Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Abstract

Objective

To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods

We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Results

There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions

The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

The coronavirus disease 2019 (COVID-19) pandemic has restructured health care systems worldwide to care for critically ill patients with COVID-19.¹ The high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19–related morbidity and mortality have strained paradigms of health care worldwide. Several neurologic manifestations have been reported in association with SARS-CoV-2, including ischemic, hemorrhagic, and cerebral venous stroke. Whereas infection can trigger an inflammatory prothrombotic cascade and ischemic stroke, stroke can induce immune dysregulation and expose a patient's vulnerability to infection.² The heterogeneity of stroke subtypes that have emerged in association with SARS-CoV-2^3,4 suggests heterogeneous mechanisms of stroke including endothelial dysfunction, thrombotic diathesis, and nonspecific effects of inflammation.⁵ Patients with COVID-19–associated stroke have been reported to have a higher risk for severe disability and mortality.^4,6,7

Whereas there has been an increase in thromboembolic events reported with COVID-19,⁸ a decline in acute stroke code activations, stroke hospitalizations, and mechanical thrombectomy volumes have been reported at local, regional, and national levels,^9-13 with most reports from comprehensive stroke centers (CSCs) in highly resourced countries. There is a relative paucity of information on the effect of the pandemic on acute stroke hospitalization volume and IV thrombolysis (IVT) acute treatment in low- or middle-income countries and in primary stroke centers (PSCs) without endovascular capability. There is also little information on the recovery of volumes in the later phases of the pandemic.

Objectives and Prespecified Hypothesis

In this context, the present study aims to broaden the scope of evaluating the effect of the COVID-19 pandemic on global stroke care to include developed and developing nations in the early and later phases of the COVID-19 pandemic. Our primary aim was to evaluate the effect of COVID-19 on stroke care as measured by the changes in volumes for (1) overall stroke hospitalizations and (2) IVT treatment (both direct presenting and patients transferred with IVT) for acute stroke across the prepandemic and pandemic periods in a multinational pool of PSCs and CSCs. In a secondary aim, the pandemic months were divided into an early (March 1, 2020, to April 30, 2020) and later phase (May 1, 2020, to June 30, 2020) to evaluate for stroke or IVT volume recovery in the later months.

We hypothesized that, in the face of the pandemic's strain on health care infrastructure, (1) a global reduction in all 3 aforementioned measurements of stroke care would occur over the pandemic in relation to both prepandemic periods, (2) hospitals with higher COVID-19 inpatient volumes would report greater decreases in stroke admissions and IVT volumes (direct and transfers) compared to hospitals with lower COVID-19 inpatient volumes, (3) the degree of decline in stroke hospitalizations and IVT volumes would be less profound in CSC compared to PSC, (4) a geographic variation would exist in the intensity of decline in stroke care, and (5) a recovery in stroke hospitalizations and IVT volumes would be observed in the 2 later pandemic months vs the early pandemic period.

Methods

Study Design

This was a cross-sectional, observational, retrospective study evaluating monthly volumes of consecutive patients hospitalized with a diagnosis of COVID-19, stroke, IVT treatment, and IVT transfers. The diagnoses were identified by their related ICD-10 codes (primary, secondary, or tertiary discharge codes) or classifications in clinical stroke databases maintained at participating centers. Case ascertainment was verified by a physician or stroke coordinator.

Setting and Participants

Data were collected from collaborators of the Society of Vascular and Interventional Neurology (SVIN) including the Latin America Stroke Group, Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO), the Japanese Society of Vascular & Interventional Neurology Society (JSVIN), and academic partners from 6 continents, 70 countries, and 457 centers. Centers were screened for potential external confounders that could explain any unexpected changes in volumes. Of the 457 centers, 54 centers were excluded due to incomplete data or confounders. One center in Africa (Zimbabwe) was excluded due to a health care worker strike from September to January. One center in Egypt was excluded due to the emergency department being closed most days in June 2020. One center in Arkansas was excluded from the stroke hospitalization volume analysis because this center became the designated center for all patients with stroke in its region during the pandemic, resulting in an abrupt increase in stroke volumes. One center in Malaysia was excluded as this was a new center in May 2020. Of the remaining 403 hospitals, 285 centers contributed to both stroke and thrombolysis volume data. For IVT transfers, centers with a mean of 4 or more transfers per month during the baseline control period were included.

