Prehospital Detection of Large Vessel Occlusion Stroke With EEG.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is standard treatment for anterior large vessel occlusion stroke (LVO-a stroke). Prehospital diagnosis of LVO-a stroke would reduce time to EVT by allowing direct transportation to an EVT-capable hospital. We aim to evaluate the diagnostic accuracy of dry electrode EEG for the detection of LVO-a stroke in the prehospital setting. METHODS: ELECTRA-STROKE was an investigator-initiated, prospective, multicenter, diagnostic study, performed in the prehospital setting. Adult patients were eligible if they had suspected stroke (as assessed by the attending ambulance nurse) and symptom onset <24 hours. A single dry electrode EEG recording (8 electrodes) was performed by ambulance personnel. Primary endpoint was the diagnostic accuracy of the theta/alpha frequency ratio for LVO-a stroke (intracranial ICA, A1, M1, or proximal M2 occlusion) detection among patients with EEG data of sufficient quality, expressed as the area under the receiver operating characteristic curve (AUC). Secondary endpoints were diagnostic accuracies of other EEG features quantifying frequency band power and the pairwise derived Brain Symmetry Index. Neuroimaging was assessed by a neuroradiologist blinded to EEG results. RESULTS: Between August 2020 and September 2022, 311 patients were included. The median EEG duration time was 151 (interquartile range [IQR] 151-152) seconds. For 212/311 (68%) patients, EEG data were of sufficient quality for analysis. The median age was 74 (IQR 66-81) years, 90/212 (42%) were women, and the median baseline NIH Stroke Scale was 1 (IQR 0-4). Six (3%) patients had an LVO-a stroke, 109/212 (51%) had a non-LVO-a ischemic stroke, 32/212 (15%) had a transient ischemic attack, 8/212 (4%) had a hemorrhagic stroke, and 57/212 (27%) had a stroke mimic. AUC of the theta/alpha ratio was 0.80 (95% CI 0.58-1.00). Of the secondary endpoints, the pairwise derived Brain Symmetry Index in the delta frequency band had the highest diagnostic accuracy (AUC 0.91 [95% CI 0.73-1.00], sensitivity 80% [95% CI 38%-96%], specificity 93% [95% CI 88%-96%], positive likelihood ratio 11.0 [95% CI 5.5-21.7]). DISCUSSION: The data from this study suggest that dry electrode EEG has the potential to detect LVO-a stroke among patients with suspected stroke in the prehospital setting. Toward future implementation of EEG in prehospital stroke care, EEG data quality needs to be improved. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT03699397. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that prehospital dry electrode scalp EEG accurately detects LVO-a stroke among patients with suspected acute stroke.

ELECTRA-STROKE: Electroencephalography controlled triage in the ambulance for acute ischemic stroke-Study protocol for a diagnostic trial.

Background: Endovascular thrombectomy (EVT) is the standard treatment for large vessel occlusion stroke of the anterior circulation (LVO-a stroke). Approximately half of EVT-eligible patients are initially presented to hospitals that do not offer EVT. Subsequent inter-hospital transfer delays treatment, which negatively affects patients' prognosis. Prehospital identification of patients with LVO-a stroke would allow direct transportation of these patients to an EVT-capable center. Electroencephalography (EEG) may be suitable for this purpose because of its sensitivity to cerebral ischemia. The hypothesis of ELECTRA-STROKE is that dry electrode EEG is feasible for prehospital detection of LVO-a stroke. Methods: ELECTRA-STROKE is an investigator-initiated, diagnostic study. EEG recordings will be performed in patients with a suspected stroke in the ambulance. The primary endpoint is the diagnostic accuracy of the theta/alpha ratio for the diagnosis of LVO-a stroke, expressed by the area under the receiver operating characteristic (ROC) curve. EEG recordings will be performed in 386 patients. Discussion: If EEG can be used to identify LVO-a stroke patients with sufficiently high diagnostic accuracy, it may enable direct routing of these patients to an EVT-capable center, thereby reducing time-to-treatment and improving patient outcomes. Clinical trial registration: ClinicalTrials.gov, identifier: NCT03699397.

Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP): an ambulance-based, multicentre, randomised, open-label, blinded endpoint, phase 3 trial.

BACKGROUND: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. METHODS: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. FINDINGS: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17]). INTERPRETATION: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

Feasibility of sonothrombolysis in the ambulance for ST-elevation myocardial infarction.

Patients with ST-elevation myocardial infarction (STEMI) due to coronary occlusion require immediate restoration of epicardial and microvascular blood flow. A potentially new reperfusion method is the use of ultrasound and microbubbles, also called sonothrombolysis. The oscillation and collapse of intravenously administered microbubbles upon exposure to high mechanical index (MI) ultrasound pulses results in thrombus dissolution and stimulates nitric oxide-mediated increases in tissue perfusion. The aim of this study was to assess feasibility of sonothrombolysis in the ambulance for STEMI patients. Patients presenting with chest pain and ST-elevations on initial electrocardiogram were included. Sonothrombolysis was applied in the ambulance during patient transfer to the percutaneous coronary intervention (PCI) center. Feasibility was assessed based on duration of sonothrombolysis treatment and number of high MI pulses applied. Vital parameters, ST-resolution, pre- and post-PCI coronary flow and cardiovascular magnetic resonance images were analyzed. Follow up was performed at six months after STEMI. Twelve patients were screened, of which three patients were included in the study. Sonothrombolysis duration and number of high MI pulses ranged between 12 and 17 min and 32-60 flashes respectively. No arrhythmias or changes in vital parameters were observed during and directly after sonothrombolysis, although one patient developed in-hospital ventricular fibrillation 20 min after sonothrombolysis completion but before PCI. In one case, sonothrombolysis on top of regular pre-hospital care resulted in reperfusion before PCI. This is the first report on the feasibility of performing sonothrombolysis to treat myocardial infarction in an ambulance. To assess efficacy and safety of pre-hospital sonothrombolysis, clinical trials with greater patient numbers should be performed. EU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.

