Headpulse measurement can reliably identify large-vessel occlusion stroke in prehospital suspected stroke patients: Results from the EPISODE-PS-COVID study.

BACKGROUND: Large-vessel occlusion (LVO) stroke represents one-third of acute ischemic stroke (AIS) in the United States but causes two-thirds of poststroke dependence and >90% of poststroke mortality. Prehospital LVO stroke detection permits efficient emergency medical systems (EMS) transport to an endovascular thrombectomy (EVT)-capable center. Our primary objective was to determine the feasibility of using a cranial accelerometry (CA) headset device for prehospital LVO stroke detection. Our secondary objective was development of an algorithm capable of distinguishing LVO stroke from other conditions. METHODS: We prospectively enrolled consecutive adult patients suspected of acute stroke from 11 study hospitals in four different U.S. geographical regions over a 21-month period. Patients received device placement by prehospital EMS personnel. Headset data were matched with clinical data following informed consent. LVO stroke diagnosis was determined by medical chart review. The device was trained using device data and Los Angeles Motor Scale (LAMS) examination components. A binary threshold was selected for comparison of device performance to LAMS scores. RESULTS: A total of 594 subjects were enrolled, including 183 subjects who received the second-generation device. Usable data were captured in 158 patients (86.3%). Study subjects were 53% female and 56% Black/African American, with median age 69 years. Twenty-six (16.4%) patients had LVO and 132 (83.6%) were not LVO (not-LVO AIS, 33; intracerebral hemorrhage, nine; stroke mimics, 90). COVID-19 testing and positivity rates (10.6%) were not different between groups. We found a sensitivity of 38.5% and specificity of 82.7% for LAMS ≥ 4 in detecting LVO stroke versus a sensitivity of 84.6% (p < 0.0015 for superiority) and specificity of 82.6% (p = 0.81 for superiority) for the device algorithm (CA + LAMS). CONCLUSIONS: Obtaining adequate recordings with a CA headset is highly feasible in the prehospital environment. Use of the device algorithm incorporating both CA and LAMS data for LVO detection resulted in significantly higher sensitivity without reduced specificity when compared to the use of LAMS alone.

Large vessel occlusion prediction scale thresholds that are sensitive for DAWN Trial patients.

BACKGROUND: Large vessel occlusion (LVO) prediction scales are used to triage prehospital suspected stroke patients with a high probability of LVO stroke to endovascular therapy centers. The sensitivities of these scales in the 6-to-24-h time window are unknown. Higher scale score thresholds are typically less sensitive and more specific. Knowing the highest scale score thresholds that remain sensitive could inform threshold selection for clinical use. Sensitivities may also vary between left and right-sided LVOs. METHODS: LVO prediction scale scores were retrospectively calculated using the National Institutes of Health Stroke Scale (NIHSS) scores of patients enrolled in the DAWN Trial. All patients had last known well times between 6 and 24 h, NIHSS scores ≥ 10, intracranial internal carotid artery or proximal middle cerebral artery occlusions, and mismatches between their clinical severities and infarct core volumes. Scale thresholds with sensitivities ≥ 85% were identified, along with scores ≥ 5% more sensitive for left or right-sided LVOs. Specificities could not be calculated because all patients had LVOs. RESULTS: A total of 201 out of 206 patients had the required NIHSS subitem scores. CPSS = 3, C-STAT ≥ 2, FAST-ED ≥ 4, G-FAST ≥ 3, RACE ≥ 5, and SAVE ≥ 3 were the highest thresholds that were still 85% sensitive for DAWN Trial LVO stroke patients. RACE ≥ 5 was the only typically used score threshold more sensitive for right-sided LVOs, though similar small differences were seen for other scales at higher thresholds. CONCLUSIONS: Our findings likely represent the maximum sensitivities of the LVO prediction scales tested for ideal thrombectomy candidates in the 6-to-24-h time window because NIHSS scores were documented in hospitals during a clinical trial rather than in the prehospital setting. Patients with NIHSS scores < 10 or more distal LVOs would lower sensitivities further. Selecting even higher scale thresholds for LVO triage would lead to many missed LVO strokes.

Headpulse Biometric Measures Following Concussion in Young Adult Athletes.