We compared the stroke, IVT, and IVT transfer diagnosis in the 4 initial months of the pandemic (March 1, 2020, to June 30, 2020) with (1) the immediately preceding 4 months (November 2019 to February 2020) as the primary analysis and (2) the equivalent 4 months in the previous year (March 1, 2019, to June 30, 2019) as the secondary analysis. The primary analysis provided a picture of stroke care utilization prior to COVID-19, whereas the secondary analysis allowed for the adjustment for seasonal variations in the risks for stroke.¹⁴

Study Variables and Outcomes Measures

Stroke hospitalization was defined as admission to a hospital with a TIA, ischemic stroke, or intracerebral hemorrhage. IVT was defined as acute ischemic stroke treatment with IVT. IVT transfer was defined as a patient who was treated with IVT and transferred to another stroke center. Centers were asked not to duplicate patients receiving IVT if both referral and recipient centers were included in this analysis; the patient was computed with the referring center, and as an IVT transfer for the recipient hospital. COVID-19 hospitalization was defined as any patient admitted with COVID-19 diagnosis to the hospital, which could encompass non-neurologic diagnosis.

Median monthly volumes for overall stroke hospitalizations and IVT treatments for direct presenting and transfer patients were computed and compared across the pandemic and prepandemic periods for the overall population and across the low, intermediate, and high volume strata based on mean monthly volume tertiles for COVID-19 hospitalizations (≤6.2 vs >6.2 to 61.9 vs >61.9 COVID-19 admissions/month), stroke admissions (≤39.0 vs >39.0 to 72.9 vs >72.9 stroke admissions/month), and IVT volume (≤4.0 vs >4.0 to 10.0 vs >10.0 IVT/month).

Standard Protocol Approvals, Registrations, and Patient Consents

This was an investigator-initiated project. The first and last authors wrote the first draft of the manuscript with subsequent input of all coauthors. There were no external funding sources. The institutional review boards from the coordinating sites (Emory University School of Medicine and Boston University School of Medicine) considered that the investigators did not have access to identifiable protected health information and thus no informed consent or institutional review board oversight was required since the study did not meet the federal description of human subject research.

Data Availability

The authors declare that all supporting data are available within the article. Supplemental data are available from Dryad (tables e-1 to e-6, figure e-1, e-2, doi.org/10.5061/dryad.g1jwstqpw). Anonymized data are available upon reasonable request.

Statistics

The monthly volumes for IVT and stroke hospitalizations were compared for the period before (1 year and immediately before) and during the COVID-19 pandemic. The normality of the data was tested with the Shapiro-Wilk test. The nonparametric Wilcoxon signed-rank test was applied to compare differences in monthly volume between 2 time periods. The analyses were repeated in the setting of low, intermediate, and high COVID-19 and stroke volume hospitals.

We looked at the percentage change in the number of IV thrombolysis and stroke admissions before and during the COVID-19 pandemic. The 95% confidence intervals (CIs) for percentage change were calculated using the Wilson procedure without correction for continuity. The relative percentage decrease in volume between low, intermediate, and high-volume hospitals was tested using the z test of proportion. All data were analyzed using SAS version 9.4 (SAS Institute) and the significance level was set at a p value of < 0.05.

Results

There were 82,465, 91,373, and 80,894 stroke hospitalizations (overall n = 254,732) and 12,527, 13,334 and 11,570 IVT therapies (overall n = 37,431) included across the 4-month prior-year pandemic, 4-month immediately prepandemic, and 4-month pandemic periods, respectively. Country-specific data contributions and relative changes across the pandemic are summarized in table e-3 (doi.org/10.5061/dryad.g1jwstqpw).

Stroke Hospitalization

Monthly stroke hospitalization as compared with COVID-19 hospitalization volumes are represented in figure 1. In the primary analysis, there were 91,373 hospitalizations in the 4 months of the prepandemic period compared to 80,894 during the pandemic months, representing an 11.5% drop (95% CI −11.7 to −11.3, p < 0.0001; monthly median [interquartile range (IQR)] stroke hospitalization volume/center 54.0 [30.8–86.5] to 43.0 [24.3–71.3], p < 0.0001, n = 325 sites) (table 1). There was geographic variation of the decline in stroke hospitalization: Asia, −6.5% (95% CI −6.8 to −6.3, p<0.0001); North America, −18.8% (95% CI −19.3 to −18.3, p < 0.0001); Europe, −10.9% (95% CI −11.3 to −10.5, p<0.0001); South America, −17.4% (95% CI −18.5 to −16.3, p < 0.0001); Africa, −30.2% (95% CI −32.2 to −28.3, p < 0.0001); whereas Oceania (−1.9%; 95% CI −2.5 to −1.5, p = 0.3) did not demonstrate significance (table e-1, doi.org/10.5061/dryad.g1jwstqpw). PSCs −17.3% (95% CI −17.9 to −16.7, n = 89) demonstrated greater declines compared to CSCs−10.3% (95% CI −10.6 to −10.1, n = 236) (table 1).

