Thrombectomy patients with minor stroke: factors of early neurological deterioration
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* Christian Heitkamp
* Laurens Winkelmeier
* Fabian Flottmann
* Maximilian Schell
* Helge Kniep
* Gabriel Broocks
* Christian Thaler
* Paul Steffen
* Goetz Thomalla
* Jens Fiehler
* Tobias D Faizy

## Abstract

**Background** A sizeable proportion of stroke patients with large vessel occlusion present with minor neurological deficits. Whether mechanical thrombectomy (MT) is beneficial in these patients is controversial. We aimed to investigate factors of early neurological deterioration (END) in thrombectomy patients with minor stroke and hypothesized that END is linked to unfavorable functional outcomes.

**Methods** Multicenter cohort study screening all patients prospectively enrolled in the German Stroke Registry–Endovascular Treatment (n=13 082) between 2015 and 2021. Patients who underwent MT for anterior circulation vessel occlusion with baseline National Institutes of Health Stroke Scale (NIHSS) score of <6 were included. END was defined as an increase in NIHSS score of ≥4 within the first 24 hours after MT. Multivariable regression analyses were performed to investigate factors associated with END and its association with unfavorable functional outcomes 90 days after treatment (modified Rankin Scale (mRS) score ≥2).

**Results** Among 817 patients included, 24% exhibited END and 48% had unfavorable functional outcomes. Prestroke mRS (adjusted odds ratio (aOR) [95% CI] 1.42 [1.13 to 1.78]), baseline NIHSS (aOR [95% CI] 0.83 [0.73 to 0.94]), time from admission to groin puncture (aOR [95% CI] 1.04 [1.02 to 1.07]), general anesthesia (aOR [95% CI] 1.68 [1.08 to 2.63]), number of passes (aOR [95% CI] 1.15 [1.03 to 1.29]), adverse events during treatment (aOR [95% CI] 1.89 [1.19 to 3.01]), successful recanalization (aOR [95% CI] 0.29 [0.17 to 0.50]), and intracranial hemorrhage on follow-up imaging (aOR [95% CI] 3.40 [1.90 to 6.07]) were independently associated with END. END was independently linked to unfavorable functional outcomes (aOR [95% CI] 7.51 [4.57 to 12.34]).

**Conclusions** Almost a quarter of thrombectomy patients with minor stroke developed END. These patients had twice the odds of experiencing unfavorable functional outcomes.

*   Thrombectomy
*   Stroke

#### WHAT IS ALREADY KNOWN ON THIS TOPIC

*   Early neurological deterioration (END) in thrombectomy patients with National Institutes of Health Stroke Scale (NIHSS) scores of ≥6 on admission occurs in up to 40% of cases and is a strong predictor of unfavorable functional outcomes after 90 days. Thrombectomy in patients with minor stroke, defined by an admission NIHSS score of <6, is controversial and research regarding incidence and factors of END in this patient group remains scarce. The objective of this study was to determine the factors associated with an increased risk of END in patients with a minor stroke.

#### WHAT THIS STUDY ADDS

*   Almost a quarter of thrombectomy patients with minor stroke developed END, doubling the likelihood of unfavorable functional outcomes 90 days after treatment. Our study provides patient-specific risk factors independently associated with END after endovascular treatment.

#### HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

*   This study provides clinicians with valuable information about the incidence and risk factors of END in patients with minor stroke who underwent mechanical thrombectomy. In the ongoing debate on whether or not mechanical thrombectomy is beneficial in patients with a minor stroke, these findings may help clinicians in identifying patients who require special clinical attention following thrombectomy.

