Predictors of favorable outcome after endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion in young patients

Abstract

Background

Mechanical thrombectomy (MT) became a standard of care for patients with acute ischemic stroke (AIS) with its efficacy demonstrated by meta-analysis and randomized studies. Although ischemic stroke is associated more with older patients, it may also have devastating neurological effects on young patients.

Purpose

To present our experience with stroke patients aged <50 years treated with endovascular means and to evaluate clinical and procedural factors associated with outcome and mortality.

Material and Methods

This study was conducted on 34 young stroke patients treated with MT. Clinical features including baseline results, radiological imaging, procedural details, and outcome results were documented and evaluated. Recanalization was assessed according to the TICI score. The clinical condition was evaluated after three months using mRS. Mortality rate was calculated.

Results

The rate of successful recanalization (TICI ≥2c) was 79% (27/34). Symptomatic intracranial hemorrhage (sICH) was observed in 5 (15%) patients. After 90 days, the mortality rate was 12%. Favorable clinical outcome (mRs 0–2) was regained in 65% of the patients whereas satisfactory clinical outcome was seen in 85%. Poor clinical outcome (mRs >2) was observed in 9 (23.7%) patients.

Conclusion

In conclusion, the results of this study demonstrate that MT for AIS in young patients is feasible and provides an excellent rate of arterial recanalization and high rate of favorable outcomes. Statistical analysis showed that shorter time from onset to arrival and reperfusion, successful recanalization and absence of hemorrhagic transformation are the predictors of favorable clinical outcome and overall survival rate.

Keywords

Ischemic stroke mechanical thrombectomy young adults long-term outcome predictors

Introduction

Mechanical thrombectomy (MT) has emerged as a standard of care for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) with its efficacy demonstrated by meta-analysis and randomized studies (1 –3). Although AIS is associated mainly with older patients, it may also have devastating neurological effects on young patients (4). However, several authors who tried to assess the impact of age on post-treatment outcomes concluded that patient's younger age is an independent prognostic factor for good clinical outcome after MT (5 –7). In their study, Nogueira et al. also showed that mortality rate was higher among older patients compared to younger patients (7). Similar results were observed in patients presenting with AIS treated with intravenous thrombolysis only (8,9). Chalouhi et al., who analyzed the data of 45 patients aged ≤55 years, concluded that endovascular treatment provides very high rate of successful recanalization and favorable outcome and should therefore be widely implemented in this age group (10). Nonetheless, data on the effects of endovascular management on ischemic stroke in a young population available in the current literature are lacking.

The aim of the present study was to present our experience with patients aged <50 years admitted with AIS due to LVO and treated with endovascular means.

Material and Methods

In this retrospective, single-center study we evaluated medical records of patients aged <50 years who underwent endovascular treatment for AIS between January 2016 and December 2020. This age group was defined as “young patients.” The definition of a young patient is difficult; however, the authors of the article “Redefining meaningful age groups in the context of disease,” who divided patients into 13 age groups, observed that risk factors characteristic for stroke patients are uncharacteristic for patients aged under 32–54 years (with a representative age of 47 years) (11).

The inclusion criteria were as follows: (i) AIS due to LVO confirmed by an on-table angiography (digital subtraction angiography [DSA]) and treated with MT; (ii) time from onset of symptoms to reperfusion within 6 h; (iii) National Institute of Health Stroke Scale (NIHSS) score ≥6 on admission; and (iv) reasonable cognitive and functional pre-stroke status (modified Rankin scale [mRs] <3).

Data including patients’ demographics, baseline NIHSS, laboratory results, co-morbidities, and medications were collected and analyzed. Cerebral baseline imaging including multi-slice computed tomography (non-contrast computed tomography [CT] and CT-angio) and/or magnetic resonance imaging (MRI; with diffusion-weighted imaging [DWI], time-of-flight [TOF], and fluid-attenuated inversion recovery [FLAIR]) was performed to confirm acute cerebral ischemia. In case of no contraindication, intravenous thrombolysis (rt-PA) (0.9 mg/kg, with 10% as a bolus) was administered according to the Guidelines of the Polish Neurological Society for the Management of Patients with Ischemic Stroke (12). This study was approved by the institutional review board (approval number KE-0254/285/2019). Informed consent was obtained from all participants in the study.

Endovascular procedure

All endovascular interventions were performed under a biplane angiography unit with 3D rotational angiography and patients under general anesthesia or conscious sedation. Once the occlusion was confirmed, the MT was processed either with aspiration catheter (ACE; Penumbra, Alameda, CA, USA), stent retriever (Solitaire; EV3, Irvine, CA, USA) or a combination of both (Solumbra technique). In case of internal carotid artery dissection or tandem occlusion, additional stenting was performed before MT. Successful recanalization was defined as mTICI 2c–3 (13). After the procedure, all patients were transferred to the intensive care stroke unit.

