Risk factors and outcomes of patients with early spontaneous recanalization after acute middle cerebral artery occlusion
Original Article

Risk factors and outcomes of patients with early spontaneous recanalization after acute middle cerebral artery occlusion

Mingyao Li1,2 ORCID logo, Weilun Fu1,3, Kai Zhang1,2, Zhikai Hou1,2, Ying Yu1,2, Ning Ma1,2

1Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 2China National Clinical Research Center for Neurological Diseases, Beijing, China; 3Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

Contributions: (I) Conception and design: W Fu, N Ma; (II) Administrative support: N Ma; (III) Provision of study materials or patients: M Li, K Zhang; (IV) Collection and assembly of data: Z Hou, Y Yu; (V) Data analysis and interpretation: Z Hou, Y Yu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Ning Ma, PhD. Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, No. 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China. Email: maning_03@hotmail.com.

Background: Several studies have shown that spontaneous recanalization after acute intracranial arterial occlusion is not uncommon. This study aimed to investigate the predictive factors and outcomes of early spontaneous recanalization following acute middle cerebral artery occlusion.

Methods: We conducted an analysis of 116 patients with acute middle cerebral artery occlusion from a prospective cohort (January 2021–December 2023). Patients aged 18–85 years with confirmed middle cerebral artery occlusion within 7 days of stroke onset who did not receive thrombolysis or thrombectomy were included. Early spontaneous recanalization was assessed by the Arterial Occlusive Lesion Scale after admission within 7 days. Outcomes included 90-day modified Rankin Scale (mRS) scores, symptomatic intracranial hemorrhage within 90 days, and mortality within 90 days. According to the degree of recanalization, early spontaneous recanalization was categorized into complete recanalization and noncomplete recanalization. The baseline characteristics and therapeutic regimen were compared between the patients with no-recanalization and early spontaneous recanalization. Outcomes were compared between the early spontaneous recanalization and no-recanalization groups and between the noncomplete recanalization and complete recanalization groups. Multivariate logistic regression analysis was conducted to identify risk factors of early spontaneous recanalization and complete recanalization.

Results: Early spontaneous recanalization occurred in 20.7% of patients (24/116). The independent predictors of early spontaneous recanalization were nonatherosclerotic etiology [adjusted odds ratio (OR) 10.40; P=0.03] and higher National Institutes of Health Stroke Scale (NIHSS) score (adjusted OR 1.31; P<0.01). Complete early spontaneous recanalization occurred in 8.6% (10/116) of patients. Atrial fibrillation was an independent predictor of complete early spontaneous recanalization (OR 21.70; P=0.01). Patients with early spontaneous recanalization (n=24) did not differ significantly from those without recanalization (n=92) in terms of median 90-day mRS (3 vs. 2; effect size =0.48; P=0.35), rates of good functional outcome (mRS 0–2; 29.2% vs. 56.5%; OR 0.78; P=0.68), symptomatic intracranial hemorrhage (16.7% vs. 7.6%; OR 1.40; P=0.65), or 90-day mortality (8.3% vs. 2.2%; OR 2.97; P=0.32).

Conclusions: Early spontaneous recanalization after acute middle cerebral artery occlusion is independently associated with nonatherosclerotic etiology and higher baseline NIHSS score. Spontaneous complete recanalization after acute middle cerebral artery occlusion is independently associated with atrial fibrillation. The absence of benefit or harm indicates that spontaneous recanalization is a neutral phenomenon after acute middle cerebral artery occlusion.

Keywords: Early spontaneous recanalization (ESR); middle cerebral artery occlusion (MCA occlusion); acute ischemic stroke; outcome


Submitted May 11, 2025. Accepted for publication Sep 02, 2025. Published online Oct 23, 2025.

doi: 10.21037/qims-2025-1114


Introduction

Acute intracranial arterial occlusion is associated with high rates of mortality and disability (1-3). Achieving arterial recanalization within the therapeutic time window is critically important for improving 90-day outcomes and reducing mortality in affected patients. However, a significant number of patients miss the therapeutic window for recanalization therapies and instead receive antiplatelet or anticoagulant therapy (AC), along with comprehensive risk factor management (4). Several randomized trials evaluating medical treatment arms have demonstrated that patients with acute intracranial arterial occlusion can experience spontaneous recanalization (SR) following optimal medical management (5-8).