## Introduction

A considerable fraction of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO) present with only minor neurological deficits.1 2 Although most patients achieve functional independence after 3 months following best medical treatment alone, milder deficits can still substantially reduce daily life activities and quality of life.3–5 The optimal treatment strategy for these patients remains the subject of current debate, as only a few patients with National Institutes of Health Stroke Scale (NIHSS) score <6 were randomized in the pivotal mechanical thrombectomy (MT) trials.3 Until the ongoing randomized trials ENDOLOW (Endovascular Therapy for Low NIHSS Ischemic Strokes)4 and MOSTE (Minor Stroke Therapy Evaluation)5 provide first-level evidence as to whether MT is beneficial or may even harm patients with minor stroke, MT is currently considered on a case-by-case basis after thorough assessment of clinical and radiological parameters.6 In anticipation of data from these upcoming randomized trials, retrospective studies might help to identify prognostic factors of an unfavorable clinical course after MT that may ultimately lead to poor long-term outcomes.

The NIHSS score after 24 hours was found to be an important predictor of long-term functional outcomes in AIS-LVO patients presenting with an NIHSS of ≥6 and can be compared with the baseline NIHSS to estimate the short-term clinical course of patients.7 8 A recently published study of patients with minor stroke comparing MT+intravenous thrombolysis (IVT) with IVT alone observed a significantly higher rate of early neurological deterioration (END) in patients who underwent MT, despite similar long-term outcomes.9 On the contrary, other studies of patients with minor stroke have shown that END is significantly associated with worse long-term outcomes.10 11 To date, there is a lack of data regarding factors that are associated with END in patients with minor stroke treated by MT. Our objective was to assess prognostic factors of END and whether END is associated with unfavorable long-term functional outcomes in patients with minor stroke who were treated by MT.

## Methods

### Study design and participating centers

This multicenter cohort study analyzed patients who were prospectively enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) between June 2015 and December 2021. The GSR-ET is an ongoing, prospective, open-label, multicenter registry including patients who underwent MT at one of 25 comprehensive stroke centers in Germany (ClinicalTrials.gov identifier: [NCT03356392](http://jnis.bmj.com/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03356392&atom=%2Fneurintsurg%2Fearly%2F2025%2F01%2F26%2Fjnis-2024-021930.atom)).12 All AIS-LVO patients with subsequent MT and an age of ≥18 years are included in the registry by the respective stroke center. Approval for the GSR-ET was granted by the ethics committee at Ludwig Maximilian University, Munich, Germany. Local ethics committees granted approval for all participating sites in accordance with their respective local regulations. Informed consent for this study was waived after review of the ethics committee of each participating center. This study was conducted in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for observational studies. All procedures adhered to the guidelines set by the Health Insurance Portability and Accountability Act (HIPAA) and the Declaration of Helsinki.

### Study inclusion criteria

The inclusion criteria for this study were defined as follows:1) acute ischemic stroke patients with an occlusion in the anterior circulation due to an isolated occlusion of the intracranial internal carotid artery (ICA) or of the M1 or M2 segment of the middle cerebral artery (MCA), 2) baseline NIHSS<6, 3) complete data on baseline NIHSS, prestroke modified Rankin Scale (mRS) score, NIHSS after 24 hours, recanalization status, and mRS after 90 days. We did not include patients with tandem occlusion or rescue MT (defined as MT following END) in our study. A detailed illustration of the inclusion and exclusion criteria can be found in online supplemental figure S1.

### Supplementary data

[[jnis-2024-021930supp001.pdf]](pending:yes)

### Clinical and radiological data acquisition

Patient characteristics, radiological parameters, and clinical outcomes were obtained from the GSR-ET database. Local investigators at each participating center assessed baseline imaging, digital subtraction angiograms, as well as follow-up imaging. The recanalization status was determined by the treating neurointerventionalist using the Thrombolysis in Cerebral Infarction (TICI) score. Successful recanalization was defined as a final TICI score of 2b-3. The patient’s clinical status was assessed at admission, after 24 hours, and after 90 days using NIHSS and mRS.