Follow-up

A non-contrast head CT scan was routinely obtained within 24 h after the intervention to diagnose hemorrhagic complications (ICH). In case of clinical deterioration of the patient or evidence of ICH on control scans, further scans were acquired every 48 h. ICH was classified as symptomatic according to the classification of the European-Australasian Acute Stroke Study (ECASS II) (14). The patient's neurological status was assessed using the NIHSS 24 h after MT and at discharge. In addition, all patients underwent extended cardiac (24-h Holter and echocardiography), neurological (transcranial Doppler ultrasound), and laboratory (protein C and S deficiency tests, lupus anticoagulant, and anti-cardiolipin antibodies) diagnostics. Procedure-related complications and adverse events occurring during hospitalization were noted. Clinical outcome was assessed based on the mRS score after three months determined either by direct contact with the patient or, in case of a patient's death, with their families. Favorable results were defined as mRS ≤2. The mortality rate was calculated.

Statistical analysis

All statistical analyses were conducted using the StatSoft Statistica 13.1 package. Data were presented as mean and range for continuous variables and as number and percentage for categorical variables. Differences between groups were examined using the Student’s t- test, Pearson's chi-square test, or Mann–Whitney test. P ≤ 0.05 was considered statistically significant.

Results

Demographic findings

In total, 34 patients (22 men [65%], 12 women [35%]; mean age = 41 ± 7.5 years; age range = 23–49 years) met the inclusion criteria for the study. The mean baseline NIHSS was 16 ± 5.9 (range = 6–34). Mean admission blood pressure was 152/87 mmHg and mean admission serum glucose was 117 mg/dL. Most common risk factors included: cardiovascular disease (previously known or diagnosed during hospitalization, 53%); smoking (47%); hypertension (29%); diabetes mellitus (15%); history of transient ischemic attach (TIA)/stroke (9%); and hormone replacement therapy (9%). Baseline medication included: antihypertensive drugs (26%); vitamin K antagonists (9%); and novel oral anticoagulants (NOACs; 6%). The mean time from symptom onset to arrival was 83 min (range = 30–240 min) and 110 min (range = 60–150 min) to administration of rt-PA. Intravenous thrombolysis was administered in 27 (79%) patients. Of the interventions, 24 (71%) were performed under general anesthesia and 10 (29%) under conscious sedation. Groin puncture occurred at 90–310 min (mean = 181 min) from the onset. Of the occlusions, 31 (91%) were occlusions of anterior circulation (ICA = 6, ICA + MCA = 2, MCA M1 = 17, and MCA M2 = 6). Three patients (9%) presented with occlusion of basilar artery. The mean time from groin puncture to recanalization was 57 min (range = 20–130 min). Demographic details are presented in Table 1.

Table 1.

Demographic aspects of the study population.

Patients (n = 34; 22 men [65%], 12 women [35%])
Demographic data
Age (years)	41 ± 7.5 (23–49)
NIHSS	16 ± 5.9 (6–34)
Blood pressure (mmHg)	152/87 ± 23/18
Blood glucose (mg/dL)	117 ± 39 (78–298)
Risk factors
Cardiovascular disease	18 (53)
Smoking	16 (47)
Hypertension	10 (29)
Diabetes mellitus	5 (15)
History of stroke/TIA	3 (9)
Hormone replacement therapy	3 (9)
Drugs on admission
Antihypertensive drugs	9 (26)
Vitamin K antagonists	3 (9)
NOACs	2 (6)
Times (min)
Onset to arrival	83 ± 43 (30–240)
Onset to groin	181 ± 59 (90–310)
Groin to reperfusion	57 ± 28 (20–130)
Occluded vessel
Basilar artery	3 (9)
ICA	Right – 2 (6)	Left – 4 (12)
ICA + MCA	Right – 1 (3)	Left – 1 (3)
MCA M1	Right – 14 (40)	Left – 3 (9)
MCA M2	Right – 3 (9)	Left – 3 (9)

Values are given as n (%) or mean ± SD (range).

ICA, internal carotid artery; MCA, middle cerebral artery; NIHSS, National Institute of Health Stroke Scale; NOAC, novel oral anticoagulant; TIA, transient ischemic attack.

