Safety and early outcomes after intravenous thrombolysis in acute ischemic stroke patients with prestroke disability.

BACKGROUND: There are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability. AIM: We aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability. METHODS: We analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3-5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h). RESULTS: Patients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60-1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83-1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73-0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21-1.61) (10.40% vs. 4.93%)). CONCLUSIONS: Intravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.

Home-Time Is a Feasible and Valid Stroke Outcome Measure in National Datasets.

Background and Purpose- Home-time (HT) is a stroke outcome measure based on time spent at home after stroke. We hypothesized that HT assessment would be feasible and valid using national data. Methods- We linked the Scottish Stroke Care Audit to routine healthcare data and calculated 90-day HT for all strokes, 2005 to 2017. We described prognostic validity (Spearman rank correlation) of HT to baseline factors. Results- We were able to calculate HT for 101 969 strokes (99.3% of total Scottish strokes). Mean HT was 46 days (95% CI, 45.8-46.2; range, 0-90). HT showed consistent correlation with our prespecified prognostic factors: age: ρ, -0.35 (95% CI, -0.35 to -0.36); National Institutes of Health Stroke Scale score, -0.54 (95% CI, -0.52 to -0.55); and 6 simple variables (ordinal), -0.61 (95% CI, -0.61 to -0.62). Conclusions- HT can be derived at scale using routine clinical data and appears to be a valid proxy measure of functional recovery. Other national databases could use HT as a time and cost efficient measure of medium and longer-term outcomes.

The positive predictive value of an ambulance prealert for stroke and transient ischaemic attack.

OBJECTIVE: Therapeutic options for ischaemic stroke, such as thrombolysis or thrombectomy, are time sensitive. Multiple innovations have been established to reduce the symptom-to-needle time. One such innovation is the prealerting of emergency department (ED) or stroke unit staff by prehospital personnel of suspected stroke patients. The diagnosis of stroke can sometimes be difficult, with stroke mimics being a recognized issue. The prealert mobilizes ED, stroke and imaging personnel, which, for a true-positive, improves door-to-needle times. However, there are a proportion of false-positive prealerts (nonstrokes) that have a significant resource activation implication. The aim of this study was to evaluate the positive predictive value of a prealert for stroke and transient ischaemic attack (TIA). METHODS: Ambulance service prealert forms for stroke and TIA collated by the ED were compared with the Scottish Stroke Audit database findings, ED electronic notes and imaging reports to establish whether the prealert was a true-positive or a false-positive. RESULTS: A prealert was obtained for 77 patients as query stroke/TIA. The true-positive rate was 52 and the false-positive rate was 25. The positive predictive value was 0.675. The median symptom-to-arrival time for prealerted patients was 97 min and the door-to-needle time for thrombolysis (n=17 patients) was 38 min. CONCLUSION: The diagnosis of true-positive stroke can be difficult in the prehospital environment. Although prealert has been shown to improve the patient's journey in terms of door-to-thrombolysis times, we have identified that the prealert has a significant false-positive rate that has important resource allocation and activation consequences. Further analysis of this may inform paramedic training and improve protocols for information handover.

Avoiding unseen obstacles: Subcortical vision is not sufficient to maintain normal obstacle avoidance behaviour during reaching.

Previous research found that a patient with cortical blindness (homonymous hemianopia) was able to successfully avoid an obstacle placed in his blind field, despite reporting no conscious awareness of it [Striemer, C. L., Chapman, C. S., & Goodale, M. A., 2009, PNAS, 106(37), 15996-16001]. This finding led to the suggestion that dorsal stream areas, that are assumed to mediate obstacle avoidance behaviour, may obtain their visual input primarily from subcortical pathways. Hence, it was suggested that normal obstacle avoidance behaviour can proceed without input from the primary visual cortex. Here we tried to replicate this finding in a group of patients (N = 6) that suffered from highly circumscribed lesions in the occipital lobe (including V1) that spared the subcortical structures that have been associated with action-blindsight. We also tested if obstacle avoidance behaviour differs depending on whether obstacles are placed only in the blind field or in both the blind and intact visual field of the patients simultaneously. As expected, all patients successfully avoided obstacles placed in their intact visual field. However, none of them showed reliable avoidance behaviour - as indicated by adjustments in the hand trajectory in response to obstacle position - for obstacles placed in their blind visual field. The effects were not dependent on whether one or two obstacles were present. These findings suggest that behaviour in complex visuomotor tasks relies on visual input from occipital areas.