Figure 1. Monthly Stroke vs Coronavirus Disease 2019 (COVID-19) Admissions.

Table 1.

Stroke Volumes Immediately Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic

IV Thrombolysis

IV thrombolytic volumes declined with 13,334 interventions in the prepandemic period vs 11,570 during the pandemic, representing a 13.2% drop (95% CI −13.8 to −12.7, p < 0.001; median [IQR] monthly IVT volume/center 6.5 [2.8–12.0] to 5.3 [2.0–10.5], p < 0.001, n = 389 centers) (table 2, figure 2). IVT decline was seen in most continents: Asia, −9.9% (95% CI −11.0 to −8.9, p<0.0001); North America, −14.4% (95% CI −15.6 to −13.3, p < 0.0001); Europe, −13.5% (95% CI −14.4 to −12.6, p < 0.0001); South America, −24.2% (95% CI −27.6 to −21.0, p < 0.0001); Africa −23.5% (95% CI −29.8 to −18.2, p < 0.01). There was no appreciable difference in IVT in Oceania −1.9% (95% CI −3.9 to −0.92, p = 0.7) (table e-2, doi.org/10.5061/dryad.g1jwstqpw). IVT declines were greater in PSCs −15.5% (95% CI −16.9 to −14.2, n = 138 centers) vs CSCs −12.6% (95% CI −13.3 to −12.0, n = 251 centers, p = 0.0001) (table 2).

Table 2.

Tissue Plasminogen Activator (tPA) Procedure Volumes Immediately Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic

Figure 2. Monthly IV Thrombolysis (IVT) vs Coronavirus Disease 2019 (COVID-19) Admissions.

Recovery of Stroke and IVT Volume Analysis

In the recovery analysis, there were 38,616 stroke hospitalizations in the early 2 months of the pandemic compared to 42,278 stroke hospitalizations in the later 2 pandemic months, representing an increase of 9.5% (95% CI 9.2–9.8, p < 0.0001, n = 325 centers). The recovery in stroke hospitalization volume was seen in all strata of COVID-19 hospitalization burden, with a gradient of recovery more significant in low (14.6%; 95% CI 14.0–15.2, p < 0.0001) vs intermediate (9.0%; 95% CI 8.4–9.5, p < 0.0001) vs high-volume (4.6%; 95% CI 4.2–5.0, p < 0.0001) COVID-19 hospitalization. There was a gradient in stroke hospitalization recovery by baseline hospital stroke volume, significant in high-volume (13.9%; 95% CI 13.5–14.3, p < 0.0001) stroke centers compared to intermediate or low volume centers, which in their strata did not demonstrate significance in recovery. Stroke hospitalization volume recovery was more significant in CSCs (10.9%; 95% CI 10.6–11.3, p < 0.0001) compared to PSCs (1.8%; 95% CI 1.5–2.1, p = 0.3) (table 3).

Table 3.

Stroke and IV Tissue Plasminogen Activator (tPA) Overall Volumes During Early and Late Coronavirus Disease 2019 (COVID-19) Pandemic

IV thrombolysis was administered to 5,714 patients in the early pandemic compared to 5,856 patients in the later pandemic months, representing a nonsignificant increase of 2.5% (95% CI 2.1–2.9, p = 0.19). Recovery in IVT volume was more significant in intermediate (6.1%, 95% CI 5.0–7.4) vs low (2.6%, 95% CI 1.9–3.6, p < 0.0001) COVID-19 hospitalization centers. A trend in IVT volume recovery was seen with CSCs (4.1%, 95% CI 3.6–4.7, p = 0.053).

IVT Transfer Analysis

There were 1,337 IVT transfers in the prepandemic compared to 1,178 in the pandemic months, representing an 11.9% drop (95% CI −13.7 to −10.3, p = 0.001). The IVT transfer declines were significant in the strata of hospitals with low (−18.3%, 95% CI −23.9 to −13.9, p = 0.03) and high (−14.9%, 95% CI −18.1 to −12.1, p = 0.008) COVID-19 volume (table 4).

Table 4.

Tissue Plasminogen Activator (tPA) Transfer Volumes Immediately Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic

Secondary Analysis

Table 5 reveals the volumes for stroke hospitalizations, IVT, and IVT transfers during the first 4 months of the pandemic vs the corresponding period in the prior year. There were significant declines in the overall and monthly volumes for all metrics.