Importance: Concussions are common in sports. Return-to-play protocols can be enhanced by objective biometrics. Objective: To characterize temporal changes of headpulse, a digital biometric, in athletes with sports-related concussion; to explore the association of unstructured physical activity with headpulse changes. Design, Setting, and Participants: This cohort study included headpulse measurements from players in the highest level of amateur Australian Rules Football in South Australia. Analysis included feasibility and validation phases, with the feasibility cohort recruited between August 5, 2021, and September 10, 2021, and the validation cohort recruited between May 5, 2022, and September 3, 2022. Data were analyzed October 2022 through January 2023. Interventions: Cranial accelerometry detected micromovements of the head following cardiac contraction (what we have described as "headpulse"). Headpulse was serially recorded for 1 month in concussed individuals. Main Outcomes and Measures: Headpulse waveforms underwent frequency transformation analysis per prespecified algorithm. Result Z scores were calculated. Headpulse Z scores exceeding 2 (2 SDs from control means) met an abnormality threshold. Headpulse sensitivity, timing, and duration of change were determined. Results: A total of 59 control and 43 concussed individuals (44 total concussions; 1 control also concussed, 1 concussed individual injured twice) provided headpulse measurements. The feasibility cohort (all male) included 17 control (median [IQR] age, 23 [19-28] years) and 15 concussed individuals (median [IQR] age, 21 [19-23] years). The validation cohort included 25 female (median [IQR] age, 21 [20-22] years) and 17 male (median [IQR] age, 26 [23-29] years) control individuals, and 8 female (median [IQR] age, 28 [20-31] years) and 20 male (median [IQR] age, 21 [19-23] years) concussed individuals. Headpulse reached abnormality threshold in 26 of 32 concussed individuals (81%; 9% on day 0, 50% by day 2, 90% by day 14). Headpulse alterations lasted 14 days longer than symptoms and were exacerbated by return-to-play or unsupervised physical activity. Conclusions and Relevance: In this study of 101 amateur Australian Rules Football athletes, the digital headpulse biometric was evaluated in 44 sports-related concussions. Compared with controls, new headpulse changes occurred after concussion; this objective metric may complement return-to-play protocols.

A Survey on Monitoring and Management of Cerebral Vasospasm and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: The Mantra Study.

INTRODUCTION: Cerebral infarction from delayed cerebral ischemia (DCI) is a leading cause of poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). We performed an international clinical practice survey to identify monitoring and management strategies for cerebral vasospasm associated with DCI in aSAH patients requiring intensive care unit admission. METHODS: The survey questionnaire was available on the European Society of Intensive Care Medicine (May 2021-June 2022) and Neurocritical Care Society (April - June 2022) websites following endorsement by these societies. RESULTS: There were 292 respondents from 240 centers in 38 countries. In conscious aSAH patients or those able to tolerate an interruption of sedation, neurological examination was the most frequently used diagnostic modality to detect delayed neurological deficits related to DCI caused by cerebral vasospasm (278 respondents, 95.2%), while in unconscious patients transcranial Doppler/cerebral ultrasound was most frequently used modality (200, 68.5%). Computed tomography angiography was mostly used to confirm the presence of vasospasm as a cause of DCI. Nimodipine was administered for DCI prophylaxis by the majority of the respondents (257, 88%), mostly by an enteral route (206, 71.3%). If there was a significant reduction in arterial blood pressure after nimodipine administration, a vasopressor was added and nimodipine dosage unchanged (131, 45.6%) or reduced (122, 42.5%). Induced hypertension was used by 244 (85%) respondents as first-line management of DCI related to vasospasm; 168 (59.6%) respondents used an intra-arterial procedure as second-line therapy. CONCLUSIONS: This survey demonstrated variability in monitoring and management strategies for DCI related to vasospasm after aSAH. These findings may be helpful in promoting educational programs and future research.

End-Of-Life Care in the Potential Donor after Circulatory Death: A Systematic Review.

