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Background: The usefulness of prehospital scales for identifying anterior circulation large vessel occlusion (aLVO) in patients with suspected stroke may vary depending on the severity of their presentation. The performance of these scales across the spectrum of deficit severity is unclear. The aim of this study was to evaluate the diagnostic performance of 8 prehospital scales for identifying aLVO across the spectrum of deficit severity. Methods: We used data from the PRESTO study (Prehospital Triage of Patients With Suspected Stroke Symptoms), a prospective observational study comparing prehospital stroke scales in detecting aLVO in suspected stroke patients. We used the National Institutes of Health Stroke Scale (NIHSS) score, assessed in-hospital, as a proxy for the Clinical Global Impression of stroke severity during prehospital assessment by paramedics. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and the difference in aLVO probabilities with a positive or negative prehospital scale test (ΔP aLVO ) for each scale for mild (NIHSS 0–4), intermediate (NIHSS 5–9), moderate (NIHSS 10–14), and severe deficits (NIHSS≥15). Results: Among 1033 patients with suspected stroke, 119 (11.5%) had an aLVO, of whom 19 (16.0%) had mild, 25 (21.0%) had intermediate, 30 (25.2%) had moderate, and 45 (37.8%) had severe deficits. The scales had low sensitivity and positive predictive value in patients with mild-intermediate deficits, and poor specificity, negative predictive value, and accuracy with moderate-severe deficits. Positive results achieved the highest ΔP aLVO in patients with mild deficits. Negative results achieved the highest ΔP aLVO with severe deficits, but the probability of aLVO with a negative result in the severe range was higher than with a positive test in the mild range. Conclusions: Commonly-used prehospital stroke scales show variable performance across the range of deficit severity. Probability of aLVO remains high with a negative test in severely affected patients. Studies reporting prehospital stroke scale performance should be appraised in the context of the NIHSS distribution of their samples.

Summary Background Due to the time-sensitive effect of endovascular treatment, rapid prehospital identification of large-vessel occlusion in individuals with suspected stroke is essential to optimise outcome. Interhospital transfers are an important cause of delay of endovascular treatment. Prehospital stroke scales have been proposed to select patients with large-vessel occlusion for direct transport to an endovascular-capable intervention centre. We aimed to prospectively validate eight prehospital stroke scales in the field. Methods We did a multicentre, prospective, observational cohort study of adults with suspected stroke (aged ≥18 years) who were transported by ambulance to one of eight hospitals in southwest Netherlands. Suspected stroke was defined by a positive Face-Arm-Speech-Time (FAST) test. We included individuals with blood glucose of at least 2·5 mmol/L. People who presented more than 6 h after symptom onset were excluded from the analysis. After structured training, paramedics used a mobile app to assess items from eight prehospital stroke scales: Rapid Arterial oCclusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), Cincinnati Stroke Triage Assessment Tool (C-STAT), Gaze-Face-Arm-Speech-Time (G-FAST), Prehospital Acute Stroke Severity (PASS), Cincinnati Prehospital Stroke Scale (CPSS), Conveniently-Grasped Field Assessment Stroke Triage (CG-FAST), and the FAST-PLUS (Face-Arm-Speech-Time plus severe arm or leg motor deficit) test. The primary outcome was the clinical diagnosis of ischaemic stroke with a proximal intracranial large-vessel occlusion in the anterior circulation (aLVO) on CT angiography. Baseline neuroimaging was centrally assessed by neuroradiologists to validate the true occlusion status. Prehospital stroke scale performance was expressed as the area under the receiver operating characteristic curve (AUC) and was compared with National Institutes of Health Stroke Scale (NIHSS) scores assessed by clinicians at the emergency department. This study was registered at the Netherlands Trial Register, NL7387. Findings Between Aug 13, 2018, and Sept 2, 2019, 1039 people (median age 72 years [IQR 61–81]) with suspected stroke were identified by paramedics, of whom 120 (12%) were diagnosed with aLVO. Of all prehospital stroke scales, the AUC for RACE was highest (0·83, 95% CI 0·79–0·86), followed by the AUC for G-FAST (0·80, 0·76–0·84), CG-FAST (0·80, 0·76–0·84), LAMS (0·79, 0·75–0·83), CPSS (0·79, 0·75–0·83), PASS (0·76, 0·72–0·80), C-STAT (0·75, 0·71–0·80), and FAST-PLUS (0·72, 0·67–0·76). The NIHSS as assessed by a clinician in the emergency department did somewhat better than the prehospital stroke scales with an AUC of 0·86 (95% CI 0·83–0·89). Interpretation Prehospital stroke scales detect aLVO with acceptable-to-good accuracy. RACE, G-FAST, and CG-FAST are the best performing prehospital stroke scales out of the eight scales tested and approach the performance of the clinician-assessed NIHSS. Further studies are needed to investigate whether use of these scales in regional transportation strategies can optimise outcomes of patients with ischaemic stroke. Funding BeterKeten Collaboration and Theia Foundation (Zilveren Kruis).

