Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

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Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

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The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

The incidence of subarachnoid haemorrhage (SAH) is stable, at around six cases per 100 000 patient years. Any apparent decrease is attributable to a higher rate of CT scanning, by which other haemorrhagic conditions are excluded. Most patients are <60 years of age. Risk factors are the same as for stroke in general; genetic factors operate in only a minority. Case fatality is approximately 50% overall (including pre-hospital deaths) and one-third of survivors remain dependent. Sudden, explosive headache is a cardinal but non-specific feature in the diagnosis of SAH: in general practice, the cause is innocuous in nine out of 10 patients in whom this is the only symptom. CT scanning is mandatory in all, to be followed by (delayed) lumbar puncture if CT is negative. The cause of SAH is a ruptured aneurysm in 85% of cases, non-aneurysmal perimesencephalic haemorrhage (with excellent prognosis) in 10%, and a variety of rare conditions in 5%. Catheter angiography for detecting aneurysms is gradually being replaced by CT angiography. A poor clinical condition on admission may be caused by a remediable complication of the initial bleed or a recurrent haemorrhage in the form of intracranial haematoma, acute hydrocephalus or global brain ischaemia. Occlusion of the aneurysm effectively prevents rebleeding, but there is a dearth of controlled trials assessing the relative benefits of early operation (within 3 days) versus late operation (day 10-12), or that of endovascular treatment versus any operation. Antifibrinolytic drugs reduce the risk of rebleeding, but do not improve overall outcome. Measures of proven value in decreasing the risk of delayed cerebral ischaemia are a liberal supply of fluids, avoidance of antihypertensive drugs and administration of nimodipine. Once ischaemia has occurred, treatment regimens such as a combination of induced hypertension and hypervolaemia, or transluminal angioplasty, are plausible, but of unproven benefit.

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Subarachnoid haemorrhage: diagnosis, causes and management

BACKGROUND Transcranial Doppler ultrasonography that is aimed at residual obstructive intracranial blood flow may help expose thrombi to tissue plasminogen activator (t-PA). Our objective was to determine whether ultrasonography can safely enhance the thrombolytic activity of t-PA. METHODS We treated all patients who had acute ischemic stroke due to occlusion of the middle cerebral artery with intravenous t-PA within three hours after the onset of symptoms. The patients were randomly assigned to receive continuous 2-MHz transcranial Doppler ultrasonography (the target group) or placebo (the control group). The primary combined end point was complete recanalization as assessed by transcranial Doppler ultrasonography or dramatic clinical recovery. Secondary end points included recovery at 24 hours, a favorable outcome at three months, and death at three months. RESULTS A total of 126 patients were randomly assigned to receive continuous ultrasonography (63 patients) or placebo (63 patients). Symptomatic intracerebral hemorrhage occurred in three patients in the target group and in three in the control group. Complete recanalization or dramatic clinical recovery within two hours after the administration of a t-PA bolus occurred in 31 patients in the target group (49 percent), as compared with 19 patients in the control group (30 percent; P=0.03). Twenty-four hours after treatment of the patients eligible for follow-up, 24 in the target group (44 percent) and 21 in the control group (40 percent) had dramatic clinical recovery (P=0.7). At three months, 22 of 53 patients in the target group who were eligible for follow-up analysis (42 percent) and 14 of 49 in the control group (29 percent) had favorable outcomes (as indicated by a score of 0 to 1 on the modified Rankin scale) (P=0.20). CONCLUSIONS In patients with acute ischemic stroke, continuous transcranial Doppler augments t-PA-induced arterial recanalization, with a nonsignificant trend toward an increased rate of recovery from stroke, as compared with placebo.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa041175

Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke.

Background and Purpose Transcranial color-coded duplex sonography (TCCS) enables visualization of the intracranial parenchymal structures and measurement of blood flow velocity in the basal cerebral arteries. The present study aims to evaluate prospectively the clinical usefulness of TCCS in patients with acute stroke.

Methods Eighty-four consecutive patients with central nervous symptoms suggesting acute stroke were investigated within the first 48 hours after clinical onset. TCCS was performed with a 2.5-MHz sector transducer through the temporal bone window. CT was available in all patients.

Results Forty-eight patients suffered from an infarction or a transient ischemic attack (TIA) in the territory of the middle cerebral artery (MCA). Fifteen of them showed an MCA occlusion, and 12 of the 15 developed recanalization during follow-up. Twelve revealed an increased, decreased, or oscillating flow pattern in the MCA main stem, and 21 patients had no ultrasonic abnormalities. The positive and negative predictive values of a pathological flow pattern in patients with MCA infarctions or TIA were .92 and .48, respectively. Fifteen patients suffered from an intracerebral hematoma, which could be diagnosed by TCCS in 14 cases. The positive and negative predictive values of a pathological parenchymal echo pattern were .88 and .96, respectively. Three patients suffered from an infarction and one from a TIA in the posterior cerebral artery territory. One female patient with an acute deterioration of a hemiparesis showed a glioma. The dropout rate due to an insufficient acoustic temporal bone window was 20% (17/84).

Conclusions TCCS is a noninvasive bedside method that provides rapid and reliable data regarding stroke subtype and mechanism immediately after onset. Window failure is a serious limitation of this method.