Background: Donation after circulatory death (DCD) is becoming increasingly common, yet little is known about the way potential donors receive end-of-life care. Purpose: The aims of this systematic review are to describe the current practice in end-of-life care for potential donors and identify metrics that are being used to assess discomfort among these patients. Research design and Study Sample: This review encompasses published literature between June 1, 2000 and June 31, 2020 of end-of-life care received by potential DCD patients. The population of interest was defined as patients eligible for Maastracht classification III donation after circulatory death for a solid organ transplantation. Outcomes examined included: analgesic or palliative protocols, and surrogates of discomfort (eg dyspnea, agitation). Results: Among 141 unique articles, 27 studies were included for full review. The primary reason for exclusion was lack of protocol description, or lack of reporting on analgesic medications. No primary research studies specifically examined distress in the DCD eligible population. Numerous professional guidelines were identified. Surveys of critical care practitioners identified concerns regarding the impact of symptom management on hastening the dying process in the DCD population as a potential barrier to end-of-life palliative treatment. Conclusions: There is a paucity of empirical evidence for end-of-life symptom assessment and management for DCD patients. Key evidence gaps identified for DCD include the need for: i) a multidisciplinary structure of treatment teams and preferred environment for DCD, ii) objective tools for monitoring of distress in this patient population, and iii) evidence guiding the administration of analgesic medications following withdrawal of life sustaining therapy.

Large vessel occlusion prediction scales provide high negative but low positive predictive values in prehospital suspected stroke patients.

Introduction: We studied a registry of Emergency Medical Systems (EMS) identified prehospital suspected stroke patients brought to an academic endovascular capable hospital over 1 year to assess the prevalence of disease and externally validate large vessel occlusion (LVO) stroke prediction scales with a focus on predictive values. Methods: All patients had last known well times within 6 hours and a positive prehospital Cincinnati Prehospital Stroke Scale. LVO prediction scale scores were retrospectively calculated from emergency department arrival National Institutes of Health Stroke Scale scores. Final diagnoses were determined by chart review. Prevalence and diagnostic performance statistics were calculated. We prespecified analyses to identify scale thresholds with positive predictive values (PPVs) ≥80% and negative predictive values (NPVs) ≥95%. A secondary analysis identified thresholds with PPVs ≥50%. Results: Of 220 EMS transported patients, 13.6% had LVO stroke, 15.9% had intracranial haemorrhage, 20.5% had non-LVO stroke and 50% had stroke mimic diagnoses. LVO stroke prevalence was 15.8% among the 184 diagnostic performance study eligible patients. Only Field Assessment Stroke Triage for Emergency Destination (FAST-ED) ≥7 had a PPV ≥80%, but this threshold missed 83% of LVO strokes. FAST-ED ≥6, Prehospital Acute Severity Scale =3 and Rapid Arterial oCclusion Evaluation ≥7 had PPVs ≥50% but sensitivities were <50%. Several standard and lower alternative scale thresholds achieved NPVs ≥95%, but false positives were common. Conclusions: Diagnostic performance tradeoffs of LVO prediction scales limited their ability to achieve high PPVs without missing most LVO strokes. Multiple scales provided high NPV thresholds, but these were associated with many false positives.

Collateral Circulation in Thrombectomy for Stroke After 6 to 24 Hours in the DAWN Trial.

BACKGROUND AND PURPOSE: Collaterals govern the pace and severity of cerebral ischemia, distinguishing fast or slow progressors and corresponding therapeutic opportunities. The fate of sustained collateral perfusion or collateral failure is poorly characterized. We evaluated the nature and impact of collaterals on outcomes in the late time window DAWN trial (Diffusion-Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). METHODS: The DAWN Imaging Core Lab prospectively scored collateral grade on baseline computed tomography angiography (CTA; endovascular and control arms) and digital subtraction angiography (DSA; endovascular arm only), blinded to all other data. CTA collaterals were graded with the Tan scale and DSA collaterals were scored by ASITN grade (American Society of Interventional and Therapeutic Neuroradiology collateral score). Descriptive statistics characterized CTA collateral grade in all DAWN subjects and DSA collaterals in the endovascular arm. The relationship between collateral grade and day 90 outcomes were separately analyzed for each treatment arm. RESULTS: Collateral circulation to the ischemic territory was evaluated on CTA (n=144; median 2, 0-3) and DSA (n=57; median 2, 1-4) before thrombectomy in 161 DAWN subjects (mean age 69.8±13.6 years; 55.3% women; 91 endovascular therapy, 70 control). CTA revealed a broad range of collaterals (Tan grade 3, n=64 [44%]; 2, n=45 [31%]; 1, n=31 [22%]; 0, n=4 [3%]). DSA also showed a diverse range of collateral grades (ASITN grade 4, n=4; 3, n=22; 2, n=27; 1, n=4). Across treatment arms, baseline demographics, clinical variables except atrial fibrillation (41.6% endovascular versus 25.0% controls, P=0.04), and CTA collateral grades were balanced. Differences were seen across the 3 levels of collateral flow (good, fair, poor) for baseline National Institutes of Health Stroke Scale, blood glucose <150, diabetes, previous ischemic stroke, baseline and 24-hour core infarct volume, baseline and 24-hour Alberta Stroke Program Early CT Score, dramatic infarct progression, final Thrombolysis in Cerebral Infarction 2b+, and death. Collateral flow was a significant predictor of 90-day modified Rankin Scale score of 0 to 2 in the endovascular arm, with 43.7% (31/71) of subjects with good collaterals, 30.8% (16/52) of subjects with fair collaterals, and 17.7% (6/34) of subjects with poor collaterals reaching modified Rankin Scale score of 0 to 2 at 90 days (P=0.026). CONCLUSIONS: DAWN subjects enrolled at 6 to 24 hours after onset with limited infarct cores had a wide range of collateral grades on both CTA and DSA. Even in this late time window, better collaterals lead to slower stroke progression and better functional outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02142283.