Procedural and clinical outcome

Successful recanalization defined as TICI 2c or 3 was achieved in 27 (79%) patients. Partial recanalization (TICI 2a or 2b) was observed in 5 (15%) patients after the procedure. In 2 (6%) cases, no recanalization was achieved (TICI 0). Mechanical thrombectomy was performed using aspiration (56%), stent retriever (18%), and combined technique (26%). In 2 (6%) cases, ICA stenting was performed before MT: in one patient due to tandem occlusion and in another patient due to ICA dissection. No procedure-related complication occurred. In one patient (3%), minor vasospasm with no hemodynamical significance was observed (Fig. 1).

Fig. 1.

A 26-year-old patient with history of ischemic stroke four months before hospitalization and clinically known arrhythmia was admitted with symptoms of stroke in the right hemisphere (NIHSS 20). (a) Initial brain CT scan disclosed hyperdense M1 segment of the right MCA (arrow) and (b) occlusion of the vessel in CT angiography (arrow). (c, d) On-table angiography confirmed these findings. (e, f) Mechanical thrombectomy was successfully performed with Solumbra technique. Minor vasospasm with no hemodynamical significance was observed in the treated segment. CT, computed tomography; MCA, middle cerebral artery.

Symptomatic intracranial hemorrhage after the intervention was observed in 5 (15%) patients. From this group, one patient developed malignant middle cerebral artery infarction and required urgent neurosurgical treatment (Fig. 2).

Fig. 2.

A 38-year-old patient was admitted with symptoms of stroke in the right hemisphere (NIHSS 18) occurring after intense physical activity. (a) Baseline CT angiography disclosed occlusion of M1 segment of the right MCA (arrow), which was confirmed by (b) DSA examination. (c) Only partial recanalization was achieved. Clinical deterioration was observed. (d) Control brain CT scan showed established right MCA infarct with extensive oedema, midline shift and compression of lateral and third ventricles. CT, computed tomography; DSA, digital subtraction angiography; MCA, middle cerebral artery.

Mean NIHSS 24 h after the procedure was 8 (range = 2–24). Mean NIHSS at discharge was 4, which indicated minor neurological impairment. Intrahospital mortality rate was 12% (4/34 patients). On average, patients spent 14 days in the hospital (range = 3–42 days).

All patients had 90 days of clinical follow-up. The rate of favorable outcome (mRs score = 0–2) was 65% (22/34), and the rate of 90-day satisfactory outcome (mRs score = 0–3) was 85% (29/34). One patient (3%) had mRs 5. The final mortality rate was 12% (4/34 patients). Procedural and clinical outcomes are shown in Table 2.

Table 2.

Procedural and clinical outcome.

Patients (n = 34; 22 men [65%], 12 women [35%])
Procedural details
Successful recanalization (TICI 2c-3)	27 (79)
Partial recanalization (TICI 2b-2a)	5 (15)
Failed recanalization (TICI 0)	2 (6)
Thrombectomy technique
Aspiration	19 (56)
Stent retriever	6 (18)
Combined	9 (26)
Symptomatic intracranial hemorrhage	5 (15)
Clinical details
NIHSS 24 h after MT	8 ± 6 (2–24)
NIHSS at discharge	4 ± 4 (0–12)
Favorable outcome at 90 days (mRs 0–2)	22 (65)
Satisfactory outcome at 90-days (mRs 0–3)	29 (85)
Unfavorable outcome at 90-days (mRs >2)	5 (15)
Mortality rate at 90 days	4 (12)

Values are given as n (%) or mean ± SD (range).

MT, mechanical thrombectomy; NIHSS, National Institute of Health Stroke Scale.

Prognostic factors

Statistical analysis identified prognostic factors of favorable outcome (mRs >2) and survival at 90 days. History of diabetes mellitus was found to be a significant predictor of both unfavorable outcome and mortality (P = 0.02 and P = 0.034, respectively) and hypertension was associated with significantly higher risk of mortality (P = 0.033). In terms of time from onset, shorter time to arrival significantly decreased the mortality risk (P = 0.02) whereas shorter time to recanalization and shorter duration of procedure was associated with significantly higher rate of favorable outcome (P = 0.04 and P = 0.01, respectively). Successful recanalization and lower post-procedural NIHSS were found to be a strong predictor of both favorable outcome and survival of the patients. Finally, statistically significant interactions were found between occurrence of hemorrhagic transformation and unfavorable clinical outcome (P < 0.001) and increased mortality (P < 0.001). Results of the statistical analysis are presented in Tables 3 and 4.

Table 3.

Predictors of clinical outcome.

