Predictors of futile recanalization in ischemic stroke patients with low baseline NIHSS

Abstract

Background:

There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale (NIHSS) <6). Prior studies of patients with admission NIHSS scores ≥6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases.

Aim:

The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors.

Methods:

Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n = 13,082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) scores of 2b–3). FR was defined by modified Rankin Scale (mRS) scores of 2–6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR.

Results:

A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio (aOR) = 1.04 (95% confidence interval (CI) = 1.02–1.06)), pre-stroke mRS 1 (aOR = 2.70 (95% CI = 1.51–4.84)), transfer from admission hospital to comprehensive stroke center (aOR = 1.67 (95% CI = 1.08–2.56)), longer time from symptom onset/last seen well to admission (aOR = 1.02 (95% CI = 1.00–1.04)), MT under general anesthesia (aOR = 1.78 (95% CI = 1.13–2.82)), higher NIHSS after 24 h (aOR = 1.09 (95% CI = 1.05–1.14)), and symptomatic intracranial hemorrhage (aOR = 16.88 (95% CI = 2.03–140.14)) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI score of 2b or 3.

Conclusions:

Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke.

Data accessibility statement:

The data that support the findings of our study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee.

Introduction

Since landmark trials demonstrated the beneficial treatment effect of mechanical thrombectomy (MT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), endovascular therapy has become the standard of care. Latest guidelines from the American Heart Association/American Stroke Association and the European Stroke Organization endorse MT for AIS-LVO patients presenting with a National Institutes of Health Stroke Scale (NIHSS) score of ⩾6, supported by first-level evidence.^1,2 However, up to 50% of all ischemic stroke patients present with only minor neurological deficits, as defined by an admission NIHSS score of <6, and previous research suggests that approximately 4% of these patients exhibit an underlying LVO. ³ The value of MT in patients with minor stroke is controversial, as only a few of these patients were randomized in the pivotal MT trials ⁴ and the randomized controlled trials MOSTE (Minor Stroke Therapy Evaluation) ⁵ and ENDOLOW (Endovascular Therapy for Low NIHSS Ischemic Strokes) ⁶ are still pending.

It is known from previous studies on AIS-LVO patients with an admission NIHSS of ⩾6 that up to 50% of patients exhibit poor functional outcomes despite successful vessel recanalization. ⁷ This condition is also referred to as futile recanalization (FR)^8,9 and was linked to age, admission NIHSS, Alberta Stroke Program Early CT Score (ASPECTS), comorbidities, and the use of intravenous tissue plasminogen activator (tPA), as well as time from symptom onset to recanalization.^7,10 However, data regarding patients with minor stroke symptoms remain scarce.

In light of the ongoing debate whether MT is beneficial in this patient group, our aim was to determine the prevalence of FR in patients with minor stroke and investigate associated patient-specific risk factors. This may help to identify patients who exhibit a lower likelihood of responding to endovascular therapy.

Materials and methods

Study design and participating centers

Our multicenter cohort study includes patients who were prospectively enrolled in the German Stroke Registry Endovascular Treatment (GSR-ET) between May 2015 and December 2021. The GSR-ET is an ongoing, prospective, open-label, multicenter registry comprising patients who underwent MT at 1 of 25 comprehensive stroke centers in Germany (ClinicalTrials.gov identifier: NCT03356392). ¹¹ All AIS-LVO patients who undergo MT and are aged 18 years or older are enrolled in the registry by the respective stroke center. Ethical approval for the GSR-ET was obtained from the ethics committee at Ludwig Maximilian University, Munich, Germany (689-15) and from local ethics committees at all participating sites, consistent with their respective local regulations. Informed consent for this study was waived after review of the ethics committee of each participating center. This study adheres to the strengthening the reporting of observational studies in epidemiology (STROBE) guideline for observational studies. ¹² All procedures followed the guidelines defined by the Health Insurance Portability and Accountability Act (HIPAA) and the Declaration of Helsinki.

Study in- and exclusion criteria

The inclusion criteria for this study were defined as follows: (1) AIS 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, (2) baseline NIHSS <6, and (3) MT with successful vessel recanalization, defined by a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b–3. Exclusion criteria were as follows: (1) a pre-stroke modified Rankin Scale (mRS) score of 2–6 and (2) missing data on baseline NIHSS, pre-stroke mRS, recanalization status, and mRS after 90 days. Please also refer to Supplemental Figure S1 for a detailed illustration of the inclusion and exclusion criteria.