Serial ASPECTS in the DAWN Trial: Infarct Evolution and Clinical Impact.

Background and Purpose: The impact of baseline ischemia on Alberta Stroke Program Early CT Score (ASPECTS) and evolution over 24 hours may be distinct in late thrombectomy. We analyzed predictors of serial ASPECTS and clinical outcomes in the DAWN trial (Diffusion-Weighted Imaging or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). Methods: The DAWN Imaging Core Laboratory independently scored ASPECTS at baseline and 24 hours. Descriptive statistics characterized ASPECTS on computed tomography/magnetic resonance imaging at baseline and 24 hours, delineating ASPECTS change over 24 hours. Results: 206 subjects (mean age 70.0±13.7 years; 54.9% (n=113) female; baseline National Institutes of Health Stroke Scale median (interquartile range) 17 (13, 21) were included. Baseline ASPECTS was median (interquartile range) 8.0 (7­8), with 92/205 (44.9%) between 0 and 7 and 113/205 (55.1%) 8 and 10. 24-hour ASPECTS was median 6.0 (4­8), with ASPECTS change or infarct evolution having median −1, ranging from −8 to +2. Multivariable logistic regression showed older age (odds ratio [OR] for 10-year interval, 1.26 [95% CI, 1.02­1.55], P=0.030) and dyslipidemia (OR, 1.84 [95% CI, 1.06­3.19], P=0.031) were independently associated with higher baseline ASPECTS. Higher 24-hour ASPECTS was predicted by endovascular treatment (OR, 2.76 [95% CI, 1.58­4.81], P=0.0004), baseline glucose <150 mg/dL (OR, 2.86 [95% CI, 1.50­5.46], P=0.001), lower baseline National Institutes of Health Stroke Scale (OR, 0.93 [95% CI, 0.89­0.98], P=0.010), and older age (OR for 10-year interval, 1.25 [95% CI, 1.01­1.55], P=0.041). Internal carotid artery lesion location (OR, 0.47 [95% CI, 0.24­0.89], P=0.021) was inversely related to 24-hour ASPECTS. Good clinical outcome (day 90 modified Rankin Scale score 0­2) was predicted by 24-hour ASPECTS (OR, 1.46 [95% CI, 1.08­1.96], P=0.014). Extensive infarct evolution (ASPECTS decrease ≥6) occurred in 14/201 (7.0%). Elevated baseline serum glucose ≥150 mg/dL was a predictor of ASPECTS decrease of ≥4 points (OR, 2.78 [95% CI, 1.21­6.35] P=0.016) as was internal carotid artery occlusion (OR, 2.49 [95% CI, 1.05­5.88]; P=0.038). ASPECTS change was influenced by treatment arm (P=0.001 by Wilcoxon), including 0 ASPECTS change in 42/105 (40.0%) of the endovascular arm and only 20/96 (20.8%) of the medical arm. Conclusions: DAWN subjects enrolled with small infarct cores had a broad range of baseline ASPECTS. Twenty-four-hour ASPECTS, strikingly influenced by endovascular therapy, predicted good clinical outcomes. Registration: https://www.clinicaltrials.gov; Unique identifier: NCT02142283.

