Acute therapeutic management of M1-middle cerebral artery occlusion with underlying intracranial atherosclerotic disease: is mechanical thrombectomy the right first-line choice?

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Martino Cavazza, Giuseppe Carità, Silvia Pizzuto, Andrea Bartolo, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7897991/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Acute occlusions of the anterior circulation with an underlying intracranial atheromatous disease (ICAD) represent a diagnostic and therapeutic challenge. The aim of this study was to compare the results of the endovascular treatment (EVT) ± intravenous thrombolysis (IVT) and the best medical treatment (BMT ± IVT) as first-line approach in a cohort of patients with certain diagnosis of M1-Middle Cerebral Artery (M1-MCA) occlusions and underlying ICAD. Methods Patients with M1-MCA and a certain diagnosis of underlying ICAD were included in this retrospective, monocentric analysis between 2018 and April 2023. Baseline, procedural and clinico-neuroradiological follow-up data were collected. EVT ± IVT and BMT ± IVT were the two study groups. An independent core lab assessed the imaging data. The primary outcome was the rate of functional independence at 3 months (mRS0-2); secondary outcomes included the extension of the ischemic lesion (∆baseline-24 hours volume), the early neurological deterioration (END), the rate of symptomatic intracranial haemorrhages (sICH). Results Thirty-four patients were included in the study (65,7 ± 16,5 y.o.; males: 52,8%), 23 were treated by EVT ± IVT and 11 with BMT ± IVT. Functional independence was less frequent in the EVT ± IVT group compared to the BMT ± IVT (26%vs81,8%, p = 0,003). The increase of ∆ volume, the rate of END and sICH were significantly lower in the BMT ± IVT group. Conclusions EVT ± IVT (only MT) was associated with worse clinical and neuroimaging outcomes compared to BMT ± IVT. Nevertheless, a beneficial effect of primary angioplasty ± stenting should be taken in account and future studies will be necessary to investigate this therapeutic option. Figures Figure 1 Figure 2 What is already known on this topic? Intracranial occlusion of the anterior circulation with underlying intracranial atheromatous disease (ICAD) are associated with controverse results in the literature. Mechanical thrombectomy seems to be associated with worse technical and clinical outcomes What this study adds - We provided clinical data about the medical management in this cohort of patients. The analysis focused on the distribution of the ischemic lesions could provide some insights about patients’ selection. How this study might affect research, practice or policy - Mechanical Thrombectomy might not be considered a proper first-choice approach for this subgroup of patients and a strict medical management could be more beneficial. However new dedicated devices and studies focused on primary angioplasty ±stenting could provide a new vision for the acute management of these patients. Introduction Acute middle cerebral artery (MCA) occlusions with underlying intracranial atherosclerotic disease (ICAD) represent a diagnostic and therapeutic dilemma.[1] From a diagnostic standpoint, even though there are some clinical and radiological clues that could strongly raise the suspicion of an underlying ICAD,[2] it is challenging to have a certain diagnosis before the endovascular treatment (EVT).[3] Mechanical Thrombectomy (MT) with intravenous thrombolysis (IVT) for eligible patients is the only approved endovascular therapy in acute large vessel occlusion (LVOs) of the anterior circulation, however in this specific subgroup of patients it may carry a high risk of reocclusions and distal embolization.[4] Furthermore, the clinical outcomes of EVT in these patients have a wide range of variability in the literature.[5,6] The purpose of this study was to compare the clinical outcomes at 3 months of patients with M1-MCA occlusion with underlying ICAD treated in our institution with EVT ± IVT versus patients treated with best medical therapy (BMT ± IVT). Methods Study population This is a monocentric, retrospective analysis of cohort of selected patients. We reviewed the clinical and neuroradiological data of 34 consecutive patients, admitted at our institution from January 2018 to April 2023, presenting with AIS secondary to an M1-MCA occlusion. All the data were collected through a national prospective database (ETIS registry, NCT:03776877). Patients with proximal and distal M1-MCA occlusions, including extension to the M2 segment and underlying ICAD, undergoing EVT ± IVT or BMT ± IVT were included in the study. The presence of ICAD was confirmed by at least one neurovascular imaging modality (CT-Angiography, CT-A; MR-Angiography, MR-A; or Digital Subtraction Angiography, DSA) in the interval between the admission and the discharge. Two subgroups were defined according to the therapeutic strategy: patients treated by EVT ± IVT and patients treated by BMT ± IVT. The local institutional review board approved this retrospective analysis. Bias minimisation In order to minimise a possible selection bias we performed an extensive retrospective analysis of all patients with M1-MCA occlusion treated by EVT ± IVT, during the study period, without a successful recanalization. Endovascular treatment failed to recanalize adequately the M1-MCA segment in 48 patients (TICI 0-2a). In 12 cases the failure was explained by technical difficulties (proximal access or distal microcatheterization), that limited the efficacy of mechanical thrombectomy and affected the number of the maneuvers; in 10 cases an intra-procedural complication occurred (clot fragmentation in 7 cases, dissection in 2 cases and 1 perforation), while in 11 cases a cardio-embolic source was identified after extensive etiologic research. Furthermore, in 8 cases the follow-up imaging showed the recanalization of the occluded artery without any sign of stenosis. In the remaining 7 cases no explanation was found for the failure of the endovascular treatment without any sign of underlying ICAD. Clinical and neuro-radiological data Baseline clinical features (NIHSS, vascular risk factors, type of onset) were evaluated by a certified stroke neurologist at admission. An imaging core lab, which was composed of two neuroradiologists (with 5 and 15 years of experience respectively) not involved in the procedures, reviewed the non-invasive exams and the angiograms; a third expert reviewer resolved eventual disagreements. Kappa interobserver agreement was calculated. All patients were screened either through MRI or Multimodal CT. The ASPECTS was assessed either on plain CT or DWI sequences and the pattern of distribution of the ischemic lesions (ILDP, ischemic lesion distribution pattern) was evaluated. ILDPs were classified as Deep, Junctional and Cortical. A “Deep" ILDP was defined when the ischemic lesion was exclusively detected in basal ganglia, “Junctional” when the ischemic lesion involved the watershed area between the vascular territories of the anterior cerebral artery and the MCA, while it was defined as “cortical" when cortical/subcortical areas were involved. In case only one of these locations was involved the ILDP was defined as single, whereas when more than one pattern was involved, we defined ILDP as mixed. The volumes of the ischemic lesions were manually evaluated using the SyngoVia (Siemens Healthineers, Forchheim, Germany) on DWI/plain CT at admission and at 24-48hours; the ∆ volume was assessed to determine the increase of the ischemic lesion. The arterial calcifications at the occlusion site were evaluated on plain CT or Cone beam CT (CBCT) in the angiosuite, when performed. The Susceptibility Vessel Sign (SVS)[7] and the overestimation ratio[8] were analysed. We used 3D-TOF MR-A and CT-A to detect the site of occlusion. ASPECTS and ECASS-III criteria were respectively used for the assessment of the ischemic extension and the eventual hemorrhagic transformation with symptomatic intracerebral hemorrhage (sICH) at 24-48hours. NIHSS was also recorded at 24h. Early neurological deterioration (END) was defined as an increase in the NIHSS score by ≥ 4 points between the baseline and 48-hours evaluations.[9] The patency of the occluded artery was assessed at 24 hours using MR/CT-A. Clinical outcome was assessed by stroke neurologists with the mRS during an outpatient visit or telephone interviews at 3 months. Functional independence was defined as mRS 0–2. Angiographic data and treatment The collateral circulation (ASITN grade) were assessed with DSA in patients undergoing MT (or left untreated after the initial angiogram) and with MRA/CTA in patients treated with BMT ± IVT. Excellent collateral circulation was defined as ASITN grade ≥ 3. We distinguished the endovascular treatment (EVT) in MT (when stent-retriever, direct aspiration and combined technique were used) and primary angioplasty ± stenting (PAS). All MT were performed by expert interventional neuroradiologists, with more than 10-years experience and a resident/fellow. The first-line technique for MT was chosen by the senior operator according to his/her personal judgment. The mFPE (mTICI ≥ 2b) and the final recanalization grade (mTICI score) were assessed on the DSA and all intra-procedural complications, including arterial perforation, arterial dissection, new territory embolization, subarachnoid hemorrhage and vasospasm were reviewed by the core lab. Successful recanalization was defined as final mTICI ≥ 2b. All time metrics were recorded. Patients not receiving EVT were treated either by IVT or BMT (best medical treatment), which included the hospitalisation in the Stroke Unit, a careful management of blood pressure (Mean blood pressure: 110 mmHg, systolic blood pressure: below 180 mmHg, 30° degrees Trendelenburg position when necessary) and continuous clinical monitoring. Endpoints and Outcome Measures The primary endpoint of the study was to assess the difference in terms of functional independence at 3 months, using the modified Rankin scale (mRS) between the two treatment subgroups. The secondary endpoints were: to compare, in the two different treatment subgroups, the increase in extension of the ischemic lesions, using the delta of the DWI volumes measured on the baseline MRI and the 24–48 hours follow-up; to assess the frequency of END, the rates of sICH and to investigate the prognostic role of the pattern of distribution of the ischemic lesions on clinical outcome at 3 months, using the dichotomous single versus mixed ILDP definition in the two different subgroups. Finally, we compared the rate of functional independence at 3 months in patients with patent intracranial arteries at 24-48h with those not recanalized. Statistical analysis The Fischer’s exact test (if cell frequency was < 5) were used to assess significant differences between the two groups and for the subgroup analysis. Continuous variables were reported as median values with interquartile ranges. Two-tailed Student’s T Test was used to assess the differences in median values between the two groups. A p < 0.05 was considered as a statistically significant result. No multivariate analysis was performed considering the limited number of patients. SPSS software was used for statistical analysis (SPSS software, IBM, version 24). In order to minimise the selection bias we adopted a strict selection of included patients. Indeed, only patients with a certain diagnosis of underlying ICAD were included. Results Overall results The clinical, radiological and procedural characteristics of the patients are summarised in Table 1 . Table 1 Baseline characteristics of the overall population and in treatment groups. Overall (n = 34) Treated with EVT (n = 23) Treated with IVT or BMT (n = 11) p value Mean Age ± SD 65,7 ± 16,5 62,7 ± 16,5 72 ± 16,1 0.06 Males, n(%) 18 (52,9) 12 (52,1) 6 (54,5) 1 Risk factors Hypertension, n(%) 21 (61,7) 12 (52,1) 9 (81,8) 0.13 Dyslipidemia, n(%) 14 (41,1) 10 (43,4) 4 (36,3) 0.7 Diabetes, n(%) 16 (47) 8 (34,7) 8 (72,7) 0.06 Smoking, n(%) 6 (17,6) 5 (21,7) 1 (9) 0.6 Atrial Fibrillation, n(%) 7 (20,5) 4 (17) 3 (27) 0.6 Baseline clinical data Baseline mRS > 2, n(%) 2 (5) 0 (0) 2 (18) 0.09 NIHSS at onset median, (IQR) 7,5 (5,25 − 14,5) 12 (5–15,2) 6 (5–12) 0.01 NIHSS at arrival median, (IQR) 8 (4,2–15) 12 (4–15,5) 5 (3–11) 0.003 Imaging modality CT, n(%) 4 (11) 1 (4) 3 (27) 0.08 MRI, n(%) 30 (88,2) 22 (95,6) 8 (72,7) Baseline imaging data Baseline ASPECTS, median (IQR) 8 (8–9) 8 (8–9) 9 (8–9) 0.05 Proximal M1-MCA Occlusion, n(%) 21 (61,8) 14 (60,8) 7 (63,6) 1 Right-sided occlusion (Right), n(%) 21 (61,7) 14 (60,8) 8 (72,7) 0.7 SVS+ 12/30 (40) 10 (45,4%) 2/8 (25%) 0,4 Overestimation Ratio, median (IQR) 1,6 (1,4 − 1,9) 1,6 (1,4 − 1,9) 1,6 (1,2 − 1,6) 0.68 ASITN grade ≥ 3, n(%) 22 (75,8) 16 (69,5) 6 (100) a 0.4 ILDP - Single 11 (32,3) 7 (30,5) 4 (36,3) 0.7 ILDP - Mixed 23 (67,6) 16 (69,5) 7 (63,6) Procedural variables IVT, n(%) 10 (29,4) 7 (30,4) 3 (27,2) 1 First Endovascular Technique, n(%) 13 (56): CA 10 (43,4): CoT mFPE (mTICI ≥ 2b), n(%) 1 (4,3) Number of passes, median (IQR) 3 (2–5,5) Final mTICI ≥ 2b-3, n(%) 7 (30,4) Procedure time (minutes), median (IQR) 90 (60–142,5) Complications, n(%) 0 (0) Adjunctive techniques, n(%) 3 (13) intracranial stenting a data available only for 6 patients EVT = Endovascular Treatment; IVT = Intravenous thrombolysis, BMT = Best medical treatment, SD = Standard deviation; mRS = modified Rankin scale; IQR = interquartile range; NIHSS = National Institutes of Health Stroke Scale; ASPECTS = Alberta stroke programme early CT score; MCA = middle cerebral artery; SVS = susceptibility vessel sign; ASITN/SIR = American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology; ILDP = ischemic lesion distribution pattern; IVT = intravenous thrombolysis; mTICI = modified treatment in cerebral infarction; mFPE = modified first pass effect; CA = Contact aspiration; CoT = Combined treatment. A total of 34 patients (mean age: 65,7 ± 16,5 y.o.; males: 52,8%) with M1-MCA occlusion and underlying ICAD were included in the study ( Supplemental Fig. 1 ). Hypertension (61,7%), dyslipidemia (41,1%) and diabetes (47%) were the most frequent risk factors, whereas atrial fibrillation was documented in 20,5%. Basal mRS2 was observed in 2 patients (5%) both in the BMT ± IVT group. Median NIHSS at onset and at the arrival in the angiosuite were respectively 7,5 (5,25 − 14,5) and 8 (4,2–15) and these were higher in the EVT ± IVT group [at onset: 12(5–15,2) vs 6 (5–12), p = 0,01; at arrival: 12(4–15,5) vs 6(5–12), p = 0,003]. Mean baseline ASPECTS was 8 (8–9) with no statistical difference between the two different treatment subgroups. The M1-MCA occlusion was proximal in 61,8% and affected the right side in 61,7% of the cases. A plain CT or a pretreatment CBCT was performed only in 4 patients (11,7%). SVS was positive in 40% of patients imaged with MRI. Excellent Collaterals (ASITN grade ≥ 3) were present in 75,8%. ILDP was classified as single in 32,3% and mixed in 67,6%. IVT was administered in 10 patients (29,4%) without any difference between the two groups. MT was performed in 23 patients (7 receiving also IVT) whereas 11 were treated with BMT (3 receiving also IVT). In the EVT group mFPE was achieved only in 1 patient (4,3%) and successful recanalization in 7 cases (30,4%). In 3 patients (13%), intracranial stenting was used as an adjunctive treatment after MT. Endpoints and outcomes Primary and secondary outcomes are summarised in Table 2 . Table 2 Clinical and neuroradiological outcomes in the two treatment groups. Outcomes Overall (n = 34) Treated with EVT (n = 23) Treated with IVT or BMT (n = 11) P value 3m-mRS ≤ 2, n (%) 15 (44,1) 6 (26) 9 (81,8) 0,003 Delta DWI lesion increase, mean (IQR) 29,8 (2–40) 39,6 (3–42,5) 8,1 (2–34) 0,029 24-48h ASPECTS, median (IQR) 7 (5–8) 6 (5–8) 8 (6–8) < 0.001 END, n(%) 12 (35,2) 12 (52,1) 0 (0) 0,002 24h NIHSS, median (IQR) 14 (4,2–21) 20 (4,7–21) 4 (4–17) < 0,001 Hemorrhagic transformation b, n (%) 8 (34,2) 7 (30,4) 1 (10) c 0,38 sICH, n (%) 3 (9) 3 (13) 0 (0) 0,53 Patency of the occluded artery at 24-48h 4/29 d (13,7) 2/21 (9,5) 2/8 (25) 0,3 Single-ILDP 3m-mRS ≤ 2, n(%) 8/11 (72,7) 4/7 (57,1) 4/4 (100) 0,03 Mixed-ILDP 3m-mRS ≤ 2, n(%) 7/23 (31,8) 2/16 (13,3) 6/7 (85,7) Mortality, n(%) 6 (17,6) 5 (21,7) 1 (9) 0,6 b includes also subarachnoid hemorrhage; c data available for 10/11 patients; d data available for 29/34 patients EVT = Endovascular Treatment; IVT = Intravenous thrombolysis, BMT = Best medical treatment, SD = Standard deviation; IQR = intequartile range; mRS = modified Rankin scale; ASPECTS = Alberta stroke programme early CT score; END = Early Neurological Deterioration; NIHSS = National Institutes of Health Stroke Scale; sICH = symptomatic intracranial hemorrhage; ILDP = ischemic lesion distribution pattern ; 3m-mRS = 3 months modified Rankin scale. Functional independence at 3 months was observed in 15 patients (44,1%), that was higher in the BMT ± IVT group (81,8% vs 26% p = 0,003). The ∆ volume was 29,8 ml with a lower increase in the BMT ± IVT group [8,1 ml (2–34) vs 39,6 ml (3–42,5), p = 0,029]. Similarly, the median 24–48 hours ASPECTS was lower in the EVT ± IVT group [6(5–8) vs 8(6–8), p < 0,001]. END was observed in 12 patients (35,2%) all treated by EVT ± IVT (p = 0,002). Furthermore, the median 24 hours NIHSS was higher in the EVT ± IVT group [20(4,7–21) vs 4(4–17), p < 0,001]. sICH was documented in 3 patients (9%), all in the EVT ± IVT group. The distribution of the functional independence at 3 months resulted higher in single ILDP compared to the mixed type (72,7% vs 31,8%, p = 0,03). We observed better results in patients of the BMT ± IVT group with both single and mixed ILDP. At 24 hours the occluded artery was patent in 4/29 patients (13,7%) and all of these reached functional independence at 3 months, whereas 5 patients did not undergo MR/CT-A follow-up. Interestingly, these patients were equally distributed in the two treatment groups and in both patients of the EVT ± IVT group an intracranial stent was released. The overall mortality was 17,6% and it was higher in the EVT ± IVT group (21,7% vs 9%). Discussion In our cohort we found significantly worse clinical outcomes in the subgroup of patients treated by EVT ± IVT in terms of functional independence at 3 months. Furthermore, the increase of ∆ volume, the rate of END and sICH were significantly lower in the BMT ± IVT group. Endovascular treatment of M1-MCA occlusions and underlying ICAD in the literature Although our results tend to support the hypothesis that BMT ± IVT would be associated with better clinical outcomes than EVT ± IVT, we aimed at comparing our findings with those previously described. However, in the literature, most of the papers report the results of EVT in Asian populations,[6,10–12] where the incidence of ICAD is higher. Furthermore, the definition of EVT is heterogenous, since it includes the MT techniques and the intracranial angioplasty ± stenting.[13–15] Identification of underlying ICAD in M1-MCA occlusions The pre-procedural identification of an underlying ICAD in patients with LVOs remains challenging. Indeed, most of the published studies rely on angiographic findings observed after partial recanalizations with MT to diagnose underlying ICAD and the criteria tend to be similar across the literature (tendency of reocclusion/residual stenosis at the occlusion site > 70% not reacting after injection of vasoactive substances or of any degree but with flow impairment).[4,6,16,17] However, these criteria could represent a concrete selection bias, particularly for those patients without recanalization after MT (patients with challenging clots[18] and/or underlying ICAD), which could be excluded. In our study, in order to minimize this bias, an extensive search of proof of the stenosis was performed using the clinical and neuroradiological data gathered at the admission, in the angiosuite and in the follow-up imaging associated with a comprehensive analysis of non recanalized patients. M1-MCA occlusions and underlying ICAD: The clot removal strategy as first-line choice? The choice of the first-line strategy of treatment of M1-MCA occlusions with underlying ICAD remains a debated issue. Indeed, the difficulty to detect an underlying ICAD lead the operators to use a “standard” technical strategy of MT for M1-MCA occlusions. However, the results reported in several studies may raise up some questions about the effectiveness of the MT techniques and the need for adjunctive/rescue treatment. Jia et al.[16] found no significant difference in the rate of functional outcome in embolic and ICAD occlusion of the anterior circulation treated by EVT, with underlying ICAD patients having 3-months mRS0-2 in 63.8%. In this retrospective analysis of the interventional arm of the EAST trial, a Chinese non-randomised trial evaluating MT with SR alone in anterior circulation LVOs, the core lab allocated 47/140 patients to the ICAD subgroup. The core lab also defined the need for rescue treatment (angioplasty ± stenting) in 30/47 patients according to specific criteria (residual arterial stenosis > 70% after MT performed with SR alone, any degree of arterial stenosis with blood flow impairment and evidence of reocclusion) only after the end of the trial. The Authors concluded that the use of rescue treatment of ICAD occlusions of the anterior circulation (not specifically limited to M1-MCA occlusions) was associated with similar favorable clinical outcomes compared to embolic occlusions. Similarly, in a retrospective analysis of patients with M1-MCA occlusions after matching two subgroups of embolic vs ICAD-related occlusions treated with EVT, Yang et al.[6] reported more favorable clinical outcomes (77,8% vs 71,1%) in patients with underlying ICAD occlusions. Interestingly, in this subgroup, the number of MT manoeuvres was lower than in the embolic subgroup. The Authors explained this finding with a tendency to avoid repeated MT maneuvers in ICAD-related occlusions since these could determine the irritation of the plaque with consequent platelet aggregation and reocclusion. The study concluded that favorable outcomes can be achieved through rescue treatment manoeuvres. Furthermore, Kasab et al.[17] reported no differences after rescue treatment (stenting ± angioplasty) in terms of functional independence at 3 months between ICAD and embolic etiology occlusions of the anterior and posterior circulation initially treated with MT (11% of posterior circulation occlusions), in a matched analysis of the STAR registry. Moreover, other studies reported poor clinical outcomes associated with choosing MT as first-line strategy for ICAD-related occlusions. Indeed, Dobrocky et al.[19] reported the results of a cohort of 10 patients with M1-MCA occlusion with underlying ICAD treated with EVT compared to patients without ICAD. The Authors defined the ICAD-related occlusion using mostly the same aforementioned criteria and reported 0% of mRS0-2 in patients with underlying ICAD despite the use of rescue treatment. Lee et al.[4] performed a retrospective analysis of 99 patients with anterior circulation occlusions and underlying ICAD (75% M1-MCA) compared to 421 patients with embolic source in the Korean registry ASIAN KR. In the ICAD subgroup all patients were treated with MT techniques and only in 20 patients angioplasty ± stenting was used as rescue treatment. Although Authors did not find significant differences in terms of mRS0-2 between the two subgroups, a multivariate analysis showed that ICAD-related occlusions were associated with a worse clinical outcome as well as longer procedure times. Moreover, Kass-Hout et al.