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, and follow-up imaging. The recanalization status was determined by the treating neurointerventionalist using the mTICI score (without mTICI score of 2c). The patient’s clinical status was assessed at admission, after 24 h and after 90 days using NIHSS and mRS. Intracranial hemorrhage (ICH) was evaluated on follow-up imaging 24 h after treatment. Symptomatic ICH (sICH) was defined per ECASS II (European Cooperative Acute Stroke Study II) criteria as any ICH within 24 h accompanied by an increase in at least 4 points on the NIHSS. ¹³

Outcome measures

Primary outcome was FR, defined as unfavorable functional outcome (mRS scores of 2–6 at 90 days) despite successful vessel recanalization (mTICI scores of 2b–3). Given the initially less severely affected patients with minor stroke and in accordance with previous studies, an unfavorable functional outcome was assumed when 2 or more mRS points were present.^14–16

We performed a secondary analysis, in which we have defined FR as mRS scores of 3–6 despite successful vessel recanalization (Supplemental material).

Statistical analysis

The study compared patient characteristics, radiological parameters, treatment details, and clinical outcomes between patients with FR and those with a 90-day mRS score of ⩽1. Group comparisons were performed using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. The normality of data distribution was assessed using Shapiro–Wilk tests. Continuous variables are displayed as medians with interquartile range (IQR), and categorical variables are presented in counts and percentages. Multivariable logistic regression analyses were conducted to identify independent factors of FR. The first model included all variables that were significant in the group comparison: age, sex, NIHSS at admission, pre-stroke mRS, diabetes mellitus, dyslipidemia, atrial fibrillation, time from symptom onset/last seen well to admission, administration of tPA, general anesthesia during endovascular procedure, time from groin puncture to flow restoration, NIHSS after 24 h, sICH, and transfer to comprehensive stroke center (drip-and-ship). The second model included only baseline and preprocedural variables to identify predictors that are present before treatment to assist the treating physician in the decision process of choosing between interventional therapy and best medical treatment. Statistical significance was considered of P values below an alpha level of 0.05. The data analysis was conducted using Stata (Stata/MP18, StataCorp, TX, USA).

Data availability statement

Data supporting the findings of this study are available from the corresponding author upon reasonable request after approval of the GSR-ET centers.

Results

Patient characteristics

A total of 13,082 patients enrolled in the GSR were screened for eligibility. Of those, 674 patients met the inclusion criteria. The median age was 71 (IQR = 62–80), and sex ratio was nearly balanced with 48% being female. Median NIHSS score at admission was 4 (IQR = 2–5), and the majority of patients exhibited no disability prior to admission indicated by a median pre-stroke mRS score of 0 (IQR = 0–0). Median ASPECTS was 9 (IQR = 8–10), general anesthesia was applied in 65% patients, and 62% achieved complete recanalization (mTICI score of 3). A favorable functional outcome, as defined by a 90-day mRS score of ⩽1, was observed in 60%.

Patient characteristics stratified by FR

Of the 674 patients, 268 (40%) experienced FR. Patients with FR were older (median = 76 vs 68 years; p < 0.001) and less often male (46% vs 56%; P = 0.011). FR patients had higher NIHSS scores at admission (median = 4 vs 3; P = 0.002), more often pre-stroke mRS scores of 1 (p < 0.001), longer time from symptom onset/last seen well to admission (215 vs 165 min; p < 0.001), and more comorbidities (Table 1). FR was more frequently observed in patients who were transferred from a primary admission hospital without thrombectomy service to a comprehensive stroke center, where MT can be performed (drip-and-ship) (43% vs 34%; P = 0.027). Intravenous tPA was less often administered (36% vs 48%; P = 0.002), and MT was more often performed under general anesthesia (73% vs 61%; P = 0.001). In terms of outcome parameters after 24 h, patients with FR had higher NIHSS scores (5 vs 2; P < 0.001) and exhibited more often early neurological deterioration (34% vs 8%; P < 0.001), as defined by an increase in NIHSS score of ⩾4 within the first 24 h after MT. They further had a higher incidence of any ICH (15% vs 6%; P < 0.001) and sICH (8% vs 1%; P < 0.001). There was no significant difference in primary outcome between achieving mTICI score of 2b or 3 (Figure 1). When defining FR by a 90-day mRS score of ⩾3 despite successful recanalization, we observed FR in 168 of 674 (25%) patients.