Computed tomography perfusion abnormalities after carotid endarterectomy help in the diagnosis of reversible cerebral vasoconstriction syndrome.

Acute neurologic deficits in the postoperative period after carotid endarterectomy (CEA) can prompt extensive diagnostic evaluation. Reversible cerebral vasoconstriction syndrome (RCVS) is an underrecognized cause of acute neurologic deficit after CEA. We present the case of RCVS in an 84-year-old male patient who had experienced left limb weakness after CEA, prompting multiple code stroke activations. The present case is novel because the obtained computed tomography perfusion imaging studies demonstrated abnormalities that have not been previously described in patients with RCVS. These findings, combined with the cerebral angiography findings, led to the rapid diagnosis and delivery of intra-arterial vasodilator therapy. He experienced subsequent resolution of his symptoms and radiologic abnormalities.

The Neurological Examination Improves Cranial Accelerometry Large Vessel Occlusion Prediction Accuracy.

BACKGROUND/OBJECTIVE: We combined cranial accelerometry, a device-based approach to large vessel occlusion (LVO) prediction, with neurological examination findings to determine if this improves diagnostic accuracy compared to either alone. METHODS: Cranial accelerometry recordings and NIHSS scores were obtained during stroke codes and thrombectomy transfers at an academic medical center using convenience sampling. The reference standard was discharge diagnosis of LVO stroke. We compared accuracy statistics between machine learning models trained using cranial accelerometry alone, with asymmetric arm weakness added, with NIHSS scores added, and retrospective examination only LVO prediction scales. An exploratory analysis required asymmetric arm weakness prior to model training or scale testing. RESULTS: Of 68 patients, there were 23 LVO strokes. Cranial accelerometry was 65% sensitive (95% CI 43-84%) and 87% specific (95% CI 73-95%). Adding asymmetric arm weakness increased specificity to 91% (95% CI 79-98%). Adding asymmetric arm weakness and the NIHSS increased sensitivity to 74% (95% CI 52-90%) and decreased specificity to 89% (95% CI 76-96%). LVO prediction scales had wide sensitivity and specificity ranges. The exploratory analysis improved sensitivity to 91% (95% CI 72-99%) and specificity to 93% (95% CI 92-99%) with only three false positives and two false negatives. CONCLUSIONS: Cranial accelerometry models are improved by various additions of asymmetric arm weakness and the NIHSS. An exploratory analysis requiring asymmetric arm weakness prior to cranial accelerometry model training minimized false positives and negatives.

Validation and iteration of CT perfusion defined malignant profile thresholds for acute ischemic stroke.

BACKGROUND: Malignant profile computed tomography perfusion (CTP) lesions are associated with poor outcomes after administration of intravenous tissue-plasminogen activator (IV-tPA) for ischemic stroke. AIMS: To determine whether published CTP-based lesion thresholds predictive of poor outcomes in a predominantly 8 cm of CTP anatomic coverage cohort would predict poor outcomes in an independent 4 cm of CTP anatomic coverage cohort and to generate optimized 4 cm CTP thresholds. METHODS: Ischemic stroke patients with baseline CTP imaging with 4 cm of anatomic coverage before receiving IV-tPA at a single institution were retrospectively studied. Perfusion lesion time to maximum of tissue residue function (Tmax) and cerebral blood flow (CBF) volumes were determined using RAPID automated software. Fisher's exact tests assessed associations between lesion thresholds and outcomes. Receiver operating characteristic (ROC) curves generated optimized thresholds for 4 cm of CTP coverage. RESULTS: Sixty-three patients were included. Poor outcomes were associated with published thresholds of Tmax >6 s > 103 mL, Tmax > 8 s > 86 mL, and Tmax > 10 s > 78 mL but not CBF core >53 mL. Thresholds optimized for 4 cm of CTP coverage and associated with poor outcomes were Tmax > 6 s > 100 mL, Tmax > 8 s > 65 mL, Tmax >10 s > 46 mL, and CBF core >39 mL. CONCLUSIONS: We validated the ability of published CTP Tmax lesion volume thresholds to predict poor outcomes despite IV-tPA in an independent cohort using only 4 cm of CTP anatomical coverage. A CBF > 39 mL threshold, rather than the predominantly 8 cm CTP coverage derived CBF threshold of >53 mL, was associated with poor outcomes in this 4 cm CTP coverage cohort.