Table 5.

Overall and Monthly Volumes 1 Year Before and During Coronavirus Disease 2019 (COVID-19) Pandemic

Intersection of COVID-19, SARS-CoV-2 Infection, and Stroke Hospitalizations

A total of 269 centers provided data on SARS-CoV-2 infection and diagnosis of stroke in the same patient. A diagnosis of any stroke was present in 1.48% (1778/119,967) of COVID-19 hospitalizations, with continental variation: Africa 1.6% (47/2879), Asia 1.5% (317/20,858), Oceania 0.4% (1/257), Europe 1.4% (507/36,871), North America 1.2% (615/49,237), South America 3.0% (291/9,865) (table e-5, doi.org/10.5061/dryad.g1jwstqpw).

SARS-CoV-2 infection was present in 3.3% (1722/52,026) of stroke hospitalizations (table e-5, doi.org/10.5061/dryad.g1jwstqpw) with continental variation: Africa 3.1% (56/1828), Asia 2.7% (342/12,686), Oceania 0.1% (1/932), Europe 3.3% (502/15,220), North America 3.0% (527/17,855), South America 8.4% (294/3,505) (table e-6, doi.org/10.5061/dryad.g1jwstqpw).

Discussion

In this temporal analysis of more than 254,000 stroke hospitalizations worldwide, there was a global decrease in stroke admissions (−11.5%), IV thrombolysis (−13.2%), and IVT transfers (−11.9%) during the first 4 pandemic months, compared to the immediately preceding period, confirming our primary hypothesis. A decrease in volume was also seen in relation to the equivalent period in the prior year for all metrics. The declines in both stroke hospitalization and IVT were greater in PSCs compared to CSCs. Recovery of stroke hospitalization volume (+9.5%) was noted in the 2 subsequent months vs the 2 initial months of the pandemic, with greater recovery in hospitals with lower COVID-19 hospitalization volume, high-volume stroke centers, and CSCs.

The decreases in the volume of stroke care provided were noted across centers with high, intermediate, and low COVID-19 hospitalization burden, and also across high, intermediate, and low volume stroke and IVT centers. As hypothesized, the magnitude of decrease of stroke hospitalizations and IVT was greater in centers with higher COVID-19 inpatient volumes.

Our results concur with other recent reports on the collateral effects of the COVID-19 pandemic on stroke systems of care including studies from China,¹¹ Italy,¹⁵ Spain,¹⁰ France,^12,16 Germany,¹⁷ Brazil,¹⁸ Canada,¹⁹ and the United States.^9,20-22 Although prior analyses have described temporal and regional changes in stroke hospitalizations and IVT, this is among the first descriptions of the change at a global level, including primary and CSCs. Hospital access related to high COVID-19 burden was unlikely a factor, as the decline was seen in centers with few or no patients with COVID-19.^23,24 Patient fear of contracting COVID-19 may have played a role, along with a decrease in presentation of TIA, mild, or moderate strokes, as reported by Diegoli et al.¹⁸ Physical distancing measures may have prevented patients from the timely witnessing of a stroke. Similar to cardiovascular events, it is conceivable that there was a true population-level reduction in cerebrovascular events, possibly related to decreased consumption of high-sodium, fast foods, reduced exposure to ambient air pollution, or improvement in patient behaviors.²⁴ A reduction in exposure to other common viruses that may play a role in triggering vascular events may have also reduced stroke risk.

In the recovery analysis, there was a gradient of recovery in stroke hospitalization in hospitals with lower compared to higher COVID-19 burden. CSCs and high-volume stroke centers demonstrated greater recovery, suggesting patients with a higher acuity of care needs seeking care in these comprehensive centers.

Our subgroup of 264 centers including 119,967 COVID-19 hospitalizations expands on prior mechanical thrombectomy analysis that was limited to CSCs (Nogueira) and represents the largest sample reporting the concomitant diagnoses of stroke and SARS-CoV-2 infection to date. Our 1.48% stroke rate in COVID-19 hospitalizations is similar to the pooled incidence of 1.1%–1.2% (range, 0.9%–2.7%) of hospitalized patients with COVID-19.⁴ The higher rate may be explained in part by the higher number of patients contracting SARS-CoV-2 over time and higher availability of testing. Some variation in the proportions are expected given the different definitions (all strokes vs ischemic only) and populations involved (all hospitalized vs severely infected only) across studies. We also provide another perspective on this relationship by reporting an incidence of 3.3% (1722/52,026) for SARS-CoV-2 infection across all stroke hospitalizations among centers with documented COVID-19 hospitalization.

