Multifocal Atraumatic Convexity Subarachnoid Hemorrhage.

Background Multifocal convexity subarachnoid hemorrhage (cSAH) has generally been described in the setting of traumatic brain injury, however, it has also been reported in the absence of trauma in conditions such as with reversible cerebral vasoconstriction syndrome. We describe the clinical and radiographic characteristics of multifocal cSAH in an academic center. Methods We analyzed our single-center retrospective database of nontraumatic convexity subarachnoid hemorrhage from January 2015-January 2018. Convexity subarachnoid hemorrhage was defined as blood in one or more cortical sulci in the absence of trauma; patients with blood in the cisterns or Sylvian fissure were excluded. Multifocal location was defined as at least two distinct foci of hemorrhage occurring in two or more lobes. Clinical and neuroimaging data were collected. Results Out of 70 total patients with convexity subarachnoid hemorrhage, 13 cases were of multifocal convexity subarachnoid hemorrhage, occurring in 18.6% of all cases. The mean age was 58 years (SD = 14.7). Eleven patients were female. Seven patients had reversible cerebral vasoconstriction syndrome (RCVS)/posterior reversible encephalopathy syndrome (PRES), two had cerebral amyloid angiopathy (CAA), three had intrinsic coagulopathy, and one patient had endocarditis as the etiology of multifocal cSAH. Headache was the most common complaint, in eight (61.5%) patients. Conclusion Multifocal cSAH occurs in approximately 18.6% of all cSAH and can occur in the absence of trauma. In our larger cohort of all cSAH, CAA was the most common cause; however, multifocal cSAH is more commonly caused by RCVS/PRES spectrum. Clinicians should be aware that multifocal cSAH can occur in the absence of trauma, and may be a harbinger of RCVS/PRES, particularly in young patients with thunderclap headaches.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

12 versus 24 h bed rest after acute ischemic stroke thrombolysis: a preliminary experience.

BACKGROUND: The practice of ≥24 h of bed rest after acute ischemic stroke thrombolysis is common among hospitals, but its value compared to shorter periods of bed rest is unknown. METHODS: Consecutive adult patients with a diagnosis of ischemic stroke who had received intravenous thrombolysis treatment from 1/1/2010 until 4/13/2016, identified from the local ischemic stroke registry, were included. Standard practice bed rest for ≥24 h, the protocol prior to 1/27/2014, was retrospectively compared with standard practice bed rest for ≥12 h, the protocol after that date. The primary outcome was favorable discharge location (defined as home, home with services, or acute rehabilitation). Secondary outcome measures included incidence of pneumonia, NIHSS at discharge, and length of stay. RESULTS: 392 patients were identified (203 in the ≥24 h group, 189 in the ≥12 h group). There was no significant difference in favorable discharge outcome in the ≥24 h bed rest protocol compared with the ≥12 h bed rest protocol in multivariable logistic regression analysis (76.2% vs. 70.9%, adjusted OR 1.20 CI 0.71-2.03). Compared with the ≥24 h bed rest group, pneumonia rates (8.3% versus 1.6%, adjusted OR 0.12 CI 0.03-0.55), median discharge NIHSS (3 versus 2, adjusted p = .034), and mean length of stay (5.4 versus 3.5 days, adjusted p = .006) were lower in the ≥12 h bed rest group. CONCLUSION: Compared with ≥24 h bed rest, ≥12 h bed rest after acute ischemic stroke reperfusion therapy appeared to be similar. A non-inferiority randomized trial is needed to verify these findings.

Baseline NIH Stroke Scale is an inferior predictor of functional outcome in the era of acute stroke intervention.