Table 1.

Patients’ baseline, procedural and outcome characteristics.

	Total	Recanalization with 90-day mRS score ⩽1	Futile recanalization with 90-day mRS score ⩾2	P
	N = 674	N = 406	N = 268
Baseline patient characteristics
Age	71 (62–80)	68 (58–77)	76 (67–82)	<0.001
Male sex	350 (52%)	227 (56%)	123 (46%)	0.011
NIHSS at admission	4 (2–5)	3 (2–4)	4 (3–5)	0.002
Pre-stroke mRS	0 (0–0)	0 (0–0)	0 (0–0)	<0.001
Hypertension	500 (74%)	292 (72%)	208 (78%)	0.098
Diabetes mellitus	134 (20%)	69 (17%)	65 (24%)	0.020
Dyslipidemia	298 (44%)	164 (40%)	134 (50%)	0.011
Atrial fibrillation	237 (35%)	128 (32%)	109 (41%)	0.012
Antithrombotic medication	192 (29%)	114 (28%)	78 (30%)	0.69
Anticoagulant medication	81 (12%)	42 (10%)	39 (15%)	0.087
Time from symptom onset/last seen well to admission (min)	180 (78–398)	165 (70–339)	215 (100–523)	<0.001
Imaging characteristics
ASPECTS	9 (8–10)	9 (8–10)	9 (8–10)	0.38
Left hemispheric stroke	370 (55%)	222 (55%)	148 (55%)	0.89
Vessel occlusion site
Intracranial ICA	72 (11%)	46 (11%)	26 (10%)	0.50
M1	296 (44%)	187 (46%)	109 (41%)	0.17
M2	306 (45%)	173 (43%)	133 (50%)	0.073
Treatment characteristics
Administration of tPA	288 (43%)	193 (48%)	95 (36%)	0.002
Transfer to comprehensive stroke center (drip-and-ship)	255 (38%)	140 (34%)	115 (43%)	0.027
Time from admission to groin puncture (min)	80 (53–120)	82 (57–115)	78 (50–137)	0.83
General anesthesia	429 (65%)	241 (61%)	188 (73%)	0.001
No. of passes	1 (1–3)	1 (1–2)	1 (1–3)	0.076
mTICI score of 2b	254 (38%)	154 (38%)	100 (37%)	0.87
mTICI score of 3	420 (62%)	252 (62%)	168 (63%)	0.87
Time from groin puncture to flow restoration (min)	40 (26–64)	35 (25–58)	46 (30–76)	<0.001
Adverse event during treatment	117 (17%)	66 (16%)	51 (19%)	0.35
Vasospasm	39 (6%)	30 (7%)	9 (3%)
Clot migration/embolization	23 (3%)	12 (3%)	11 (4%)
Dissection or perforation	17 (3%)	8 (2%)	9 (3%)
Follow-up characteristics
NIHSS after 24 h	2 (1–5)	2 (0–3)	5 (2–10)	<0.001
Early neurological deterioration a	125 (19%)	33 (8%)	92 (34%)	<0.001
Any ICH after 24 h	63 (9%)	<24 (6%)	39 (15%)	<0.001
Symptomatic ICH after 24 h	24 (4%)	3 (1%)	21 (8%)	<0.001
Outcome characteristics
mRS score at 90-day follow-up	1 (0–2)	0 (0–1)	3 (2–5)	<0.001
mRS scores 0–1	406 (60%)	406 (100%)	0 (0%)	<0.001
mRS scores 0–2	506 (75%)	406 (100%)	100 (37%)	<0.001
mRS scores 3–4	97 (14%)	0 (0%)	97 (36%)	<0.001
mRS scores 5–6	71 (11%)	0 (0%)	71 (26%)	<0.001

Data are presented as median (IQR) for continuous measures and No (%) for categorical measures. Characteristics were compared by using either the Mann–Whitney U test for continuous variables or a chi-square test for categorical variables. Statistical significance: P < 0.05.

NIHSS: National Institutes of Health Stroke Scale; mRS: modified Rankin Scale; ASPECTS: Alberta Stroke Program Early CT score; ICA: internal carotid artery; M1/M2: M1 or M2 segment of the middle cerebral artery; tPA: tissue plasminogen activator; mTICI: modified Thrombolysis in Cerebral Infarction; ICH: intracerebral hemorrhage.