Finally, 25 years after the landmark National Institute of Neurological Disorders and Stroke trials showing the benefit of tPA, we learned from this global analysis that as of 2020, the availability of IVT for acute stroke therapy continues to be lacking in multiple countries in Africa (i.e., Nigeria, Kenya, Zimbabwe, Ghana, Ethiopia, Sudan) owing to its high cost and relative implementation complexity, limiting our analysis of temporal IVT treatment trends for this continent. This void highlights a disparity of access to basic stroke therapy in multiple low-income countries across the world.

To our knowledge, this is the largest global study to date evaluating the intersection of the COVID-19 pandemic with stroke care. Our study included the participation of diverse geography of centers from 6 continents, 70 countries, and 457 CSCs and PSCs.

Our study has several limitations. The diagnosis of stroke/TIA in some centers was obtained using administrative coding of hospital ICD codes and hence there is a possibility of misclassification of diagnosis, potentially compounded by regional and national variations in stroke diagnosis and delivery of care. However, centers contributing to these data have systems to track stroke metrics of care, thus the relative changes in volume from this analysis are likely robust. Details on patient-level data including demographics, stroke subtypes, and clinical outcomes were not collected as these were outside the scope of the study. The definition of the pandemic period was arbitrary because the outbreak started and peaked at different times at different locations. This led to the computation of relative increases in volumes during the study period in the earlier affected regions, such as China, resulting in a potential underestimation of the global effect. Finally, the sampling varied with the availability of complete data in each subset of the analysis.

The COVID-19 pandemic was associated with an initial global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. These reductions were observed regardless of COVID-19 hospitalization burden and prepandemic stroke and IVT volumes. PSCs and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization but not IVT volume was noted in the later phase of the pandemic months and associated with lower COVID-19 hospital burden, high volume, and CSCs. The findings of our study can inform future studies, preparedness,^25-27 and local policies in the event of a second COVID-19 surge or future pandemic.

Glossary

CI

confidence interval

COVID-19

coronavirus disease 2019

CSC

comprehensive stroke center

ICD-10

International Classification of Diseases–10

IQR

interquartile range

IVT

IV thrombolysis

PSC

primary stroke center

SARS-CoV-2

severe acute respiratory syndrome coronavirus 2

Appendix 1. Authors

Appendix 2. Coinvestigators

Study Funding

The authors report no targeted funding.