[20] in a monocentric, retrospective analysis of 38 patients with LVO and underlying ICAD (M1-MCA: 47,4%) treated by MT had lower rates of functional independence (7,9%) compared to non-ICAD occlusions. No adjunctive treatment was performed in this cohort because of the lack of evidence for acute intracranial angioplasty or stenting. M1-MCA occlusions and underlying ICAD: The strategy of plaque stabilisation as first-line choice? The aforementioned studies tend to reflect the message that MT in underlying ICAD is associated with controversial results on clinical outcome. Some retrospective Asian studies used PAS as a first-line strategy. Chen et al.[13] reported a 60% rate of mRS0-2 in a cohort of 68 patients with LVO and underlying ICAD (M1-MCA: 40%) treated with PAS. Furthermore, Yang et al.[14] compared the clinical outcomes of patients with LVO and underlying ICAD treated by MT as first-line strategy with those treated with PAS (about 50% were M1-MCA occlusions) in the ACTUAL multicenter registry. Functional independence at 3-months was reached in 69% of patients in the PAS group versus 47% in the first-line MT group. In addition, Zhang et al.[15] compared different treatment strategies (MT alone, first-line MT with adjunctive treatments and PAS) in LVO with underlying ICAD in 396 patients included in a retrospective Chinese registry. The Authors reported a rate of functional independence respectively in 45%, 50,8% and 59% of patients, further highlighting the promising results of PAS. The authors concluded that first-line MT with a bailout angioplasty ± stenting is a reasonable option for ICAD-LVO, and PAS is an effective option when underlying ICAD is strongly suspected before EVT. However, it must be acknowledged that dedicated devices for the treatment of ICAD are currently very limited and this could represent a potential field for technical innovation. M1-MCA occlusions and underlying ICAD: observations derived from daily practice in treated and untreated patients The results that we observed in the EVT ± IVT group (where all patients were treated with first-line MT), although the small sample, are not in favour of a first-line strategy based on clot removal. Indeed, in our subgroup of patients undergoing EVT ± IVT a successful recanalization was achieved only in 7 patients (30,4%) and functional independence in 6 patients (26%). Indeed, MT in this specific subgroup of patients is frequently associated with a high number of passes[4,21] and the detrimental effect of MT devices on the mechanical and biochemical destabilisation of the plaque has already been described (Fig. 1 ).[6] Furthermore, in this study we observed the patency of the M1-MCA at 24-48h only in 4 patients (2 belonging to the EVT ± IVT and 2 in the BMT ± IVT group), all reaching functional independence at 3-months. Notably, in the 2 patients undergoing MT we had to release a stent in order to maintain the patency of the occluded artery. However, we have to acknowledge that patients treated by EVT ± IVT had more severe stroke compared to the BMT ± IVT group and that this difference could have been a determining factor in the decision to treat. Moreover, in our cohort the 11 patients treated with BMT ± IVT had higher rates of functional independence than those treated by MT (Fig. 2 ). We could not find, to the best of our knowledge, any other studies in the literature reporting data about this subgroup of patients for comparison. Our conservative approach in patients with a high suspicion of underlying ICAD was based on the physiopathological assumption that ICAD-related strokes can be associated with multiple, concomitant etiologies. Indeed, although a “thrombus-on-plaque” phenomenon occurs, the clinical manifestations could be secondary to a hemodynamic impairment. However, the former should be considered an acute event of a chronic disease. The chronic nature of ICAD would allow the development of an excellent pial collateral circulation (75,8% in our cohort, Table 1 ) and lead the microcirculation to specifically modulate the cerebral autoregulation during several years in order to adapt to this hemodynamic demand.[22–24] This could probably explain the low NIHSS at onset and arrival at the hospital, as well as the high baseline ASPECTS compared to patients with embolic etiology.[3,4] The analysis of the ischemic lesions: from the onset to the final infarct Likewise, we also found that single-ILDP was associated with significantly higher rates of functional independence than mixed-ILDP, independently on the treatment ( single-ILDP: 72,7% vs mixed-ILDP: 31,8%, p = 0,03; Table 2 ). Although we could not compare these findings with other studies in the literature, we referred to the classification proposed by Bang,[25] describing different DWI-patterns of lesion in ICAD-related MCA strokes depending on the physiopathological mechanism (branch occlusive disease in basal ganglia lesion, artery-to-artery emboli in cortical scattered lesions, watershed lesion in hemodynamic impairment and territorial lesions in very compromised hemodynamic impairment). We interpreted this as a possible explanation of our results: multiple, concomitant pathophysiology mechanism are associated with worse clinical outcomes. Additionally, in our cohort, we observed a significantly lower infarct growth in patients treated by BMT ± IVT (8,1 ml vs 39,6 ml, p = 0,029; Table 2 ) despite only in 25% of them we observed a patent artery at 24h (Table 2 ). This could reflect the effectiveness of a solid collateral circulation.[26] Therefore, the choice to focus on the hemodynamic management could also be considered as a reasonable approach, when the patients are strictly followed in the Stroke Units. However, there is currently no consensus about the acute management of patients with anterior circulation LVOs with low NIHSS, independently on the etiology. ENDOLOW (NCT:04167527) and MOSTE[27] are ongoing randomized controlled trials that will hopefully shed some light on this topic. Secondary Endpoints In our cohort the rate of END was significantly higher in the EVT ± IVT group (52,1% vs 0%, p = 0,002; Table 2 ). Wu et al.[11] reported a lower rate of END (16,8%) in a multicenter prospective cohort study including patients with anterior circulation LVOs and underlying ICAD treated by first-line MT. However, only 17,7% of these received more than 3 MT passes, which supports the hypothesis that multiple MT manoeuvres may not be effective in this specific subgroup of patients.[6] Furthermore, in our cohort, almost in half of the patients treated by MT (11/23, 47,8%, unpublished data) more than 3 passes were performed. Concerning the rates of sICH in patients treated with EVT ± IVT our results (13%) were in line with those published by Wu et al.[11] (9,7%) and Dobrocky et al.[19] (10%) but higher than those reported by Jia et al.[16] (4,3%) and Lee et al.(7,1%).[5] Limitations This study has several limitations due to its retrospective, monocentric nature, the small sample and the lack of a control group. The diagnosis of underlying ICAD remains challenging, although some clinico-neuroradiological red flags may be helpful, such as the fluctuating symptoms, lower NIHSS then embolic occlusions, the absence of atrial fibrillation, hypertension and diabetes, the presence of other ICAD, good collaterals, a small core and a large penumbra.[1–3] Although we used strict selection criteria and bias minimisation it could be possible that we excluded some patients. Conclusions We observed higher rates of functional independence in patients with ICAD-related M1-MCA occlusions treated by BMT ± IVT compared to the EVT ± IVT. MT in this subgroup of patients is associated with a high number of passes, END and an increased volume of the ischemic lesion. A careful hemodynamic management could provide favourable clinical results. Nevertheless, a beneficial effect of primary angioplasty ± stenting should be taken in account and future studies will be necessary to investigate this therapeutic option. Declarations Competing interests None Ethics approval statement The local Institutional Review Board approved the data collection and analysis for this study. Funding None Data availability statement Data are available upon reasonable request to the corresponding author. Contributorship Statement AC, MC, GC, SP participated on the study design and conception, JG, AB, NM, AS, LS, DWL, AW participated on data collection, AC, FDM, GR, BL, OC, AS, DWL, AW made critical revisions and supervision on drafting, MC was in charge for manuscript drafting. All the authors had access to and agreed on the final version of the manuscript. References Lee JS, Lee SJ, Hong JM, Alverne FJAM, Lima FO, Nogueira RG (2022) Endovascular Treatment of Large Vessel Occlusion Strokes Due to Intracranial Atherosclerotic Disease. J Stroke 24:3–20 Li H, Liu P, Liu P, Hua W, Yang W, Zhang Y, Zhang L, Xing P, Li Z, Zhang Y et al (2020) Current knowledge of large vascular occlusion due to intracranial atherosclerosis: focusing on early diagnosis. Chin Neurosurg J 6:32 Liao G, Zhang Z, Tung TH, He Y, Hu L, Zhang X, Chen H, Huang J, Du W, Li C et al (2022) A simple score to predict atherosclerotic or embolic intracranial large-vessel occlusion stroke before endovascular treatment. J Neurosurg. :1–8 Lee JS, Lee SJ, Yoo JS, Hong JH, Kim CH, Kim YW, Kang DH, Kim YS, Hong JM, Choi JW et al (2018) Prognosis of Acute Intracranial Atherosclerosis-Related Occlusion after Endovascular Treatment. J Stroke 20:394–403 Tsang ACO, Orru E, Klostranec JM, Yang IH, Lau KK, Tsang FCP, Lui WM, Pereira VM, Krings T (2019) Thrombectomy Outcomes of Intracranial Atherosclerosis-Related Occlusions. Stroke 50:1460–1466 Yang W, Zhang Y, Li Z, Zhang L, Li H, Hua W, Zhang H, Feng M, Shen H, Xing P et al (2021) Differences in Safety and Efficacy of Endovascular Treatment for Acute Ischemic Stroke: A Propensity Score Analysis of Intracranial Atherosclerosis-Related Occlusion versus Embolism. Clin Neuroradiol 31:457–464 Bourcier R, Volpi S, Guyomarch B, Daumas-Duport B, Lintia-Gaultier A, Papagiannaki C, Serfaty JM, Desal H (2015) Susceptibility Vessel Sign on MRI Predicts Favorable Clinical Outcome in Patients with Anterior Circulation Acute Stroke Treated with Mechanical Thrombectomy. AJNR Am J Neuroradiol 36:2346–2353 Zhang R, Zhou Y, Liu C, Zhang M, Yan S, Liebeskind DS, Lou M (2017) Overestimation of Susceptibility Vessel Sign: A Predictive Marker of Stroke Cause. Stroke 48:1993–1996 Siegler JE, Martin-Schild S (2011) Early Neurological Deterioration (END) after stroke: the END depends on the definition. Int J Stroke 6:211–212 Baek JH, Kim BM, Kim DJ, Heo JH, Nam HS, Yoo J (2016) Stenting as a Rescue Treatment After Failure of Mechanical Thrombectomy for Anterior Circulation Large Artery Occlusion. Stroke 47:2360–2363 Wu C, Chang W, Wu D, Wen C, Zhang J, Xu R, Liu X, Lian Y, Xie N, Li C et al (2019) Angioplasty and/or stenting after thrombectomy in patients with underlying intracranial atherosclerotic stenosis. Neuroradiology 61:1073–1081 Yan Y, Du L, He X, Huang Q, Pan Y, Xin T (2022) Endovascular treatment of acute M1 occlusions due to underlying intracranial atherosclerotic severe stenosis. Chin Neurosurg J 8:22 Chen W, Gong J, Song R, Liu J, Wang M, Zhang T, Sun H, Zhao Z, Liu Y, Zhu Q, Wang X (2021) Efficacy and safety of direct balloon angioplasty in the treatment of large atherosclerotic stroke. Clin Neurol Neurosurg 211:107035 Yang D, Lin M, Wang S, Wang H, Hao Y, Zi W, Lv P, Zheng D, Xiao G, Xu G et al (2018) Primary angioplasty and stenting may be superior to thrombectomy for acute atherosclerotic large-artery occlusion. Interv Neuroradiol 24:412–420 Zhang J, Jia B, Pan Y, Yu Z, Deng Y, Mo D, Ma N, Gao F, Miao Z (2022) A comparison between different endovascular treatment strategies for acute large vessel occlusion due to intracranial artery atherosclerosis: data from ANGEL-ACT Registry. Neuroradiology 64:1627–1638 Jia B, Feng L, Liebeskind DS, Huo X, Gao F, Ma N, Mo D, Liao X, Wang C, Zhao X et al (2018) Mechanical thrombectomy and rescue therapy for intracranial large artery occlusion with underlying atherosclerosis. J Neurointerv Surg 10:746–750 Al Kasab S, Almallouhi E, Alawieh A, Wolfe S, Fargen KM, Arthur AS, Goyal N, Dumont T, Kan P, Kim JT et al (2021) Outcomes of Rescue Endovascular Treatment of Emergent Large Vessel Occlusion in Patients With Underlying Intracranial Atherosclerosis: Insights From STAR. J Am Heart Assoc 10:e020195 Ospel JM, Mirza M, Clarençon F, Siddiqui A, Doyle K, Consoli A, Mokin M, Ullberg T, Zaidat O, Bourcier R et al (2023) What is a Challenging Clot? A DELPHI Consensus Statement from the CLOTS 7.0 Summit. Clin Neuroradiol . 