Studies have identified varying factors associated with SR of intracranial arterial occlusions. Outcomes of SR remain inconsistent across studies, potentially due to differences in study populations and assessment time of SR events. A study based on the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) database found that SR at 24 hours following acute arterial occlusion is positively correlated with a history of hypercholesterolemia and the proximal location of the intracranial arterial occlusion, while it is negatively correlated with an impaired level of consciousness, extracranial carotid artery stenosis, and basilar artery occlusion (9). Another investigation reported that atrial fibrillation is negatively associated with SR of the large and middle cerebral artery (MCA) within 3 months of acute ischemic stroke, whereas stage 3 hypertension is positively associated with SR (10). In a cohort of 34 consecutive stroke survivors with a perfusion-diffusion mismatch and M3 or M4 segment pathology within 24 hours of symptom onset, a high rate of SR (71%) and modest infarct growth were observed, with no significant difference in infarct growth between patients with and without recanalization. Furthermore, there was no association between functional outcomes at discharge and recanalization status or infarct volume at days 4–6. The high rate of SR and favorable functional outcomes in patients with distal MCA pathology may mask the potential benefits of recanalization therapy in this subgroup (11).

This study aimed to investigate the risk factors and outcomes associated with early SR after acute intracranial artery occlusion, to determine which patients are more likely to experience early spontaneous recanalization (ESR), and to assess their prognosis. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1114/rc).


Methods

Population

This study was approved by the Ethics Committee of Beijing Tiantan Hospital (approval number: KY2021-075-02) and conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The requirement for informed consent was waived due to the retrospective nature of the analysis. We performed a retrospective analysis of patients with acute MCA occlusion within a prospective cohort treated at a high-volume stroke center (Beijing Tiantan Hospital, Affiliated to Capital Medical University) from January 2021 to December 2023. The inclusion criteria were as follows: aged 18–85 years and computed tomography angiography (CTA) or digital subtraction angiography (DSA) confirming MCA occlusion as the causative artery within 1 week of ischemic stroke onset. Meanwhile, the exclusion criteria were as follows: thrombolytic therapy or mechanical thrombectomy administered after the appearance of symptoms of neurological impairment and failure to reassess the occluded artery within 7 days after admission, including with magnetic resonance angiography (MRA), CTA, or DSA. The sample size was determined based on the number of available cases that met the inclusion criteria during the study period. Demographic and clinical data were collected, including age, sex, National Institutes of Health Stroke Scale (NIHSS) grade, MCA occlusion site, comorbidities, etiology of cerebral infarction, low-density lipoprotein (LDL) level, total cholesterol (TC), triglycerides (TG), homocysteine (Hcy), fibrinogen, high-sensitivity C-reactive protein (hsCRP), antiplatelet therapy (APT) or AC, and lipid-lowering therapy.

Definition and assessment

For patients presenting with acute intracranial arterial occlusion who did not undergo intravenous thrombolysis or endovascular thrombectomy, ESR was defined as an initial cerebral CTA or DSA confirming the occlusion and subsequent cerebral CTA or MRA demonstrating recanalization within 7 days. Assessment of ESR was performed according to the Arterial Occlusive Lesion (AOL) Scale, in which grade 0 indicates complete occlusion of the target artery; grade 1 indicates incomplete occlusion or partial recanalization, characterized by the absence of distal blood flow; grade 2 indicates incomplete occlusion or partial recanalization with partial restoration of distal blood flow; and grade 3 indicates complete recanalization with full restoration of distal blood flow.

The etiology was classified as atherosclerotic or nonatherosclerotic. If a patient had at least one of the following conditions, the etiology was considered to be atherosclerotic: (I) imaging findings on carotid ultrasound, CTA, or MRA revealing the presence of significant atherosclerotic plaques that were considered to be the source of the embolus; (II) clinical and laboratory data showing elevated levels of LDL cholesterol (LDL-C) and TC consistent with atherosclerotic disease; and (III) a medical history of atherosclerotic cardiovascular disease, such as prior myocardial infarction, peripheral artery disease, or documented atherosclerotic plaques in other vascular territories. With consideration to the above criteria and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria (12), the stroke etiology was classified as large-artery atherosclerosis, which includes evidence of significant stenosis or occlusion of a major cerebral artery or its branches, typically associated with atherosclerotic plaques. The etiology subgroups for MCA occlusion are summarized in Table S1.

