patients with diabetic autonomic neuropathy and this may guide development and evaluation of new treatment modalities.