A Unique Signature of Cardiac-Induced Cranial Forces During Acute Large Vessel Stroke and Development of a Predictive Model.

BACKGROUND: Cranial accelerometry is used to detect cerebral vasospasm and concussion. We explored this technique in a cohort of code stroke patients to see whether a signature could be identified to aid in the diagnosis of large vessel occlusion (LVO) stroke. METHODS: A military-grade three-axis accelerometer was affixed to a headset. Accelerometer and electrocardiogram (ECG) outputs were digitized at 1.6 kHz. We call the resulting digitized signals the "headpulse." Three-minute recordings were performed immediately after computed tomography (CT) angiography (CTA) and/or immediately before and after attempted mechanical thrombectomy in patents with suspected stroke. The resulting waveforms were inspected by eye and then subjected to supervised machine learning (MATLAB Classification Learner R2018a) to train a model using fivefold cross-validation. RESULTS: Of 42 code stroke subjects with recordings, 19 (45%) had LVO and 23 (55%) had normal CTAs. In patients without LVO, ECG-triggered waveforms followed a self-similar time course revealing that the headpulse is highly coupled to the cardiac contraction. However, in most patients with LVO, headpulses showed little cardiac contraction correlation. We term this abnormality "chaos" and parameterized it with 156 measures of trace-by-trace variation from the ECG-signal-averaged mean for machine learning model training. Selecting the best model, using biometric data only, we properly classified 15/19 LVOs and 20/23 non-LVO patients, with receiver operating characteristic curve area = 0.79, sensitivity of 73%, and specificity of 87%, P < 0.0001. Headpulse waveforms following thrombectomy showed return of cardiac contraction correlation. CONCLUSIONS: Headpulse recordings performed on patients with suspected acute stroke significantly identify those with LVO. The lack of temporal correlation of the headpulse with cardiac contraction and resolution to normal may reflect changes in cerebral blood flow and may provide a useful technique to triage stroke patients for thrombectomy using a noninvasive device.

Impact of Periprocedural and Technical Factors and Patient Characteristics on Revascularization and Outcome in the DAWN Trial.

Background and Purpose- Because of unique attributes of mechanical thrombectomy performed between 6 and 24 hours after symptom onset in acute ischemic stroke patients, it is not known if predictors of angiographic recanalization and favorable outcome in patients treated with thrombectomy in the late (6-24 hour) time window are similar to those treated in the early time window. Methods- We analyzed data from the DAWN trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) which enrolled patients with symptom onset 6 to 24hours after last known well and occlusion of the intracranial internal carotid artery or proximal middle cerebral artery with a mismatch between severity of clinical deficit and infarct core volume as identified by computed tomography-perfusion or diffusion magnetic resonance imaging. We evaluated the effect of tandem occlusions, periprocedural heparin use, procedural speed (from puncture to procedure completion), general anesthesia, balloon-guide catheters, thrombectomy device size, and number of passes on substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) and on likelihood of obtaining a modified Rankin Scale at 3 months indicating functional independence. Results- Of 107 patients who underwent MT in the interventional arm of DAWN, substantial reperfusion and modified Rankin Scale score 0 to 2 at 3 months was seen in 90 (84%) and 52 (49%), respectively. In univariate analysis, general anesthesia (odds ratio [OR] 0.27; P=0.042) and ≥3 passes with stent retriever (OR, 0.17; P=0.002) were inversely associated with substantial reperfusion. In multivariate analyses, only ≥3 passes were associated with lack of revascularization (OR, 0.17; P=0.002). in univariate analysis ≥3 passes (OR, 0.24; P =0.003) and baseline National Institutes of Health Stroke Scale score >17 (OR, 0.19; P<0.001) were inversely associated with functional independence at 3 months. In multivariate analyses, ≥3 passes (OR, 0.24; P=0.003) and National Institutes of Health Stroke Scale score >17 (OR, 0.19; P<0.001) remained inversely associated with favorable outcome at 3 months. Conclusions- Patients requiring ≥3 thrombectomy passes had reduced substantial reperfusion and favorable outcome at 3 months in DAWN. Whether or not additional thrombectomy techniques beyond ≥3 thrombectomy passes with the Trevo stent retriever are beneficial for patient outcomes in this patient population remains to be clarified by future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.