Classification

AOL grades 1 and 2 were classified as partial recanalization, while grade 3 was classified as complete recanalization (Figure 1). ESR was considered to include partial recanalization and complete recanalization. Patients were classified into a no-recanalization group if the artery remained occluded and was graded 0 between 7 and 90 days after the initial assessment. Patients were classified into a noncomplete recanalization group if no-recanalization or partial recanalization. All images were independently analyzed by two experienced neuroradiologists. Disagreements were resolved by consensus reading.

Figure 1 Different degrees of recanalization. (A) Occlusion of the left cerebral artery. (B) Complete recanalization of the left middle cerebral artery (yellow arrows). (C) Occlusion of the left cerebral artery. (D) Partial recanalization of the left middle cerebral artery (green arrows).

Outcome

The primary outcome of this study was the 90-day modified Rankin Scale (mRS) score. Secondary outcomes included a 90-day mRS score of 0–2 and a 90-day mRS score of 0–3. Safety outcomes comprised symptomatic intracranial hemorrhage within 90 days as assessed according to the Heidelberg Bleeding Classification and death within 90 days.

Statistical analysis

Continuous variables are presented as the mean ± standard deviation or as the interquartile range (IQR). Categorical variables are presented as frequency and percentage. Ordinal variables are presented as the median and IQR. Continuous variables were compared between groups via analysis of variance (ANOVA) or the Kruskal-Wallis test. Categorical variables were compared with the Pearson chi-squared test or Fisher exact test. Ordinal variables were compared between groups via the Kruskal-Wallis test. Univariate and multivariate binary logistic regression analyses were performed to identify predictors of ESR and complete recanalization. For primary outcomes, ordinal logistic regression was employed to assess differences in the 90-day mRS distribution between the ESR and no-recanalization group, as well as between the noncomplete recanalization and complete recanalization group, after it was confirmed that the proportional odds assumption was satisfied. For secondary outcomes, univariate and multivariate binary logistic regression analyses were performed to assess effect size. Differences in symptomatic intracranial hemorrhage and mortality between the groups were compared with the adjusted chi-squared test. The significance level was set at a two-sided α of 0.05. All statistical analyses were performed via SPSS software version 26.0 (IBM Corp., Armonk,
NY, USA).


Results

Study population

A total of 332 patients with ischemic stroke caused by MCA occlusion within 7 days of onset underwent screening. Initially, 175 patients were excluded due to thrombolysis (n=87), thrombectomy (n=13), bridging therapy (n=39), or lack of imaging data for the re-evaluation of occluded arteries (n=36), leaving 157 enrolled patients with re-evaluation of the occluded arteries. Additionally, 41 patients were further excluded: 36 patients lacked reassessments between 7 and 90 days, and 5 patients showed SR between 7 and 90 days. Finally, 116 eligible patients were enrolled: 24 achieved ESR (10 complete, 14 partial) and 92 had persistent occlusion. By recanalization completeness, 10 had complete and 106 noncomplete (Figure 2).

Figure 2 Flowchart of patient screening.

Baseline characteristics

A total of 116 patients were divided into no-recanalization (n=92) and ESR (n=24) groups. The ESR group, compared to the no-recanalization group, had a significantly higher median NIHSS score (11.50 vs. 7.00; P<0.001) and higher median hsCRP levels (8.58 vs. 2.78 mg/L; P=0.004). Atrial fibrillation was more prevalent in the ESR group (45.83% vs. 13.04%; P<0.001), and atherosclerotic etiology was more common in the no-recanalization group (84.78% vs. 54.17%; P=0.001). Other variables, including LDL-C, TC, TG, Hcy, and fibrinogen levels, were not significantly different between the groups (Table 1).