### Outcome measures

Primary outcome was an END, defined as an increase in NIHSS score of ≥4 within the first 24 hours following MT. The secondary outcome was an unfavorable functional outcome 90 days after MT, defined by an mRS score of ≥2, in line with previous research on patients with minor stroke.1 11 13

### Statistical analysis

Patient characteristics, radiological findings, treatment details, and clinical outcomes were compared across study outcomes. Continuous variables were analyzed using the Mann–Whitney U test, and categorical variables were examined with the chi-square test. Data distribution normality was evaluated through Shapiro–Wilk tests. Continuous variables are displayed as medians with interquartile ranges (IQRs), while categorical variables are presented in counts and percentages. A subgroup analysis was conducted, including only successfully recanalized patients (TICI 2b-3), to evaluate the incidence of END in this patient group. Multivariable logistic regression analyses were performed to identify independent factors of END and unfavorable functional outcome. Variables that were clinically meaningful and significant with a p-value of below 0.05 in the group comparison between patients who exhibited END and those who did not (table 1) were included in the models. Following this objective, the independent variables with END as the dependent variable were NIHSS at admission, prestroke mRS, atrial fibrillation, occlusion of intracranial ICA, time from admission to groin puncture, administration of tissue plasminogen activator (tPA), general anesthesia, number of passes, successful recanalization, adverse event during treatment, and intracranial hemorrhage (ICH) on follow-up imaging after 24 hours. Covariates adjusting the model for unfavorable functional outcome were selected a priori and included age, prestroke mRS, NIHSS at admission, diabetes mellitus, time from symptom onset/last seen well to admission, general anesthesia, administration of tPA, successful recanalization, END, and ICH.

View this table:
[Table 1](http://jnis.bmj.com/content/early/2025/01/26/jnis-2024-021930/T1)

Table 1 
Patients' baseline, procedural, and outcome characteristics

We provided adjusted odds ratios (aORs) together with associated p-values and 95% confidence intervals (CIs) for every independent variable. Statistical significance was considered when the p-value was below 0.05. The variance inflation factor for each independent variable was calculated to mitigate the possibility of multicollinearity in the regression model. The data analysis was conducted using Stata (Stata/MP18, StataCorp, TX, USA).

## Results

### Baseline characteristics of patients

Of 13 082 patients enrolled in the GSR-ET, a total of 817 patients met the inclusion criteria (online supplemental figure S1). Median age was 72 (IQR 62–80) years and the sex ratio was balanced (51% male). The median NIHSS on admission was 4 (IQR 2–5) and the median ASPECTS (Alberta Stroke Program Early CT Score) was 9 (8–10). The most frequent vessel occlusion sites were the M1 (43%) and M2 (45%) segment of the MCA. Vessel recanalization was successfully (TICI≥2b) achieved in 703 (86%) patients and complete (TICI3) in 435 (53%) patients. Adverse events during endovascular treatment occurred in 147 (18%) patients including vasospasm, clot migration, and embolization as well as dissection or perforation. The median NIHSS score after 24 hours was 3 (IQR 1–6) and follow-up imaging revealed ICH in 72 (9%) patients. Table 1 displays further baseline, procedural, and outcome characteristics.

### Primary and secondary outcomes

A total of 192 (24%) patients experienced END. These patients had a higher prestroke mRS score (IQR 0–1 vs 0–0; p=0.002), lower NIHSS score at admission (3 vs 4; p=0.002), and less often atrial fibrillation as a comorbidity (29% vs 37%; p=0.029) compared with patients who did not exhibit END. The intracranial ICA was more often occluded in patients with END (18% vs 10%; p=0.003). Regarding treatment characteristics, patients with END were less often treated with intravenous tPA (34% vs 43%; p=0.017), time from admission to groin puncture was longer (90 min vs 79 min; p=0.017), and they underwent more often general anesthesia (74% vs 63%; p=0.008). There was a higher number of passes (2 vs 1; p<0.001) performed in END patients, successful recanalization was less often achieved (74% vs 90%; p<0.001), and adverse events during endovascular treatment were more frequent (27% vs 15%; p<0.001). On follow-up imaging after 24 hours, patients with END were more often diagnosed with ICH (17% vs 6%; p<0.001). Patients with END were more likely to achieve unfavorable functional outcomes at 90 days compared with those without END (mRS of 2–6: 80% vs 38%; p<0.001, figure 1).