Benefit of Endovascular Thrombectomy by Mode of Onset: Secondary Analysis of the DAWN Trial.

Background and Purpose- It is unknown whether the benefit of thrombectomy in late presenting acute stroke patients with imaging evidence of clinical-infarct mismatch is different in patients presenting with wake-up stroke compared with those presenting with witnessed onset or unwitnessed onset. Methods- Prespecified secondary analysis was performed from DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention), a multicenter, prospective, randomized clinical trial with blinded end point assessment comparing thrombectomy with the Trevo device against standard medical therapy in patients with acute stroke and clinical-infarct mismatch presenting 6 to 24 hour after the time last seen well. For the purposes of this study, the primary outcome was the proportion of modified Rankin Scale score 0 to 2 at 90 days. Univariable analysis and multivariable logistic regression was used to assess the relationship between outcome and mode of onset. Results- All 206 enrolled patients were included in the study. Mode of onset was: wake-up stroke (55.3%, n=114), witnessed onset (12.1%, n=25), and unwitnessed onset (32.5%, n=67) with median time last seen well to randomization (13.4±3.7, 10.0±3.7, 14.1±4.9 hours) respectively. Rates of 90-day modified Rankin Scale score of 0 to 2 and symptomatic intracerebral hemorrhage in the thrombectomy arm were not statistically different across patient onset subtypes (P=0.79 and P=0.40, respectively). The benefit of thrombectomy compared with best medical therapy was maintained across all 3 onset modes (rates of 90-day modified Rankin Scale score of 0 to 2 in patients allocated to thrombectomy versus control: wake-up stroke-49.3% versus 10.6%, witnessed onset-63.6% versus 21.4%, UW-41.4% versus 13.2%; P×interaction=0.79). In univariable and multivariable analyses, mode of onset was not identified as a significant predictor of modified Rankin Scale score 0 to 2 at 90 days. Conclusions- In patients with acute ischemic stroke presenting between 6 and 24 hours from time last seen well and harboring clinical-infarct mismatch, the benefit of thrombectomy was similar regardless of the wake-up, unwitnessed, or witnessed mode of onset.

Outcome in Direct Versus Transfer Patients in the DAWN Controlled Trial.

Background and Purpose- The impact of transfer status on clinical outcomes in the DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) population is unknown. We analyzed workflow and clinical outcome differences between direct versus transfer patients in the DAWN population. Methods- The following time metrics were analyzed for each group: (1) last known well to hospital arrival, (2) hospital arrival to eligibility imaging, (3) hospital arrival to arterial puncture, (4) qualifying imaging to arterial puncture, (5) last known well to arterial puncture, (6) last known well to reperfusion. The primary end point was the rate of functional independence (90-day modified Rankin Scale [mRS] score, 0-2). Using univariate unconditional logistic regression, we calculated odds ratios and 95% CIs for the association between clinically relevant time metrics, transfer status, and functional independence (mRS 0-2). Results- A total of 206 patients were enrolled. Among these, 121 (59%) patients were transferred, and 85 (41%) patients presented directly to a thrombectomy capable center. Median time last seen well to hospital arrival time was similar between the 2 groups (678 versus 696 minutes). The time from hospital arrival to groin puncture was significantly longer in direct patients compared with transferred patients 140 minutes (interquartile range, 105.5-177.5 minutes) and 88 minutes (interquartile range, 55-125 minutes), respectively (P<0.001). Differences in treatment effect or differences in rates of mRS 0-2 in the thrombectomy treated patients were not statistically significant in direct versus transfer patients (odds ratios for mRS 0-2, thrombectomy versus control, were 5.62 in direct and 6.63 in transfer patients, respectively, Breslow-Day P=0.817). Conclusions- Although transfer patients had a faster door to puncture time, benefits of thrombectomy, and rates of mRS 0 to 2 in the treatment group were similar between direct and transferred patients in the DAWN population. These results may inform prehospital and primary stroke centers triage protocols in patients presenting in the late time window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.

Endovascular Stroke Therapy.

