Botulinum Toxin-A for the Treatment of Neuropathic Pain after Decompressive Craniotomy in Stroke: Two Cases.

Botulinum toxin-A (BoNT-A) is recommended as third-line off-label treatment for the management of neuropathic pain. BoNT-A has been reported as treatment for different neuropathic pain conditions; however, not for neuropathic pain after decompressive craniotomy for stroke. The aim of this retrospective case series is to provide information on safety, the effect, and the application method of BoNT-A in clinical practice for the treatment of neuropathic pain after trepanation. This case series describes 2 patients treated in 2021 at a BoNT outpatient clinic for chronic neuropathic pain at the incisional site after decompressive craniotomy for stroke who were resistant to pain medication. Cases were a 48-year-old woman and a 63-year-old man suffering from chronic neuropathic pain since 3 and 6 years, respectively. They were treated regularly with BoNT-A with a total dose of 100 mouse units of incobotulinumtoxin-A injected into peri-incisional sites of the scalp. Both patients reported subjective decrease in pain frequency (40% and 60%), in pain intensity (60% and 90%), and an increase of quality of life (80%). BoNT-A should be further investigated as treatment for neuropathic pain - especially in underreported conditions such as neuropathic pain after craniotomy in stroke.

Flow dynamics in acute ischemic stroke due to embolic occlusion of a fetal posterior cerebral artery treated with endovascular thrombectomy - report of two cases.

The fetal variant of the posterior cerebral artery (fPCA) conserves a major blood flow from the anterior to the posterior cerebral circulation via a strong persistent caudal portion of the embryonic internal carotid artery. We present two cases where endovascular treatment in acute ischemic stroke was complicated by this flow diversion. Though direct thrombectomy of the fPCA using a stent retriever was feasible and successful in both cases outcome remained unfavourable due to a continuous redirection of embolic material into the posterior circulation. Knowledge of flow dynamics in a fPCA is important for endovascular treatment in acute ischemic stroke.

COVID-19-related delays of botulinum toxin injections have a negative impact on the quality of life of patients with dystonia and spasticity: a single-center ambulatory care study.

BACKGROUND: Botulinum toxin A (BoNT-A) is considered a safe and effective treatment for spasticity and dystonia. Individual interinjection intervals are critical for the maintenance of the effect. In Austria, BoNT outpatient clinics were shutdown from November to December 2020 during COVID-19 control measures, leading to rescheduling of BoNT-A injections. This survey aimed at investigating the influence of injection delays on symptoms, physical functioning, and quality of life (QoL) of the affected patients. METHODS: Between April and July 2021, 32 outpatients (21 females, mean age: 63.4 ± 12.1 years) treated ≥ 12 months at the BoNT outpatient clinic Horn-Allentsteig (Austria) and experienced ≥ 2 week injection delays, completed a structured face-to-face questionnaire. RESULTS: Indications were dystonia (34%), spasticity (63%), and hyperhidrosis (3%). Injections were delayed by 10 weeks (median, range: 2-15). Muscle cramps increased in 95% of patients with spasticity, muscle twitches in 91% of those with dystonia, and pain in 9% and 60% for dystonia and spasticity, respectively. Overall, 75% reported functional worsening, and deterioration in QoL by 62.6% ± 16.8 (mean ± SD). The impact on QoL correlated with the subjective global improvement induced by BoNT-A (Rs: 0.625; p < 0.001). For 75%, long-term assurance of BoNT-A therapy was very important, and 81% felt their patient rights not respected. CONCLUSIONS: COVID-19-related delays in BoNT-A injections illustrate the importance of this therapy for symptom relief, functional outcome, and QoL in patients suffering from involuntary muscle hyperactivity. BoNT-A therapy is essential and has to be guaranteed even in circumstances such as the COVID-19 pandemic.

Comparison of oral glucose tolerance test and HbA1c in detection of disorders of glucose metabolism in patients with acute stroke.

BACKGROUND: Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients. DESIGN: Secondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS). METHODS: A total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after 1 year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared. RESULTS: By any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After 1 year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference). The study intervention led to a more favourable evolution of glycemic status after 1 year. CONCLUSION: The OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes. Trial registration http://clinicaltrials.gov . Unique identifier: NCT01109836.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Systematic dysphagia screening and dietary modifications to reduce stroke-associated pneumonia rates in a stroke-unit.