Relationship between primary stroke center volume and time to endovascular thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated whether the annual volume of patients with acute ischemic stroke referred from a primary stroke center (PSC) for endovascular treatment (EVT) is associated with treatment times and functional outcome. METHODS: We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) registry (2014-2017). We included patients with acute ischemic stroke of the anterior circulation who were transferred from a PSC to a comprehensive stroke center (CSC) for EVT. We examined the association between EVT referral volume of PSCs and treatment times and functional outcome using multivariable regression modeling. The main outcomes were time from arrival at the PSC to groin puncture (PSC-door-to-groin time), adjusted for estimated ambulance travel times, time from arrival at the CSC to groin puncture (CSC-door-to-groin time), and modified Rankin Scale (mRS) score at 90 days after stroke. RESULTS: Of the 3637 patients in the registry, 1541 patients (42%) from 65 PSCs were included. Mean age was 71 years (SD ± 13.3), median National Institutes of Health Stroke Scale score was 16 (interquartile range [IQR]: 12-19), and median time from stroke onset to arrival at the PSC was 53 min (IQR: 38-90). Eighty-three percent had received intravenous thrombolysis. EVT referral volume was not associated with PSC-door-to-groin time (adjusted coefficient: -0.49 min/annual referral, 95% confidence interval [CI]: -1.27 to 0.29), CSC-door-to-groin time (adjusted coefficient: -0.34 min/annual referral, 95% CI: -0.69 to 0.01) or 90-day mRS score (adjusted common odds ratio: 0.99, 95% CI: 0.96-1.01). CONCLUSIONS: In patients transferred from a PSC for EVT, higher PSC volumes do not seem to translate into better workflow metrics or patient outcome.

Detection of Large Vessel Occlusion Stroke in the Prehospital Setting: Electroencephalography as a Potential Triage Instrument.

A reliable and fast instrument for prehospital detection of large vessel occlusion (LVO) stroke would be a game-changer in stroke care, because it would enable direct transportation of LVO stroke patients to the nearest comprehensive stroke center for endovascular treatment. This strategy would substantially improve treatment times and thus clinical outcomes of patients. Here, we outline our view on the requirements of an effective prehospital LVO detection method, namely: high diagnostic accuracy; fast application and interpretation; user-friendliness; compactness; and low costs. We argue that existing methods for prehospital LVO detection, including clinical scales, mobile stroke units and transcranial Doppler, do not fulfill all criteria, hindering broad implementation of these methods. Instead, electroencephalography may be suitable for prehospital LVO detection since in-hospital studies have shown that quantification of hypoxia-induced changes in the electroencephalography signal have good diagnostic accuracy for LVO stroke. Although performing electroencephalography measurements in the prehospital setting comes with challenges, solutions for fast and simple application of this method are available. Currently, the feasibility and diagnostic accuracy of electroencephalography in the prehospital setting are being investigated in clinical trials.

Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP): study protocol for a randomised controlled trial.

BACKGROUND: Some studies have suggested that transdermal administration of glyceryl trinitrate (GTN; nitroglycerin) in the first few hours after symptom onset increases the chance of a favourable outcome after ischaemic stroke or intracerebral haemorrhage, possibly through an increase in intracranial collateral blood flow and a reduction in blood pressure. The Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP) aims to assess the effect of transdermal GTN, started within 3 h after stroke onset in the prehospital setting, on functional outcome at 90 days in patients with acute ischaemic stroke or intracerebral haemorrhage. METHODS: MR ASAP is a phase III, multicentre, randomised, open-label clinical trial with a blinded outcome assessment. A total of 1400 adult patients with suspected stroke and a systolic blood pressure ≥ 140 mmHg will be randomised to transdermal GTN (5 mg/day), administered as a transdermal patch by paramedics in the prehospital setting within 3 h of stroke onset and continued for 24 h or to standard care. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days, analysed with ordinal logistic regression. Secondary outcomes include blood pressure and collateral circulation at hospital admission, neurological deficit measured with the National Institutes of Health Stroke Scale at 24 h, and mortality and poor outcome (mRS score 3 to 6) at 90 days. This trial will be conducted in the Netherlands and will use a deferred consent procedure. The trial is part of the Collaboration for New Treatments of Acute Stroke (CONTRAST) programme. DISCUSSION: MR ASAP will assess whether very early administration of GTN improves outcome after stroke in a setting where rates of intravenous thrombolysis and endovascular treatment for acute ischaemic stroke are high. The deferred consent procedure facilitates prompt GTN treatment and will prevent delay to revascularisation therapies. If early transdermal GTN treatment proves to be effective, this low-cost treatment can be readily implemented into daily clinical practice. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN99503308 . Registered on 2 January 2018.