Disclosure

Dr. Nogueira reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Imperative Care, Medtronic, Phenox, Prolong Pharmaceuticals, Stryker Neurovascular and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, and Perfuze. Dr. Martins reports receiving lecture fees from Bayer, Medtronic, Penumbra and speaker / advisory board fees from Boehringer Ingelheim. Dr. Czlonkowska reports service as Expert Witness. Dr. Siegler served as a consultant for Ceribell and the institution of Dr. Siegler has received research support from the National Institutes of Health. The institution of Dr. Czap has received research support from the National Institutes of Health. Dr. Holmstedt served as a consultant for Astrazeneca and the institution of Dr. Holmstedt has received research support from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and CSPC Pharmaceuticals. Dr. Holmstedt served as a Study Adjudicator with Ischemia Care. Dr. Turan served on a scientific advisory or DSMB for Pfizer/Merck and Gore Inc. and has received publishing royalties from a publication relating to health care. Dr. Alexandrov served on a speakers bureau for Genentech and the institution of Dr. Alexandrov has received research support from the National Institutes of Health. Dr. Huang served on a scientific advisory or DSMB for ReNeuron and KMPHC. Dr. Raz served as an expert witness for law firms and has received publishing royalties from a publication relating to health care. Dr. Sheth served as a consultant for Penumbra and Cerenovus. The institution of Dr. Frankel has received research support from Nico Corporation, Inc. Dr. Rahman served as a consultant for the Ministry of Health and family Planning, Bangladesh, has received research support from the Ministry of Science and Technology, Bangladesh, and has received publishing royalties from a publication relating to health care. The institution of Dr. Sylaja has received research support from Sree Chitra Tirunal Institute for Medical Sciences and Technology. Dr. Farhoudi served as an officer or member of the board of directors for Kenes. Dr. Hokmabadi served on a speakers bureau for ArvandPharmed and Osve Pharmaceutical Company. The institution of Dr. Sakai has received research support from DaiichiSankyo and Terumo. Dr. Sakai has served as a lecture honoralium with Asahi Intec. Dr. Yagita served on a scientific advisory or DSMB for Shionogi, has served on a speakers bureau for Daiichi-Sankyo, Eisai, Bristol-Myers Squibb, Abbvie, Astellas, Pfizer, Otsuka, Sumitomo Dainippon, Mitsubishi Tanabe, Kowa, Bayer, and Kyowa Kikaku. The institution of Dr. Yagita has received research support from Takeda. Dr. Matsumaru served on a speakers bureau for Medtronic, Stryker, Terumo, J&J, and Kaneka. The institution of Dr. Todo has received research support from JSPS KAKENHI Grant Number 20K07885. Dr. Todo has served as a lecturer with Medtronic, Bristol-Myers Squibb, Pfyzer, Byer, Daiichi Sankyo, and Stryker. The institution of Dr. Sonoda has received research support from The Ministry of Education, Culture, Sports, Science and Technology, Japan. Dr. Zaidi served as a consultant for Boehringer Ingelheim and Medtronic and The institution of Dr. Zaidi has received research support from The George Institute and The Florey Institute of Neuroscience and Mental Health. Dr. Al-Jehani served as an editor, associate editor, or editorial advisory board member for Boerhinger Ingelheim. Dr. Chen has received research support from the Ministry of Science and Technology. The institution of Dr. Gattringer has received research support from the Austrian Neurological Society. Dr. Killer-Oberpfalzer served as a consultant for Medtronic and Microvention. Dr. Vanhooren served as a consultant for BAYER. Dr. Pierre Rutgers served on a scientific advisory or DSMB for Novartis, Daiichi Sankyo, Bayer, Boehringer Ingelheim, and Piramal Imaging Limited. Dr. Budincevic served on a scientific advisory or DSMB for Boehringer Ingelheim, served on a speakers bureau for Bayer, and The institution of Dr. Budincevic has received research support from Novo Nordisk. Dr. Klecka served as a consultant for Novartis and served on a scientific advisory or DSMB for Novartis and Teva. The institution of Dr. Hlinovsky has received research support from AstraZeneca. Dr. Klingenberg Iversen served on a scientific advisory or DSMB for BAYER and Boehringer Ingelheim, has served as an officer or member of the board of directors for the Danish Stroke Society, and has received publishing royalties from a publication relating to health care. The institution of Dr. Simonsen has received research support from Novo Nordisk Foundation. Dr. Gross-Paju served on a scientific advisory or DSMB for Sanofi Genzyme and Novartis, and has served on a speakers bureau for Merck. Dr. Cordonnier served on a scientific advisory or DSMB for Biogen (steering committee) and BMS (steering committee), has served on a speakers bureau for Boehringer-Ingelheim, and as an editor, associate editor, or editorial advisory board member for Stroke journal. The institution of Dr. Cordonnier has received research support from the French ministry of health. Dr. Eker served as a consultant for Cerenovus. Dr. Ondze served as a consultant for Novartis. Dr. Fernando Pico served on a speakers bureau for Boehringer. Dr. Krishnan has served on the speakers bureau for Daiichi Sankyo. Dr. Nagel served as a consultant for Brainomix, and has served on a speakers bureau for Böhringer Ingelheim and BMS Pfizer. Dr. Ringleb served on a scientific advisory or DSMB for Boehringer Ingelheim, and has served on a speakers bureau for Boehringer Ingelheim, Bayer, Daiichi Sankyo, and Pfizer. The institution of Dr. Schmidt has received research support from Biomerieux and GBA, German