Potential and Limitations of Transcranial Color-Coded Sonography in Stroke Patients

We studied the effect of transcranial 2 MHz Doppler ultrasound (US) on the recanalization and outcome of stroke patients suffering from acute middle cerebral artery occlusion. All patients underwent intravenous recombinant tissue-type plasminogen activator thrombolysis. Eleven patients were randomly selected for continuous US monitoring (C-US) over 1 hour; 14 patients were selected for the control group. The C-US group showed a higher grade of recanalization after 1 hour but also a higher number of intraparenchymal bleedings. Overall, a favorable functional outcome occurred more frequently in the C-US group (Barthel index, p = 0.037) after 3 months.

Effect of ultrasound on thrombolysis of middle cerebral artery occlusion.

Background and Purpose— Sonothrombolysis is a new treatment approach in acute ischemic stroke. The results of a monocenter, randomized clinical study are presented. Methods— Subjects with acute middle cerebral artery main stem occlusion were randomized into a target group receiving 1-hour transcranial continuous insonation using a 1.8-MHz Doppler ultrasound (US) probe or a control group. All underwent standard thrombolysis with intravenous recombinant tissue-type plasminogen activator. Results— Thirty-seven subjects were included; 19 subjects were treated in the target (US) group and 18 in the control (no-US) group, all with no residual flow in the middle cerebral artery main stem occlusion (Thrombolysis in Brain Ischemia recanalization grade 0). Compared with the no-US group, the US group showed greater improvement in National Institutes of Health Stroke Scale values at days 1 and 4 and a higher median Thrombolysis in Brain Ischemia grade 1 hour after recombinant tissue-type plasminogen activator initiat...

Sonothrombolysis With Transcranial Color-Coded Sonography and Recombinant Tissue-Type Plasminogen Activator in Acute Middle Cerebral Artery Main Stem Occlusion Results From a Randomized Study

Transcranial duplex color-flow sonography provides visualization of intracranial structures, and measures angle-corrected blood flow velocity in the basal cerebral arteries of adults. In 44 patients with central nervous system disease, the oblique diameters of the third and the middle part of the lateral ventricle were measured by transcranial duplex color-flow sonography using a system with a 2.5-MHz transducer, and compared to computed tomography measurements. The correlation coefficients for the third and lateral ventricle measurements were r = 0.83 (p < 0.0001, N = 38) and 0.73 (p < 0.0001, N = 78), respectively. A second investigation was performed by transcranial duplex to evaluate intraobserver and interobserver reproducibility. The correlation coefficient representing interobserver reproducibility in 27 patients was r = 0.87 (p < 0.0001, N = 47) for the lateral ventricle and r = 0.9 (p < 0.0001, N = 49) for the third ventricle. The intraobserver reproducibility correlation coefficient was r = 0.93 (p < 0.0001, N = 22) for the lateral ventricle in 12 patients. In 49 healthy volunteers the oblique diameters of the lateral and third ventricles were age dependent, measuring 16.7 +/- 2.3 mm and 4.8 +/- 1.9 mm, respectively, in those younger than 59 years, compared to 19.0 +/- 2.9 mm and 7.6 +/- 2.1 mm in those 60 years or older. Therefore, transcranial duplex color-flow sonography measures noninvasively the third and the lateral ventricle in adults.

Evaluation of the ventricular system in adults by transcranial duplex sonography.

Objectives: To evaluate in a prospective multicentre setting the feasibility of transcranial colour coded duplex sonography (TCCS) for examination of the middle cerebral artery (MCA) in patients with acute hemispheric stroke, and to assess the validity of sonographic findings in a subgroup of patients who also had a correlative angiographic examination. Methods: TCCS was performed in 58 consecutive patients within six hours of the onset of a moderate to severe hemispheric stroke. Ultrasound contrast agent (Levovist) was applied if necessary. Thirty two patients also had computed tomography angiography (n=13), magnetic resonance angiography (n=18), or digital subtraction angiography (n=1). In 14 of these patients, both the sonographic and corresponding angiographic examination were performed within six hours of stroke onset (mean time difference between TCCS and angiography 0.8 hours). Eighteen patients, in whom angiography was carried out more than 24 hours after stroke onset, had a follow up TCCS for method comparison (mean time difference 6.1 hours). Results: Initial unenhanced TCCS performed 3.4 (SD 1.2) hours after the onset of symptoms depicted the symptomatic MCA mainstem in 32 patients (55%) (13 occlusions, one stenosis, 18 patent arteries). After signal enhancement, MCA status could be determined in 54 patients (93%) (p<0.05), showing an occlusion in 25, a stenosis in two, and a patent artery in 27 patients. In 31 of the 32 patients who had correlative angiography, TCCS and angiography produced the same diagnosis of the symptomatic MCA (10 occlusions, three stenoses, 18 patent arteries); TCCS was inconclusive in the remaining one. Conclusion: TCCS is a feasible, fast, and valid non-invasive bedside method for evaluating the MCA in an acute stroke setting, particularly when contrast enhancement is applied. It may be a valuable and cost effective alternative to computed tomography and magnetic resonance angiography in future stroke trials.

https://jnnp.bmj.com/content/jnnp/73/1/17.full.pdf

Günter Seidel

Papers

Potential and Limitations of Transcranial Color-Coded Sonography in Stroke Patients

Effect of ultrasound on thrombolysis of middle cerebral artery occlusion.

Sonothrombolysis With Transcranial Color-Coded Sonography and Recombinant Tissue-Type Plasminogen Activator in Acute Middle Cerebral Artery Main Stem Occlusion Results From a Randomized Study

Evaluation of the ventricular system in adults by transcranial duplex sonography.

Feasibility and validity of transcranial duplex sonography in patients with acute stroke