10.1007/s00062-023-01301-2 . Epub ahead of print. PMID: 37284876 Dobrocky T, Kaesmacher J, Bellwald S, Piechowiak E, Mosimann PJ, Zibold F, Jung S, Arnold M, Fischer U, Gralla J et al (2019) Stent-Retriever Thrombectomy and Rescue Treatment of M1 Occlusions Due to Underlying Intracranial Atherosclerotic Stenosis: Cohort Analysis and Review of the Literature. Cardiovasc Intervent Radiol 42:863–872 Kass-Hout T, Morsi RZ, Thind S, Karrison T, Lee H, Nahab F, Gupta R, Carrión-Penagos J, Awad IA, Coleman E et al (2023) Underlying intracranial atherosclerotic disease is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy. J Stroke Cerebrovasc Dis 32:107227 Epub 2023 Jul 10. PMID: 37437522 Kang DH, Yoon W (2019) Current Opinion on Endovascular Therapy for Emergent Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Stenosis. Korean J Radiol 20:739–748 Leng X, Leung TW (2023) Collateral Flow in Intracranial Atherosclerotic Disease. Transl Stroke Res 14:38–52 Maguida G, Shuaib A (2023) Collateral Circulation in Ischemic Stroke: An Updated Review. J Stroke 25:179–198 Guo ZN, Sun X, Liu J, Sun H, Zhao Y, Ma H, Xu B, Wang Z, Li C, Yan X et al (2018) The Impact of Variational Primary Collaterals on Cerebral Autoregulation. Front Physiol 9:759 Bang OY (2014) Intracranial atherosclerosis: current understanding and perspectives. J Stroke 16:27–35 Rocha M, Jovin TG (2017) Fast Versus Slow Progressors of Infarct Growth in Large Vessel Occlusion Stroke: Clinical and Research Implications. Stroke 48:2621–2627 Arquizan C, Lapergue B, Gory B, Labreuche J, Henon H, Albucher JF, Sibon I, Turc G, Richard S, Nouri N et al (2023) Evaluation of acute mechanical revascularization in minor stroke (NIHSS score ⩽ 5) and large vessel occlusion: The MOSTE multicenter, randomized, clinical trial protocol. Int J Stroke. :17474930231186039. doi: 10.1177/17474930231186039. Epub ahead of print. PMID: 37350574. Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":1342025,"visible":true,"origin":"","legend":"\u003cp\u003eA patient in his 60s, presented at a Primary Stroke Center with a fluctuatingaphasia, right hemianopsia and right central facial paralysis\u003cstrong\u003e \u003c/strong\u003e(NIHSS at onset:10). Baseline MRI did not show any visible ischemic lesion on the DWI sequence (A-B; ASPECTS 10, ischemic volume=0 ml) and a proximal left M1-MCA occlusion.\u003cstrong\u003e \u003c/strong\u003eIVT was not administered due to a piastrinopenia. At the arrival at the Angiosuite a partial clinical improvement was observed (NIHSS at arrival: 4). Digital Subtraction Angiography was performed confirming the proximal left M1 occlusion and an excellent collateral circulation (C-D, AP view early and late arterial phase). Endovascular treatment was performed using a combined technique (E, AP view showing the stent-retriever positioned bridging the occlusion) and after 6 passes only a partial recanalization was achieved (F, AP view, final angiogram, mTICI 2a). 24h-CT scan, axial plane, showing an extensive ischemic lesion of the entire superficial left MCA territory without involvement of the basal ganglia (G-H; 24h-ASPECTS=4; ischemic volume=175 ml). NIHSS at 24h was 20, and 3-months mRS was 5.\u003c/p\u003e","description":"","filename":"Fig1TIFF1200vf.png","url":"https://assets-eu.researchsquare.com/files/rs-7897991/v1/56f9bb8d4c887f44596cb623.png"},{"id":95064203,"identity":"5570b998-f58b-4846-bef3-886e7a4323eb","added_by":"auto","created_at":"2025-11-04 01:21:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":452820,"visible":true,"origin":"","legend":"\u003cp\u003eA patient in his 60s was admitted with dysarthria (NIHSS at onset 2) with a fluctuating trend (NIHSS 0 at arrival at our Comprehensive Stroke Center with fluctuation tup to NIHSS4). Baseline MRI was performed, showing small puntiform ischemic lesions in the posterior portion of the left lentiform nucleus (A) and watershed ischemic lesions (B) on the axial DWI sequence (ASPECTS 9, volume: 8 ml). The 3D-TOF (C) showed the left, distal, M1-MCA occlusion (white asterisk) and the Time-resolved angiography With Interleaved Stochastic Trajectories (TWIST, D) sequence demonstrated an extended retrograde, pial collateral circulation up to the MCA bifurcation (white arrowheads). Intravenous thrombolysis was administered and best medical treatment was adopted. Mechanical thrombectomy was not performed. MRI performed at 24-hours showed the stability of the lesions with an associated asymptomatic hyperacute reperfusion marker (HARM) sign in the left fronto-temporal sulci. 24h-NIHSS was 1. CT (G) and CT-Angiography (H) performed 5 days later showed a the recanalization of the M1-MCA the underlying intracranial atheromatous disease (ICAD, white arrowhead) without any associated calcification. 3-months mRS was 0.\u003c/p\u003e","description":"","filename":"Fig2vf1200DPI.png","url":"https://assets-eu.researchsquare.com/files/rs-7897991/v1/ea703f56b0d5539daab5c5e5.png"},{"id":95229786,"identity":"5451760b-9a56-455e-b1d7-545fc46ea6c7","added_by":"auto","created_at":"2025-11-05 16:36:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2986305,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7897991/v1/ef6b18b2-1ecc-47bf-9e12-91ce38170047.pdf"},{"id":95064201,"identity":"eee4549d-f94e-4e93-9cc6-5d6c281a7991","added_by":"auto","created_at":"2025-11-04 01:21:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":59756,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterialFlowchartV1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7897991/v1/83da74831eda673658501b9a.pdf"},{"id":95064208,"identity":"ca5efacf-def6-4cfa-8cca-3d72284ad26f","added_by":"auto","created_at":"2025-11-04 01:21:18","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":126985,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEchecklistcohortUNDERM1V2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7897991/v1/f5c8d7a8c6c061030df383bf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute therapeutic management of M1-middle cerebral artery occlusion with underlying intracranial atherosclerotic disease: is mechanical thrombectomy the right first-line choice?","fulltext":[{"header":"What is already known on this topic? ","content":"\u003cp\u003e\u003cem\u003eIntracranial occlusion of the anterior circulation with underlying intracranial atheromatous disease (ICAD) are associated with controverse results in the literature. Mechanical thrombectomy seems to be associated with worse technical and clinical outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat this study adds\u0026nbsp;\u003c/strong\u003e-\u003cem\u003e\u0026nbsp;We provided clinical data about the medical management in this cohort of patients. The analysis focused on the distribution of the ischemic lesions could provide some insights about patients’ selection.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHow this study might affect research, practice or policy\u003c/strong\u003e -\u003cem\u003e\u0026nbsp;Mechanical Thrombectomy might not be considered a proper first-choice approach for this subgroup of patients and a strict medical management could be more beneficial. However new dedicated devices and studies focused on primary angioplasty\u003c/em\u003e\u003cem\u003e±stenting\u003c/em\u003e\u003cem\u003e\u0026nbsp;could provide a new vision for the acute management of these patients.\u003c/em\u003e\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eAcute middle cerebral artery (MCA) occlusions with underlying intracranial atherosclerotic disease (ICAD) represent a diagnostic and therapeutic dilemma.[1] From a diagnostic standpoint, even though there are some clinical and radiological clues that could strongly raise the suspicion of an underlying ICAD,[2] it is challenging to have a certain diagnosis before the endovascular treatment (EVT).[3] Mechanical Thrombectomy (MT) with intravenous thrombolysis (IVT) for eligible patients is the only approved endovascular therapy in acute large vessel occlusion (LVOs) of the anterior circulation, however in this specific subgroup of patients it may carry a high risk of reocclusions and distal embolization.[4] Furthermore, the clinical outcomes of EVT in these patients have a wide range of variability in the literature.[5,6] The purpose of this study was to compare the clinical outcomes at 3 months of patients with M1-MCA occlusion with underlying ICAD treated in our institution with EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT versus patients treated with best medical therapy (BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eThis is a monocentric, retrospective analysis of cohort of selected patients. We reviewed the clinical and neuroradiological data of 34 consecutive patients, admitted at our institution from January 2018 to April 2023, presenting with AIS secondary to an M1-MCA occlusion. All the data were collected through a national prospective database (ETIS registry, NCT:03776877). Patients with proximal and distal M1-MCA occlusions, including extension to the M2 segment and underlying ICAD, undergoing EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT or BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT were included in the study. The presence of ICAD was confirmed by at least one neurovascular imaging modality (CT-Angiography, CT-A; MR-Angiography, MR-A; or Digital Subtraction Angiography, DSA) in the interval between the admission and the discharge. Two subgroups were defined according to the therapeutic strategy: patients treated by EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT and patients treated by BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT. The local institutional review board approved this retrospective analysis.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBias minimisation\u003c/h3\u003e\n\u003cp\u003eIn order to minimise a possible selection bias we performed an extensive retrospective analysis of all patients with M1-MCA occlusion treated by EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT, during the study period, without a successful recanalization. Endovascular treatment failed to recanalize adequately the M1-MCA segment in 48 patients (TICI 0-2a). In 12 cases the failure was explained by technical difficulties (proximal access or distal microcatheterization), that limited the efficacy of mechanical thrombectomy and affected the number of the maneuvers; in 10 cases an intra-procedural complication occurred (clot fragmentation in 7 cases, dissection in 2 cases and 1 perforation), while in 11 cases a cardio-embolic source was identified after extensive etiologic research. Furthermore, in 8 cases the follow-up imaging showed the recanalization of the occluded artery without any sign of stenosis. In the remaining 7 cases no explanation was found for the failure of the endovascular treatment without any sign of underlying ICAD.