Federal Government. Dr. Schmidt has received intellectual property interests from a discovery or technology relating to health care and served as an examiner with Board of Physicians Lower Saxony. The institution of Dr. Siepmann has received research support from the German Federal Ministry of Health. Dr. Siepmann has received publishing royalties from a publication relating to health care. Dr. Szabo has received research support from Ministry of Science and Research, Baden-Württemberg, Germany. Dr. Szabo has received publishing royalties from a publication relating to health care. Dr. Thomalla served as a consultant for Acandis, Strykern, and Portolam, and served on a speakers bureau for Daiichi Sankyo and Bristol Myers Squibb / Pfizer. Dr. Klivenyi served as a consultant for Biogen and Abbvie. Dr. Karlinski, served as a consultant for Boehringer Ingelheimm, served on a scientific advisory or DSMB for Boehringer Ingelheim, Bayer, Medtronic, and Boehringer Ingelheim, and has served on a speakers bureau for Bayer and Medtronic. Dr. Sienkiewicz-Jarosz served on a speakers bureau for Servier and Medical Tribune. The institution of Dr. Sienkiewicz-Jarosz received research support from The National Centre for Research and Development. Dr. Fryze served as a consultant for Roche, Merck, and Biogen, served on a speakers bureau for Roche, Merck, and Novartis and has received research support from Roche, Merck, Biogen, Alkermes, AstraZeneca, Bayer, and Actelion. Dr. Arenillas has served as a consultant for Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Amgen, and Pfizer, served on a scientific advisory or DSMB for AstraZeneca, Amgen, Fundació Ictus Barcelona, and served on a speakers bureau for Daiichi-Sankyo, Bayer, and Boehringer. The institution of Dr. Arenillas has received research support from Carlos III Health Institute, Madrid, Spain, the European Union–European Commission, and the Department of Education, Castilla y Leon Regional GVNT. Dr. Ayo Martin served as an expert witness for Daiichi-Sankyo and the institution of Dr. Ayo Martin has received research support from Daiichi-Sankyo and the Spanish Society of Neurosonology. The institution of Dr. Montaner has received research support from the Spanish government and has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Fischer has received research support from Medtronic. The institution of Dr. Gralla has received research support from Medtronic. Dr. Michel has served as a consultant for Medtronic, served on a scientific advisory or data safety monitoring board for Penumbra, and has received research support from the Swiss National Science Foundation; Swiss Heart Foundation. Dr. Strambo has received research support from University of Lausanne and the institution of Dr. Strambo has received research support from Swiss Heart Foundation. Dr. Catanese served as a consultant for IschemiaCare. Dr. Demchuk served as a consultant for Medtronic, served on a scientific advisory or data safety monitoring board for Lumosa, and served on a speakers bureau for Pfizer/BMS and Boehringer Ingelheim. Dr. Demchuk has received stock or an ownership interest from Circle NVI and has received intellectual property interests from a discovery or technology relating to health care. Dr. Field has received personal compensation for serving as an employee of Springer. Dr. Field served as an expert witness for the Canadian Medical Protective Association. The institution of Dr. Field has received research support from Bayer Canada. Dr. Hill served as a consultant for Boehringer Ingelheim, served on a scientific advisory or data safety monitoring board for Sun Pharma, and has received stock or an ownership interest from Circle Neurovascular. Dr. Saposnik served as a consultant for Roche, Celgene, and Servier, and served on a scientific advisory or data safety monitoring board for the NIHSS. The institution of Dr. Saposnik has received research support from Roche and the Heart and Stroke Foundation of Canada. Dr. Shoamanesh served on a scientific advisory or data safety monitoring board for Bayer AG and Daiichi Sankyo and has served on a speakers bureau for Servier Inc. Dr. Shoamanesh served as an editor, associate editor, or editorial advisory board member for Neurodiem.ca. The institution of Dr. Shoamanesh has received research support from Servier Canada Inc., Daiichi Sankyo Ltd., Bayer AG, Bristol-Myers Squibb, and Octapharma Canada. Dr. Abraham served as a consultant for Stryker Neurovascular. An immediate family member of Dr. Altschul has received personal compensation in the range of $50,000-$99,999 for serving as a consultant for Microvention and Stryker. The institution of Dr. Altschul has received research support from Max Kade. Dr. Badruddin has received intellectual property interests from a discovery or technology relating to health care. Dr. Chaturvedi served as an editor, associate editor, or editorial advisory board member for the American Heart Association. Dr. Chaturvedi served as an expert witness for Various and the institution of Dr. Chaturvedi has received research support from NINDS. Dr. Choi has received intellectual property interests from a discovery or technology relating to health care. Dr. Devlin served as a consultant for Neural Analytics, Viz.ai, and Medtronic, has served on a speakers bureau for Medtronic, Viz.ai, and served as an officer or member of the board of directors for Neuroscience Innovation Foundation. Dr. Devlin has received stock or an ownership interest from Neural Analytics and Viz.ai. The institution of Dr. Devlin has received research support from Viz.ai. Dr. Devlin has received research support from Neural Analytics. Dr. Etherton served as a consultant for WorldCare Clinical and has received research support from