BACKGROUND AND PURPOSE: While formal screening for dysphagia following acute stroke is strongly recommended, there is little evidence on how multi-consistency screening and dietary modifications affect the rate of stroke-associated pneumonia (SAP). This observational study reports which factors affect formal screening on a stroke-unit and how dietary recommendations relate to SAP. METHOD: Analyses from a database including 1394 patients admitted with acute stroke at our stroke-unit in Austria between 2012 and 2014. Dietary modifications were performed following the recommendations from the Gugging Swallowing Screen (GUSS). Patients evaluated with GUSS were compared to the unscreened patients. RESULTS: Overall, 993 (71.2%) patients were screened with GUSS; of these 50 (5.0%) developed SAP. In the 401 unscreened patients, the SAP rate was similar: 22 (5.5%). Multivariable analysis showed that either mild to very mild strokes or very severe strokes were less likely to undergo formal screening. Older age, pre-existing disability, history of hypertension, atrial fibrillation, stroke severity, cardiological and neurological complications, nasogastric tubes, and intubation were significant markers for SAP. Out of 216 patients, 30 (13.9%) developed SAP in spite of receiving nil per mouth (NPO). CONCLUSION: The routine use of GUSS is less often applied in either mild strokes or very severe strokes. While most patients with high risk of SAP were identified by GUSS and assigned to NPO, dietary modifications could not prevent SAP in 1 of 7 cases. Other causes of SAP such as silent aspiration, bacteraemia or central breathing disturbances should be considered.

Cut stroke in half: Polypill for primary prevention in stroke.

This review summarizes the potential for polypill therapies for stroke prevention. While a number of studies applying different approaches regarding polypill have been performed, none of them has had a focus on stroke as the main outcome. A combination pill containing drugs such as statins, diuretics, and other antihypertensives is currently available in various formats. Estimates focusing mostly on primary prevention show that using such a combination drug a reduction in the 5-year stroke incidence by 50% can be achieved - especially in low- and middle-income countries with a high prevalence of risk factors even among people at young ages. A combination of a large supporting population-wide program with a registry-based quality control is the most likely perspective and can be achieved within a reasonable time frame and potentially have significant influence in young stroke populations.

Preventive effects of multiple domain interventions on lifestyle and risk factor changes in stroke survivors: Evidence from a two-year randomized trial.

Background and aim Behavioral and lifestyle interventions in stroke patients need to be intense enough to result in sustainable treatment differences among groups of a randomized trial. Therefore, we report the effects of multidomain interventions on lifestyle and laboratory parameters after 12 and 24 months from a trial that examined whether intensive risk factor management can prevent cognitive decline in ischemic stroke patients. Methods This prospective randomized, open-label, blinded endpoint trial recruited patients within three months after acute stroke in five Austrian neurological clinics during June 2010 and November 2012. One hundred and one patients were randomized into multidomain intervention and 101 into standard care. Lifestyle interventions were individualized to match predefined targets of regular physical activity, healthy diet, and adequate physiological risk factor control. Results A total of 167 participants (80 intervention, 87 control) completed the 12-month visit and 155 (76 intervention, 79 control) the 24-month visit. During the first 12 months, adherence to healthy lifestyle and adequately controlled physiological parameters (measured by summary scores) improved significantly in the intervention group compared to controls (p < 0.01). The consumption of reduced-fat milk (p = 0.031), reduced-fat spreads (p = 0.007), and fish (p = 0.021) increased in the intervention group from baseline to 12 months but not in controls. After 24 months, the group difference was significant for the lifestyle summary score but no longer for the combined laboratory lifestyle score. Conclusions These results demonstrate that intensified individualized multidomain lifestyle interventions in stroke patients are effective in promoting healthy lifestyle in stroke care.

Post-stroke dementia - a comprehensive review.

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

Post-stroke pneumonia at the stroke unit - a registry based analysis of contributing and protective factors.

