First‐Line Treatment of Symptomatic Subocclusive Large‐Vessel Stroke: Results of a Nationwide StrokeNet Survey

Abstract

Background

Limited evidence is available for the treatment of acute symptomatic subocclusive lesions in ischemic stroke. We sought to identify current treatment patterns of stroke teams at academic health centers.

Methods

We conducted an email survey of the National Institutes of Health StrokeNet regional coordinating centers (RCCs). Each RCC principal investigator was asked to nominate a local stroke interventionalist, or a neurologist if the RCC principal investigator was an interventionalist, most aligned with the typical practice pattern of the RCC's lead hospital, to receive a survey. The survey consisted of a clinical vignette and displayed a subocclusive lesion in the left middle cerebral artery on computed tomography angiogram followed by subsequent scenarios, revising only 1 historical, clinical, or radiographic variable at a time. Participants were asked to select initial management for each scenario. Results were reviewed and analyzed by stroke‐trained physicians.

Results

Responses were received from 42 (77.8%) of 54 surveyed individuals, representing 25 (92.6%) of 27 RCCs nationwide, including 25 (59.5%) interventionalists. The majority (76.2%) of respondents treated the patient in the primary clinical vignette with mechanical thrombectomy. Among all 6 clinical scenarios, respondents chose mechanical thrombectomy with or without medical management as first‐line treatment for 4 (67%) vignettes. Exceptions were low National Institutes of Health Stroke Scale score and known ipsilateral stenosis, where respondents chose medical management as first‐line treatment.

Conclusion

Despite limited evidence to support mechanical thrombectomy versus other treatment strategies, the majority of StrokeNet RCC respondents would use mechanical thrombectomy with or without medical therapy to treat acute ischemic stroke due to intracranial subocclusive lesions.

Nonstandard Abbreviations and Acronyms

AIS

acute ischemic stroke

CTA

computed tomography angiogram

CTH

computed tomography head

MCA

middle cerebral artery

MT

mechanical thrombectomy

NIH

National Institutes of Health

NIHSS

National Institutes of Health Stroke Scale

RCC

regional coordinating center

Clinical Perspective

What Is New?

• Guidelines for treating subocclusive lesions are lacking, and most studies predate the advent of mechanical thrombectomy.

• We conducted a survey of an interventionalist and a noninterventionalist at each National Institutes of Health StrokeNet site regarding first‐line therapy of for various clinical scenarios involving subocclusive lesions causing acute stroke.

What Are the Clinical Implications?

• The majority of StrokeNet physicians opt for mechanical thrombectomy, with or without medical therapy, as first‐line treatment of subocclusive lesions with the exception of low Stroke Scale score and a history of known atherosclerosis. Future research and guidelines should focus on optimizing treatment of this challenging pathology.

Subocclusive lesions of the proximal intracranial vasculature are an infrequent but known cause of acute ischemic stroke (AIS). ¹ , ² Guidelines currently exist for the treatment of fully occlusive thrombi but are lacking for subocclusive lesions. ³ Furthermore, studies pertaining to treatment of this pathology largely predate the establishment of mechanical thrombectomy (MT) as first‐line therapy for large‐vessel occlusion stroke. ³ , ⁴

We surveyed 27 regional coordinating centers (RCCs) in the National Institutes of Health (NIH) StrokeNet, a nationwide infrastructure for designing and implementing clinical trials in stroke, to understand current practice patterns for the management of subocclusive intracranial lesions causing AIS. ⁵ Our goal was to understand if and how treatment of these lesions has changed since the advent of MT. We hypothesized that MT would be the leading therapy chosen by respondents.

Methods

Participants

The data that support findings of this study are available fromthe corresponding author upon reasonable request. We conducted an email survey of an interventionalist and a noninterventionalist at every NIH StrokeNet RCC. Each RCC contact principal investigator was emailed before release of the survey and asked to nominate an acute stroke interventionalist, or acute stroke noninterventionalist if the RCC principal investigator was an acute stroke interventionalist, who best represented regional practice of stroke care. If no response was obtained, an alternate interventionalist or noninterventionalist representative of treatment practice (“alternate”) was selected on the basis of personal experience of the investigators before sending the survey (P.H., P.K.).