the American Academy of Neurology. Dr. Etherton has received research support from MGH Executive Council on Research and received publishing royalties from a publication relating to health care. Dr. Frei served as a consultant for Philips, Stryker, and Siemens, has served on a scientific advisory or data safety monitoring board for Shape Memory Medical and has served on a speakers bureau for Genentech, Stryker, Penumbra, and Viz.ai. Dr. Frei has received stock or an ownership interest from Penumbra, and has received research support from Penumbra. Dr. Ameer Hassan served as a consultant for Medtronic, Stryker, Penumbra, Cerenovus, and Viz.ai. Dr. Hassan served on a speakers bureau for Genentech and has received research support from GE Healthcare. Dr. Leung has received research support from NIH. Dr. Linfante has received personal compensation for serving as an employee of Medtronic, Stryker, Cerenovus. Dr. Linfante has received personal compensation in the range of $100,000-$499,999 for serving as a consultant for Medtronic, and has received stock or an ownership interest from InNeuroCO and Stryker/Surpass. Dr. Lutsep served as a consultant for Abbott and served on a scientific advisory or data safety monitoring board for BMS, Coherex Medical, and NINDS/Mayo Cinic. Dr. Lutsep served as an editor, associate editor, or editorial advisory board member for Medscape Neurology. Dr. McDermott has served as an editor, associate editor, or editorial advisory board member for the American College of Cardiology, served as an expert reviewer with Michigan LARA, and has a noncompensated relationship as a consultant with Mitovation that is relevant to AAN interests or activities. Dr. Nahab served as an expert witness for legal consultation and has received intellectual property interests from a discovery or technology relating to health care. Dr. Ortega Gutierrez served as a consultant for Stryker and Medtronic and served as an officer or member of the board of directors for SVIN. The institution of Dr. Ortega Gutierrez received research support from Stryker. Dr. Ramakrishnan served as a symposium honorarium with Cerenovus. The institution of Dr. Romero has received research support from the NIH/NIA. Dr. Rost served on a scientific advisory or data safety monitoring board for Omiox and Abbvie, and served as an editor, associate editor, or editorial advisory board member for Stroke–AHA/ASA Journal. The institution of Dr. Rost has received research support from the NIH. Dr. Rost has received intellectual property interests from a publication relating to health care and served as an instructor with the Heart and Rhythm Society. Dr. Ruland served as an editor, associate editor, or editorial advisory board member for Up to Date and served as an expert witness for law firms. Dr. Silver served as an expert witness for various legal firms, has received intellectual property interests from a discovery or technology relating to health care, has received publishing royalties from a publication relating to health care, and served as a consultant with Women's Health Initiative and Best Doctors, Inc. Dr. Silver has a noncompensated relationship as a consultant with ABPN that is relevant to AAN interests or activities. Dr. Silver has a noncompensated relationship as a member of the regional board of directors with the American Heart Association that is relevant to AAN interests or activities. Dr. Szeder served as a consultant for Medtronic and as an expert witness for Carroll, Kelly, Trotter, Franzen, McBride & Peabody LLP. Dr. Szeder served as an expert witness for Peabody and Buccini LLP. Dr. Tsai served as a consultant for Cerenovus. Dr. Conforto has received research support from the NIH, FAPESP, CNPq, and MIT, served as an author with Springer, and served as a speaker with Manole and EEP-USP. Fabricio Oliveira Lima served on a speakers bureau for Boehringer Ingelheim. Dr. Lavados served on a scientific advisory or data safety monitoring board for Boehringer Ingelheim and served on a speakers bureau for Boehringer Ingelheim. Dr. Lavados has received research support from ANID-FONDECYT. Dr. Hankey served as a consultant for Bayer, served on a scientific advisory or data safety monitoring board for AC Immune, and served as an editor, associate editor, or editorial advisory board member for the American Heart Association. Dr. Thijs served as a consultant for Medtronic, Allergan, BMS, and served on a speakers bureau for Pfizer and Boehringer Ingelheim. Dr. Haussen served as a consultant for Stryker and received stock or an ownership interest from Viz.ai. Dr. Liebeskind has received research support from Cerenovus, Genentech, Medtronic, and Stryker. Dr. Yavagal served as a consultant for Johnson & Johnson, Neural Analytics, Inc., Rapid Medical Ltd., and Guidepoint Global, has served on a scientific advisory or data safety monitoring board for Neural Analytics, Inc., Carnival Cruises, Medtronic, Royal Carribean Cruises Ltd., and Guidepoint Global, has served on a speakers bureau for Medtronic, and served as an editor, associate editor, or editorial advisory board member for Goldberg Segalla LLP. Dr. Yavagal served as an expert witness for Rourke and Blumenthal, LLP, Eadie Hill Trial Lawyers, and Goldberg Segalla LLP. Dr. Jovin served as a consultant for Cerenovus, served on a scientific advisory or data safety monitoring board for Contego Medical, served as an expert witness for several law firms, and. has received stock or an ownership interest from Corindus, Methinks, and Viz.ai. The institution of Dr. Jovin has received research support from Stryker and Medtronic. The institution of Dr. Nguyen received research support from Medtronic and SVIN. The remaining authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.