\u003c/p\u003e\n\u003ch3\u003eClinical and neuro-radiological data\u003c/h3\u003e\n\u003cp\u003eBaseline clinical features (NIHSS, vascular risk factors, type of onset) were evaluated by a certified stroke neurologist at admission. An imaging core lab, which was composed of two neuroradiologists (with 5 and 15 years of experience respectively) not involved in the procedures, reviewed the non-invasive exams and the angiograms; a third expert reviewer resolved eventual disagreements. Kappa interobserver agreement was calculated. All patients were screened either through MRI or Multimodal CT. The ASPECTS was assessed either on plain CT or DWI sequences and the pattern of distribution of the ischemic lesions (ILDP, ischemic lesion distribution pattern) was evaluated. ILDPs were classified as Deep, Junctional and Cortical. A \u0026ldquo;Deep\" ILDP was defined when the ischemic lesion was exclusively detected in basal ganglia, \u0026ldquo;Junctional\u0026rdquo; when the ischemic lesion involved the watershed area between the vascular territories of the anterior cerebral artery and the MCA, while it was defined as \u0026ldquo;cortical\" when cortical/subcortical areas were involved. In case only one of these locations was involved the ILDP was defined as single, whereas when more than one pattern was involved, we defined ILDP as mixed. The volumes of the ischemic lesions were manually evaluated using the SyngoVia (Siemens Healthineers, Forchheim, Germany) on DWI/plain CT at admission and at 24-48hours; the ∆ volume was assessed to determine the increase of the ischemic lesion. The arterial calcifications at the occlusion site were evaluated on plain CT or Cone beam CT (CBCT) in the angiosuite, when performed. The Susceptibility Vessel Sign (SVS)[7] and the overestimation ratio[8] were analysed. We used 3D-TOF MR-A and CT-A to detect the site of occlusion. ASPECTS and ECASS-III criteria were respectively used for the assessment of the ischemic extension and the eventual hemorrhagic transformation with symptomatic intracerebral hemorrhage (sICH) at 24-48hours. NIHSS was also recorded at 24h. Early neurological deterioration (END) was defined as an increase in the NIHSS score by \u0026ge;\u0026thinsp;4 points between the baseline and 48-hours evaluations.[9] The patency of the occluded artery was assessed at 24 hours using MR/CT-A. Clinical outcome was assessed by stroke neurologists with the mRS during an outpatient visit or telephone interviews at 3 months. Functional independence was defined as mRS 0\u0026ndash;2.\u003c/p\u003e\n\u003ch3\u003eAngiographic data and treatment\u003c/h3\u003e\n\u003cp\u003eThe collateral circulation (ASITN grade) were assessed with DSA in patients undergoing MT (or left untreated after the initial angiogram) and with MRA/CTA in patients treated with BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT. Excellent collateral circulation was defined as ASITN grade\u0026thinsp;\u0026ge;\u0026thinsp;3. We distinguished the endovascular treatment (EVT) in MT (when stent-retriever, direct aspiration and combined technique were used) and primary angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting (PAS). All MT were performed by expert interventional neuroradiologists, with more than 10-years experience and a resident/fellow. The first-line technique for MT was chosen by the senior operator according to his/her personal judgment. The mFPE (mTICI\u0026thinsp;\u0026ge;\u0026thinsp;2b) and the final recanalization grade (mTICI score) were assessed on the DSA and all intra-procedural complications, including arterial perforation, arterial dissection, new territory embolization, subarachnoid hemorrhage and vasospasm were reviewed by the core lab. Successful recanalization was defined as final mTICI\u0026thinsp;\u0026ge;\u0026thinsp;2b. All time metrics were recorded. Patients not receiving EVT were treated either by IVT or BMT (best medical treatment), which included the hospitalisation in the Stroke Unit, a careful management of blood pressure (Mean blood pressure: 110 mmHg, systolic blood pressure: below 180 mmHg, 30\u0026deg; degrees Trendelenburg position when necessary) and continuous clinical monitoring.\u003c/p\u003e\n\u003ch3\u003eEndpoints and Outcome Measures\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint of the study was to assess the difference in terms of functional independence at 3 months, using the modified Rankin scale (mRS) between the two treatment subgroups. The secondary endpoints were: to compare, in the two different treatment subgroups, the increase in extension of the ischemic lesions, using the delta of the DWI volumes measured on the baseline MRI and the 24\u0026ndash;48 hours follow-up; to assess the frequency of END, the rates of sICH and to investigate the prognostic role of the pattern of distribution of the ischemic lesions on clinical outcome at 3 months, using the dichotomous single versus mixed ILDP definition in the two different subgroups. Finally, we compared the rate of functional independence at 3 months in patients with patent intracranial arteries at 24-48h with those not recanalized.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe Fischer\u0026rsquo;s exact test (if cell frequency was \u0026lt;\u0026thinsp;5) were used to assess significant differences between the two groups and for the subgroup analysis. Continuous variables were reported as median values with interquartile ranges. Two-tailed Student\u0026rsquo;s T Test was used to assess the differences in median values between the two groups. A p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as a statistically significant result. No multivariate analysis was performed considering the limited number of patients. SPSS software was used for statistical analysis (SPSS software, IBM, version 24).\u003c/p\u003e\u003cp\u003eIn order to minimise the selection bias we adopted a strict selection of included patients. Indeed, only patients with a certain diagnosis of underlying ICAD were included.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eOverall results\u003c/h2\u003e\u003cp\u003eThe clinical, radiological and procedural characteristics of the patients are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics of the overall population and in treatment groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTreated with EVT (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTreated with IVT or BMT (n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean Age\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65,7\u0026thinsp;\u0026plusmn;\u0026thinsp;16,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62,7\u0026thinsp;\u0026plusmn;\u0026thinsp;16,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;16,1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMales, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (52,9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (52,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (54,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRisk factors\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (61,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (52,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (81,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (41,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (43,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (36,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (34,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (72,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (17,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (21,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAtrial Fibrillation, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (20,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline clinical data\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline mRS\u0026thinsp;\u0026gt;\u0026thinsp;2, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNIHSS at onset\u003c/p\u003e\u003cp\u003emedian, (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7,5 (5,25\u0026thinsp;\u0026minus;\u0026thinsp;14,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (5\u0026ndash;15,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (5\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNIHSS at arrival\u003c/p\u003e\u003cp\u003emedian, (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (4,2\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (4\u0026ndash;15,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (3\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eImaging modality\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCT, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMRI, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (88,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (95,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (72,7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline imaging data\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline ASPECTS,\u003c/p\u003e\u003cp\u003emedian (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (8\u0026ndash;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (8\u0026ndash;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (8\u0026ndash;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProximal M1-MCA Occlusion, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (61,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (60,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (63,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRight-sided occlusion (Right), n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (61,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (60,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (72,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSVS+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/30 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (45,4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2/8 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverestimation Ratio,\u003c/p\u003e\u003cp\u003emedian (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,6 (1,4\u0026thinsp;\u0026minus;\u0026thinsp;1,9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,6 (1,4\u0026thinsp;\u0026minus;\u0026thinsp;1,9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,6 (1,2\u0026thinsp;\u0026minus;\u0026thinsp;1,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASITN grade\u0026thinsp;\u0026ge;\u0026thinsp;3, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (75,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (69,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (100)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eILDP - Single\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (32,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (30,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (36,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eILDP - Mixed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (67,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (69,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (63,6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProcedural variables\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVT, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (29,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (30,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (27,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst\u003c/p\u003e\u003cp\u003eEndovascular\u003c/p\u003e\u003cp\u003eTechnique, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (56): CA\u003c/p\u003e\u003cp\u003e10 (43,4): CoT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emFPE (mTICI\u0026thinsp;\u0026ge;\u0026thinsp;2b), n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (4,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of passes,\u003c/p\u003e\u003cp\u003emedian (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2\u0026ndash;5,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFinal mTICI\u0026thinsp;\u0026ge;\u0026thinsp;2b-3, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (30,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProcedure time (minutes),\u003c/p\u003e\u003cp\u003emedian (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90 (60\u0026ndash;142,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplications, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdjunctive techniques, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (13) intracranial stenting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e data available only for 6 patients\u003c/p\u003e\u003cp\u003eEVT\u0026thinsp;=\u0026thinsp;Endovascular Treatment; IVT\u0026thinsp;=\u0026thinsp;Intravenous thrombolysis, BMT\u0026thinsp;=\u0026thinsp;Best medical treatment, SD\u0026thinsp;=\u0026thinsp;Standard deviation; mRS\u0026thinsp;=\u0026thinsp;modified Rankin scale; IQR\u0026thinsp;=\u0026thinsp;interquartile range; NIHSS\u0026thinsp;=\u0026thinsp;National Institutes of Health Stroke Scale; ASPECTS\u0026thinsp;=\u0026thinsp;Alberta stroke programme early CT score; MCA\u0026thinsp;=\u0026thinsp;middle cerebral artery; SVS\u0026thinsp;=\u0026thinsp;susceptibility vessel sign; ASITN/SIR\u0026thinsp;=\u0026thinsp;American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology; ILDP\u0026thinsp;=\u0026thinsp;ischemic lesion distribution pattern; IVT\u0026thinsp;=\u0026thinsp;intravenous thrombolysis; mTICI\u0026thinsp;=\u0026thinsp;modified treatment in cerebral infarction; mFPE\u0026thinsp;=\u0026thinsp;modified first pass effect; CA\u0026thinsp;=\u0026thinsp;Contact aspiration; CoT\u0026thinsp;=\u0026thinsp;Combined treatment.