Table 1

Baseline characteristics and comparisons between the no-recanalization and early spontaneous recanalization groups

Variable Total (n=116) No-recanalization (n=92) Early spontaneous recanalization (n=24) P
Age 57.71±12.74 57.88±12.18 57.04±14.97 0.775
Male 23 (19.83) 18 (19.57) 5 (20.83) >0.999
NIHSS score 8.00 (5.00, 12.00) 7.00 (5.00, 11.00) 11.50 (8.00, 16.00) <0.001
LDL 2.53±0.77 2.48±0.76 2.70±0.80 0.218
TC 4.10±0.84 4.06±0.84 4.24±0.86 0.358
TG 1.15 (0.86, 1.51) 1.17 (0.89, 1.60) 1.04 (0.79, 1.37) 0.220
Hcy 14.54 (11.04, 19.69) 14.54 (11.13, 19.17) 15.67 (10.86, 27.08) 0.356
Fibrinogen 3.25 (2.86, 3.83) 3.19 (2.86, 3.71) 3.47 (3.03, 3.97) 0.383
hsCRP 4.37 (1.30, 9.29) 2.78 (1.11, 7.92) 8.58 (4.26, 15.57) 0.004
   Hypertension 88 (75.86) 70 (76.09) 18 (75.00) 0.912
   Diabetes 38 (32.76) 30 (32.61) 8 (33.33) 0.946
   Atrial fibrillation 23 (19.83) 12 (13.04) 11 (45.83) <0.001
Smoking status 0.339
   Never-smoker 49 (42.24) 37 (40.22) 12 (50.00)
   Current smoker 61 (52.59) 51 (55.43) 10 (41.67)
   Former smoker 6 (5.17) 4 (4.35) 2 (8.33)
Culprit artery 0.790
   MCA-M1 97 (83.62) 76 (82.61) 21 (87.50)
   MCA-M2 19 (16.38) 16 (17.39) 3 (12.50)
Etiology 0.001
   Atherosclerotic 91 (78.45) 78 (84.78) 13 (54.17)
   Nonatherosclerotic 25 (21.55) 14 (15.22) 11 (45.83)
Antiplatelet or anticoagulation 0.479
   Dual antiplatelet 78 (67.24) 63 (68.48) 15 (62.50)
   Mono-antiplatelet and mono-anticoagulation 5 (4.31) 3 (3.26) 2 (8.33)
   Single antiplatelet 23 (19.83) 19 (20.65) 4 (16.67)
   Single anticoagulation 10 (8.62) 7 (7.61) 3 (12.50)
Lipid-modulating strategy 0.331
   Intensive statin 97 (83.62) 79 (85.87) 18 (75.00)
   Moderate statin 19 (16.38) 13 (14.13) 6 (25.00)

Data are presented as mean ± standard deviation, n (%), or median (interquartile range). Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; LDL, low-density lipoprotein cholesterol; MCA, middle cerebral artery; NIHSS, National Institutes of Health Stroke Scale; TC, total cholesterol; TG, triglycerides.

Risk factors

We identified the significant risk factors associated with ESR. In the univariable analysis, nonatherosclerotic etiology (ESR: 45.8%; no-recanalization: 18.5%) and higher NIHSS scores (ESR: 11; no-recanalization: 7) were significantly associated with ESR. After adjustments were made for NIHSS score and etiology in the multivariable analysis, nonatherosclerotic etiology remained a significant risk factor [odds ratio (OR) 10.40; 95% confidence interval (CI): 1.31–82.65; P=0.03], as did a higher NIHSS score (OR 1.31; 95% CI: 1.10–1.54; P<0.01) (Table 2).

Table 2

Independent risk factors associated with ESR

Factor ESR (n=24) No-recanalization (n=92) Univariable analysis Multivariable analysis
OR (95% CI) P OR (95% CI) P
Etiology
   Atherosclerosis 13 (54.2) 75 (81.5) 1 (Reference)
   Nonatherosclerosis 11 (45.8) 17 (18.5) 3.71 (1.33–10.32) 0.01 10.40 (1.31–82.65) 0.03
NIHSS 11 (8–16) 7 (5–11) 1.20 (1.08–1.33) <0.01 1.31 (1.10–1.54) <0.01

Data are presented as n (%) or median (interquartile range), unless otherwise indicated. , adjusted for NIHSS score and etiology. Patients in the spontaneous recanalization group and no-recanalization group had significant differences in NIHSS score and etiology (P<0.05). CI, confidence interval; ESR, early spontaneous recanalization; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio.