Outcome	All patients	mRS ≤ 2	mRS > 2	P
No. of patients (n)	34	22	12
Pre-procedural factors
NIHSS at arrival	16 ± 5.9	15 ± 7	18 ± 3	0.17^*
Cardiovascular disease	18 (53)	14 (64)	4 (33)	0.09^†
Diabetes mellitus	5 (15)	1 (5)	4 (33)	0.02 ^†
Administration of i.v. trombolysis	27 (79)	17 (77)	8 (83)	0.68^†
Procedural factors
Onset-recanalization time	235 ± 66	218 ± 52	267 ± 80	0.04 ^*
Procedure duration	57 ± 28	48 ± 19	73 ± 34	0.01 ^*
Successful recanalization	27 (79)	20 (91)	7 (58)	0.025 ^†
Post-procedural factors
Hemorrhagic transformation of stroke	5 (15)	0 (0)	5 (42)	<0.001 ^†
NIHSS at 24 h	8 ± 6	4.7 ± 2	14 ± 5	0.01 ^*

Values are given as n (%) or mean ± SD. Statistical significance is marked with bold text.

Student’s t-test.

†

Pearson's chi-square test.

mRS, modified Rankin Scale; NIHSS, National Institute of Health Stroke Scale.

Table 4.

Predictors of survival and mortality.

Mortality	All patients	Survivors	Non-survivors	P
No. of patients	34	30	4
Pre-procedural factors
NIHSS at arrival	16 ± 5.9	16 ± 6	17.5 ± 3	0.62^*
Hypertension	10 (29)	7 (23)	3 (75)	0.033 ^†
Diabetes mellitus	5 (15)	3 (10)	2 (50)	0.034 ^†
Administration of i.v. trombolysis	27 (79)	25 (83)	2 (50)	0.12^†
Procedural factors
Onset–Arrival time	83 ± 43	77 ± 28	128 ± 100	0.02 ^*
Procedure duration	57 ± 28	56 ± 27	65 ± 34	056^*
Successful recanalization	27 (79)	26 (87)	1 (25)	0.004 ^†
Post-procedural factors
Hemorrhagic transformation	5 (15)	1 (3)	4 (100)	<0.001 ^†
NIHSS at 24 h	8 ± 6	6.6 ± 4	18.5 ± 4	0.001 ^*

Values are given as n (%) or mean ± SD. Statistical significance is marked with bold text.

Student’s t-test.

†

Pearson's chi-square test.

NIHSS, National Institute of Health Stroke Scale.

Discussion

The aim of this study was to evaluate the outcome of endovascular treatment among patients aged <50 years presenting with AIS due to LVO and to find the most important factors influencing clinical outcome and mortality. Surprisingly, only a few retrospective studies on MT among young patients are available in the literature, most of which are small series with limited numbers of cases (10,15,16). The biggest group of young stroke patients is included in the HERMES trial (17). The authors analyzed the data of 158 patients aged <50 years treated either with MT with or without IVT or IVT alone and concluded that the interventional approach increases the chances of neurological recovery.

Radiographic outcomes after MT for AIS among young patients have been reported to be very good, with consistently high rates of recanalization (75% according to Mocco et al., 93% according to Zanaty et al., and 93% according to Chalouhi et al.) (10,15,16). We experienced complete recanalization in 79% of cases. The authors of the above-mentioned studies on young stroke patients highlighted the importance of achieving arterial recanalization. Indeed, successful recanalization predicted both favorable outcome (91% in mRs ≤2 vs. 58% in mRs >2; P = 0.025) and survival (87% in the survivor group vs. 25% in the non-survivor group; P = 0.004). The very high rate of unsuccessful recanalization among non-survivors (75%) shows how low the chances are of a favorable outcome without achieving vessel patency.

Our analysis included three patients with occlusion of the basilar artery. A recent multicenter registry showed that endovascular thrombectomy in posterior circulation stroke has similar effectiveness compared to anterior circulation stroke (18). All three patients in our study had a good clinical outcome (two had mRs score 0 and one had mRs score 1 at the 90-day follow-up).

Previous studies have reported relatively low rates of symptomatic ICH (sICH) in young patients (10,16). In our study, the observed rate of sICH was 15% (5/34 patients). Hemorrhagic transformation was a strong predictive factor for both unfavorable clinical outcome (0% in mRs ≤2 vs. 42% in mRs >2; P < 0.001) and increased mortality rate (3% in the survivor group vs. 100% in the non-survivor group; P < 0.001).

Favorable clinical outcomes three months after MT were seen in 65% of patients in our study compared with rates of 77%–87% for favorable outcomes reported in similar analyses (15,16). The 90-day overall mortality rate was 12% (4/34 patients). Apart from the previously mentioned factors influencing clinical outcome and final mortality, time from onset to arrival and reperfusion as well as duration of the procedure were found to be statistically important factors. On average, patients who survived arrived 51 min earlier than patients who died (77 vs. 128 min; P = 0.02). Shorter time from onset to recanalization and shorter time of endovascular procedure were found to predict favorable clinical outcome.