\u003c/p\u003e\u003cp\u003eA total of 34 patients (mean age: 65,7\u0026thinsp;\u0026plusmn;\u0026thinsp;16,5 y.o.; males: 52,8%) with M1-MCA occlusion and underlying ICAD were included in the study (\u003cb\u003eSupplemental Fig.\u0026nbsp;1\u003c/b\u003e). Hypertension (61,7%), dyslipidemia (41,1%) and diabetes (47%) were the most frequent risk factors, whereas atrial fibrillation was documented in 20,5%. Basal mRS2 was observed in 2 patients (5%) both in the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group. Median NIHSS at onset and at the arrival in the angiosuite were respectively 7,5 (5,25\u0026thinsp;\u0026minus;\u0026thinsp;14,5) and 8 (4,2\u0026ndash;15) and these were higher in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group [at onset: 12(5\u0026ndash;15,2) vs 6 (5\u0026ndash;12), p\u0026thinsp;=\u0026thinsp;0,01; at arrival: 12(4\u0026ndash;15,5) vs 6(5\u0026ndash;12), p\u0026thinsp;=\u0026thinsp;0,003]. Mean baseline ASPECTS was 8 (8\u0026ndash;9) with no statistical difference between the two different treatment subgroups. The M1-MCA occlusion was proximal in 61,8% and affected the right side in 61,7% of the cases. A plain CT or a pretreatment CBCT was performed only in 4 patients (11,7%). SVS was positive in 40% of patients imaged with MRI. Excellent Collaterals (ASITN grade\u0026thinsp;\u0026ge;\u0026thinsp;3) were present in 75,8%. ILDP was classified as single in 32,3% and mixed in 67,6%. IVT was administered in 10 patients (29,4%) without any difference between the two groups. MT was performed in 23 patients (7 receiving also IVT) whereas 11 were treated with BMT (3 receiving also IVT). In the EVT group mFPE was achieved only in 1 patient (4,3%) and successful recanalization in 7 cases (30,4%). In 3 patients (13%), intracranial stenting was used as an adjunctive treatment after MT.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eEndpoints and outcomes\u003c/h2\u003e\u003cp\u003ePrimary and secondary outcomes are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical and neuroradiological outcomes in the two treatment groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTreated with EVT (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTreated with IVT or BMT (n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3m-mRS\u0026thinsp;\u0026le;\u0026thinsp;2, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (44,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (81,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta DWI lesion increase, mean (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29,8 (2\u0026ndash;40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39,6 (3\u0026ndash;42,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8,1 (2\u0026ndash;34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24-48h ASPECTS, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (5\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (5\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (6\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEND, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (35,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (52,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h NIHSS, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (4,2\u0026ndash;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (4,7\u0026ndash;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (4\u0026ndash;17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0,001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhagic transformation\u003csup\u003eb,\u003c/sup\u003e n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (34,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (30,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (10)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esICH, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatency of the occluded artery at 24-48h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4/29\u003csup\u003ed\u003c/sup\u003e (13,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2/21 (9,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2/8 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSingle-ILDP 3m-mRS\u0026thinsp;\u0026le;\u0026thinsp;2, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8/11 (72,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4/7 (57,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4/4 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0,03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMixed-ILDP 3m-mRS\u0026thinsp;\u0026le;\u0026thinsp;2, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7/23 (31,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2/16 (13,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6/7 (85,7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMortality, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (17,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (21,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e includes also subarachnoid hemorrhage; \u003csup\u003ec\u003c/sup\u003edata available for 10/11 patients; \u003csup\u003ed\u003c/sup\u003edata available for 29/34 patients\u003c/p\u003e\u003cp\u003eEVT\u0026thinsp;=\u0026thinsp;Endovascular Treatment; IVT\u0026thinsp;=\u0026thinsp;Intravenous thrombolysis, BMT\u0026thinsp;=\u0026thinsp;Best medical treatment, SD\u0026thinsp;=\u0026thinsp;Standard deviation; IQR\u0026thinsp;=\u0026thinsp;intequartile range; mRS\u0026thinsp;=\u0026thinsp;modified Rankin scale; ASPECTS\u0026thinsp;=\u0026thinsp;Alberta stroke programme early CT score; END\u0026thinsp;=\u0026thinsp;Early Neurological Deterioration; NIHSS\u0026thinsp;=\u0026thinsp;National Institutes of Health Stroke Scale; sICH\u0026thinsp;=\u0026thinsp;symptomatic intracranial hemorrhage; ILDP\u0026thinsp;=\u0026thinsp;ischemic lesion distribution pattern ; 3m-mRS\u0026thinsp;=\u0026thinsp;3 months modified Rankin scale.\u003c/p\u003e\u003cp\u003eFunctional independence at 3 months was observed in 15 patients (44,1%), that was higher in the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group (81,8% vs 26% p\u0026thinsp;=\u0026thinsp;0,003). The ∆ volume was 29,8 ml with a lower increase in the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group [8,1 ml (2\u0026ndash;34) vs 39,6 ml (3\u0026ndash;42,5), p\u0026thinsp;=\u0026thinsp;0,029]. Similarly, the median 24\u0026ndash;48 hours ASPECTS was lower in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group [6(5\u0026ndash;8) vs 8(6\u0026ndash;8), p\u0026thinsp;\u0026lt;\u0026thinsp;0,001]. END was observed in 12 patients (35,2%) all treated by EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT (p\u0026thinsp;=\u0026thinsp;0,002). Furthermore, the median 24 hours NIHSS was higher in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group [20(4,7\u0026ndash;21) vs 4(4\u0026ndash;17), p\u0026thinsp;\u0026lt;\u0026thinsp;0,001]. sICH was documented in 3 patients (9%), all in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group. The distribution of the functional independence at 3 months resulted higher in single ILDP compared to the mixed type (72,7% vs 31,8%, p\u0026thinsp;=\u0026thinsp;0,03). We observed better results in patients of the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group with both single and mixed ILDP. At 24 hours the occluded artery was patent in 4/29 patients (13,7%) and all of these reached functional independence at 3 months, whereas 5 patients did not undergo MR/CT-A follow-up. Interestingly, these patients were equally distributed in the two treatment groups and in both patients of the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group an intracranial stent was released. The overall mortality was 17,6% and it was higher in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group (21,7% vs 9%).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our cohort we found significantly worse clinical outcomes in the subgroup of patients treated by EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT in terms of functional independence at 3 months. Furthermore, the increase of ∆ volume, the rate of END and sICH were significantly lower in the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group.\u003c/p\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eEndovascular treatment of M1-MCA occlusions and underlying ICAD in the literature\u003c/h2\u003e\u003cp\u003eAlthough our results tend to support the hypothesis that BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT would be associated with better clinical outcomes than EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT, we aimed at comparing our findings with those previously described. However, in the literature, most of the papers report the results of EVT in Asian populations,[6,10\u0026ndash;12] where the incidence of ICAD is higher. Furthermore, the definition of EVT is heterogenous, since it includes the MT techniques and the intracranial angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting.[13\u0026ndash;15]\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eIdentification of underlying ICAD in M1-MCA occlusions\u003c/h2\u003e\u003cp\u003eThe pre-procedural identification of an underlying ICAD in patients with LVOs remains challenging. Indeed, most of the published studies rely on angiographic findings observed after partial recanalizations with MT to diagnose underlying ICAD and the criteria tend to be similar across the literature (tendency of reocclusion/residual stenosis at the occlusion site\u0026thinsp;\u0026gt;\u0026thinsp;70% not reacting after injection of vasoactive substances or of any degree but with flow impairment).[4,6,16,17] However, these criteria could represent a concrete selection bias, particularly for those patients without recanalization after MT (patients with challenging clots[18] and/or underlying ICAD), which could be excluded. In our study, in order to minimize this bias, an extensive search of proof of the stenosis was performed using the clinical and neuroradiological data gathered at the admission, in the angiosuite and in the follow-up imaging associated with a comprehensive analysis of non recanalized patients.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eM1-MCA occlusions and underlying ICAD: The clot removal strategy as first-line choice?\u003c/h2\u003e\u003cp\u003eThe choice of the first-line strategy of treatment of M1-MCA occlusions with underlying ICAD remains a debated issue. Indeed, the difficulty to detect an underlying ICAD lead the operators to use a \u0026ldquo;standard\u0026rdquo; technical strategy of MT for M1-MCA occlusions. However, the results reported in several studies may raise up some questions about the effectiveness of the MT techniques and the need for adjunctive/rescue treatment.\u003c/p\u003e\u003cp\u003eJia et al.