BACKGROUND: To investigate prevalence and risk factors for post stroke pneumonia (PSP) in patients with acute ischemic stroke treated at stroke units (SU). METHOD: We analysed data from the Austrian Stroke Unit registry concerning admissions from January 2003 to December 2013 and assessed the prevalence of PSP at the stroke unit. Patients with and without PSP were compared in univariate and multivariate models searching for factors associated with the occurrence of PSP at the SU. RESULTS: Three thousand one hundred eleven patients (5.2%) of 59,558 analysed patients were diagnosed with PSP. While age and stroke severity were non-modifiable factors associated with PSP, modifiable risk factors included chronic alcohol consumption and atrial fibrillation. Patients who developed neurological, cardiac, and other infective complications showed a higher prevalence of PSP, an increased prevalence was also found in connection with the placement of nasogastric tubes or urinary catheters. Female sex, left hemispheric stroke, cryptogenic stroke pathogenesis and additionally, treatment with lipid lowering drugs were factors associated with a lower PSP prevalence. CONCLUSION: Pneumonia in acute ischemic stroke is associated with a variety of modifiable and unmodifiable factors that allow to identify patients at high risk of developing PSP and to focus on early preventive measures at the SU. Further studies could use the results of this study to explore potential benefits of specific interventions targeted at these factors.

Multidomain Lifestyle Interventions for the Prevention of Cognitive Decline After Ischemic Stroke: Randomized Trial.

BACKGROUND AND PURPOSE: Cognitive impairment occurs in ≤30% of all stroke survivors. However, effective therapies aimed at preventing poststroke cognitive decline are lacking. We assessed the efficacy of a multidomain intervention on preventing cognitive decline after stroke. METHODS: In this randomized, observer-blind trial patients were recruited within 3 months after an acute stroke in 5 Austrian neurological centers. Patients were assigned to a 24-month lifestyle-based multidomain intervention or standard stroke care. Primary outcomes were the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) and occurrence of cognitive decline in the composite scores of at least 2 of 5 cognitive domains at 24 months. RESULTS: A total of 101 patients were randomized into multi-intervention and 101 into standard care during June 2010 and November 2012. Of them, 76 patients in the intervention group and 83 in the control group were included in the final intention-to-treat analysis. At 24 months, 8 of 76 (10.5%) patients in the intervention group and 10 of 83 (12.0%) patients in the control group showed cognitive decline corresponding to a relative risk reduction of 0.874 (95% confidence interval, 0.364-2.098). The change in ADAS-cog from baseline to 24 months was not different either (median 0 [IQR, -1 to 2] in both groups; P=0.808). CONCLUSIONS: This trial found no benefit of 24-month multidomain intervention with focus on improvement in lifestyle and vascular risk factors on the incidence of poststroke cognitive decline in comparison with standard stroke care. Studies with a larger sample size are needed. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01109836.

Prevention of poststroke cognitive decline: ASPIS--a multicenter, randomized, observer-blind, parallel group clinical trial to evaluate multiple lifestyle interventions--study design and baseline characteristics.

BACKGROUND: Cognitive impairment after stroke is a considerable burden to patients and their caregivers and occurs in one-third of stroke survivors. No strategy to prevent cognitive decline after stroke exists thus far. Established vascular risk factors have been associated with cognitive decline and may be a target for therapeutic interventions in stroke survivors. AIM: To test whether intensive multifactorial non-pharmacologic interventions based on lifestyle modification can reduce the risk of cognitive decline in patients who recently suffered ischemic stroke. METHODS: A randomized, controlled, multicenter, observer-blind trial was designed. The reference group obtains stroke care according to standard guidelines. The intervention group additionally receives intensive control and motivation for better compliance with prescribed evidence-based medication, regular blood pressure measurements, healthy diet, regular physical activity and cognitive training. Primary outcomes are the rate of cognitive decline at 24 months, assessed by a neuropsychological test battery and the cognitive subscale of the Alzheimer's Disease Assessment Scale. RESULTS: 202 patients (29% women), aged 62 ± 9 years, were recruited during 2010 to 2012. Stroke related impairment at inclusion was low (mean National Institutes of Health Stroke Scale: 1.9±1.8, median modified Rankin Scale: 1 (0-1)). At baseline, groups did not differ significantly in demographic, clinical or lifestyle characteristics. CONCLUSION: The recruitment was successful and the groups are balanced regarding potential confounding variables. The study will provide essential data about the feasibility and efficacy of lifestyle intervention after stroke in order to develop a new approach to prevent cognitive decline in patients with mild ischemic stroke.

Time trends in patient characteristics treated on acute stroke-units: results from the Austrian Stroke Unit Registry 2003-2011.