The present study has some limitations. First, the retrospective nature of the study and relatively small number of patients limit the validity of the data. Second, there is no control group treated with intravenous rt-PA alone. Although our study lacked a control group treated with rt-PA administration alone, a non-interventional approach is associated with extremely poor results; therefore, all patients eligible for endovascular treatment were referred for MT (19). Finally, a potential drawback could be a cutoff of 50 years, which was set as a definition of young age in AIS. Nonetheless, there is currently no standard definition for young stroke patients available in the literature.

In conclusion, the results of this study demonstrate that MT for AIS in young patients is feasible and provides an excellent rate of arterial recanalization and high rate of favorable outcomes, which support aggressive endovascular strategies in this age group. Furthermore, the statistical analysis showed that the most important predictors of favorable clinical outcome and overall survival rate (i.e. shorter time from onset to arrival and reperfusion, successful recanalization as well as absence of hemorrhagic transformation) are similar to those observed across the age groups. Nonetheless, further prospective investigations with larger numbers of patients are indicated.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship and/or publication of this article.

ORCID iD

Maciej Szmygin

References

Lambrinos

Schaink

Dhalla

, et al. Mechanical thrombectomy in acute ischemic stroke: a systematic review. Can J Neurol Sci 2016;43:455–460.

Goyal

Menon

van Zwam

, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723–1731.

Yang

Zhang

, et al. DIRECT-MT investigators. endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med 2020;382:1981–1993.

Furlan

Higashida

Wechsler

, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA Neurol 1999;282:2003–2011.

Sweid

Weinberg

, et al. Mechanical thrombectomy in acute ischemic stroke patients greater than 90 years of age: experience in 26 patients in a large tertiary care center and outcome comparison with younger patients. World Neurosurg 2020;133:e835–e841.

Raoult

Eugène

Ferré

, et al. Prognostic factors for outcomes after mechanical thrombectomy with solitaire stent. J Neuroradiol 2013;40:252–259.

Nogueira

Liebeskind

Sung

, et al. Predictors of good clinical outcomes, mortality, and successful revascularization in patients with acute ischemic stroke undergoing thrombectomy: pooled analysis of the mechanical embolus removal in cerebral ischemia (MERCI) and multi MERCI trials. Stroke 2009;40:3777–3783.

Engelter

Bonati

Lyrer

. Intravenous thrombolysis in stroke patients of > or = 80 versus < 80 years of age — a systematic review across cohort studies. Age Ageing 2006;35:572–580.

Toni

Ahmed

Anzini

, et al. Intravenous thrombolysis in young stroke patients: results from the SITS-ISTR. Neurology 2012;78:880–887.

10.

Chalouhi

Tjoumakaris

Starke

, et al. Endovascular stroke intervention in young patients with large vessel occlusions. Neurosurg Focus 2014;36:1–4.

11.

Geifman

Cohen

Rubin

. Redefining meaningful age groups in the context of disease. Age (Dordr) 2013;35:2357–2366.

12.

Błażejewska-Hyżorek

Czernuszenko

Członkowska

, et al. Ischemic stroke guidelines. Polski Przegląd Neurologiczny 2019;15:53–55.

13.

Dargazanli

Fahed

Blanc

, et al. ASTER trial investigators. Modified thrombolysis in cerebral infarction 2C/thrombolysis in cerebral infarction 3 reperfusion should be the aim of mechanical thrombectomy: insights from the ASTER trial (contact aspiration versus stent retriever for successful revascularization). Stroke 2018;49:1189–1196.

14.

Larrue

von Kummer R

Müller

, et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian acute stroke study (ECASS II). Stroke 2001;32:438–441.

15.

Mocco

Tawk

Jahromi

, et al. Endovascular intervention for acute thromboembolic stroke in young patients: an ideal population for aggressive intervention? J Neurosurg 2009;110:30–34.

16.

Zanaty

Chalouhi

Starke

, et al. Endovascular stroke intervention in the very young. Clin Neurol Neurosurg 2014;127:15–18.

17.

Goyal

Menon

van Zwam

, et al. HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723–1731.

18.

Weber

Minnerup

Nordmeyer

, et al. Thrombectomy in posterior circulation stroke: differences in procedures and outcome compared to anterior circulation stroke in the prospective multicentre REVASK registry. Eur J Neurol 2019;26:299–305.

19.

Broderick

Palesch

Demchuk

, et al. Interventional management of stroke (IMS) III investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013;368:893–903.