^aDefined by an increase in NIHSS score of ⩾4 within the first 24 h after mechanical thrombectomy.

Figure 1.

Sensitivity analysis of functional outcome with regard to final angiographic result: (a) distribution of the modified Rankin Scale at 90 days stratified by final modified Thrombolysis in Cerebral Infarction score. Grade 2b indicates reperfusion of ⩾50% and grade 3 reperfusion of 100% of the middle cerebral artery territory at the end of mechanical thrombectomy. Note that there was no significant difference in the rate of futile recanalization, defined by an mRS score of ⩾1, between achieving mTICI score of 2b or 3 (dotted line, P = 0.87), and (b) there was no significant difference in final angiographic results between the groups of patients with FR and those with a favorable functional outcome at 90 days.

Independent factors of FR

We performed a multivariable logistic regression analysis to identify independent factors of FR. The analysis suggests that higher age (adjusted odds ratio (aOR) = 1.04 (95% confidence interval (CI) = 1.02–1.06); P < 0.001), pre-stroke mRS score of 1 (aOR = 2.70 (95% CI = 1.51–4.84); P = 0.001), transfer from admission hospital to comprehensive stroke center (aOR = 1.67 (95% CI = 1.08–2.56); P = 0.020), longer time from symptom onset/last seen well to admission (aOR = 1.02 (95% CI = 1.00–1.04); P = 0.049), MT under general anesthesia (aOR = 1.78 (95% CI = 1.13–2.82); P = 0.013), higher NIHSS after 24 h (aOR = 1.09 (95% CI = 1.05–1.14); P < 0.001, Figure 2), and sICH after 24 h (aOR = 16.88 (95% CI = 2.03–140.14)); P = 0.009) increase the odds of FR in patients with minor stroke (Table 2).

Figure 2.

Predicted probabilities for futile recanalization stratified by (a) age and (b) National Institutes of Health Stroke Scale score at admission. The model was adjusted for baseline and preprocedural variables displayed in Supplemental Table S1. Shaded backgrounds in light blue indicate the 95% confidence intervals.

Table 2.

Multivariable logistic regression analysis to determine factors independently associated with futile recanalization (mRS ⩾ 2 at 90 days after treatment despite mTICI scores of 2b–3).

Independent variables	Adjusted odds ratio	95% confidence interval		P
Age (per year)	1.04	1.02	1.06	<0.001
Male sex	0.72	0.47	1.11	0.133
NIHSS at admission (per point)	1.13	0.99	1.30	0.074
Pre-stroke mRS score of 1 (ref. 0)	2.70	1.51	4.84	0.001
Diabetes mellitus	1.21	0.73	2.01	0.460
Dyslipidemia	1.24	0.81	1.89	0.327
Atrial fibrillation	0.90	0.57	1.43	0.664
Time from symptom onset/last seen well to admission (per 30 min)	1.02	1.00	1.04	0.049
Administration of tPA	0.72	0.46	1.14	0.168
General anesthesia	1.78	1.13	2.82	0.013
Time from groin puncture to flow restoration (per 30 min)	1.08	0.93	1.25	0.306
NIHSS after 24 h (per point)	1.09	1.05	1.14	<0.001
Symptomatic ICH after 24 h	16.88	2.03	140.14	0.009
Transfer to comprehensive stroke center (drip-and-ship)	1.67	1.08	2.56	0.020

In total, 526 patients included in multivariable logistic regression model. Statistical significance: P < 0.05.

NIHSS: National Institutes of Health Stroke Scale; mRS: modified Rankin Scale; tPA: tissue plasminogen activator; ICH: intracerebral hemorrhage.

When focusing on baseline and preprocedural variables, we found that higher age (aOR = 1.04 (95% CI = 1.03–1.06); P < 0.001), higher NIHSS at admission (aOR = 1.15 (95% CI = 1.02–1.29); P = 0.022), and a pre-stroke mRS score of 1 (aOR = 2.44 (95% CI = 1.44–4.17); P = 0.001) increase the likelihood of FR. Figure 2 depicts the predicted probabilities of age and NIHSS score at admission for FR in patients with minor stroke.