Background: Due to the time-sensitive effect of endovascular treatment (EVT), rapid prehospital identification of large vessel occlusion (LVO) in suspected stroke patients is essential to optimize outcome. Inter-hospital transfers are an important cause of delay of EVT. Prehospital stroke scales have been proposed to select patients with LVO for direct transport to an endovascular-capable intervention centre. We aimed to prospectively validate eight prehospital stroke scales in the field. Methods: In a multi-centre prospective observational cohort study, we included suspected stroke patients transported by ambulance in the Southwest Netherlands. Paramedics assessed items from eight prehospital stroke scales: Rapid Arterial oCclusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), Cincinnati Stroke Triage Assessment Tool (C-STAT), Gaze-Face-Arm-Speech-Time (G-FAST), Prehospital Acute Stroke Severity (PASS), Cincinnati Prehospital Stroke Scale (CPSS), Conveniently-Grasped Field Assessment Stroke Triage (CG-FAST), and the FAST PLUS Test. Patients that presented beyond six hours from symptom onset were excluded. Primary outcome was the clinical diagnosis of ischaemic stroke with a proximal intracranial LVO in the anterior circulation (aLVO) on CT-angiography. Prehospital stroke scale performance was expressed as the area under the receiver operating characteristic curve (AUC) and was compared with National Institute of Health Stroke Scale (NIHSS) scores assessed by physicians at the emergency department. Findings: We included 1039 patients, of which 121 patients (12%) were diagnosed with aLVO. AUCs for the prehospital stroke scales ranged from 0·69 (FAST PLUS) to 0·82 (RACE). The performance of RACE was not significantly different from G-FAST (AUC=0·80, p=0·14) and CG-FAST (AUC=0·80, p=0·09), but was significantly different from the other scales (p-values

Rationale In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37·0°C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1·43; 95% confidence interval: 1·02–1·97). This relation was also found in the patients with a body temperature of 36·5°C or higher (odds ratio 1·31; 95% confidence interval 1·01–1·68). These findings need confirmation. Aim The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36·5°C or above on functional outcome. Design The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0·05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36·5°C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. Study outcomes The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. Discussion If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide.

Health education aims at the acquisition of skills and attitudes to modify behaviour that influences health, leads to a modification of risk factors and ultimately to a decrease in disability and case fatality from stroke. Health education is an underdeveloped but important aspect of stroke care. Health education could promote compliance and healthy behaviour, improve patients' understanding of their health status and treatment options and facilitate communication. We reviewed the effect of health education in stroke and transient ischaemic attack patients, aiming at feasibility, effectiveness at the level of knowledge, attitude and skills, health behaviour changes and stroke outcome. We also describe the current status of health education for patients with recent coronary artery disease and public health education in stroke. Basic knowledge of stroke and transient ischaemic attack patients of their disease and associated risk factors is not sufficient. This is also observed in patients with coronary artery disease and in the general population. A beneficial effect of health education in stroke and transient ischaemic attack patients on health behaviour, risk reduction or stroke outcome has not been proven. Trials in patients with coronary artery disease, however, have shown that health education could result in a change of lifestyle. No specific method is superior, although the individualised, repetitive and active methods appear more successful. More intervention studies of health education in stroke and transient ischaemic attack patients are needed. Future trials should be large, have a long follow-up, should use an intensive and repetitive approach and involve patients' relatives to induce and maintain a healthy lifestyle.