![Figure 1](http://jnis.bmj.com/https://jnis.bmj.com/content/neurintsurg/early/2025/01/26/jnis-2024-021930/F1.medium.gif)

[Figure 1](http://jnis.bmj.com/content/early/2025/01/26/jnis-2024-021930/F1)

Figure 1 
Distribution of the modified Rankin Scale (mRS) at 90 days stratified by early neurological deterioration (END). Patients with END had more often unfavorable functional outcomes at 90 days (mRS 2–6; line; 80% vs 38%; p<0.001).

Table 2 displays a subgroup analysis of successfully recanalized patients (TICI 2b-3). In this specific group of patients, END was slightly lower (20%) compared with the overall cohort (24%). Also refer to online supplemental table S1 for more details regarding group differences with respect to long-term functional outcomes. Noteworthy, END occurred more frequently in patients with unfavorable functional outcomes (39% vs 9%; p<0.001).

View this table:
[Table 2](http://jnis.bmj.com/content/early/2025/01/26/jnis-2024-021930/T2)

Table 2 
Characteristics of patients with successful recanalization (Thrombolysis in Cerebral Infarction (TICI) 2b-3) stratified by early neurological deterioration

### Independent factors associated with END and unfavorable functional outcomes (mRS of 2–6 90 days after treatment)

In multivariable logistic regression, a higher prestroke mRS score (aOR [95% CI] 1.42 [1.13 to 1.78]; p=0.003), longer time from admission to groin puncture (aOR [95% CI] 1.04 [1.02 to 1.07]; p=0.001), general anesthesia (aOR [95% CI] 1.68 [1.08 to 2.63]; p=0.022), higher number of passes (aOR [95% CI] 1.15 [1.03 to 1.29]; p=0.012), adverse events during treatment (aOR [95% CI] 1.89 [1.19 to 3.01]; p=0.007), and the occurrence of ICH within 24 hours (aOR [95% CI] 3.40 [1.90 to 6.07]; p<0.001) increased the odds of END (figure 2). A higher NIHSS score at admission (aOR [95% CI] 0.83 [0.73 to 0.94]; p=0.004) and successful recanalization (aOR [95% CI] 0.29 [0.17 to 0.50]; p<0.001) decreased the odds of END.

![Figure 2](http://jnis.bmj.com/https://jnis.bmj.com/content/neurintsurg/early/2025/01/26/jnis-2024-021930/F2.medium.gif)

[Figure 2](http://jnis.bmj.com/content/early/2025/01/26/jnis-2024-021930/F2)

Figure 2 
Multivariable logistic regression analyses with respective odds diagrams assessing independent factors of (A) early neurological deterioration and (B) unfavorable functional outcome (mRS≥2) in patients with minor stroke. Model A included 705 patients while Model B included 708 patients. END, early neurological deterioration; ICA, internal carotid artery; ICH, intracranial hemorrhage; mRS, modified Rankin Scale; mRS90, modified Rankin Scale at 90 days’ follow-up; NIHSS, National Institutes of Health Stroke Scale; TICI, Thrombolysis in Cerebral Infarction; tPA, tissue plasminogen activator.

Multivariable logistic regression analysis with unfavorable functional outcome as the dependent variable highlights the strong association between END and unfavorable functional outcomes at 90 days (aOR [95% CI] 7.51 [4.57 to 12.34]; p<0.001). Figure 2 displays further independently associated factors of unfavorable functional outcome.