Discussion

In our large-scale multicenter, retrospective study of patients with minor stroke symptoms, defined by an NIHSS score of <6 on admission, we observed that two out of five patients (40%) experienced unfavorable functional outcomes despite successful vessel recanalization. Our results suggest that higher age, a pre-stroke mRS score of 1, higher NIHSS after 24 h, sICH, the application of general anesthesia, longer time from symptom onset/last seen well to admission, and transfer from admission hospital to comprehensive stroke center are independently associated with FR. We did not observe a significant association between FR and achieving successful (mTICI score of 2b) or complete recanalization (mTICI score of 3).

The term “FR” is commonly used in the literature to refer to patients who have undergone MT and achieved complete or near-complete vessel recanalization, but still exhibit unfavorable functional outcomes 90 days after treatment. Previous research defined FR as mRS scores of 3–6 despite achieving mTICI scores of 2b–3 recanalization. A recently published meta-analysis of 3037 patients and the highly effective reperfusion evaluated in multiple endovascular stroke trials (HERMES) collaboration reported incidences of up to 50%, mainly in patients with an NIHSS score of ⩾6 on admission.^4,7 However, data with respect to FR in patients with minor stroke remain sparse. In light of the initially less severely affected patients and according to prior studies on patients with minor stroke, we defined FR as successfully recanalized patients with mRS scores of 2–6 after 90 days^14–16 and observed an incidence of 40%.

We found that older age increases the odds of FR in patients with minor stroke, which is consistent with previous studies on patients with high admission NIHSS.^9,10 Physiologically, increasing age results in a decreased cerebral tissue perfusion (e.g. through cerebral atrophy, altered metabolism, and lower cardiac output), ¹⁷ compromised autoregulation, ¹⁸ and worse collateral circulation. ¹⁹ Beyond the physiological changes of aging, another important aspect may arise from the higher prevalence of cerebral small vessel disease in the elderly population. ²⁰ Cerebral small vessel disease has been found to have a detrimental effect on collateral recruitment, ²¹ final infarct volume, ²² and long-term functional outcome after MT. ²³ In contrast, recently published studies indicate that the detrimental effect of aging on functional outcomes may be overestimated in light of fast and effective reperfusion and that older individuals could potentially derive greater benefits from MT than younger patients.^24,25 Future research is warranted to elucidate the effects of both an increasing age and small vessel disease on patients with minor stroke who have undergone successful vessel recanalization.

To minimize the impact of an already high pre-stroke mRS score on FR, patients with an mRS score of >1 were excluded from our analysis. In spite of this, we observed that a pre-stroke mRS score of 1 was linked to FR. An mRS score of 1 corresponds to no significant disability and reflects the capability to perform all daily activities as prior to stroke. It is important to note that the pre-stroke mRS, particularly in low scores, lacks standardization and is based solely on the initial clinical impression, which may be inherently linked to interobserver variability. Still, it may indicate comorbidities or prior strokes which may decrease chances of favorable functional outcomes, though it is important to consider that the association may be related to the ordinal scale of the mRS and the threshold of unfavorable functional outcomes. In patients with an initial pre-stroke mRS of 1, further functional deterioration is more likely to result in an mRS of 2 (and, therefore, be categorized as FR) compared with patients in whom the initial mRS was 0.

Prior studies highlighted the prognostic value of the NIHSS score determined 24 h after treatment and found a robust link to long-term functional outcomes.^26–28 Our study affirms these results, as we also observed a significant association between FR and increased NIHSS scores 24 h after treatment. The 24-h period following stroke treatment is crucial with respect to outcome prognostication, as it encompasses a number of key factors including the formation of infarct volume in distinct brain areas, brain edema development, as well as complications including sICH, all of which may largely impact long-term neurological status.^26,29 In this regard, our results further yield an independent association between the occurrence of sICH and FR, which is consistent with observations from studies on patients with an admission NIHSS of ⩾6.^30–32 sICH has been reported in 5–7% of AIS-LVO patients who underwent MT and may aggravate brain injury by oxidative stress, blood–brain barrier disruption, hemorrhage resorption, and cerebral inflammation.^33,34