Background and aims Baseline National Institutes of Health Stroke Scale (NIHSS) scores have frequently been used for prognostication after ischemic stroke. With the increasing utilization of acute stroke interventions, we aimed to determine whether baseline NIHSS scores are still able to reliably predict post-stroke functional outcome. Methods We retrospectively analyzed prospectively collected data from a high-volume tertiary-care center. We tested strength of association between NIHSS scores at baseline and 24 h with discharge NIHSS using Spearman correlation, and diagnostic accuracy of NIHSS scores in predicting favorable outcome at three months (defined as modified Rankin Scale 0-2) using receiver operating characteristic curve analysis with area under the curve. Results There were 1183 patients in our cohort, with median baseline NIHSS 8 (IQR 3-17), 24-h NIHSS 4 (IQR 1-11), and discharge NIHSS 2 (IQR 1-8). Correlation with discharge NIHSS was r = 0.60 for baseline NIHSS and r = 0.88 for 24-h NIHSS. Of all patients with follow-up data, 425/1037 (41%) had favorable functional outcome at three months. Receiver operating characteristic curve analysis for predicting favorable outcome showed area under the curve 0.698 (95% CI 0.664-0.732) for baseline NIHSS, 0.800 (95% CI 0.772-0.827) for 24-h NIHSS, and 0.819 (95% CI 0.793-0.845) for discharge NIHSS; 24 h and discharge NIHSS maintained robust predictive accuracy for patients receiving mechanical thrombectomy (AUC 0.846, 95% CI 0.798-0.895; AUC 0.873, 95% CI 0.832-0.914, respectively), while accuracy for baseline NIHSS decreased (AUC 0.635, 95% CI 0.566-0.704). Conclusion Baseline NIHSS scores are inferior to 24 h and discharge scores in predicting post-stroke functional outcomes, especially in patients receiving mechanical thrombectomy.

Level of consciousness at discharge and associations with outcome after ischemic stroke.

BACKGROUND: Many factors may potentially complicate the stroke recovery process, including persistently impaired level of consciousness (LOC)-whether from residual stroke effects or from superimposed delirium. We aimed to determine the degree to which impaired LOC at hospital discharge is associated with outcomes after ischemic stroke. METHODS: We conducted a single-center retrospective cohort study using prospectively-collected data from 2015 to 2017, collecting total NIHSS-LOC score at discharge as well as subscores for responsiveness (LOC-R), orientation questions (LOC-Q), and command-following (LOC-C). We determined associations between LOC scores and 3-month outcome using logistic regression, with discharge location (skilled nursing facility [SNF] vs. inpatient rehabilitation) representing a pre-specified secondary outcome. RESULTS: We identified 1003 consecutive patients with ischemic stroke who survived to discharge, of whom 32% had any LOC score > 0. Total LOC score at discharge was associated with unfavorable 3-month outcome (OR 4.9 [95% CI 2.4-9.8] for LOC = 1; OR 8.0 [2.7-23.9] for LOC = 2-3; OR 6.3 [2.1-18.5] for LOC = 4-5; all patients with LOC = 6-7 had poor outcomes), as were subscores for LOC-R (OR 5.3 [1.3-21.2] for LOC-R = 1; all patients with LOC-R = 2-3 had poor outcomes) and LOC-Q (OR 4.1 [2.1-8.3] for LOC-Q = 1; OR 4.9 [1.8-13.5] for LOC-Q = 2). Total LOC score (OR 2.6 [1.3-5.3] for LOC = 1; OR 3.1 [1.2-8.2] for LOC = 2-3) and LOC-Q (OR 3.3 [1.6-6.6] for LOC-Q = 1; OR 3.4 [1.3-9.0] for LOC-Q = 2) were also associated with discharge to SNF rather than to inpatient rehabilitation. CONCLUSIONS: The presence of impaired consciousness or disorientation at discharge is associated with markedly worse outcomes after ischemic stroke. Further studies are necessary to determine the separate effects of residual stroke-related LOC changes and those caused by superimposed delirium.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

OBJECTIVES: Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. METHODS: We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. RESULTS: We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). CONCLUSION: Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.

Perfusion imaging and recurrent cerebrovascular events in intracranial atherosclerotic disease or carotid occlusion.