## Discussion

In this multicenter study of 817 AIS-LVO patients who presented with a NIHSS score of <6 and were treated by MT, 192 (24%) patients experienced END and 392 (48.0%) patients had unfavorable functional outcomes after 90 days. The first 24 hours after endovascular therapy proved to be prognostically relevant, as the occurrence of END was found to be an independent factor that is strongly associated with unfavorable long-term functional outcomes. To date, studies on END with regard to minor strokes predominantly focused on patients who were treated by IVT alone where incidences of END range between 13% and 24%.2 10 14 In our study of patients treated with MT, we observed a comparable incidence and our findings confirm the results of previous research that END is strongly associated with unfavorable long-term functional outcomes.2 15 16

The limited inclusion of patients with minor stroke in landmark endovascular trials has left uncertainty as to whether endovascular therapy is beneficial in these patients.3 Thus, the decision to obtain endovascular treatment is currently based on a careful case-by-case evaluation,17 pending the results of ongoing prospective studies such as ENDOLOW4 and MOSTE.5 To determine the factors that contribute to a negative clinical course after MT, we report patient-specific factors that contribute to END after MT in patients with minor stroke due to LVO.

We observed an independent association between higher prestroke mRS scores and both END and unfavorable functional outcomes. A higher prestroke mRS score has been discussed to indicate previous stroke or comorbidities, which could impede favorable early clinical recovery.18 We observed that the occlusion of the intracranial ICA was significantly more frequent in patients with END. Equivalently, prior studies found that patients with minor stroke and proximal vessel occlusion sites are at a high risk of developing END.10 19 However, these studies predominantly focused on patients treated by IVT alone. Failure of early recanalization of a proximal vessel by means of IVT may lead to an extension of ischemic tissue beyond the initial penumbra into the adjacent, previously asymptomatic tissue, ultimately resulting in an increment of NIHSS scores.20 21 Interestingly in our study, after adjusting for other covariates including recanalization status, we did not find a significant correlation between a proximal vessel occlusion site and END. Yet, we found a strong and inverse correlation between recanalization success and END. As higher penumbra salvage volume is largely driven by a complete vessel recanalization and restored blood supply to downstream brain parenchyma, successful recanalization prevents infarct progression and may therefore be protective with respect to an early increase in NIHSS scores.21–23

Numerous studies have evaluated whether local anesthesia, conscious sedation, or general anesthesia serves patients best in endovascular therapy. However, there is currently no definitive recommendation as to which procedure is most appropriate for respective subtypes of stroke patients.24 Research suggests that patients with a baseline NIHSS of ≥6 are at an increased risk of END when administered general anesthesia.25 26 Our study affirms these findings for patients with minor stroke. In patients presenting with LVO and minor stroke symptoms it is likely that cerebral perfusion is sustained to a certain extent by favorable collaterals. During general anesthesia, a (transient) reduction in blood pressure may occur, which may result in an exhaustion of collateral supply, leading to infarct progression and ultimately early clinical worsening.27 28 However, it is also important to consider a potential selection bias inherently linked to the retrospective design of our study: Interventionalists might select general anesthesia for patients whom they perceive as having a higher risk of complications. This decision may have been influenced by confounding factors, such as a deterioration of the patient’s clinical status between admission and transport to the angiography unit, or a necessitation of general anesthesia due to other comorbidities, which per se might indicate poor prognosis. It is thus imperative to emphasize that the findings of this study do not justify any assertion regarding the superiority of one specific anesthetic regimen. General anesthesia may even derive benefit in patients with minor stroke who exhibit distal vessel occlusion that requires demanding catheter navigation and a calm patient. Consequently, the selection of an anesthetic regimen should be based on an assessment of patient-specific characteristics, to reduce the risk of adverse events, given the uncertainty of whether MT is superior to best medical management alone.

A higher number of passes during MT required to achieve successful recanalization was identified as an independent predictor of END in our investigation. This was also found for patients with a baseline NIHSS of ≥6.25 The correlation between an increasing number of passes and END may be explained by higher probabilities of vessel wall injury with every pass, resulting in an endothelial dysfunction and clot fragmentation.29 Presently, there is no established threshold indicating the number of passes beyond which the procedure should be discontinued. Future research is warranted to elucidate optimal thresholds for patients with minor stroke.