[16] found no significant difference in the rate of functional outcome in embolic and ICAD occlusion of the anterior circulation treated by EVT, with underlying ICAD patients having 3-months mRS0-2 in 63.8%. In this retrospective analysis of the interventional arm of the EAST trial, a Chinese non-randomised trial evaluating MT with SR alone in anterior circulation LVOs, the core lab allocated 47/140 patients to the ICAD subgroup. The core lab also defined the need for rescue treatment (angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting) in 30/47 patients according to specific criteria (residual arterial stenosis\u0026thinsp;\u0026gt;\u0026thinsp;70% after MT performed with SR alone, any degree of arterial stenosis with blood flow impairment and evidence of reocclusion) only after the end of the trial. The Authors concluded that the use of rescue treatment of ICAD occlusions of the anterior circulation (not specifically limited to M1-MCA occlusions) was associated with similar favorable clinical outcomes compared to embolic occlusions. Similarly, in a retrospective analysis of patients with M1-MCA occlusions after matching two subgroups of embolic vs ICAD-related occlusions treated with EVT, Yang et al.[6] reported more favorable clinical outcomes (77,8% vs 71,1%) in patients with underlying ICAD occlusions. Interestingly, in this subgroup, the number of MT manoeuvres was lower than in the embolic subgroup. The Authors explained this finding with a tendency to avoid repeated MT maneuvers in ICAD-related occlusions since these could determine the irritation of the plaque with consequent platelet aggregation and reocclusion. The study concluded that favorable outcomes can be achieved through rescue treatment manoeuvres. Furthermore, Kasab et al.[17] reported no differences after rescue treatment (stenting\u0026thinsp;\u0026plusmn;\u0026thinsp;angioplasty) in terms of functional independence at 3 months between ICAD and embolic etiology occlusions of the anterior and posterior circulation initially treated with MT (11% of posterior circulation occlusions), in a matched analysis of the STAR registry. Moreover, other studies reported poor clinical outcomes associated with choosing MT as first-line strategy for ICAD-related occlusions. Indeed, Dobrocky et al.[19] reported the results of a cohort of 10 patients with M1-MCA occlusion with underlying ICAD treated with EVT compared to patients without ICAD. The Authors defined the ICAD-related occlusion using mostly the same aforementioned criteria and reported 0% of mRS0-2 in patients with underlying ICAD despite the use of rescue treatment. Lee et al.[4] performed a retrospective analysis of 99 patients with anterior circulation occlusions and underlying ICAD (75% M1-MCA) compared to 421 patients with embolic source in the Korean registry ASIAN KR. In the ICAD subgroup all patients were treated with MT techniques and only in 20 patients angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting was used as rescue treatment. Although Authors did not find significant differences in terms of mRS0-2 between the two subgroups, a multivariate analysis showed that ICAD-related occlusions were associated with a worse clinical outcome as well as longer procedure times. Moreover, Kass-Hout et al.[20] in a monocentric, retrospective analysis of 38 patients with LVO and underlying ICAD (M1-MCA: 47,4%) treated by MT had lower rates of functional independence (7,9%) compared to non-ICAD occlusions. No adjunctive treatment was performed in this cohort because of the lack of evidence for acute intracranial angioplasty or stenting.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eM1-MCA occlusions and underlying ICAD: The strategy of plaque stabilisation as first-line choice?\u003c/h2\u003e\u003cp\u003eThe aforementioned studies tend to reflect the message that MT in underlying ICAD is associated with controversial results on clinical outcome. Some retrospective Asian studies used PAS as a first-line strategy. Chen et al.[13] reported a 60% rate of mRS0-2 in a cohort of 68 patients with LVO and underlying ICAD (M1-MCA: 40%) treated with PAS. Furthermore, Yang et al.[14] compared the clinical outcomes of patients with LVO and underlying ICAD treated by MT as first-line strategy with those treated with PAS (about 50% were M1-MCA occlusions) in the ACTUAL multicenter registry. Functional independence at 3-months was reached in 69% of patients in the PAS group versus 47% in the first-line MT group. In addition, Zhang et al.[15] compared different treatment strategies (MT alone, first-line MT with adjunctive treatments and PAS) in LVO with underlying ICAD in 396 patients included in a retrospective Chinese registry. The Authors reported a rate of functional independence respectively in 45%, 50,8% and 59% of patients, further highlighting the promising results of PAS. The authors concluded that first-line MT with a bailout angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting is a reasonable option for ICAD-LVO, and PAS is an effective option when underlying ICAD is strongly suspected before EVT. However, it must be acknowledged that dedicated devices for the treatment of ICAD are currently very limited and this could represent a potential field for technical innovation.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eM1-MCA occlusions and underlying ICAD: observations derived from daily practice in treated and untreated patients\u003c/h2\u003e\u003cp\u003eThe results that we observed in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group (where all patients were treated with first-line MT), although the small sample, are not in favour of a first-line strategy based on clot removal. Indeed, in our subgroup of patients undergoing EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT a successful recanalization was achieved only in 7 patients (30,4%) and functional independence in 6 patients (26%). Indeed, MT in this specific subgroup of patients is frequently associated with a high number of passes[4,21] and the detrimental effect of MT devices on the mechanical and biochemical destabilisation of the plaque has already been described (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).[6] Furthermore, in this study we observed the patency of the M1-MCA at 24-48h only in 4 patients (2 belonging to the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT and 2 in the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group), all reaching functional independence at 3-months. Notably, in the 2 patients undergoing MT we had to release a stent in order to maintain the patency of the occluded artery. However, we have to acknowledge that patients treated by EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT had more severe stroke compared to the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group and that this difference could have been a determining factor in the decision to treat.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMoreover, in our cohort the 11 patients treated with BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT had higher rates of functional independence than those treated by MT (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). We could not find, to the best of our knowledge, any other studies in the literature reporting data about this subgroup of patients for comparison. Our conservative approach in patients with a high suspicion of underlying ICAD was based on the physiopathological assumption that ICAD-related strokes can be associated with multiple, concomitant etiologies. Indeed, although a \u0026ldquo;thrombus-on-plaque\u0026rdquo; phenomenon occurs, the clinical manifestations could be secondary to a hemodynamic impairment. However, the former should be considered an acute event of a chronic disease. The chronic nature of ICAD would allow the development of an excellent pial collateral circulation (75,8% in our cohort, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and lead the microcirculation to specifically modulate the cerebral autoregulation during several years in order to adapt to this hemodynamic demand.[22\u0026ndash;24] This could probably explain the low NIHSS at onset and arrival at the hospital, as well as the high baseline ASPECTS compared to patients with embolic etiology.[3,4]\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eThe analysis of the ischemic lesions: from the onset to the final infarct\u003c/h2\u003e\u003cp\u003eLikewise, we also found that single-ILDP was associated with significantly higher rates of functional independence than mixed-ILDP, independently on the treatment \u003cb\u003e(\u003c/b\u003esingle-ILDP: 72,7% vs mixed-ILDP: 31,8%, p\u0026thinsp;=\u0026thinsp;0,03; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Although we could not compare these findings with other studies in the literature, we referred to the classification proposed by Bang,[25] describing different DWI-patterns of lesion in ICAD-related MCA strokes depending on the physiopathological mechanism (branch occlusive disease in basal ganglia lesion, artery-to-artery emboli in cortical scattered lesions, watershed lesion in hemodynamic impairment and territorial lesions in very compromised hemodynamic impairment). We interpreted this as a possible explanation of our results: multiple, concomitant pathophysiology mechanism are associated with worse clinical outcomes. Additionally, in our cohort, we observed a significantly lower infarct growth in patients treated by BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT (8,1 ml vs 39,6 ml, p\u0026thinsp;=\u0026thinsp;0,029; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) despite only in 25% of them we observed a patent artery at 24h (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This could reflect the effectiveness of a solid collateral circulation.[26] Therefore, the choice to focus on the hemodynamic management could also be considered as a reasonable approach, when the patients are strictly followed in the Stroke Units. However, there is currently no consensus about the acute management of patients with anterior circulation LVOs with low NIHSS, independently on the etiology. ENDOLOW (NCT:04167527) and MOSTE[27] are ongoing randomized controlled trials that will hopefully shed some light on this topic.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eSecondary Endpoints\u003c/h2\u003e\u003cp\u003eIn our cohort the rate of END was significantly higher in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group (52,1% vs 0%, p\u0026thinsp;=\u0026thinsp;0,002; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Wu et al.[11] reported a lower rate of END (16,8%) in a multicenter prospective cohort study including patients with anterior circulation LVOs and underlying ICAD treated by first-line MT. However, only 17,7% of these received more than 3 MT passes, which supports the hypothesis that multiple MT manoeuvres may not be effective in this specific subgroup of patients.[6] Furthermore, in our cohort, almost in half of the patients treated by MT (11/23, 47,8%, unpublished data) more than 3 passes were performed. Concerning the rates of sICH in patients treated with EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT our results (13%) were in line with those published by Wu et al.[11] (9,7%) and Dobrocky et al.[19] (10%) but higher than those reported by Jia et al.[16] (4,3%) and Lee et al.(7,1%).[5]\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThis study has several limitations due to its retrospective, monocentric nature, the small sample and the lack of a control group. The diagnosis of underlying ICAD remains challenging, although some clinico-neuroradiological red flags may be helpful, such as the fluctuating symptoms, lower NIHSS then embolic occlusions, the absence of atrial fibrillation, hypertension and diabetes, the presence of other ICAD, good collaterals, a small core and a large penumbra.[1\u0026ndash;3] Although we used strict selection criteria and bias minimisation it could be possible that we excluded some patients.