Utstein recommendation for emergency stroke care.

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. CONCLUSIONS: Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability.

Effectiveness of a shared team approach between nurses and doctors for improved risk factor management in survivors of stroke: a cluster randomized controlled trial.

BACKGROUND AND PURPOSE: Limited evidence exists on the benefits of organized care for improving risk factor control in patients with stroke or transient ischaemic attack. The effectiveness of an individualized management programme in reducing absolute cardiovascular disease risk in this high-risk population was determined. METHODS: This was a prospective, multicentre, cluster-randomized controlled trial with blinded assessment of outcomes and intention-to-treat analysis. Patients hospitalized for stroke/transient ischaemic attack and aged ≥18 years were recruited from four hospitals. General practices treating recruited patients were randomized to provide either usual care or an individualized management programme comprising nurse-led education and review of care plans by stroke specialists in addition to usual care. The primary outcome was a change in cardiovascular Framingham Risk Score between baseline and 12 months. RESULTS: From January 2010 to November 2013, 156 general practices (280 patients) were randomly assigned to usual care (control) and 159 (283 patients) to the intervention. The median age was 70.1 years; 65% were male. Overall, >80% of participants were prescribed recommended secondary prevention therapies at baseline. The primary efficacy analysis comprised 533 participants, with 30 either dying or lost to follow-up. In adjusted analyses, no significant between-group difference was found in the cardiovascular risk score at 12 months (0.04, 95% confidence interval -1.7, 1.8). CONCLUSIONS: The effectiveness of an organized secondary prevention programme for stroke may be limited in patients from high-performing hospitals with regular post-discharge follow-up and communication with general practices.

Victorian Stroke Telemedicine Project: implementation of a new model of translational stroke care for Australia.

BACKGROUND: Stroke telemedicine is widely used to treat patients with acute stroke in Europe and North America but is seldom used in Australia. The Victorian Stroke Telemedicine (VST) programme aims to enhance acute stroke care in regional Australia. METHODS: Twelve-month pilot prospective, historical-controlled, implementation cohort study. Emergency Department (ED) at a large regional hospital in Victoria. Patients ≥ 18 years of age arriving < 4.5 h in the ED with a possible diagnosis of acute stroke. Telemedicine consultation by a Melbourne-based stroke specialist. Stroke thrombolysis rate, timelines for clinical processes, discharge outcomes. RESULTS: In the initial 12 month VST implementation, 62 patients arrived < 4.5 h of stroke onset (60% male; median age 75 years). Compared to pre-VST data (n = 58; 52% male; median age 77 years), stroke thrombolysis use increased from 17% to 26% (P = 0.26). Clinical process timelines improved including door to computed tomography time (reduced by 29 min, P = 0.006), and door to needle time (reduced by 21 min, P = 0.21). There was no significant increase in deaths (pre-VST 7% vs VST 10%), or symptomatic intracerebral haemorrhage (n = 1 tPA patient). More patients who received tPA were discharged to home or rehabilitation (pre-VST 33% vs VST 80%, P = 0.02), with significantly fewer transfers to other acute care services. CONCLUSIONS: The VST pilot implementation provides evidence that telemedicine can enhance the quality of acute stroke care in a regional hospital. Expanding VST to 16 regional hospitals, Australia's largest telestroke programme, will allow for a more comprehensive clinical and economic analysis.

Is telemedicine helping or hindering the delivery of stroke thrombolysis in rural areas? A qualitative analysis.

BACKGROUND: Fast diagnosis and delivery of treatment to patients experiencing acute stroke can reduce subsequent disability. While telemedicine can improve rural community access to specialists and facilitate timely diagnosis and treatment decisions, it is not widely used for stroke in Australia. AIM: Identifying the barriers and facilitators to clinician engagement with, and utilisation of, telemedicine consultations could expedite implementation in rural and remote locations. METHODS: Purposive sampling was used to identify and recruit medical and nursing staff varying in telemedicine experience across one hospital department. Twenty-four in-depth, face-to-face interviews were conducted examining aspects surrounding stroke telemedicine uptake. Inductive qualitative thematic analysis was undertaken, and two further researchers verified coding. RESULTS: The main barriers identified were contrasting opinions about the utility of thrombolysis for treating acute stroke, lack of confidence in the telemedicine system, perceived limited need for specialist advice and concerns about receiving advice from an unfamiliar doctor. Facilitators included assistance with diagnosis and treatment, the need for a user-friendly system and access to specialists for complex cases. CONCLUSIONS: Acceptability of telemedicine for acute stroke was multifaceted and closely aligned with regional clinician beliefs about the value of thrombolysis for stroke, highlighting an important area for education. Addressing beliefs about treatment efficacy and other perceived barriers is important for establishing a stroke telemedicine programme.