BACKGROUND AND PURPOSE: Demographic changes, increased awareness of vascular risk factors, better diagnostic, progress in medical care, and increasing primary stroke prevention influence the profile of patients admitted to stroke-units. Changes in patient population and stroke type have important consequences on outcome and management at stroke-units. METHODS: Data from the national database of the Austrian Stroke Unit Registry were analyzed for time-trends in demography, risk factors, cause, and stroke severity. RESULTS: Data of 48 038 ischemic and 5088 hemorrhagic strokes were analyzed. Between 2003 and 2011, median age increased significantly for ischemic strokes from 68 to 71 years in men and from 76 to 78 years in women, respectively. Ischemic stroke patients showed significantly increased rates of hypertension, hypercholesterolemia, and atrial fibrillation. In hemorrhagic strokes an increase for hypercholesterolemia and cardiac diseases other than atrial fibrillation and myocardial infarction were only found in men. A small but significant decrease in stroke severity was found for ischemic strokes from 4 to 3 points on the National Institutes of Health Stroke Scale in men and from 5 to 4 in women, and for hemorrhagic strokes from 9 to 6 points in men and from 9 to 7 in women. Cardioembolic strokes increased slightly, whereas macroangiopathy decreased. CONCLUSIONS: Significant time trends were seen for characteristics of ischemic and hemorrhagic stroke patients admitted to acute stroke-units in Austria. These include trends for older age and toward milder strokes with more cardioembolic causes. This signals a need for increased resources for managing multimorbidity and enabling early mobilization.

Use of intravenous recombinant tissue plasminogen activator in patients outside the defined criteria: safety and feasibility issues.

Currently, intravenous thrombolysis is by far the most effective treatment of acute ischemic stroke, and its use can independently strongly increase the proportion of stroke patients surviving. While the use of recombinant tissue plasminogen activator in accordance to licensed criteria has continuously risen, off-label use is also frequent. In this review the most important reasons to transcend current license criteria are discussed and evidence is summarized from new studies, such as IST-3, contributing to the balance of increased benefit as opposed to possible harm in situations of off-label use of recombinant tissue plasminogen activator in stroke. In addition, several scores to predict risk and outcome in patients undergoing thrombolysis are compared.

The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial.

BACKGROUND: Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. METHODS: In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. FINDINGS: 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1·13, 95% CI 0·95-1·35, p=0·181; a non-significant absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a significant shift in OHS scores; common OR 1·27 (95% CI 1·10-1·47, p=0·001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6·94, 95% CI 4·07-11·8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1·60, 95% CI 1·22-2·08, p=0·001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). INTERPRETATION: For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients. FUNDING: UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council (NHMRC), Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria, Italy, and Danube University.

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. RESULTS: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. CONCLUSION: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. TRIAL REGISTRATION: ISRCTN25765518.

Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry.

BACKGROUND AND PURPOSE: Acute stroke management requires minimization of prehospital time. This study addresses the value of helicopter transport compared with other means of transportation to a stroke unit and compares their rates of thrombolysis on a nationwide basis. METHODS: Prospective data collection and prespecified evaluation of data from 32 stroke units between 2003 and 2009 were used. We distinguished between patients transported either directly to a stroke unit or transferred indirectly via a peripheral hospital. Thus, there were 6 transport groups: helicopter emergency service (HEMS) direct and indirect, ambulance accompanied by an emergency physician direct and indirect, and ambulance without physician direct and indirect. Demographic and clinical factors, time delays, and rates of thrombolysis of patients transported by helicopter were compared with factors of patients transported otherwise. RESULTS: Of 21 712 ischemic stroke patients, 905 patients (4.1%) were transported by helicopter. Of these, 752 patients (3.4%) were transported by direct HEMS, and 153 patients (0.7%) were transported by indirect HEMS. Thrombolysis rates were highest for HEMS (24% direct, 29% indirect) transport, followed by ambulance accompanied by an emergency physician (18% direct, 15% indirect). The probability of receiving thrombolysis was highest for indirect HEMS transport (OR 3.6, 2.2-6.0), followed by indirect ambulance accompanied by an emergency physician transport (OR 1.5, 1.1-1.9). The shortest times, 90 minutes or less from stroke onset to hospital arrival, were achieved with direct AMBP and direct HEMS transport. CONCLUSIONS: The shortest hospital arrival times and highest thrombolysis rates were seen in ischemic stroke patients transported by helicopter.

Third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit. DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With 3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit. TRIAL PROCEDURES: Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24-48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0-2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol). TRIAL REGISTRATION: ISRCTN25765518.