Background Large vessel disease stroke subtype carries the highest risk of early recurrent stroke. In this study we aim to look at the association between impaired perfusion and early stroke recurrence in patients with intracranial atherosclerotic disease or total cervical carotid occlusion. Methods This is a retrospective study from a comprehensive stroke center where we included consecutive patients 18 years or older with intracranial atherosclerotic disease or total cervical carotid occlusion admitted with a diagnosis of ischemic stroke within 24 h from symptom onset with National Institute Health Stroke Scale < 15, between 1 December 2016 and 30 June 2017. Patients with (1) evidence of ≥ 50% stenosis of a large intracranial artery or total carotid artery occlusion, (2) symptoms referable to the territory of the affected artery, and (3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable perfusion imaging defined as Tmax > 6 s mismatch volume (penumbra volume-infarct volume) of 15 ml or more. The outcome was recurrent cerebrovascular events at 90 days defined as worsening or new neurological symptoms in the absence of a nonvascular cause attributable to the decline, or new infarct or infarct extension in the territory of the affected artery. We used Cox proportional hazards models to determine the association between impaired perfusion and recurrent cerebrovascular events. Results Sixty-two patients met our inclusion criteria; mean age 66.4 ± 13.1 years, 64.5% male (40/62) and 50.0% (31/62) with intracranial atherosclerotic disease. When compared to patients with favorable perfusion pattern, patients with unfavorable perfusion pattern were more likely to have recurrent cerebrovascular events (55.6% (10/18) versus 9.1% (4/44), p < 0.001). This association persisted after adjusting for potential confounders (adjusted hazard ratio 10.44, 95% confidence interval 2.30-47.42, p = 0.002). Conclusion Perfusion mismatch predicts recurrent cerebrovascular events in patients with ischemic stroke due to intracranial atherosclerotic disease or total cervical carotid occlusion. Studies are needed to determine the utility of revascularization strategies in this patient population.

Left Atrial Appendage Morphology and Embolic Stroke of Undetermined Source: A Cross-Sectional Multicenter Pilot Study.

BACKGROUND: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation, and there is an association between non-chicken wing (NCW) LAA morphology and stroke. We hypothesized that the prevalence of NCW LAA morphology would be higher among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with noncardioembolic stroke (NCS). METHODS: This multicenter retrospective pilot study included consecutive patients with ischemic stroke from 3 comprehensive stroke centers who previously underwent a qualifying chest computed tomography (CT) to assess LAA morphology. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology was determined using clinically performed contrast enhanced thin-slice chest CT by investigators blinded to stroke subtype. The primary predictor was NCW LAA morphology and the outcome was stroke subtype (CE, ESUS, NCS). RESULTS: We identified 172 patients with ischemic stroke who had a clinical chest CT performed. Mean age was 70.1 ± 14.3 years and 51.7% were male. Compared with patients with NCS, the prevalence of NCW LAA morphology was higher in patients with CE stroke (58.7% versus 46.3%, P = .1) and ESUS (58.8% versus 46.3%, P = .2), but this difference did not achieve statistical significance. CONCLUSION: The prevalence of NCW LAA morphology may be similar in patients with ESUS and CE, and may be higher than that in those with NCS. Larger studies are needed to confirm these associations.

Early Elevated Troponin Levels After Ischemic Stroke Suggests a Cardioembolic Source.

BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). METHODS: We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct. RESULTS: We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002). CONCLUSIONS: We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

Association of a Primary Stroke Center Protocol for Suspected Stroke by Large-Vessel Occlusion With Efficiency of Care and Patient Outcomes.