The study also examined factors associated with complete recanalization. In the univariable analysis, atrial fibrillation was significantly associated with complete recanalization (OR 13.12; 95% CI: 3.07–56.14; P=0.01). After adjustments were made for NIHSS score in the multivariable analysis, atrial fibrillation remained a significant risk factor (OR 21.70; 95% CI: 4.04–116.58; P=0.01) (Table 3).

Table 3

Independent risk factors associated with complete recanalization

Factor Noncomplete recanalization (n=106) Complete recanalization (n=10) Univariable analysis Multivariable analysis
OR (95% CI) P OR (95% CI) P
Atrial fibrillation 16 (15.1%) 7 (70.0%) 13.12 (3.07–56.14) 0.01 21.70 (4.04–116.58) 0.01

, adjusted for NIHSS score. Patients in the complete recanalization group and noncomplete recanalization group had significant differences in NIHSS score (P<0.05). CI, confidence interval; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio.

Outcomes

For the no-recanalization group, the proportion of patients achieving an mRS score of 0–2 at 90 days was 56.5% (52 out of 92 patients). In contrast, for the ESR group, this proportion was 29.2% (7 out of 24 patients). After adjustments were made for NIHSS score, the primary outcome of 90-day mRS score showed no significant difference between the ESR and no-recanalization groups (OR 0.48, 95% CI: 0.10–2.28; P=0.35). Secondary outcomes included a 90-day mRS score of 0–2 and 0–3, with no significant differences noted. The proportion of symptomatic intracranial hemorrhage was higher in the ESR group (16.7%) than in the no-recanalization group (7.6%), although the difference was not statistically significant (OR 1.40, 95% CI: 0.33–6.04; P=0.65) (Table 4).

Table 4

Comparison of outcomes between the no-recanalization and early spontaneous recanalization groups

Outcome No-recanalization (n=92) Early spontaneous recanalization (n=24) OR (95% CI) P
Primary outcome
   90-day mRS 2 (1, 3) 3 (2, 4) 0.48 (0.1, 2.28) 0.35
Secondary outcomes
   90-day mRS 0–2 52 (56.5) 7 (29.2) 0.78 (0.23, 2.58) 0.68
   90-day mRS 0–3 61 (66.3) 21 (87.5) 3.28 (0.82, 13.07) 0.09
Safety outcomes
   Symptomatic intracranial hemorrhage within 90 days 7 (7.61) 4 (16.67) 1.40 (0.33, 6.04) 0.65
   Death within 90 days 2 (2.17) 2 (8.33) 2.97 (0.34, 25.5) 0.32

Data are presented as median (interquartile range) or n (%), unless otherwise indicated. , adjusted for NIHSS grade and atrial fibrillation. Patients in the early spontaneous recanalization group and no-recanalization group had significant differences in NIHSS score (P<0.05). CI, confidence interval; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio.

For the noncomplete recanalization group, the proportion of patients achieving an mRS score of 0–2 at 90 days was 56.4% (57 out of 106 patients). For the complete recanalization group, this proportion was 20.0% (2 out of 10 patients). After adjustments were made for NIHSS score, the primary outcome of 90-day mRS scores again showed no significant difference between the noncomplete recanalization and complete recanalization groups (OR 0.29; 95% CI: 0.1–0.88; P=0.23). The proportion of symptomatic intracranial hemorrhage was higher in the complete recanalization group (20.0%) than in the noncomplete recanalization group (8.9%), although the difference was not statistically significant (OR 1.02; 95% CI: 0.16–6.67; P=0.98) (Table 5).

