Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024.

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.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

BACKGROUND: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

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.

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.

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.

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.

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.

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.

Field Assessment Stroke Triage for Emergency Destination: A Simple and Accurate Prehospital Scale to Detect Large Vessel Occlusion Strokes.

BACKGROUND AND PURPOSE: Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS. METHODS: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale was based on items of the National Institutes of Health Stroke Scale (NIHSS) with higher predictive value for LVOS and tested in the Screening Technology and Outcomes Project in Stroke (STOPStroke) cohort, in which patients underwent computed tomographic angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial internal carotid artery, middle cerebral artery-M1, middle cerebral artery-2, or basilar arteries. Patients with partial, bihemispheric, and anterior+posterior circulation occlusions were excluded. Receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value of FAST-ED were compared with the NIHSS, Rapid Arterial Occlusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity (CPSS) scale. RESULTS: LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the receiver operating characteristic curve: FAST-ED=0.81 as reference; NIHSS=0.80, P=0.28; RACE=0.77, P=0.02; and CPSS=0.75, P=0.002). A FAST-ED ≥4 had sensitivity of 0.60, specificity of 0.89, positive predictive value of 0.72, and negative predictive value of 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, and 0.79, and CPSS ≥2 of 0.56, 0.85, 0.65, and 0.78, respectively. CONCLUSIONS: FAST-ED is a simple scale that if successfully validated in the field, it may be used by medical emergency professionals to identify LVOS in the prehospital setting enabling rapid triage of patients.

Cranial Accelerometry Can Detect Cerebral Vasospasm Caused by Subarachnoid Hemorrhage.

BACKGROUND: We previously reported the presence of a cranial "bruit" in patients with cerebral vasospasm by signal processing cranial accelerometry signals time locked to the cardiac cycle. This shift to higher frequencies is likely related to the turbulence of blood flow produced by vascular narrowing. We sought to build a more quantitative model to predict cerebral vasospasm then test the accuracy of this technique to detect cerebral vasospasm in a prospective blinded study. METHODS: Skull accelerometry was performed using an array of 6 highly sensitive accelerometers placed in contact with the scalp. Paired transcranial Doppler (TCD) recordings and accelerometry epochs were obtained in consecutive patients with subarachnoid hemorrhage undergoing TCD recordings for surveillance of cerebral vasospasm. The energy of rectified acceleration measurements within systolic and diastolic bands of the cardiac cycle were measured and correlated with TCD-defined spasm. This model was then tested prospectively in a blinded consecutive sample of subarachnoid hemorrhage patients to determine accuracy of the technique. RESULTS: We developed a model predicting cerebral vasospasm from analysis of 14 unblinded subjects with varying degrees of cerebral vasospasm as detected by TCD. We then recorded from 58 subjects obtaining 125-paired recordings of accelerometry and TCD to test this model in a blinded analysis. Accelerometry detection of any spasm versus non-spasm correlated with TCD-defined vasospasm (P < 0.001). The model was 81 % sensitive for detecting any cerebral vasospasm in patients, while the negative predictive value was 61 %. CONCLUSION: Highly sensitive skull accelerometry can detect cerebral vasospasm with clinically meaningful accuracy. This tool holds promise in the ICU environment to detect as well as reject cerebral vasospasm as the cause of neurological deficits in subarachnoid hemorrhage.

Emergency Neurologic Life Support (ENLS): Evolution of Management in the First Hour of a Neurological Emergency.

Emergency neurological life support (ENLS) is an educational program designed to provide users advisory instruction regarding management for the first few hours of a neurological emergency. The content of the course is divided into 14 modules, each addressing a distinct category of neurological injury. The course is appropriate for practitioners and providers from various backgrounds who work in environments of variable medical complexity. The focus of ENLS is centered on a standardized treatment algorithm, checklists to guide early patient care, and a structured format for communication of findings and concerns to other healthcare professionals. Certification and training in ENLS is hosted by the Neurocritical Care Society. This document introduces the concept of ENLS and describes the revisions that constitute this second version.

Detection of concussion using cranial accelerometry.

OBJECTIVE: To determine whether skull motion produced by pulsatile cerebral blood flow, as measured by cranial accelerometry, is altered during concussion. DESIGN: In phase 1, to identify a specific pattern indicative of concussion, cranial accelerometry of subjects who sustained a concussion underwent analysis of waveforms, which was compared with accelerometry from subjects without a concussion (baseline). In phase 2, this concussion pattern was tested against prospectively acquired, blinded data. SETTING: High school tackle football practice and game play. PARTICIPANTS: Eighty-four football players. INTERVENTIONS: Subjects had accelerometry measurements and concurrent 2-lead electrocardiograms. In players with a concussion, multiple sequential measurements were obtained. Sport Concussion Assessment Tool 2 was used to assist clinical determination of concussion. MAIN OUTCOME MEASURES: Whether a characteristic waveform pattern of cranial accelerometry occurs in subjects with concussion. RESULTS: Phase 1 demonstrated a consistent pattern correlated to concussion. Phase 2 found this pattern in 10 of 13 subjects with concussion (76.9% sensitivity). Seventy-nine of 82 baseline plus nine postseason (total = 91) recordings from nonconcussed subjects did not show the concussion pattern (87% specificity). CONCLUSIONS: In subjects with concussion, we observed a unique pattern determined by cranial accelerometry. This may provide a method to noninvasively detect and longitudinally observe concussion. CLINICAL RELEVANCE: There is no objective, real-time, noninvasive, and easily accessible measure for concussion. If accelerometry is validated, it could provide a critical diagnostic tool for sports medicine physicians.

Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial.

IMPORTANCE: Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in symptomatic intracranial arterial stenosis. OBJECTIVE: To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (≥70%). DESIGN, SETTING, AND PATIENTS: VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013. INTERVENTIONS: Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53). PRIMARY OUTCOME MEASURE: a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12. RESULTS: Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (5/53; 9.4% [95% CI, 3.1%-20.7%]) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% [95% CI, 2.9%-19.0%]) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% [95% CI, 24.0-49.9]) vs the medical group (8/53; 15.1% [95% CI, 6.7-27.6]) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (6/53; 11.3% [95% CI, 4.3%-23.0%]) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up. CONCLUSIONS AND RELEVANCE: Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00816166.

Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes.

BACKGROUND AND PURPOSE: High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy. METHODS: We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization. RESULTS: Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence. CONCLUSIONS: One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867.

Time from onset of SIRS to antibiotic administration and outcomes after subarachnoid hemorrhage.

INTRODUCTION: The interval from presentation with systemic inflammatory response syndrome (SIRS) to the start of antibiotic administration affects mortality in patients with sepsis. However, patients with subarachnoid hemorrhage (SAH) often develop SIRS directly from their brain injury, making it a less useful indicator of infection. We therefore hypothesized that SIRS would not be a suitable trigger for antibiotics in this population. METHODS: We examined the time from the development of SIRS until antibiotic initiation and its relationship to long-term neurological outcomes in patients with nontraumatic SAH. Patients' baseline characteristics, time of antibiotic administration, and hospital course were collected from retrospective chart review. The primary outcome, 6-month functional status, was prospectively determined using blinded, structured interviews incorporating the modified Rankin Scale (mRS). RESULTS: Sixty-six of 70 patients with SAH during the study period had 6-month follow-up and were included in this analysis. SIRS developed in 57 patients (86%, 95% CI 78-95%). In ordinal logistic regression models controlling for age and illness severity, the time from SIRS onset until antibiotic initiation was not associated with 6-month mRS scores (OR per hour, 0.994; 95% CI 0.987-1.001). CONCLUSIONS: In this cohort of patients with SAH, time from SIRS onset until antibiotic administration was not related to functional outcomes. Our results indicate that SIRS is nonspecific in patients with SAH, and support the safety of withholding antibiotics in those who lack additional evidence of infection or hemodynamic deterioration.

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.

Pilot randomized trial of outpatient cardiac monitoring after cryptogenic stroke.

BACKGROUND AND PURPOSE: Observational studies indicate that outpatient cardiac monitoring detects previously undiagnosed atrial fibrillation (AF) in 5% to 20% of patients with recent stroke. However, it remains unknown whether the yield of monitoring exceeds that of routine clinical follow-up. METHODS: In a pilot trial, we randomly assigned 40 patients with cryptogenic ischemic stroke or high-risk transient ischemic attack to wear a Cardionet mobile cardiac outpatient telemetry monitor for 21 days or to receive routine follow-up alone. After thorough investigation, we excluded patients with documented AF or other apparent stroke pathogenesis. We contacted patients and their physicians at 3 months and at 1 year to ascertain any diagnoses of AF or recurrent stroke or transient ischemic attack. RESULTS: The baseline characteristics of our cohort broadly matched those of previous observational studies of monitoring after stroke. In the monitoring group, patients wore monitors for 64% of the assigned days, and 25% of patients were not compliant at all with monitoring. No patient in either study arm received a diagnosis of AF. Cardiac monitoring revealed AF in zero patients (0%; 95% confidence interval, 0%-17%), brief episodes of atrial tachycardia in 2 patients (10%; 95% confidence interval, 1%-32%), and nonsustained ventricular tachycardia in 2 patients (10%; 95% confidence interval, 1%-32%). CONCLUSIONS: In the first reported randomized trial of cardiac monitoring after cryptogenic stroke, the rate of AF detection was lower than expected, incidental arrhythmias were frequent, and compliance with monitoring was suboptimal. Our findings highlight the challenges of prospectively identifying stroke patients at risk for harboring paroxysmal AF and ensuring adequate compliance with cardiac monitoring. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00715533.