Importance: While prehospital triage to the closest comprehensive stroke center (CSC) may improve the delivery of care for patients with suspected emergent large-vessel occlusion (ELVO), efficient systems of care must also exist for patients with ELVO who first present to a primary stroke center (PSC). Objective: To describe the association of a PSC protocol focused on 3 key steps (early CSC notification based on clinical severity, vessel imaging at the PSC, and cloud-based image sharing) with the efficiency of care and the outcomes of patients with suspected ELVO who first present to a PSC. Design, Setting, and Participants: In this retrospective cohort study, 14 regional PSCs unfamiliar with the management of patients with ELVO were instructed on the use of the following protocol for patients presenting with a Los Angeles Motor Scale score 4 or higher: (1) notify the CSC on arrival, (2) perform computed tomographic angiography concurrently with noncontract computed tomography of the brain and within 30 minutes of arrival, and (3) share imaging data with the CSC using a cloud-based platform. A total of 101 patients were transferred from regional PSCs to the CSC between July 1, 2015, and May 31, 2016, and received mechanical thrombectomy for acute ischemic stroke. The CSC serves approximately 1.7 million people and partners with 14 PSCs located between 6.4 and 73.6 km away. All consecutive patients with internal carotid artery or middle cerebral artery occlusions transferred over an 11-month period were reviewed, and they were divided into 2 groups based on whether the PSC protocol was partially or fully executed. Main Outcomes and Measures: The primary outcomes were efficiency measures including time from PSC door in to PSC door out, time from PSC door to CSC groin puncture, and 90-day modified Rankin Scale score (range, 0-6; scores of 0-2 indicate a good outcome). Results: Although 101 patients were transferred, only 70 patients met the inclusion criteria during the study period. The protocol was partially executed for 48 patients (68.6%) (mean age, 77 years [interquartile range, 65-84 years]; 22 of the 48 patients [45.0%] were women) and fully executed for 22 patients (31.4%) (mean age, 76 years [interquartile range, 59-86 years]; 13 of the 22 patients [59.1%] were women). When fully executed, the protocol was associated with a reduction in the median time for PSC arrival to CSC groin puncture (from 151 minutes [95% CI, 141-166 minutes] to 111 minutes [95% CI, 88-130 minutes]; P < .001). This was primarily related to an improvement in the time from PSC door in to door out that reduced from a median time of 104 minutes (95% CI, 82-112 minutes) to a median time of 64 minutes (95% CI, 51-71.0 minutes) (P < .001). When the protocol was fully executed, patients were twice as likely to have a favorable outcome (50% vs 25%, P < .04). Conclusions and Relevance: When fully implemented, a standardized protocol at PSCs for patients with suspected ELVO consisting of early CSC notification, computed tomographic angiography on arrival to the PSC, and cloud-based image sharing is associated with a reduction in time to groin puncture and improved outcomes.

Continuous aspiration prior to intracranial vascular embolectomy (CAPTIVE): a technique which improves outcomes.

BACKGROUND: Modern stent retriever-based embolectomy for patients with emergent large vessel occlusion improves outcomes. Techniques aimed at achieving higher rates of complete recanalization would benefit patients. OBJECTIVE: To evaluate the clinical impact of an embolectomy technique focused on continuous aspiration prior to intracranial vascular embolectomy (CAPTIVE). METHODS: A retrospective review was performed of 95 consecutive patients with intracranial internal carotid artery or M1 segment middle cerebral artery occlusion treated with stent retriever-based thrombectomy over an 11-month period. Patients were divided into a conventional local aspiration group (traditional group) and those treated with a novel continuous aspiration technique (CAPTIVE group). We compared both early neurologic recovery (based on changes in National Institute of Health Stroke Scale (NIHSS) score), independence at 90 days (modified Rankin score 0-2), and angiographic results using the modified Thrombolysis in Cerebral Ischemia (TICI) scale including the TICI 2c category. RESULTS: There were 56 patients in the traditional group and 39 in the CAPTIVE group. Median age and admission NIHSS scores were 78 years and 19 in the traditional group and 77 years and 19 in the CAPTIVE group. Median times from groin puncture to recanalization in the traditional and CAPTIVE groups were 31 min and 14 min, respectively (p<0.0001). While rates of TICI 2b/2c/3 recanalization were similar (81% traditional vs 100% CAPTIVE), CAPTIVE offered higher rates of TICI 2c/3 recanalization (79.5% vs 40%, p<0.001). Median discharge NIHSS score was 10 in the traditional group and 3 in the CAPTIVE group; this difference was significant. There was also an increased independence at 90 days (25% traditional vs 49% CAPTIVE). CONCLUSIONS: The CAPTIVE embolectomy technique may result in higher recanalization rates and better clinical outcomes.