Reciprocal Interaction of 24-Hour Blood Pressure Variability and Systolic Blood Pressure on Outcome in Stroke Thrombolysis.

BACKGROUND AND PURPOSE: Significance and management of blood pressure (BP) changes in acute stroke care are unclear. Here, we aimed to investigate the impact of 24-hour BP variability (BPV) on outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. METHODS: From the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis registry, 28 976 patients with documented pre-treatment systolic BP at 2 and 24 hours were analyzed. The primary measure of BP variability was successive variability. Data were preprocessed using coarsened exact matching. We assessed early neurological improvement, symptomatic intracerebral hemorrhage (SICH), and long-term functional outcome (modified Rankin Scale [mRS] at 90 days) by binary and ordinal regression analyses. RESULTS: Attempts to explain successive variation for analysis of BPV with patients characteristics at admission found systolic BP (5.5% variance) to be most influential, yet 92% of BPV variance remained unexplained. Independently from systolic BP, successive variation for analysis of BPV was associated with poor functional outcome mRS score of 0 to 2 (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90-0.98), disadvantage across the shift of mRS (OR, 1.04; 95% CI, 1.01-1.08), mortality (OR, 1.10; 95% CI, 1.01-1.08), SICHSITS (OR, 1.14; 95% CI, 1.06-1.23), and SICHECASS (OR, 1.24; 95% CI, 1.10-1.40; ECASS [European Cooperative Acute Stroke Study 2]). Analyzing successive variation for analysis of BPV as a function of pre-treatment, systolic BP significantly improved the prediction of functional outcome (mRS score of 0-1, mRS score of 0-2, neurological improvement, mRS-shift: all Pinteraction<0.01). Excluding patients with atrial fibrillation in a sensitivity analysis gave consistent results overall. CONCLUSIONS: This study suggests the need for a more individual BP management accounting for pre-treatment BP and the acute BP course (ie, BPV) to achieve best possible outcome for the patient.

The role of emotion regulation on social participation following stroke.

UNLABELLED: Following stroke, individuals often experience reduced social participation, regardless of physical limitations. Impairments may also occur in a range of cognitive and emotional functions. Successful emotion regulation, which has been identified as important in psychological adaptation to chronic illness, is associated with better perceived psychological well-being and social functioning. However, there is little evidence about the effect of stroke on emotion regulation difficulties, and associated impact on important outcomes in recovery from stroke. OBJECTIVES: The objectives were (1) to determine whether people who have had a stroke reported greater difficulties in emotion regulation than controls and (2) to establish whether emotion regulation difficulties relate to social participation. METHODS: 75 stroke and 40 healthy participants completed measures of emotion regulation (DERS), social participation (Modified Functional Limitation Profile [mFLP], WHOQoL-Bref) and activity limitations (mFLP). Stroke participants were seen at the acute stage (63 days post-stroke) for Study 1 and 18 months post-stroke for Study 2. RESULTS: In Study 1, acute-stage stroke patients had significant impairments on impulse control, awareness of emotions, and strategies for emotion regulation. There was also evidence that emotion regulation difficulties (impulse control, awareness and clarity about emotions) were associated with social participation in the stroke sample, even after controlling for potential confounders. In Study 2, there was evidence that, in the chronic-stage post-stroke, difficulties with strategy and acceptance of emotions were associated with social participation restrictions. Whilst emotion regulation as a whole in the acute phase predicted social participation in the chronic phase of stroke, no one domain of emotion regulation was a significant predictor of social participation >1 year later. DISCUSSION: These results indicate that multiple aspects of emotion regulation are impaired following stroke, with implications for social participation and recovery. PRACTITIONER POINTS: This research highlights the following important clinical implications: Following a stroke, emotion regulation can be immediately and persistently affected, with post-stroke individuals experiencing greater difficulties with their emotion regulation than control participants. Emotion regulation can significantly predict important stroke outcomes including social participation and quality of life, over and above physical limitations and other post-stroke confounders. This study highlights the potential for developing a behaviour change intervention to address emotion regulation difficulties and thus ensuring individuals maximize their potential rehabilitation outcome. Cautions of the study for consideration: Emotion regulation was a self-report measure, and proxy measures would have been desirable. We are unable to establish if the post-stroke individuals differed from the controls on their emotion regulation prior to stroke.