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe observed higher rates of functional independence in patients with ICAD-related M1-MCA occlusions treated by BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT compared to the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT. MT in this subgroup of patients is associated with a high number of passes, END and an increased volume of the ischemic lesion. A careful hemodynamic management could provide favourable clinical results. Nevertheless, a beneficial effect of primary angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting should be taken in account and future studies will be necessary to investigate this therapeutic option.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe local Institutional Review Board approved the data collection and analysis for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributorship Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAC, MC, GC, SP participated on the study design and conception, JG, AB, NM, AS, LS, DWL, AW participated on data collection, AC, FDM, GR, BL, OC, AS, DWL, AW made critical revisions and supervision on drafting, MC was in charge for manuscript drafting. All the authors had access to and agreed on the final version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee JS, Lee SJ, Hong JM, Alverne FJAM, Lima FO, Nogueira RG (2022) Endovascular Treatment of Large Vessel Occlusion Strokes Due to Intracranial Atherosclerotic Disease. J Stroke 24:3\u0026ndash;20\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi H, Liu P, Liu P, Hua W, Yang W, Zhang Y, Zhang L, Xing P, Li Z, Zhang Y et al (2020) Current knowledge of large vascular occlusion due to intracranial atherosclerosis: focusing on early diagnosis. Chin Neurosurg J 6:32\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiao G, Zhang Z, Tung TH, He Y, Hu L, Zhang X, Chen H, Huang J, Du W, Li C et al (2022) A simple score to predict atherosclerotic or embolic intracranial large-vessel occlusion stroke before endovascular treatment. J Neurosurg. :1\u0026ndash;8\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee JS, Lee SJ, Yoo JS, Hong JH, Kim CH, Kim YW, Kang DH, Kim YS, Hong JM, Choi JW et al (2018) Prognosis of Acute Intracranial Atherosclerosis-Related Occlusion after Endovascular Treatment. J Stroke 20:394\u0026ndash;403\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTsang ACO, Orru E, Klostranec JM, Yang IH, Lau KK, Tsang FCP, Lui WM, Pereira VM, Krings T (2019) Thrombectomy Outcomes of Intracranial Atherosclerosis-Related Occlusions. Stroke 50:1460\u0026ndash;1466\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang W, Zhang Y, Li Z, Zhang L, Li H, Hua W, Zhang H, Feng M, Shen H, Xing P et al (2021) Differences in Safety and Efficacy of Endovascular Treatment for Acute Ischemic Stroke: A Propensity Score Analysis of Intracranial Atherosclerosis-Related Occlusion versus Embolism. Clin Neuroradiol 31:457\u0026ndash;464\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBourcier R, Volpi S, Guyomarch B, Daumas-Duport B, Lintia-Gaultier A, Papagiannaki C, Serfaty JM, Desal H (2015) Susceptibility Vessel Sign on MRI Predicts Favorable Clinical Outcome in Patients with Anterior Circulation Acute Stroke Treated with Mechanical Thrombectomy. AJNR Am J Neuroradiol 36:2346\u0026ndash;2353\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang R, Zhou Y, Liu C, Zhang M, Yan S, Liebeskind DS, Lou M (2017) Overestimation of Susceptibility Vessel Sign: A Predictive Marker of Stroke Cause. Stroke 48:1993\u0026ndash;1996\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSiegler JE, Martin-Schild S (2011) Early Neurological Deterioration (END) after stroke: the END depends on the definition. Int J Stroke 6:211\u0026ndash;212\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaek JH, Kim BM, Kim DJ, Heo JH, Nam HS, Yoo J (2016) Stenting as a Rescue Treatment After Failure of Mechanical Thrombectomy for Anterior Circulation Large Artery Occlusion. Stroke 47:2360\u0026ndash;2363\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu C, Chang W, Wu D, Wen C, Zhang J, Xu R, Liu X, Lian Y, Xie N, Li C et al (2019) Angioplasty and/or stenting after thrombectomy in patients with underlying intracranial atherosclerotic stenosis. Neuroradiology 61:1073\u0026ndash;1081\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYan Y, Du L, He X, Huang Q, Pan Y, Xin T (2022) Endovascular treatment of acute M1 occlusions due to underlying intracranial atherosclerotic severe stenosis. Chin Neurosurg J 8:22\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen W, Gong J, Song R, Liu J, Wang M, Zhang T, Sun H, Zhao Z, Liu Y, Zhu Q, Wang X (2021) Efficacy and safety of direct balloon angioplasty in the treatment of large atherosclerotic stroke. Clin Neurol Neurosurg 211:107035\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang D, Lin M, Wang S, Wang H, Hao Y, Zi W, Lv P, Zheng D, Xiao G, Xu G et al (2018) Primary angioplasty and stenting may be superior to thrombectomy for acute atherosclerotic large-artery occlusion. Interv Neuroradiol 24:412\u0026ndash;420\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang J, Jia B, Pan Y, Yu Z, Deng Y, Mo D, Ma N, Gao F, Miao Z (2022) A comparison between different endovascular treatment strategies for acute large vessel occlusion due to intracranial artery atherosclerosis: data from ANGEL-ACT Registry. Neuroradiology 64:1627\u0026ndash;1638\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJia B, Feng L, Liebeskind DS, Huo X, Gao F, Ma N, Mo D, Liao X, Wang C, Zhao X et al (2018) Mechanical thrombectomy and rescue therapy for intracranial large artery occlusion with underlying atherosclerosis. J Neurointerv Surg 10:746\u0026ndash;750\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl Kasab S, Almallouhi E, Alawieh A, Wolfe S, Fargen KM, Arthur AS, Goyal N, Dumont T, Kan P, Kim JT et al (2021) Outcomes of Rescue Endovascular Treatment of Emergent Large Vessel Occlusion in Patients With Underlying Intracranial Atherosclerosis: Insights From STAR. J Am Heart Assoc 10:e020195\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOspel JM, Mirza M, Claren\u0026ccedil;on F, Siddiqui A, Doyle K, Consoli A, Mokin M, Ullberg T, Zaidat O, Bourcier R et al (2023) What is a Challenging Clot? A DELPHI Consensus Statement from the CLOTS 7.0 Summit. \u003cem\u003eClin Neuroradiol\u003c/em\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00062-023-01301-2\u003c/span\u003e\u003cspan address=\"10.1007/s00062-023-01301-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub ahead of print. PMID: 37284876\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDobrocky T, Kaesmacher J, Bellwald S, Piechowiak E, Mosimann PJ, Zibold F, Jung S, Arnold M, Fischer U, Gralla J et al (2019) Stent-Retriever Thrombectomy and Rescue Treatment of M1 Occlusions Due to Underlying Intracranial Atherosclerotic Stenosis: Cohort Analysis and Review of the Literature. Cardiovasc Intervent Radiol 42:863\u0026ndash;872\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKass-Hout T, Morsi RZ, Thind S, Karrison T, Lee H, Nahab F, Gupta R, Carri\u0026oacute;n-Penagos J, Awad IA, Coleman E et al (2023) Underlying intracranial atherosclerotic disease is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy. J Stroke Cerebrovasc Dis 32:107227 Epub 2023 Jul 10. PMID: 37437522\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKang DH, Yoon W (2019) Current Opinion on Endovascular Therapy for Emergent Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Stenosis. Korean J Radiol 20:739\u0026ndash;748\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLeng X, Leung TW (2023) Collateral Flow in Intracranial Atherosclerotic Disease. Transl Stroke Res 14:38\u0026ndash;52\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaguida G, Shuaib A (2023) Collateral Circulation in Ischemic Stroke: An Updated Review. J Stroke 25:179\u0026ndash;198\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo ZN, Sun X, Liu J, Sun H, Zhao Y, Ma H, Xu B, Wang Z, Li C, Yan X et al (2018) The Impact of Variational Primary Collaterals on Cerebral Autoregulation. Front Physiol 9:759\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBang OY (2014) Intracranial atherosclerosis: current understanding and perspectives. J Stroke 16:27\u0026ndash;35\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRocha M, Jovin TG (2017) Fast Versus Slow Progressors of Infarct Growth in Large Vessel Occlusion Stroke: Clinical and Research Implications. Stroke 48:2621\u0026ndash;2627\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArquizan C, Lapergue B, Gory B, Labreuche J, Henon H, Albucher JF, Sibon I, Turc G, Richard S, Nouri N et al (2023) Evaluation of acute mechanical revascularization in minor stroke (NIHSS score ⩽ 5) and large vessel occlusion: The MOSTE multicenter, randomized, clinical trial protocol. Int J Stroke. :17474930231186039. doi: 10.1177/17474930231186039. Epub ahead of print. PMID: 37350574.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7897991/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7897991/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAcute occlusions of the anterior circulation with an underlying intracranial atheromatous disease (ICAD) represent a diagnostic and therapeutic challenge. The aim of this study was to compare the results of the endovascular treatment (EVT)\u0026thinsp;\u0026plusmn;\u0026thinsp;intravenous thrombolysis (IVT) and the best medical treatment (BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT) as first-line approach in a cohort of patients with certain diagnosis of M1-Middle Cerebral Artery (M1-MCA) occlusions and underlying ICAD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePatients with M1-MCA and a certain diagnosis of underlying ICAD were included in this retrospective, monocentric analysis between 2018 and April 2023. Baseline, procedural and clinico-neuroradiological follow-up data were collected. EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT and BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT were the two study groups. An independent core lab assessed the imaging data. The primary outcome was the rate of functional independence at 3 months (mRS0-2); secondary outcomes included the extension of the ischemic lesion (∆baseline-24 hours volume), the early neurological deterioration (END), the rate of symptomatic intracranial haemorrhages (sICH).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThirty-four patients were included in the study (65,7\u0026thinsp;\u0026plusmn;\u0026thinsp;16,5 y.o.; males: 52,8%), 23 were treated by EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT and 11 with BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT. Functional independence was less frequent in the EVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group compared to the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT (26%vs81,8%, p\u0026thinsp;=\u0026thinsp;0,003). The increase of ∆ volume, the rate of END and sICH were significantly lower in the BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT group.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eEVT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT (only MT) was associated with worse clinical and neuroimaging outcomes compared to BMT\u0026thinsp;\u0026plusmn;\u0026thinsp;IVT. Nevertheless, a beneficial effect of primary angioplasty\u0026thinsp;\u0026plusmn;\u0026thinsp;stenting should be taken in account and future studies will be necessary to investigate this therapeutic option.\u003c/p\u003e","manuscriptTitle":"Acute therapeutic management of M1-middle cerebral artery occlusion with underlying intracranial atherosclerotic disease: is mechanical thrombectomy the right first-line choice?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-04 01:21:13","doi":"10.21203/rs.3.rs-7897991/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f71ff58a-5c0a-406d-885f-01905630e4c8","owner":[],"postedDate":"November 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-05T02:38:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-04 01:21:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7897991","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7897991","identity":"rs-7897991","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}