Background and Purpose— Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods— Nine hundred seventy-two patients with transient ischemic attack or ischemic stroke were prospectively and consecutively enrolled in the Netherlands Stroke Survey. We applied 7 large antiplatelet trials’ enrollment criteria. Results— In total, 886 patients were discharged alive and available for secondary prevention. Mean follow-up was 2.5 years. The annual rate of transient ischemic attack, stroke, or nonfatal myocardial infarction was 6.7%. The proportions of patients fulfilling the trial enrollment criteria ranged from 25% to 67%. Mortality was significantly higher in ineligible patients (27% to 41%) than in patients fulfilling enrollment criteria (16% to 20%). Rates of vascular events were not higher in trial-eligible patients than in ineligible patients. Conclusions— Our data confirm that patients with ischemic attack and stroke enrolled in randomized clinical trials are only partially representative of patients in clinical practice. Use of less strict enrollment criteria could enhance “generalizability” and result in more efficient selection of patients for randomized clinical trials.

An increase in body temperature in the first days following stroke is related to poor functional outcome. High-dose paracetamol (acetaminophen) reduces the body temperature by 0.3°C and can prevent fever. Paracetamol treatment is simple, cheap and has few side effects. In the first "Paracetamol (Acetaminophen) in Stroke" (PAIS) study, there was a beneficial effect of high-dose paracetamol on functional outcome in patients with stroke and a body temperature of 37.0°C or above. Because this result was found in a subgroup analysis, a new study is needed to confirm this finding. Recently the randomised PAIS 2 study was initiated. This study aims to assess the effect of high-dose paracetamol on functional outcome in patients with acute stoke and a body temperature of 37.0°C or above.

Background and Purpose— The combination of low-dose aspirin and dipyridamole is more effective than aspirin alone in reducing the risk of recurrent stroke and other major cardiovascular events in patients with a recent transient ischemic attack or minor stroke. It is unknown whether this also applies to patients with a disabling stroke. Methods— We reanalyzed the data of 5700 patients from ESPRIT and ESPS-2 to study the effect of aspirin and dipyridamole according to modified Rankin scale (mRS) score at baseline. Primary outcome was vascular events (stroke, myocardial infarction, or vascular death). We used proportional hazards regression to estimate the treatment effect across mRS strata at baseline, and we tested for interactions with treatment. Results— In total, 426 patients (7.5%) had mRS score of 4 or 5 at baseline. The risk of an outcome event increased with mRS score. The relative risk associated with the combination of aspirin and dipyridamole compared to aspirin alone in patients with mRS score 0 to 5 was 0.79 (95% confidence interval, 0.69–0.91). The relative risk according to mRS subcategory score 0 to 4 at baseline varied between 0.73 and 0.96 for vascular events and between 0.62 and 0.96 for stroke. The number of patients with mRS score 5 was too small for reliable estimates, but the data suggest a beneficial effect. There was no evidence of interaction between treatment effect and mRS score at baseline. Conclusion— The beneficial effect of the combination of low-dose aspirin and dipyridamole was present in all subcategories of the mRS score.

Background: Patients with acute stroke often have a striking lack of knowledge of causes, warning signs, and risk factors. Lack of knowledge may lead to inappropriate secondary prevention behavior. We investigated the knowledge of patients with a TIA or minor stroke about specific aspects of their disease 3 months after the event. Methods: Patients with a TIA or minor stroke who participated in a randomized controlled trial of the effect of health education by an individualized multimedia computer program (IMCP) were included. All patients received information about their disease from their treating neurologist and half of the patients received extra information through the IMCP. The patients’ knowledge was tested after 3 months by means of a questionnaire that contained items on pathogenesis, warning signs, vascular diseases, risk factors, lifestyle and treatment. The highest possible score was 71 points. Results: The 57 patients had a mean total score of 41.2 points (SD 10.4) of the maximum 71. Only 15 (26%) correctly identified the brain as the affected organ in stroke and TIA, and only 21 (37%) could give a correct description of a TIA or stroke. In contrast, 80–90% of the patients identified hypertension and/or obesity as vascular risk factors. Knowledge of various treatment modalities of hypertension, hypercholesterolemia and obesity was moderate to high (40–91% adequate responses). Conclusion: The vast majority of patients with TIA or stroke lack specific knowledge about their disease, but they do have a reasonable knowledge of general vascular risk factors and treatment. This suggests that counseling by neurologists of patients with a TIA or stroke can be improved.