Are suspected stroke patients identified by paramedics transported to appropriate stroke centres in Victoria, Australia?

Emergency medical services (EMS) are vital to ensuring acute stroke patients are transported to thrombolysis and/or stroke unit centres. This 6-month audit of Victorian EMS cases found the majority of suspected acute strokes are transported to appropriate stroke centres. However, there is still room for improvement, in particular, strategies to improve access to stroke services in some rural regions and to ensure patients/relatives are fully informed when requesting transport to a non-stroke service hospital.

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch.

OBJECTIVE: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. METHODS: EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. RESULTS: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. CONCLUSIONS: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.

Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.

BACKGROUND: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. METHODS: We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. FINDINGS: Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. INTERPRETATION: Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. FUNDING: None.

Baseline diabetic status and admission blood glucose were poor prognostic factors in the EPITHET trial.

BACKGROUND: Previous data have suggested that diabetes and hyperglycemia predict poor outcome following stroke. We studied the prognostic impact of diabetes and admission blood glucose in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was a prospective randomized placebo-controlled trial of intravenous tissue plasminogen activator (tPA) in the 3- to 6-hour time window. A preexisting diagnosis of diabetes was noted and baseline serum glucose was measured. RESULTS: Intravenous tPA attenuated infarct growth in non-diabetics, but not in diabetics (p = 0.029). In the tPA treatment group, admission blood glucose was higher among patients with poor functional outcome (p = 0.002). CONCLUSIONS: Diabetes and hyperglycemia attenuate the effects of tPA on infarct evolution. Future thrombolytic trials should consider randomizing patients by subgroups based on diabetic status and serum glucose levels.

Thrombolytic therapy for acute ischaemic stroke: successful implementation in an Australian tertiary hospital.

The use of tissue-type plasminogen activator (t-PA) in ischaemic stroke outside of experienced stroke centres remains controversial. The aim of this study was to present the initial experience with t-PA in patients with ischaemic stroke at an institution with no prior experience in i.v. stroke thrombolysis and to compare results to published reports. Prospective audit of 888 patients with consecutive stroke and transient ischaemic attack admitted to a 426-bed tertiary referral hospital from March 2003 to October 2005. Main outcome measures were treatment rate, exclusion criteria, protocol violations, intracerebral haemorrhage, disability (modified Rankin scale) and mortality at 3 months. Over the study period, 72 patients received t-PA (11% of ischaemic strokes). The main reason for exclusion was presentation beyond 3 h of onset (44%); if all eligible patients had arrived within 3 h, treatment rate was estimated at 32.5%. Protocol violations occurred in 15 (21%) patients. There were seven (10%) asymptomatic intracerebral haemorrhage and one (1%) non-fatal symptomatic intracerebral haemorrhage. At 3 months, 37% had achieved excellent recovery (modified Rankin scale 0-1) and seven (10%) had died. The delivery and outcomes associated with the use of t-PA were comparable to the results of the National Institute of Neurological Disorders and Stroke trial and meta-analysis of open-labelled studies. With appropriate infrastructure and protocols, previously inexperienced tertiary referral centres can replicate the experience and outcome measures reported by clinical trials of t-PA in patients with stroke.

Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke.

BACKGROUND: Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy. METHODS: Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion. RESULTS: Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group. CONCLUSIONS: These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.

Refining the perfusion-diffusion mismatch hypothesis.

BACKGROUND AND PURPOSE: The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. METHODS: Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day 90-vol)-DWI(Acute-vol)) were also assessed. RESULTS: Mean age was 68+/-11, time to MRI 4.5+/-0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P<0.001). Mismatch > or =20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s (relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R=-0.51; P=0.009). CONCLUSIONS: Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

Seizures after stroke: a prospective multicenter study.

