Management of acute ischemic stroke in patients with COVID-19 infection: Insights from an international panel.

OBJECTIVE: To present guidance for clinicians caring for adult patients with acuteischemic stroke with confirmed or suspected COVID-19 infection. METHODS: The summary was prepared after review of systematic literature reviews,reference to previously published stroke guidelines, personal files, and expert opinionby members from 18 countries. RESULTS: The document includes practice implications for evaluation of stroke patientswith caution for stroke team members to avoid COVID-19 exposure, during clinicalevaluation and conduction of imaging and laboratory procedures with specialconsiderations of intravenous thrombolysis and mechanical thrombectomy in strokepatients with suspected or confirmed COVID-19 infection. RESULTS: Conclusions-The summary is expected to guide clinicians caring for adult patientswith acute ischemic stroke who are suspected of, or confirmed, with COVID-19infection.

Impact of advanced healthcare directives on treatment decisions by physicians in patients with acute stroke.

BACKGROUND: The implementation of advanced healthcare directives, prepared by almost half of the adult population in United States remains relatively under studied. We determined the impact of advanced healthcare directives on treatment decisions by multiple physicians in stroke patients. METHODS: A deidentified summary of clinical and radiological records of 28 patients with stroke was given to six stroke physicians who were not involved in the care of the patients. Each physician independently rated 28 treatment decisions per patient in the presence or absence of advanced healthcare directives 1 month apart to allow memory washout. The percentage agreement to treat/intervene per patient and proportion of treatment withheld as a group were estimated for each of the 28 treatment decision items. We also determined the interobserver reliability between the two raters (attorneys) in interpretation of six items characterizing the adequacy of documentation within the 28 advanced healthcare directives. RESULTS: The percentage agreement among physician raters for treatment decisions in 28 stroke patients was highest for treatment of hyperpyrexia (100%, 100%) and lowest for ICU monitoring duration based on family-physician considerations outside of accepted criteria within institution (68%, 69%) in presence and absence of advanced healthcare directives. The physician rater agreement in choosing "yes" was highest for "routine-complexity" treatment decisions and lowest for "moderate-complexity" treatment decisions. The choice of withholding treatment in "routine-complexity," "moderate-complexity," or "high-complexity" treatment decisions was remarkably similar among raters in presence or absence of advanced healthcare directives. The only treatment decision that showed an impact of advanced healthcare directives was ICU monitoring withheld in 32% of treatment decisions in presence of directives (compared with 8% in the absence of directives). IV medication and defibrillation for cardiac arrest was withheld in 29% (compared with 19%) of the treatment decisions in the presence of advanced healthcare directives. The two attorney raters found the description of acceptable outcome inadequate in 14 and 21 of 28 advanced healthcare directives reviewed, respectively. The overall mean kappa for agreement regarding adequacy of documentation was modest (43%) for "does the advanced healthcare directive specify which treatments the patient would choose, or refuse to receive if they were diagnosed with an acute, terminal condition?" and lowest (3%) for "description of acceptable outcome." CONCLUSIONS: We did not find any prominent differences in most "routine-complexity," "moderate-complexity," or "high-complexity" treatment decisions in patient management in the presence of advanced healthcare directives. Presence of advanced healthcare directives also did not reduce the prominent variance among physicians in treatment decisions.

Combination of noninvasive neurovascular imaging modalities in stroke patients: patterns of use and impact on need for digital subtraction angiography.

BACKGROUND: The diagnostic work-up of acute stroke relies on the use of proper imaging studies. We sought to determine the use of a combination of 2 noninvasive tests, namely magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) in diagnosing vascular lesions and the necessity for a subsequent digital subtraction angiography (DSA) for the definitive diagnosis. METHODS: Patients admitted to 2 comprehensive stroke centers between January 2008 and July 2010 who had an equivocal initial noninvasive test were reviewed. The proportions of patients who underwent CTA and MRA in combination and those who required additional DSA for definitive diagnosis were determined. The diagnostic yield and impact on management in patients with CTA and MRA combination was compared with patients who underwent CTA and MRA followed by DSA. RESULTS: Among a total of 1063 patients (mean age ± SD 63 ± 16), 384 (36%) underwent >1 vascular imaging study. There was no difference in the rates of cardiovascular risk factors and stroke subtype between different combination groups. The agreement between CTA and MRA was high (concordance 81%). Among the 164 patients who underwent both CTA and MRA, a DSA was required for resolution/confirmation in only 27 (16%) patients. Among these 27, DSA findings changed the clinical decision-making in 22 (82%) patients (11 stenotic severities and 11 diagnoses of arteriovenous fistula, aneurysm, or dissection). CONCLUSIONS: In our experience, a combination of CTA and MRA was frequently used in patients in whom the initial noninvasive imaging was determined insufficient. The combination of findings from CTA and MRA were considered adequate in a large portion of patients resulting in a lower requirement for DSA and higher treatment impact from DSA.