Table 5

Outcomes of complete recanalization and noncomplete recanalization

Outcome Noncomplete recanalization (n=106) Complete recanalization (n=10) OR (95% CI) P
Primary outcome
   90-day mRS 2 (2, 4) 3 (1, 4) 0.29 (0.1, 0.88) 0.23
Secondary outcomes
   90-day mRS 0–2 57 (56.4) 2 (20.0) 0.52 (0.08, 3.42) 0.50
   90-day mRS 0–3 73 (68.9) 9 (90.0) 4.42 (0.66, 29.63) 0.13
Safety outcomes
   Symptomatic intracranial hemorrhage within 90 days 9 (8.9) 2 (20.0) 1.02 (0.16, 6.67) 0.98
   Death within 90 days 4 (3.9) 0

Data are presented as median (interquartile range) or n (%), unless otherwise indicated. , adjusted for NIHSS grade. Patients in the noncomplete recanalization and complete recanalization groups had significant differences in NIHSS score (P<0.05). CI, confidence interval; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio.

Among the 24 patients with ESR, the distribution of antithrombotic strategies was as follows: APT, 12 patients; AC, 6 patients; combination therapy (APT + AC), 4 patients; and nonantithrombotic therapy, 2 patients. The incidence of symptomatic intracranial hemorrhage within 90 days in each subgroup was as follows: APT, 2 out of 12 patients (16.7%); AC, 1 out of 6 patients (16.7%); combination therapy, 1 out of 4 patients (25.0%); and nonantithrombotic therapy, 0 out of 2 patients (0%).


Discussion

This study investigated the incidence, predictive factors, and outcomes of patients with ESR after acute MCA occlusion. The findings provide valuable insights into the factors influencing ESR and complete recanalization, as well as their implications for functional and safety outcomes. Nonatherosclerotic etiology and NIHSS scores were independently associated with ESR, and atrial fibrillation was independently associated complete recanalization. There was no notable difference in the mRS distribution between patients with no-recanalization and those with ESR, nor between those with noncomplete recanalization and those with complete recanalization. Early recanalization and complete recanalization were not significantly associated with the 90-day outcome.

In this study, the incidence of SR was 20.7%, with partial SR occurring more frequently than complete recanalization. Such rapid recanalization may reflect underlying inflammatory or fibrinolytic processes that enhance thrombus resolution. These results highlight a consistent pattern across vascular territories, suggesting that SR may be more common and beneficial than previously assumed among patients with acute MCA occlusion (13).

The underlying mechanism of occlusion plays a critical role in the likelihood of SR. Nonatherosclerotic etiologies, such as cardioembolism or hypercoagulable states, may result in thrombi that are less adherent or more amenable to endogenous fibrinolytic processes as compared to the stable, lipid-rich plaques characteristic of atherosclerosis. This finding aligns with a prior study, which noted that SR may be influenced by thrombus composition and etiology (10). Different etiologies usually represent different thrombotic components (14-16). Thrombi rich in red blood cells, characterized by a looser structure and larger pores within their fibrin networks, are more prone to SR or embolus autolysis than are fibrin-rich thrombi (17,18). Patients with nonatherosclerotic MCA occlusion may represent a subgroup for whom aggressive recanalization therapies could be deferred, depending on the observation for spontaneous resolution, provided the therapeutic window has been missed.

In our study, higher NIHSS scores, indicative of greater stroke severity, were associated with an increased likelihood of ESR. This could indicate that SR is a response to larger or more proximal occlusions, which typically produce greater neurological impairment, and it may be that larger, more symptomatic clots trigger a more robust endogenous response, such as activation of the fibrinolytic system. Alternatively, it could suggest that patients with higher NIHSS scores had occlusions more prone to spontaneous resolution due to their etiology or location. This finding contrasts with a previous study that linked impaired consciousness with reduced recanalization rates (9). The discrepancy may stem from differences in timing (24 hours vs. 7 days) or population characteristics, underscoring the need for further research into the interplay between stroke severity and recanalization dynamics.

For complete recanalization, atrial fibrillation stood out as a highly significant independent risk factor. This strong association suggests that cardioembolic occlusions, commonly linked to atrial fibrillation, are particularly prone to complete recanalization within 7 days. This may be attributable to the nature of cardioembolic thrombi, which are often fresh and fibrin-rich, rendering them more susceptible to dissolution by intrinsic mechanisms as compared to atherosclerotic thrombi. A previous study reported a negative association between atrial fibrillation and SR within 3 months of symptom onset (10), but our study focuses on the early 7-day window might have identified a different phase of thrombus evolution. Clinicians might use this finding to stratify patients with atrial fibrillation for closer monitoring, as complete recanalization could alter the risk-benefit profile of delayed interventions.