Ischemic stroke is a leading cause of death and disability throughout the world and is both preventable and treatable. This review focuses on the treatment of the most severe form of ischemic stroke, namely large-vessel ischemic stroke, using endovascular techniques. Such therapies were proven effective in 2015. These therapies are among the most beneficial surgical therapies ever subjected to randomized clinical trials. Recent research has explored treating patients up to 24 h following the onset of stroke using advanced imaging techniques to select patients with brain tissue still at risk. These new findings suggest there exists a tissue clock rather than a time clock when selecting patients for therapy. Stroke systems throughout the world are now embracing endovascular stroke therapy. Improving regional stroke systems of care and expanding eligibility for patients are a major focus of current research.

The Speech Arm Vision Eyes (SAVE) scale predicts large vessel occlusion stroke as well as more complicated scales.

INTRODUCTION: The Speech Arm Vision Eyes (SAVE) scale, a 4-item clinical scale emphasizing binary scoring and avoidance of nuanced examination distinctions, predicts LVOs with similar characteristics as more complex scales. METHODS: Receiver operating characteristic analyses of the prospective STOPStroke study assessed the ability of the SAVE scale and other published scales to predict LVO. We identified scale thresholds with positive likelihood ratios with 95% confidence intervals of ≥5.0 or negative likelihood ratios with 95% confidence intervals of ≤0.5. RESULTS: 735patients were studied. LVO prevalence was 33%. Area under the curve was 0.79 for SAVE, 0.82 for FAST-ED, 0.80 for mNIHSS and NIHSS, and lower for all other scales. SAVE=4, EMSA=6, mNIHSS≥10, NIHSS≥16, and RACE≥8 had positive likelihood ratios with 95% confidence intervals ≥5.0. SAVE≥2, CPSS≥2, C-STAT≥1, EMSA≥4, FAST-ED≥3, G-FAST≥3, mNIHSS≥6, NIHSS≥9, PASS≥1, RACE≥2, VAN=1, and 3I-SS≥1 had negative likelihood ratios with 95% confidence intervals ≤0.5. CONCLUSIONS: SAVE=4 performed similarly to more complex scales at predicting LVO. Other simplified scales did not have thresholds with positive likelihood ratios with 95% confidence intervals ≥5.0. Validation is need in a prehospital cohort of patients with suspected stroke.

Mechanical Thrombectomy in Patients With Milder Strokes and Large Vessel Occlusions.

Background and Purpose- We aimed to describe the safety and efficacy of immediate mechanical thrombectomy (MT) in patients with large vessel occlusions and low National Institutes of Health Stroke Scale (NIHSS) versus best medical management. Methods- Patients from prospectively collected databases of 6 international comprehensive stroke centers with large vessel occlusions (distal intracranial internal carotid, middle cerebral artery-M1 and M2 segments, or basilar artery with or without tandem occlusions) and NIHSS 0 to 5 were identified and divided into 2 groups for analysis: immediate MT or initial best medical management which included rescue MT after neurological deterioration (best medical management-MT). Uni- and multivariate analyses and patient-level matching for age, baseline NIHSS, and occlusion site were performed to compare baseline and outcome variables across the 2 groups. The primary outcome was defined as good outcome (modified Rankin Scale score, 0-2) at day 90. Safety outcome was symptomatic intracranial hemorrhage as defined by the ECASS (European Cooperative Acute Stroke Study) II and mortality at day 90. Results- Compared with best medical management-MT (n=220), patients with immediate MT (n=80) were younger (65.3±13.5 versus 69.5±14.1; P=0.021), had more often atrial fibrillation (44.8% versus 28.2%; P=0.012), higher baseline NIHSS (4, 0-5 versus 3, 0-5; P=0.005), higher Alberta Stroke Program Early CT Score (10, 7-10 versus 10, 5-10; P=0.023), more middle cerebral artery-M1, and less middle cerebral artery-M2 (41.3% versus 21.9% and 28.8% versus 49.3%; P=0.016) occlusions. The adjusted odds ratio for good outcome was 3.1 (95% CI, 1.4-6.9) favoring immediate MT. In the matched analysis, there was a 14.4% absolute difference in good outcome (84.4% versus 70.1%; P=0.03) at day 90 favoring immediate MT. There were no safety concerns. Conclusions- Our retrospective, pilot analysis suggests that immediate thrombectomy in large vessel occlusions patients with low NIHSS on presentation may be safe and has the potential to result in improved outcomes. Randomized clinical trials are warranted to establish the optimal management for this patient population.