Intraprocedural Back Pain Associated with Awake Neuroendovascular Procedures.

BACKGROUND AND PURPOSE: The prevalence and characteristics of intraprocedural back pain is not well studied in awake patients undergoing neuroendovascular procedures. METHODS: We performed a prospective study as part of quality improvement initiative in which all patients who underwent neuroendovascular procedures in awake state were inquired regarding presence, severity (using a numeric rating scale score ranging from 0 [no pain] to 10 [worst pain possible]), and location (using anatomical chart) of back pain immediately after the procedure. The primary endpoint was the proportion of patients with moderate to severe pain (score of ≥3). RESULTS: A total of 100 (41.3%) of 242 patients reported intraprocedural back pain with a median severity of 5/10 (range 1-10). The mean age was 58.7 ± 16.2 years. The mean duration of the procedure was 82.3 minutes (range 15-410 minutes). The pain was classified as moderate to severe in 86 of 100 patients. The locations of pain were identified in lumbar (n = 77), thoracic (n = 6), cervical (n = 7), cervical and lumbar (n = 8), and cervical with thoracolumbar (n = 2) regions. There was a significant relationship between patients' history of the previous neck and/or back surgery and frequency of moderate to severe back pain (P = .02). No significant relationship was observed between frequency of none to mild and moderate to severe back pain among the strata by patients' age, body mass index, or duration of procedures. CONCLUSIONS: The relatively high prevalence of intraprocedural back pain in patients undergoing neuroendovascular procedures in awake state must be recognized, and strategies to reduce the occurrence need to be identified.

The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis Trial: Reanalysis Using the FDA "On Label" Criteria.

BACKGROUND AND PURPOSE: Due to higher rates of 1-month stroke and death with Wingspan intracranial stent placement observed in SAMMPRIS, the Food and Drug Administration (FDA) announced a more limited indication for Wingspan stent. METHODS: We compared the results of intracranial stent placement with best medical treatment in patients recruited in SAMMPRIS who met the new "on label" criteria with those who were categorized as "off label." The primary endpoint was any stroke or death occurring within 30 days of enrollment, or an ischemic stroke in the territory of the symptomatic intracranial artery from day 31 after study entry to completion of follow-up. RESULTS: A total of 31 (7%) among 451 recruited patients met the "on label" criteria. The relative risk of primary endpoint was lower in "on label" patients treated with stent placement compared with best medical treatment (relative risk .61, 95% confidence interval .2-1.7) but higher in "off label" patients (relative risk 1.81, 95% confidence interval 1.2-2.6). Primary endpoint was seen in 20% and 23.4% of patients treated with stent placement in "on label" and "off label" patients, respectively. Primary endpoint was seen in 25% and 14.2% of patients treated with best medical treatment in "on label" and "off label" patients, respectively. CONCLUSION: The new FDA "on label" criteria may identify a small group of people, who may benefit from intracranial stent placement due to higher risk of primary endpoint in those treated with best medical treatment.

The Effect of Ticagrelor on Platelet Reactivity in Patients with Clopidogrel Resistance Undergoing Neuroendovascular Procedures.

BACKGROUND AND PURPOSE: Suboptimal platelet inhibition by clopidogrel (clopidogrel resistance) may be associated with high rates of stent thrombosis and ischemic events. Our objective was to determine if ticagrelor, a P2Y12 receptor inhibitor, can result in platelet inhibition in patients with clopidogrel resistance. METHODS: A thromboelastography-platelet mapping assay was used in all patients undergoing neuroendovascular procedures requiring oral clopidogrel. In patients with suboptimal platelet inhibition (<60%) on clopidogrel, ticagrelor was imitated after an oral bolus of 180 mg followed by 90 mg twice daily and the platelet mapping assay was repeated. The primary endpoint was hemorrhagic complications classified as major (hemoglobin decrease >5 g/dL or intracranial hemorrhage with deficits), minor (hemoglobin decrease 3-5 g/dL or intracranial hemorrhage without residual deficits), or insignificant. RESULTS: Suboptimal platelet inhibition on clopidogrel was seen in 70 of 106 patients undergoing neuroendovascular procedures. There was a significantly higher magnitude of platelet inhibition with ticagrelor compared with clopidogrel in patients with clopidogrel resistance (mean ± SD: 85.90 ± 10.74% vs. 29.26 ± 17.71%; P < .001); 50 of 70 patients showed optimal inhibition. Two patients had major (fatal) hemorrhagic events (both received either intravenous thrombolytics and/or eptifibatide infusion). Three patients had minor hemorrhagic events, and two patients had insignificant hemorrhagic events. Four of seven hemorrhagic events occurred in patients with optimal response to clopidogrel, two occurred in patients with suboptimal response to ticagrelor, and one occurred in a patient with optimal response to ticagrelor. CONCLUSIONS: Oral ticagrelor can augment platelet inhibition in patients who have clopidogrel resistance.

Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel.

BACKGROUND AND PURPOSE: On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. METHODS: The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. RESULTS: This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. CONCLUSIONS: These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.

Trophic factors and stem cells for promoting recovery in stroke.

BACKGROUND: Stem cell therapy for stroke is in its initial stages as an option to restore lost neurological functions after stroke. OBJECTIVE: To provide a comprehensive review of studies involving stem cells in stroke treatment and to highlight new evidence from the ongoing clinical trials. METHODOLOGY: We performed a systematic study of various published journals in online medical libraries using Pubmed, Sciencedirect, and hajournal. Evidence synthesis is done with specific search words of - stem cell therapy, stroke, trophic factor, neural progenitor cell, pathophysiology, mechanism of action, clinical trial and mesenchymal stem cell in various combinations. Emphasis was given to articles published in year 2000 and onwards. RESULTS: Current research on stem cell therapy for stroke focuses on transplantation and endogenous neurogenesis of stem cells in brain. The sub-ventricular zone in the adult brain is identified as an endogenous resource of neuronal precursors that can be recruited to adjacent lesioned areas. Several factors can increase adult neurogenesis by stimulating formation or improving survival of new neurons, such as FGF-2, EGF, stem cell factor, erythropoietin, BDNF, caspase inhibitors, and anti-inflammatory drugs. Much of the beneficial effects of stem cell in stroke models are related to secretion of trophic factors. CONCLUSION: The complex pathophysiology involving various trophic factors, growth factor and gene modification in animal studies have showed promising result. Future research involving these trophic factors should open up new additional or clinically significant alternative for the treatment of stroke.

Drug evaluation of clevidipine for acute hypertension.

BACKGROUND: Clevidipine is an investigational agent undergoing late-stage clinical development to evaluate its potential as a novel short-acting intravenous agent for treating acute hypertension, either in hypertensive emergencies encountered in the emergency department and intensive care units, or in the perioperative period. METHOD: Clevidipine has been evaluated in four Phase I studies, nine Phase II studies and six Phase III clinical studies. The patient populations studied include healthy volunteers, patients with essential hypertension, patients undergoing cardiac surgery, and patients presenting to the emergency department with hypertensive emergencies. Studies providing comparative data of clevidipine versus nitroglycerin, nicardipine or sodium nitroprusside are also available. OBJECTIVE: This article reviews the results of clinical studies evaluating the pharmacological properties, clinical effects and safety profiles of clevidipine in various patient populations. RESULTS/CONCLUSION: Clevidipine is an effective agent for reducing acute elevation in blood pressure in various settings, including hypertensive emergencies and perioperative hypertension with a good safety profile.

Timing of neurologic deterioration in massive middle cerebral artery infarction: a multicenter review.

OBJECTIVE: To determine the time interval between symptom onset and neurologic deterioration related to cerebral edema in patients with massive middle cerebral artery infarction. The time period between onset and neurologic deterioration represents the window for surgical intervention. DESIGN: Multicenter retrospective chart review. SETTINGS: Five university-affiliated medical centers. PATIENTS: Fifty-three patients with massive middle cerebral artery infarction who experienced neurologic deterioration defined by a decrease in the Glasgow Coma Scale score of two or more points attributable to mass effect. MEASUREMENTS AND MAIN RESULTS: A total of 53 patients (mean age, 62 +/- 18 yrs; 25 [47%] were men) with neurologic deterioration were identified by using International Classification of Diseases (9th revision) codes and local registries. Medical records and neuroimaging studies were reviewed by a stroke neurologist or neurointensivist to identify the time of neurologic deterioration. Thrombolytics were used at presentation in 19 (35%) patients. A total of 19 (36%) patients had neurologic deterioration within 24 hrs of symptom onset. By 48 hrs, 36 (68%) patients had manifested clinical deterioration. A few patients had later neurologic deterioration on day 3 (n = 10), day 4 (n = 2), day 5 (n = 2), and day 6 or after (n = 3). A total of 25 (47%) of the 53 patients died during hospitalization. The highest frequency of deaths occurred on day 3. CONCLUSIONS: Neurologic deteriorations related to cerebral edema after massive middle cerebral artery infarction occur in most patients within 48 hrs of symptom onset.