Questionnaire

The survey asked for the participant's specialty and region of practice. A clinical vignette and associated computed tomography angiogram (CTA) indicating a subocclusive lesion in the middle cerebral artery (MCA) was then presented (Figure S1). In addition to the absence of prestroke disability, pertinent details included:

• History: Last known normal within 6 hours (last known normal 5 hours)

• Vitals: Hypertensive (160/80 mm Hg)

• Examination: NIH Stroke Scale (NIHSS) score >6 with disabling deficits (NIHSS score, 9)

• CT head (CTH): No infarct on CTH (Alberta Stroke Program Early Computed Tomography Score, 10)

• CTA: Left MCA location; excellent collaterals (both variables displayed in CTA)

Participants were asked to select the treatment they would offer first from the following options: aspirin, dual antiplatelet, heparin, MT, or other. If >1 answer or “other” was selected, participants were asked to clarify in the free text area.

For the subsequent 6 questions, only 1 variable from the clinical stem was changed. Participants were asked to assume all other variables in the clinical stem remained consistent. These variations were as follows:

1. History: Last known normal 12 hours ago with favorable advanced imaging

2. History: History of ipsilateral intracranial stenosis

3. Vitals: Severe hypertension (210/200 mm Hg)

4. Examination: Low NIHSS score with nondisabling deficits (NIHSS score, 3)

5. CTH: Moderate core infarct on CTH (Alberta Stroke Program Early Computed Tomography Score, 6)

6. CTA: Poor collateral blood flow

Finally, participants were asked if their response to the vignette would differ if the subocclusive lesion was in the right MCA, with options being Yes, No, or Other.

Data Acquisition and Review

Data from each participant were collected in Google Forms. Respondents’ answers were reviewed independently for quality assurance by investigators (P.H., Y.A.).

Results

Among 54 physicians surveyed at 27 StrokeNet RCCs, 42 (77.8%) from 25 (92.6%) RCCs responded (Figure 1). Only 4 responses were from alternates. Two sites had no respondents, 8 sites had 1 respondent, and 17 sites had both respondents. Of the 42 stroke specialists who responded to the survey, 18 (42.9%) were noninterventionalists and 24 (57.1%) were interventionalists (Figure 2).

Figure 1.

National Institutes of Health (NIH) StrokeNet geographic distribution. The NIH StrokeNet is composed of regional coordinating centers (RCCs) across the United States.

Figure 2.

Respondent distribution by discipline and specialty. All respondents were asked to self‐report their discipline and specialty in the survey.

For the initial clinical vignette, 32 respondents (76.2%) chose MT with or without medical management as first‐line treatment, 7 respondents (16.7%) elected medical therapy only, and 3 (7.1%) selected other approaches (Figure 3). The majority of both stroke interventionalists (21/24 [87.5%]) and noninterventionalists (11/18 [61.1%]) chose MT with or without medical therapy as first‐line treatment.

Figure 3.

Initial treatment selection for anterior circulation subocclusive lesion causing acute ischemic stroke. The survey clinical vignette was followed by multiple variations to the stem question to determine if these changes would impact the choice of first‐line therapy by experienced StrokeNet providers. ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; MT, mechanical thrombectomy; and NIHSS, National Institutes of Health Stroke Scale.

Most respondents chose MT with or without medical management as first‐line treatment in the following modifications to the original clinical vignette: Alberta Stroke Program Early Computed Tomography Score of 6 (78.6%), last known normal 12 hours prior (83.3%), and severe hypertension (69.0%). Only 2 scenarios did not have MT as an initial treatment selection for the majority of respondents. If the patient presented with a low NIHSS score and nondisabling symptoms, 36 (85.7%) respondents chose medical management, with either dual antiplatelet (17/36 [47.2%]) or heparin (14/36 [38.9%]) as initial therapies. Similarly, if the patient had known atherosclerosis, respondents were divided between medical management (21 [50.0%]) versus MT with or without angioplasty or stenting (20 [47.6%]) (Figure 3).