Elevated hsCRP, a marker of inflammation, might have reflected an active inflammatory process facilitating thrombus breakdown in the complete recanalization group. This aligns with emerging evidence suggesting that inflammation modulates thrombus stability and recanalization potential, warranting further investigation into inflammatory biomarkers as predictors of ESR (19-21).

ESR and complete recanalization did not appear to have a significant impact on the long-term functional outcomes or safety endpoints. This is an important consideration for clinicians managing these patients, as it suggests that SR may not be a strong predictor of clinical outcomes. Therefore, treatment strategies should not be solely based on the presence or absence of ESR or complete recanalization. This may be due to reperfusion injury, hemorrhage risk, or incomplete neuroprotection despite SR, as seen in the elevated (albeit nonsignificant) rates of symptomatic intracranial hemorrhage in patients with ESR (16.67%) and complete recanalization (20.0%). This aligns with findings from a study examining spontaneous occlusion of the distal branch of the MCA (11). Further studies on this subject may need to increase the sample size to clarify the impact of ESR and complete recanalization on the prognosis of certain subgroups.

Our subgroup analysis showed that the incidence of symptomatic intracranial hemorrhage was highest in the combination therapy group (25.0%), followed by the APT and AC groups (both 16.7%). No hemorrhagic events were observed in the nonantithrombotic therapy subgroup. However, due to the small sample size in each subgroup, these differences did not reach statistical significance. These findings suggest that the combination of antiplatelet and anticoagulant therapies might be associated with a higher risk of hemorrhagic complications in patients with ESR. This aligns with the general understanding that combining antithrombotic agents can increase bleeding risk. However, the lack of significant differences across subgroups highlights the need for larger studies to confirm these associations. In clinical practice, the choice of antithrombotic strategy should be carefully considered, especially in patients with ESR, given the potential for increased bleeding risk. Future studies should include larger cohorts to provide more robust data on the relationship between antithrombotic strategies and hemorrhagic complications in this patient population.

One review reported that carotid SR occurs in 2.3–10.3% of patients but rarely results in a cerebrovascular event (22), and carotid SR seems to have a benign long-term course (23).

This study involved several limitations that should be acknowledged. The retrospective design and single-center setting limit generalizability, while the small complete recanalization sample (n=10) constrains the statistical power. Subsequent research should include detailed assessments of infarct growth and edema to further clarify the interplay between recanalization and secondary injury mechanisms. Furthermore, these studies should examine the relationship between a more detailed analysis of reperfusion timing and spontaneous hemorrhage. Longitudinal imaging and biomarker studies could further elucidate the temporal dynamics of ESR.


Conclusions

ESR after acute MCA occlusion is independently associated with a nonatherosclerotic etiology and a higher baseline NIHSS score. Spontaneous complete recanalization after acute MCA occlusion is independently associated with atrial fibrillation. The absence of benefit or harm indicates that SR is a neutral phenomenon after acute MCA occlusion.


Acknowledgments

None.


Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1114/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1114/dss

Funding: This work was supported by the National Natural Science Foundation of China (grant No. 82171894, Principal Investigator: N.M.; and grant No. 82401517, Principal Investigator: W.F.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1114/coif). All authors report that this work was supported by the National Natural Science Foundation of China (grant No. 82171894, Principal Investigator: N.M.; and grant No. 82401517, Principal Investigator: W.F.). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by Ethics Committee of Beijing Tiantan Hospital (approval number: KY2021-075-02) and individual consent for this retrospective analysis was waived. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


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(English Language Editor: J. Gray)

Cite this article as: Li M, Fu W, Zhang K, Hou Z, Yu Y, Ma N. Risk factors and outcomes of patients with early spontaneous recanalization after acute middle cerebral artery occlusion. Quant Imaging Med Surg 2025;15(11):10459-10469. doi: 10.21037/qims-2025-1114

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