Ilaria Casetta

Aim: Migraine is the second most disabling condition worldwide. Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway represent an effective prophylactic treatment; however, their impact on cerebral hemodynamics remains unclear. The aim of this pilot study was to evaluate cerebrovas- cular risk in patients with migraine without aura treated with these therapies, by calculating the breath-holding index (BHI) of the anterior cerebral circulation using transcranial color-coded Doppler (TCCD) ultrasonography. Material and methods: Cerebral vasomotor reactivity to hypercapnia was assessed using the breath-holding test combined with TCCD ultrasonography in 40 patients with migraine without aura undergoing treatment with anti-CGRP monoclonal antibodies and 40 healthy subjects. BHI values and other key cerebrovascular parameters were compared between the groups. Results: The BHI values in patients with migraine without aura were not below the threshold predictive of increased cerebrovascular risk (less than 0.69% per second, as referenced in the general population). No significant differences were observed in major cerebrovascular parameters between cases and controls. Additionally, a subanalysis revealed no significant differences based on the specific monoclonal antibody (erenumab, fremanezumab, or galcanezumab) or clinical response status (responders versus non-responders). Conclusions: Our findings suggest that treatment with anti-CGRP monoclonal antibodies is not associated with a BHI indicative of increased cerebrovascular risk. Notably, this is the first study to include galcanezumab and fremanezumab in the evaluation of cerebrovascular risk using ultrasound, highlighting TCCD ultrasonography as a practical and non-invasive tool for the assessment of cerebrovascular reactivity in migraine.

Background: The triglyceride glucose index (TyG-i), a biomarker of insulin resistance, has been associated with adverse vascular outcomes and risk stratification in several cardiovascular and cerebrovascular phenotypes. However, data on TyG-i as a prognostic marker in spontaneous intracerebral hemorrhage (ICH) remain limited. Objective: To explore the association between TyG-i and 90-day functional outcome in patients with ICH. Methods: A retrospective analysis of adult patients admitted for non-traumatic small vessel disease-related ICH at three Italian neurological institutions was conducted. TyG-i was calculated on admission as Ln[(fast triglycerides (mg/dL) × fast glucose (mg/dL))]/2. Functional outcome was measured with the modified Rankin Scale (mRS) at 90 days from the index event. TyG-i was analyzed as a continuous variable and categorized in quintiles (Q1 to Q5). Predictors of poor outcome (mRS 4–6) were investigated with multivariable logistic regression. Results: A total of 463 patients were included, of whom 197 (42.5%) had poor outcome at 90 days. TyG-i analyzed as a continuous variable was not associated with unfavorable prognosis. TyG-i analyzed as a categorical variable stratified by quintiles showed a non-linear U-shaped relationship with functional outcome; patients in Q4 had the lowest risk of poor outcome (Q1 reference, OR 0.44, 95% CI 0.22–0.87, p = 0.019). Discussion: We found a potential non-linear relationship between TyG-i and ICH outcome, with higher odds of good prognosis in patients with intermediate values. Conclusions: TyG-i may represent a promising, low-cost and widely available biomarker that might improve prognostication in clinical practice, but further studies are needed.

CT-perfusion (CTP) may underestimate the size of the ischemic core, a phenomenon known as "perfusion scotoma". We aimed to investigate the prevalence of perfusion scotoma, characterize its baseline predictors, and explore its association with functional outcomes in a real-world population of stroke patients treated with endovascular treatment (EVT). Data were obtained from a prospective EVT registry, selecting patients with successful recanalization (final mTICI ≥2b), a good quality baseline CTP, and an available 24-hour non-contrast CT. Ischemic core underestimated volume (ICuV) was calculated as the difference between follow-up infarct volume and CTP-estimated ischemic core. The primary outcome was the presence of perfusion scotoma, defined as ICuV ≥10 mL. Baseline characteristics with p value <0.20 in univariable comparisons were entered in a backward stepwise, multivariable logistic regression analysis to identify factors independently associated with perfusion scotoma. A total of 464 patients of 672 (69%) were included in the analysis. The median age was 74 years (IQR=68-83), 215 (46.3%) were males, and 116 (25%) had a perfusion scotoma. Perfusion scotoma was independently associated with male sex (adjusted OR 1.62 [95%CI 1.01-2.51]; p=0.04), more distal site of occlusion (adjusted OR 1.60 [95%CI 1.10-2.34]; p=0.01; per each 1-point increase: terminal ICA to M1 to M2), lower ASPECTS at admission (adjusted OR 0.64 [95%CI 0.54-0.76]; p<0.001; per each 1-point increase), and longer onset-to-CT time (adjusted OR 1.05, [95%CI 1.01-1.10]; p=0.03; per each 1-hour increase). The optimal onset-to-CT time cutoff to distinguish between patients without and with perfusion scotoma was 420 minutes. Perfusion scotoma was associated with 90-day ordinal mRS (adjusted common OR [acOR] 3.16 [95%CI 2.12-4.76]). Perfusion scotoma occurred in 1 out of every 4 patients. Baseline predictors included male sex, lower ASPECTS, more distal vessel occlusion, and longer onset-to-CT time. Perfusion scotoma was associated with poorer functional outcomes.

Background: Nearly half of the patients who received endovascular thrombectomy (EVT) for large vessel occlusion experience poor functional outcomes. Reliable tools for early post-procedural prognostication are needed. We aimed to assess and compare the performance of existing, pragmatic post-EVT prognostic scores in a large national multicenter cohort. Methods: We conducted a systematic literature search to identify pragmatic post-thrombectomy prognostic scores predicting 90-day functional outcomes. Models relying on advanced imaging, small derivation samples, or machine learning were excluded. We analyzed data from the IRETAS registry—a prospective, multicenter Italian cohort of stroke patients treated with EVT. Inclusion criteria were pre-stroke modified Rankin Scale (mRS) ⩽ 2 and available 90-day mRS. The primary outcome was good functional outcome (mRS ⩽ 2). Prognostic performance was assessed using c-statistics in the samples where each individual score was measurable. Scores were compared using DeLong tests in the subset of patients for whom all scores were measurable. Results: Three scores were identified: HERMES-24, BET, and SNARL. Among 22,768 patients in the registry, 18,408 (89.1%) had a measurable HERMES-24 score, 13,593 (59.7%) had a measurable BET score, and 19,007 (83.5%) had a measurable SNARL score. Median age was 75 years (IQR 65–82), and 11,528 (50.6%) were female. In the subset in which each test was measurable, HERMES-24 showed the best performance for predicting mRS ⩽ 2 (c-statistic = 0.889), followed by BET (c-statistic = 0.794) and SNARL (c-statistic = 0.762) ( p < 0.001). In the subset of 12,233 patients for whom all three prognostic scores were calculable, a head-to-head comparison confirmed the superior performance of the HERMES-24 model: HERMES-24 score versus BET score (c-statistic difference = 0.098 [95% CI = 0.092–0.105]; p < 0.001) and HERMES-24 score versus SNARL score (c-statistic difference = 0.124 [95% CI = 0.116–0.132]; p < 0.001). Conclusions: In this large, multicenter, national cohort, the post-EVT HERMES-24 score—which accounts only for age and 24-h NIHSS—demonstrated the highest prognostic performance among existing, pragmatic post-EVT scores. Its simplicity and robust performance support its routine adoption in clinical practice.

Introduction: We aim to evaluate the association between door-to-needle time (DTN) and outcomes in a population of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) + mechanical thrombectomy (MT) in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). Materials and methods: Patients with AIS secondary to middle cerebral artery or intracranial internal carotid artery occlusion with known times of symptoms onset, directly presenting to an MT-capable center, were included in the analysis. According to pre-defined DTN cut-off values (⩽30, ⩽45, and ⩽60 min), we evaluated the association between DTN and outcomes by multivariate logistic regression analyses. Effectiveness outcomes were 3-month functional independence, 3-month excellent outcome and successful reperfusion. Safety outcomes were any intracranial hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 3-month mortality. Results: About 1602 patients were included in our analysis. After logistic regression analysis, a DTN ⩽ 60 min was significantly associated with 3-month functional independence (OR 1.36; 95% CI 1.02–1.82). DTNs ⩽ 30, ⩽45, and ⩽60 min were significantly associated with successful reperfusion (OR 2.66; 95% CI 1.6–4.43; OR 1.68; 95%CI 1.25-2.26; OR 1.57; 95% CI 1.21–2.05; respectively). A DTN ⩽ 60 min was also significantly associated with lower rate of any ICH (OR 0.61; 95% CI 0.43–0.86). DTNs ⩽ 30, ⩽45, and ⩽60 min were significantly associated with lower 3-month mortality (OR 0.24; 95% CI 0.08–0.67; OR 0.45; 95% CI 0.29–0.72; OR 0.58; 95% CI 0.39–0.84; respectively). Conclusions: In patients with AIS treated with IVT + MT, a shorter DTN is associated with better outcomes if IVT is initiated within 1 h of hospital admission.

Introduction: The efficacy of endovascular treatment (EVT) in ischemic stroke patients with distal-medium vessel occlusion (DMVO) remains unclear. We evaluated whether CT-perfusion target mismatch criteria (TMC) could predict functional independence in patients with M2 non- or codominant middle cerebral artery DMVO. Materials and methods: This retrospective study analyzed consecutive patients with M2 DMVO receiving EVT and imaged with multimodal CT study protocol within 24 h from onset. A receiver operating characteristic curve analysis was used to identify the infarct core volume cutoff to predict functional independence (modified Rankin Scale 0–2 at 3-months). This parameter was subsequently considered as part of TMC together with penumbra volume ⩾ 10 mL and mismatch ratio ⩾1.2. The association between TMC and functional independence was tested with logistic regression. Results: A total of 115 patients with M2 were included. Infarct core volume had good discriminative ability for functional independence (AUC 0.75; 95%CI 0.64–0.84) and the best cut-off value was ⩽30 mL (77% sensitivity, 61% specificity, 69% positive predictive value, 70% negative predictive value). TMC were independently associated with functional independence (OR [odds ratio] = 6.50, 95%CI = 2.37–17.77, p < 0.001), excellent outcome (modified Rankin scale 0–1 at 3-months, OR = 3.28, 95%CI = 1.30–8.31, p = 0.012) and final infarct volume (B = −35.52, p = 0.004). After including interaction terms, a significant treatment effect on functional independence was observed between successful recanalization and TMC (OR = 3.82, 95%CI = 1.64–8.89, p = 0.002). Discussion and conclusion: In patients with M2 non- or codominant DMVO receiving EVT, TMC identified as core volume ⩽30 mL, penumbra volume ⩾ 10 mL, and mismatch ratio ⩾ 1.2, were associated with better functional outcome. Our findings suggest that functional independence after EVT was not directly related to successful recanalization, which is indeed effective only in patients with a favorable baseline imaging profile, including a small infarct core size, and in the presence of small penumbra volumes.

Introduction: We aim to evaluate the association between door-to-needle time (DTN) and outcomes in a population of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) + mechanical thrombectomy (MT) in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). Materials and methods: Patients with AIS secondary to middle cerebral artery or intracranial internal carotid artery occlusion with known times of symptoms onset, directly presenting to an MT-capable center, were included in the analysis. According to pre-defined DTN cut-off values (⩽30, ⩽45, and ⩽60 min), we evaluated the association between DTN and outcomes by multivariate logistic regression analyses. Effectiveness outcomes were 3-month functional independence, 3-month excellent outcome and successful reperfusion. Safety outcomes were any intracranial hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 3-month mortality. Results: About 1602 patients were included in our analysis. After logistic regression analysis, a DTN ⩽ 60 min was significantly associated with 3-month functional independence (OR 1.36; 95% CI 1.02–1.82). DTNs ⩽ 30, ⩽45, and ⩽60 min were significantly associated with successful reperfusion (OR 2.66; 95% CI 1.6–4.43; OR 1.68; 95%CI 1.25-2.26; OR 1.57; 95% CI 1.21–2.05; respectively). A DTN ⩽ 60 min was also significantly associated with lower rate of any ICH (OR 0.61; 95% CI 0.43–0.86). DTNs ⩽ 30, ⩽45, and ⩽60 min were significantly associated with lower 3-month mortality (OR 0.24; 95% CI 0.08–0.67; OR 0.45; 95% CI 0.29–0.72; OR 0.58; 95% CI 0.39–0.84; respectively). Conclusions: In patients with AIS treated with IVT + MT, a shorter DTN is associated with better outcomes if IVT is initiated within 1 h of hospital admission.

Introduction: The efficacy of endovascular treatment (EVT) in ischemic stroke patients with distal-medium vessel occlusion (DMVO) remains unclear. We evaluated whether CT-perfusion target mismatch criteria (TMC) could predict functional independence in patients with M2 non- or codominant middle cerebral artery DMVO. Materials and methods: This retrospective study analyzed consecutive patients with M2 DMVO receiving EVT and imaged with multimodal CT study protocol within 24 h from onset. A receiver operating characteristic curve analysis was used to identify the infarct core volume cutoff to predict functional independence (modified Rankin Scale 0–2 at 3-months). This parameter was subsequently considered as part of TMC together with penumbra volume ⩾ 10 mL and mismatch ratio ⩾1.2. The association between TMC and functional independence was tested with logistic regression. Results: A total of 115 patients with M2 were included. Infarct core volume had good discriminative ability for functional independence (AUC 0.75; 95%CI 0.64–0.84) and the best cut-off value was ⩽30 mL (77% sensitivity, 61% specificity, 69% positive predictive value, 70% negative predictive value). TMC were independently associated with functional independence (OR [odds ratio] = 6.50, 95%CI = 2.37–17.77, p < 0.001), excellent outcome (modified Rankin scale 0–1 at 3-months, OR = 3.28, 95%CI = 1.30–8.31, p = 0.012) and final infarct volume ( B = −35.52, p = 0.004). After including interaction terms, a significant treatment effect on functional independence was observed between successful recanalization and TMC (OR = 3.82, 95%CI = 1.64–8.89, p = 0.002). Discussion and conclusion: In patients with M2 non- or codominant DMVO receiving EVT, TMC identified as core volume ⩽30 mL, penumbra volume ⩾ 10 mL, and mismatch ratio ⩾ 1.2, were associated with better functional outcome. Our findings suggest that functional independence after EVT was not directly related to successful recanalization, which is indeed effective only in patients with a favorable baseline imaging profile, including a small infarct core size, and in the presence of small penumbra volumes.

Introduction: Data on safety and efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke in older patients are limited and controversial, and people aged 80 or older were under-represented in randomized trials. Our aim was to assess EVT effect for ischemic stroke patients aged ⩾80 at a nationwide level. Patients and methods: The cohort included stroke patients undergoing EVT from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). Patients were a priori divided into younger and older groups (<80 vs ⩾80). Primary outcome was good functional outcome (modified Rankin scale, mRS, 0–2 at 90 days). Secondary outcomes were symptomatic intracranial hemorrhage (sICH), successful reperfusion, EVT abortion. Propensity score matching (PSM) was performed between age groups for baseline features, functional status, stroke severity and neuroradiological features. Logistic regression was implemented to test the weight of age group on the predefined outcomes. Results: Overall, 5872 individuals (1:1 matching, n = 2936 aged ⩾80 vs n = 2936 < 80) were matched from 13,922 records. In ⩾80 group 34.1% had good functional outcome, vs 51.2% in <80 group (absolute difference = −17.1%, p < 0.001), with a 4.4% excess in EVT abortion. Age ⩾80 was a negative independent predictor of good functional outcome (aOR = 0.4, 95% CI = 0.3–0.5), but had no impact on sICH. Discussion and conclusion: Age ⩾80 years represents a consistent predictor of worse functional outcome, independently from successful reperfusion and sICH. Cost-effectiveness studies are needed for tailored and implement sustainable care, and research should focus on strategies to improve functional outcome in older age patient groups.