The clinical vignette variation, in which the patient had poor collateral blood flow but preserved Alberta Stroke Program Early Computed Tomography Score, was removed due to multiple responses stating this scenario was confusing. Finally, 38 (90.5%) respondents reported that they would not have changed their approach if the subocclusive lesion was in the right (versus left) MCA distribution.

Discussion

We found that the majority of acute stroke care providers representing high‐volume RCCs in the NIH StrokeNet would use MT, with or without medical management, as first‐line treatment of subocclusive MCA lesions causing AIS in most clinical scenarios. Choice of first‐line therapy other than MT was strongly influenced by a low NIHSS score and a history of intracranial atherosclerotic disease.

Historically, acute treatment of these lesions has been medical management only. In a retrospective observational study of consecutive patients presenting with transient ischemic attack or AIS between 2002 and 2007 with subocclusive intracranial lesion confirmed on CTA, all were treated with heparin, antiplatelets, or combination therapy. ¹ Similarly, another observational study of consecutive patients with CTA‐confirmed subocclusive thrombus between 2015 and 2017 indicated that none were treated with MT. ² The use of medical management was likely in the context of numerous failed reperfusion trials using thrombolysis and the still‐evolving role of MT for large‐vessel occlusion stroke.

Treatment with heparin has been extrapolated largely from carotid artery studies and subsequently supported by a small case series of patients with both intracranial and extracranial subocclusive thrombi presenting with AIS. ⁴ , ⁶ This case series showed that a goal partial thromboplastin time range of 50 to 70s was both feasible and potentially efficacious when added to standard therapy. ⁴ Alternatively, antiplatelet therapy of acute subocclusive lesions is likely extrapolated from studies of patients with a low NIHSS score at presentation and symptomatic intracranial atherosclerosis, driven by the concern for a higher reocclusion rate of large‐vessel occlusion in these patients following MT. ³ , ⁷

Only case studies of MT treatment for intracranial subocclusive lesions have been published, all since 2020. ⁸ , ⁹ In 1 report, MT was administered after a patient's clinical examination declined despite thrombolysis. ⁸ In a second, the patient was treated with MT after presenting with a high NIHSS score and contraindication to thrombolysis. ⁹ The acute stroke guidelines in 2018 establishing MT as first‐line therapy for large‐vessel occlusion stroke may have influenced this change in management of subocclusive thrombi. ³

Our study is strengthened by a high response rate from StrokeNet centers. It is limited by a survey format that cannot account for patient complexities, such as symptom fluctuations, or multidisciplinary care decisions. The survey respondents represented high‐volume, experienced centers, limiting the generalizability of our findings. Furthermore, we relied on representative interventionalists and noninterventionalists to describe local practice, and variability within an institution could not be captured. Nevertheless, the consistency of responses across centers was reassuring.

Conclusion

The majority of StrokeNet RCC interventionalists and noninterventionalists routinely opt for MT with or without medical therapy as first‐line treatment of subocclusive intracranial lesions. This study demonstrates a clear treatment pattern of a rare but known pathogenesis of AIS. A multicenter registry may provide key insights into best practices for management of these patients.

Sources of Funding

The NIH StrokeNet National Coordinating Center is support by NIH/National Institute of Neurological Disorders and Stroke U01 NS086872.

Disclosures

Drs Aziz, Ayala, and Ades and V. Vagal have no disclosures. Dr Harker: stock and consulting fees from Magnendo. Dr Khatri: grant funding from NIH and Cerenovus; consulting fees from Lumosa, Basking Biosciences, and Shionogi; drug and assays for NIH Strategy for Improving Stroke Treatment Response (SISTER) trial from Translational Sciences; and royalties from UpToDate. All disclosures are outside the submitted work.

Supporting information

Figure S1–S2