Genome-wide analysis of blood pressure variability and ischemic stroke.

BACKGROUND AND PURPOSE: Visit-to-visit variability in blood pressure (vBP) is associated with ischemic stroke. We sought to determine whether such variability has genetic causes and whether genetic variants associated with BP variability are also associated with ischemic stroke. METHODS: A Genome Wide Association Study (GWAS) for loci influencing BP variability was undertaken in 3802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, in which long-term visit-to-visit and within-visit BP measures were available. Because BP variability is strongly associated with ischemic stroke, we genotyped the sentinel single nucleotide polymorphism in an independent ischemic stroke population comprising 8624 cases and 12 722 controls and in 3900 additional (Scandinavian) participants from the ASCOT study to replicate our findings. RESULTS: The ASCOT discovery GWAS identified a cluster of 17 correlated single nucleotide polymorphisms within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (P=1.4×10(-8)). Conditional analysis of rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in patients with ischemic stroke found no association for overall stroke (odds ratio, 1.02; 95% CI, 0.97-1.07; P=0.52) or its subtypes: cardioembolic (odds ratio, 1.07; 95% CI, 0.97-1.16; P=0.17), large vessel disease (odds ratio, 0.98; 95% CI, 0.89-1.07; P=0.60), and small vessel disease (odds ratio, 1.07; 95% CI, 0.97-1.17; P=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (P=0.18). CONCLUSIONS: We identified a cluster of single nucleotide polymorphisms at the NLGN1 locus showing significant association with BP variability. Follow-up analyses did not support an association with risk of ischemic stroke and its subtypes.

Emotion processing and social participation following stroke: study protocol.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) defines participation as a person's performance in life situations, including the size of social networks, and satisfaction with social contacts. Stroke survivors are known to experience a reduction in the number of their social networks and contacts, which cannot be explained solely in terms of activity limitations caused by physical impairment. Problems of emotional processing, including impaired mood, emotion regulation and emotion perception, are known to occur following stroke and can detrimentally influence many aspects of social interaction and participation. The aim of this study is to investigate whether emotion processing impairments predict stroke survivors' restricted social participation, independent of problems with activity limitation. METHODS/DESIGN: We aim to recruit 125 patients admitted to NHS Grampian with a confirmed diagnosis of stroke. All participants will be assessed on measures of emotion processing, social participation and activity limitation at approximately one month post stroke and again at approximately one year post stroke in order to assess change over time. DISCUSSION: It is important to develop a greater understanding of the emotional factors which may underlie key social deficits in stroke recovery in an ageing population where stroke is one of the leading causes of severe, complex disability. This research may enable us to identify those who are risk of participation restriction and target them in the acute stroke phase of stroke so that adverse outcome is avoided and rehabilitation potential is fulfilled.

Computed tomography and magnetic resonance perfusion imaging in ischemic stroke: definitions and thresholds.

OBJECTIVE: Cerebral perfusion imaging with computed tomography (CT) or magnetic resonance (MR) is widely available. The optimum perfusion values to identify tissue at risk of infarction in acute stroke are unclear. We systematically reviewed CT and MR perfusion imaging in acute ischemic stroke. METHODS: We searched for papers on MR or CT perfusion performed <24 hours after stroke that assessed perfusion thresholds, mean perfusion lesion values, or lesion volumes. We extracted definitions and perfusion values. We compared definitions and evaluated perfusion thresholds for "nonviable"/"at risk" and "at risk"/"not at risk tissue" thresholds. RESULTS: Among 7,152 papers, 69 met inclusion criteria for analysis of definitions (49 MR and 20 CT), 21 MR (n = 551), and 10 CT (n = 266) papers, median sample size 22, provided thresholds. We found multiple definitions for tissue states, eg, tissue at risk, 18; nonviable tissue, 12; 16, no definition. Perfusion parameters varied widely; eg, 9 different MR, 6 different CT parameters for the "at risk"/"not at risk threshold." Median threshold values varied up to 4-fold, eg, for the "at risk"/"not at risk threshold," median cerebral blood flow ranged from 18 to 37ml/100g/min; mean transit time from 1.8 to 8.3 seconds relative to the contralateral side. The influence of reperfusion and duration of ischemia could not be assessed. INTERPRETATION: CT and MR perfusion imaging viability thresholds in stroke are derived from small numbers of patients, variable perfusion analysis methods and definitions of tissue states. Greater consistency of methods would help determine reliable perfusion viability values for wider clinical use of perfusion imaging.

Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

OBJECTIVE: To perform a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, which tested the effect of treatment with atorvastatin in reducing stroke in subjects with a recent stroke or transient ischemic attack, to explore the effects of treatment in subjects with type 2 diabetes mellitus or metabolic syndrome (MetS). METHODS: The 4731 subjects enrolled in the SPARCL trial were classified as having type 2 diabetes mellitus at enrollment (n = 794), MetS retrospectively (n = 642), or neither diabetes nor MetS (n = 3295, the reference group) based on data collected at baseline. Cox regression models were used to determine whether the effect of treatment on the primary end point (combined risk of nonfatal and fatal stroke) and secondary end points (major coronary events, major cardiovascular events, any coronary heart disease event, and any revascularization procedure) varied based on the presence of type 2 diabetes mellitus or MetS. RESULTS: Subjects with type 2 diabetes mellitus had increased risks of stroke (hazard ratio [HR] = 1.62; 95% confidence interval [CI], 1.33-1.98; P < .001), major cardiovascular events (HR = 1.66; 95% CI, 1.39-1.97; P < .001), and revascularization procedures (HR = 2.39; 95% CI, 1.78-3.19; P < .001) compared with the reference group. Subjects with MetS were not at increased risk for stroke (P = .78) or major cardiovascular events (P = .38) but more frequently had revascularization procedures (HR = 1.78; 95% CI, 1.26-2.5; P = .001). There were no treatment × subgroup interactions for the SPARCL primary end point (P = .47). CONCLUSIONS: The SPARCL subjects with type 2 diabetes were at higher risk for recurrent stroke and cardiovascular events. This exploratory analysis found no difference in the effect of statin treatment in reducing these events in subjects with or without type 2 diabetes or MetS. Trial Registration clinicaltrials.gov Identifier: NCT00147602.

Procedures to evaluate the importance of dietary polyamines.

Polyamines not only play vital physiological functions including modulating transcription and translation of genetic material, cell proliferation and growth, ion channel regulation and cell signaling, but have also been cited in the pathogenesis of diseases. Many plant and animal sources used as food contain high amounts of polyamines. Knowledge of the content of polyamines in food as a source of these growth factors is therefore critical. A 2-step perchloric acid precipitation method to obtain acid soluble extracts from food that are subsequently taken through a dansylation process to produce dansyl polyamine derivatives for HPLC measurement is described. Examples are provided to illustrate mathematical correction factors.

Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

BACKGROUND AND PURPOSE: Laboratory experiments suggest statins reduce stroke severity and improve outcomes. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized trial designed to determine whether treatment with atorvastatin reduces strokes in subjects with recent stroke or transient ischemic attack (n=4731). We analyzed SPARCL trial data to determine whether treatment favorably shifts the distribution of severities of ischemic cerebrovascular outcomes. METHODS: Severity was assessed with the National Institutes of Health Stroke Scale, Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial. RESULTS: Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale score 5 or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (P<0.001 unadjusted and adjusted). Results were similar for all outcome events (ischemic and hemorrhagic, P<0.001 unadjusted and adjusted) with no effect on outcome hemorrhagic stroke severity (P=0.174 unadjusted, P=0.218 adjusted). If the analysis is restricted to those having an outcome ischemic stroke (ie, excluding those having a transient ischemic attack or no event), there was only a trend toward lesser severity with treatment based on the modified Rankin Scale score (P=0.0647) with no difference based on the National Institutes of Health Stroke Scale or Barthel Index. CONCLUSIONS: The present exploratory analysis suggests that the outcome of recurrent ischemic cerebrovascular events might be improved among statin users as compared with nonusers.

Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.

OBJECTIVE: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. METHODS: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were subsequently genotyped in 2,528 additional cases and 2,189 additional control subjects from Europe and North America. RESULTS: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% for atherosclerotic stroke. INTERPRETATION: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease.