Perfusion Imaging to select patients with large ischemic core for mechanical thrombectomy

International audienceBackground and purpose: Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods: This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0-3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results: A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusion: s In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted

Diagnostic performance of dynamic 3D magnetic resonance angiography in daily practice for the detection of intracranial arteriovenous shunts in patients with non-traumatic intracranial hemorrhage

IntroductionIdentification of treatable causes of intracranial hemorrhage (ICH) such as intracranial arteriovenous shunt is crucial to prevent recurrence. However, diagnostic approaches vary considerably across centers, partly because of limited knowledge of the diagnostic performance of first-line vascular imaging techniques. We assessed the diagnostic performance of dynamic three-dimensional magnetic resonance angiography (dynamic 3D MRA) in daily practice to detect intracranial arteriovenous shunts in ICH patients against subsequent digital subtraction angiography (DSA) as reference standard.MethodsWe reviewed all adult patients who underwent first-line dynamic 3D MRA and subsequent DSA for non-traumatic ICH between January 2016 and September 2021 in a tertiary center. Sensitivity, specificity, accuracy, positive and negative predictive values of dynamic 3D MRA for the detection of intracranial arteriovenous shunt were calculated with DSA as reference standard.ResultsAmong 104 included patients, 29 (27.9%) had a DSA-confirmed arteriovenous shunt [19 pial arteriovenous malformations, 10 dural arteriovenous fistulae; median onset-to-DSA: 17 (IQR: 3–88) days]. The sensitivity and specificity of dynamic 3D MRA [median onset-to-dynamic 3D MRA: 14 (3–101) h] for the detection of intracranial arteriovenous shunt were 66% (95% CI: 48–83) and 91% (95% CI: 84–97), respectively. The corresponding accuracy, positive and negative predictive values were 84% (95% CI: 77–91), 73% (95% CI: 56–90), and 87% (95% CI: 80–95), respectively.ConclusionThis study suggests that although first-line evaluation with dynamic 3D MRA may be helpful for the detection of intracranial arteriovenous shunts in patients with ICH, additional vascular imaging work-up should not be withheld if dynamic 3D MRA is negative. Comparative prospective studies are needed to determine the best imaging strategy to diagnose arteriovenous shunts after non-traumatic ICH

Endovascular therapy in patients with a large ischemic volume at presentation: An aggregate patient-level analysis.

INTRODUCTION Recently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup. METHODS We conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0-2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0-3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0-2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH). RESULTS A total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0-3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73-8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22-0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups. CONCLUSIONS In this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Incidence, severity and impact on functional outcome of persistent hypoperfusion despite large-vessel recanalization, a potential marker of impaired microvascular reperfusion: systematic review of the clinical literature

International audienceThe reported incidence of persistent hypoperfusion despite complete recanalization as surrogate for impaired microvascular reperfusion (IMR) has varied widely among clinical studies, possibly due to differences in i) definition of complete recanalization, with only recent Thrombolysis in Cerebral Infarction (TICI) grading schemes allowing distinction between complete (TICI3) and partial recanalization with distal occlusions (TICI2c); ii) operational definition of IMR; and iii) consideration of potential alternative causes for hypoperfusion, notably carotid stenosis, re-occlusion and post-thrombectomy hemorrhage. We performed a systematic review to identify clinical studies that carried out brain perfusion imaging within 72 hrs post-thrombectomy for anterior circulation stroke and reported hypoperfusion rates separately for TICI3 and TICI2c grades. Authors were contacted if this data was missing. We identified eight eligible articles, altogether reporting 636 patients. The incidence of IMR after complete recanalization (i.e., TICI3) tended to decrease with the number of considered alternative causes of hypoperfusion: range 12.5–42.9%, 0–31.6% and 0–9.1% in articles that considered none, two or all three causes, respectively. No study reported the impact of IMR on functional outcome separately for TICI-3 patients. Based on this systematic review, IMR in true complete recanalization appears relatively rare, and reported incidence highly depends on definition used and consideration of confounding factors

Design and Methodology of a Pilot Randomized Controlled Trial of Transcranial Direct Current Stimulation in Acute Middle Cerebral Artery Stroke (STICA)

Background: Stroke is a major cause of death and disability worldwide. The related burden is expected to further increase due to aging populations, calling for more efficient treatment. Ischemic stroke results from a focal reduction in cerebral blood flow due to the sudden occlusion of a brain artery. Ischemic brain injury results from a sequence of pathophysiological events that evolve over time and space. This cascade includes excitotoxicity and peri-infarct depolarizations (PIDs). Focal impairment of cerebral blood flow restricts the delivery of energetics substrates and impairs ionic gradients. Membrane potential is eventually lost, and neurons depolarize. Although recanalization therapies target the ischemic penumbra, they can only rescue the penumbra still present at the time of reperfusion. A promising novel approach is to “freeze” the penumbra until reperfusion occurs. Transcranial direct current stimulation (tDCS) is a non-invasive method of neuromodulation. Based on preclinical evidence, we propose to test the penumbra freezing concept in a clinical phase IIa trial assessing whether cathodal tDCS—shown in rodents to reduce infarction volume—prevents early infarct growth in human acute Middle Cerebral Artery (MCA) stroke, in adjunction to conventional revascularization methods.Methods: This is a monocentric randomized, double-blind, and placebo-controlled trial performed in patients with acute MCA stroke eligible to revascularization procedures. Primary outcome is infarct volume growth on diffusion weighted imaging (DWI) at day 1 relative to baseline. Secondary outcomes include safety and clinical efficacy.Significance: Results from this clinical trial are expected to provide rationale for a phase III study.Clinical trial registration—EUDRACT: 2016-A00160-5

Tissue outcome prediction in hyperacute ischemic stroke: Comparison of machine learning models

International audienceMachine Learning (ML) has been proposed for tissue fate prediction after acute ischemic stroke (AIS), with the aim to help treatment decision and patient management. We compared three different ML models to the clinical method based on diffusion-perfusion thresholding for the voxel-based prediction of final infarct, using a large MRI dataset obtained in a cohort of AIS patients prior to recanalization treatment. Baseline MRI (MRI 0 ), including diffusion-weighted sequence (DWI) and Tmax maps from perfusion-weighted sequence, and 24-hr follow-up MRI (MRI 24h ) were retrospectively collected in consecutive 394 patients AIS patients (median age = 70 years; final infarct volume = 28mL). Manually segmented DWI 24h lesion was considered the final infarct. Gradient Boosting, Random Forests and U-Net were trained using DWI, apparent diffusion coefficient (ADC) and Tmax maps on MRI 0 as inputs to predict final infarct. Tissue outcome predictions were compared to final infarct using Dice score. Gradient Boosting had significantly better predictive performance (median [IQR] Dice Score as for median age, maybe you can replace the comma with an equal sign for consistency 0.53 [0.29–0.68]) than U-Net (0.48 [0.18–0.68]), Random Forests (0.51 [0.27–0.66]), and clinical thresholding method (0.45 [0.25–0.62]) ( P < 0.001). In this benchmark of ML models for tissue outcome prediction in AIS, Gradient Boosting outperformed other ML models and clinical thresholding method and is thus promising for future decision-making

Tissue no-reflow despite full recanalization following thrombectomy for anterior circulation stroke with proximal occlusion: A clinical study

International audienceDespite early thrombectomy, a sizeable fraction of acute stroke patients with large vessel occlusion have poor outcome. The no-reflow phenomenon, i.e. impaired microvascular reperfusion despite complete recanalization, may contribute to such "futile recanalizations". Although well reported in animal models, no-reflow is still poorly characterized in man. From a large prospective thrombectomy database, we included all patients with intracranial proximal occlusion, complete recanalization (modified thrombolysis in cerebral infarction score 2c-3), and availability of both baseline and 24 h follow-up MRI including arterial spin labeling perfusion mapping. No-reflow was operationally defined as i) hypoperfusion ≥40% relative to contralateral homologous region, assessed with both visual (two independent investigators) and automatic image analysis, and ii) infarction on follow-up MRI. Thirty-three patients were eligible (median age: 70 years, NIHSS: 18, and stroke onset-to-recanalization delay: 208 min). The operational criteria were met in one patient only, consistently with the visual and automatic analyses. This patient recanalized 160 min after stroke onset and had excellent functional outcome. In our cohort of patients with complete and stable recanalization following thrombectomy for intracranial proximal occlusion, severe ipsilateral hypoperfusion on follow-up imaging associated with newly developed infarction was a rare occurrence. Thus, no-reflow may be infrequent in human stroke and may not substantially contribute to futile recanalizations

Internal carotid artery patency after mechanical thrombectomy for stroke due to occlusive dissection: Impact on outcome

Introduction: Internal carotid artery dissection (ICAD) is a rare cause of acute ischemic stroke with large vessel occlusion (AIS-LVO). We aimed investigating the impact on outcome of internal carotid artery (ICA) patency after mechanical thrombectomy (MT) for AIS-LVO due to occlusive ICAD.Patients and methods: We included consecutive patients with AIS-LVO due to occlusive ICAD treated with MT from January 2015 to December 2020 in three European stroke centers. We excluded patients with unsuccessful intracranial reperfusion after MT (modified Thrombolysis in Cerebral Infarction (mTICI) score &lt; 2b). We compared 3-month favorable clinical outcome rate, defined as a modified Rankin scale (mRS) score ?2, according to ICA status (patency vs occlusion) at the end of MT and at 24-h follow-up imaging, using univariate and multivariable models.Results: Among 70 included patients, ICA was patent in 54/70 (77%) at the end of MT, and in 36/66 (54.5%) patients with 24-h follow-up imaging. Among patients with ICA patency at the end of MT, 32% presented ICA occlusion at 24-h control imaging. Favorable 3-month outcome occurred in 41/54 (76%) patients with ICA patency post-MT and in 9/16 (56%) patients with occluded ICA post-MT (p= 0.21). Rates of favorable outcome were significantly higher in patients with 24-h ICA patency compared to patients with 24-h ICA occlusion (32/36 [89%] vs 15/30 [50%]), with an adjusted odds ratio of 4.67 (95% CI: 1.26-17.25).Discussion and conclusion: Obtaining sustained (24-h) ICA patency after MT could be a therapeutic target for improving functional outcome in patients with AIS-LVO due to ICAD