When evaluating patients with minor stroke for MT it is crucial to consider safety concerns and (peri-)procedural risks inherently linked to endovascular treatment.17 Complications may occur and may foster embolism to new vascular territories or ICH.30 A recently published meta-analysis of 5190 patients with minor stroke exhibits a three-fold increased risk of symptomatic ICH when patients were treated by MT.1 In our study, both adverse events during treatment and the occurrence of ICH on 24 hours’ follow-up imaging were independently associated with END.

As MT evolves and devices improve, new indications and frontiers are constantly being discussed (e.g., treatment of medium vessel occlusions and low NIHSS patients). Conversely, developments in medical management (for instance the advanced use of tenecteplase) and patient monitoring also need to be taken into account when deciding whether or not to perform MT, as in our context in patients with minor stroke. Eventually, upcoming prospective randomized trials will shed new light on proper patient selection and treatment management of patients with minor stroke for whom MT may be beneficial or for whom the risks outweigh the benefits. Our retrospective, multicenter study provides valuable additional information about the clinical course of patients with minor stroke, and we present various factors that should advocate caution as to which patients may be at risk for END after MT treatment.

## Limitations

This study is subject to limitations. The study’s retrospective and nonrandomized design potentially introduces selection bias, diminishing the overall generalizability of the primary findings. Additionally, all clinical parameters, including mRS, occlusion site, and NIHSS, were reported at individual sites, which may be susceptible to site-related bias resulting in limited interrater reliability. Due to the retrospective nature of our study, we encountered instances of missing data and therefore cannot detail all adverse events during treatment, apart from vasospasm, clot migration, embolization, and dissection or perforation. Comorbidities that may occur early in the clinical course, such as infectious diseases or cardiorespiratory adverse events, which could increase the NIHSS score, were not documented. Regrettably, our data do not provide information on intracranial atherosclerosis as stroke etiology, which may be overrepresented in patients with minor stroke and LVO. Our study does not incorporate information regarding thrombus length or collateral parameters, both of which have been found to influence END in previous studies.10

## Conclusions

Early neurological deterioration, defined by a NIHSS score increase of ≥4 within the first 24 hours after MT, occurred in almost a quarter of patients with minor stroke undergoing MT. These patients had twice the odds of experiencing unfavorable functional outcomes. Factors associated with END include a higher prestroke mRS score, general anesthesia, higher number of passes during MT to achieve successful recanalization, and the occurrence of adverse events during treatment.

## Data availability statement

Data are available upon reasonable request.

## Ethics statements

### Patient consent for publication

Not applicable.

### Ethics approval

This study involves human participants and approval for the German Stroke Registry-Endovascular Treatment (GSR-ET) was granted by the ethics committee at Ludwig Maximilian University, Munich, Germany (689-15). Local ethics committees granted approval for all participating sites in accordance with their respective local regulations. Participants gave informed consent to participate in the study before taking part.

## Acknowledgments

The authors acknowledge the German Stroke Registry (GSR) investigators and the GSR steering committee. See online supplemental figure S2.

## Footnotes

*   X @WinkelmeierMD, @Fie0815

*   Contributors CH, LW, JF, GT, and TDF developed the study concept and design. CH, FF, MS, HK, CT, PS, and GB acquired, analyzed, and interpreted the data. CH, LW, GB, GT, and TDF drafted the manuscript. The project was supervised by JF, GT, and TDF. CH is the guarantor for this article. All authors have agreed to the conditions of authorship and endorse the final version of the article.

*   Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

*   Competing interests FF reported receiving personal fees from Eppdata GmbH outside the submitted work. HK reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. GB reported receiving compensation as a speaker from Balt and personal fees from Eppdata GmbH outside the submitted work. CT reported receiving personal fees from Eppdata GmbH outside the submitted work. GT reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. JF reported an ownership stake in Eppdata GmbH and grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, Phenox, and grants from Route 92 outside the submitted work. TDF reported grants from the German Research Foundation (DFG) (Project Number: 411621970) and personal fees from Eppdata GmbH outside the submitted work.

*   Provenance and peer review Not commissioned; externally peer reviewed.

*   Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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