We noted that patients who underwent general anesthesia during thrombectomy were more likely to encounter FR. The optimal anesthetic protocol for MT remains unclear, and there is currently no definitive guideline on the most appropriate procedure for different subgroups of stroke patients.^35,36 This divergence continues with regard to FR, as some studies are concordant to our results,^30,37–39 while others could not affirm an association.^7,10 It is of particular interest in patients with minor stroke, as one can assume that mildly affected patients are more amenable to local anesthesia or conscious sedation. However, in the setting of distal vessel occlusions, this must be taken under careful consideration, as it may require more precise and demanding catheter navigation, which may be more feasible under general anesthesia. ⁴⁰ Another important procedural consideration is whether there is a clinically relevant difference in achieving mTICI score of 2b or 3. Several studies have proposed improved functional outcomes associated with mTICI score of 3 reperfusion compared with mTICI score of 2b, primarily encompassing patients with NIHSS ⩾ 6 on admission.^41,42 In our study, there was no significant difference regarding the occurrence of FR comparing patients with mTICI scores of 2b or 3. This finding implies that in patients with minor stroke, recanalization of the (most) peripheral vessel branches may have less impact on the already low symptom burden compared with more severely affected patients. Therefore, continuing MT beyond mTICI score of 2b should be carefully weighed against the risk of additional passes in neurologically less severely affected patients.

Longer time from symptom onset/last seen well to admission and transfer from admission hospital to comprehensive stroke center were modifiable risk factors of FR in our study. From a pathophysiological perspective, prolonged vascular occlusion leads to infarct growth and the exhaustion of recruited collateral blood supply, which may have initially maintained cerebral tissue perfusion to a certain extent. ³³ As a result, the exacerbation of ischemic cerebral damage proceeds in the disruption of the blood–brain barrier, which subsequently increases the risk of reperfusion damage and bleeding.^7,43,44 It has been identified that a transfer from the admission hospital to a comprehensive stroke center results in a prolongation of time from symptom onset to groin puncture, presumably due to transportation, treatment protocols of both participating hospitals and repeated imaging.^45,46 This may yield to unfavorable clinical outcomes despite successful vessel recanalization, which is supported by a recently published meta-analysis. ⁴⁶ It is important to consider these pathophysiological processes when determining whether MT should be employed in patients with minor stroke. However, a timely decision-making is important to avoid jeopardizing patients who were initially mildly affected with treatment-associated complications.

MT in AIS-LVO patients with minor stroke symptoms remains a case-by-case decision and should not be routinely recommended in unselected patients, given the good prognosis following best medical management alone and the differing benefit/risk ratio as compared with more severely affected LVO patients.^14,47 However, a subset of patients with minor stroke, including those with disabling deficits, a long thrombus length, a high risk of early neurological deterioration, and a large penumbra, may still derive benefit from endovascular therapy. ⁴⁸ Eventually, only upcoming randomized controlled trials will provide new answers to this question.

Limitations

This study has limitations. First, this study inherently incorporates all limitations associated with a retrospective study design—thus generalization of our findings is limited. Second, from a semantic perspective, FR is a questionable term, since there is variability in the definition of an unfavorable outcome and perspectives among patients and caregivers regarding what constitutes such an outcome are diverse. Although we adhered to definitions and cutoff values commonly used in stroke studies, minor alterations in the definitions of FR or minor stroke may lead to altered results. However, FR is widely used in the literature, and estimating its prevalence and identifying patient-specific risk factors is essential for optimizing inpatient monitoring and therapeutic approaches that may foster a potential benefit of MT. Due to the lack of a control group, we cannot make any statements regarding specific treatment effects. It is important to note that there may be additional factors which could impact the outcome after 90 days and which we did not address, such as the presence of newly diagnosed comorbidities or other detrimental events. In addition, final recanalization results were scored by local investigators, potentially leading to an overestimation of mTICI scores. Unfortunately, we cannot provide data on whether or not eloquent regions were affected and why MT was the favored option. The GSR-ET does not include data on advanced imaging markers such as collateral circulation or penumbra imaging, and we did not analyze the influence of thrombectomy technique (first-line aspiration vs stent-retriever vs mixed) on FR or hemorrhagic complications.

Conclusion

Two of five patients with minor stroke symptoms on admission encounter FR. We have identified higher age, a pre-stroke mRS score of 1, longer time from symptom onset/last seen well to admission, transfer from admission hospital to comprehensive stroke center, higher NIHSS scores after 24 h, MT under general anesthesia, and sICH as patient-specific risk factors that increase the likelihood of FR. These factors merit consideration by health care providers in routine clinical practice to facilitate optimal clinical surveillance and prognosis evaluation.