BACKGROUND: Studies of seizures after stroke have largely been retrospective, with small patient numbers and limited statistical analysis. Much of the doctrine about seizures after stroke is not evidenced based. OBJECTIVE: To determine the incidence, outcome, and risk factors for seizures after stroke. DESIGN: International, multicenter, prospective, analytic inception cohort study conducted for 34 months. PATIENTS AND SETTING: There were 2021 consecutive patients with acute stroke admitted to university teaching hospitals with established stroke units. After exclusion of 124 patients with previous epilepsy or without computed tomographic diagnosis, 1897 were available for analysis. Mean follow-up was 9 months. MAIN OUTCOME MEASURES: Occurrence of 1 or more seizures after stroke, stroke disability, and death after stroke. RESULTS: Seizures occurred in 168 (8.9%) of 1897 patients with stroke (28 [10.6%] of 265 with hemorrhagic and 140 [8.6%] of 1632 with ischemic stroke). On Kaplan-Meier survival analysis, patients with hemorrhagic stroke were at significantly greater risk of seizures (P =.002), with an almost 2-fold increase in risk of seizure after stroke (hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.26-2.73; P =.002). On multivariate analysis, risk factors for seizures after ischemic stroke were cortical location of infarction (HR, 2.09; 95% CI, 1. 19-3.68; P<.01) and stroke disability (HR, 2.10; 95% CI, 1.16-3.82; P<.02). The only risk factor for seizures after hemorrhagic stroke was cortical location (HR, 3.16; 95% CI, 1.35-7.40; P<.008). Recurrent seizures (epilepsy) occurred in 47 (2.5%) of 1897 patients. Late onset of the first seizure was an independent risk factor for epilepsy after ischemic stroke (HR, 12.37; 95% CI, 4.74-32.32; P<. 001) but not after hemorrhagic stroke. CONCLUSIONS: Seizures occur more commonly with hemorrhagic stroke than with ischemic stroke. Only a small minority later develop epilepsy. Patients with a disabling cortical infarct or a cortical hemorrhage are more likely to have seizures after stroke; those with late-onset seizures are at greater risk of epilepsy.

The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke.

We studied 24 patients up to 51 hours after ischemic stroke using 18F-fluoromisonidazole positron emission tomography to determine the fate of hypoxic tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were detected on positron emission tomography in 15 patients, and computed tomography was available in 12 patients, allowing comparison with the infarct volume to determine the proportions of the hypoxic tissue volume that infarcted and survived. The proportion of patients with hypoxic tissue and the amount of hypoxic tissue detected declined with time. On average, 45% of the total hypoxic tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct volume was initially hypoxic. Most of the tissue "initially affected" proceeded to infarction. We correlated hypoxic tissue volumes with neurological and functional outcome assessed using the National Institutes of Health Stroke Scale, Barthel Index, and Rankin Score. Initial stroke severity correlated significantly with the "initially affected" volume, neurological deterioration during the first week after stroke with the proportion of the "initially affected" volume that infarcted, and functional outcome with the infarct volume. Significant reductions in the size of the infarct and improved clinical outcomes might be achieved if hypoxic tissue can be rescued.

No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage.

We studied six patients after intracerebral hemorrhage (ICH) and eight controls using positron emission tomography (PET) with to determine whether a zone of tissue hypoxia, possibly representing "penumbral" tissue, exists surrounding an intracerebral hemorrhage. None of the stroke patients, studied 24 to 43 hours after symptom onset, nor any of the controls exhibited areas of tissue hypoxia on 18F-fluoromisonidazole PET images. These findings may have implications for the treatment of intracerebral hemorrhage with neuroprotective strategies.

Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole.

OBJECTIVE: To show that PET with 18F-fluoromisonidazole (18F-FMISO) can detect peri-infarct hypoxic tissue in patients after ischemic stroke. BACKGROUND: PET with (15)O-labeled oxygen and water is the only established method for identifying the ischemic penumbra in humans. We used PET with 18F-FMISO in patients after ischemic stroke to identify hypoxic but viable peri-infarct tissue likely to represent the ischemic penumbra, and to determine how long hypoxic tissues persist after stroke. METHODS: Patients with acute hemispheric ischemic stroke were studied using PET with 18F-FMISO either within 48 hours or 6 to 11 days after stroke onset. The final infarct was defined by CT performed 6 to 11 days after stroke. Tracer uptake was assessed objectively by calculating the mean activity in the contralateral (normal) hemisphere, then identifying pixels with activity greater than 3 SDs above the mean in both hemispheres. Positive studies were those with high-activity pixels ipsilateral to the infarct. RESULTS: Fifteen patients were studied; 13 within 48 hours of stroke, 8 at 6 to 11 days, and 6 during both time periods. Hypoxic tissue was detected in 9 of the 13 patients studied within 48 hours of stroke, generally distributed in the peripheries of the infarct and adjacent peri-infarct tissues. None of the 8 patients studied 6 to 11 days after stroke exhibited increased 18F-FMISO activity. All 6 patients studied both early and late exhibited areas of increased activity during the early but not the late study. CONCLUSIONS: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).