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BackgroundTIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician’s attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry’s stroke are scanty.MethodsThe study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event.DiscussionThe potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke.

Background Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness. Methods Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced. Results In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential “patients” and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people’s tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination. Conclusions The IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process. Trial registration NCT01881152 . Retrospectively registered June 7 2013

Background Mechanical thrombectomy (MT) was found to be beneficial in acute ischemic stroke patients with anterior tandem occlusion (a-TO). Instead, little is known about the effectiveness of MT in stroke patients with posterior tandem occlusion (p-TO). We aimed to compare MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO. Methods We conducted a cohort study on prospectively collected data of patients registered in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) who were treated with MT within 24 h from last known well time for acute ischemic stroke with p-TO ( n  = 275) or a-TO ( n  = 1853). Results After adjustment for unbalanced pre-procedure variables (year 2015–2021, age, sex, NIHSS score, ASPECTS, and time strata for puncture groin) and pre-stroke mRS score as pre-defined predictor, p-TO was significantly associated with lower probability of mRS score 0–2 (OR 0.415, 95% CI 0.268–0.644) and with higher risk of death (OR 2.813, 95% CI 2.080–3.805) at 3 months. After adjustment for unbalanced procedural and post-procedure variables (IVT, general anesthesia, TICI 3, and 24-h HT) and pre-stroke mRS score as pre-defined predictor, association between p-TO and lower probability of mRS score 0–2 (OR 0.444, 95% CI 0.304–0.649) and association between p-TO and with higher risk of death (OR 2.971, 95% CI 1.993–4.429) remained significant. Conclusions MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO was associated with worse outcomes at 3 months.

BackgroundHeart failure (HF) is the second most important cardiac risk factor for stroke after atrial fibrillation (AF). Few data are available on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with HF.MethodsThe source of data is the multicentre Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). All AIS patients ≥ 18 years receiving MT were categorised in two groups: HF and no-HF. Baseline clinical and neuroradiological findings on admission were analysed.ResultsOf 8924 patients, 642 (7.2%) had HF. Compared to the no-HF group, HF patients had higher prevalence of cardiovascular risk factors. Rate of complete recanalisation (TICI 2b-3) was 76.9% in HF vs 78.1% in no-HF group (p = 0.481). Rate of symptomatic intracerebral haemorrhage at 24-h non-contrast computed tomography (NCCT) was 7.6% in HF vs 8.3% in no-HF patients (p = 0.520). At 3 months, 36.4% of HF patients and 48.2% of no-HF patients (p < 0.001) had mRS 0–2, and mortality was, respectively, 30.7% and 18.5% (p < 0.001). In multivariate logistic regression, HF was independently associated with mortality at 3 months (OR 1.53, 1.24–1.88 95% CI, p < 0.001). In multivariate ordinal regression, HF patients had a probability of transitioning to a higher mRS level of 1.23 (1.05–1.44 95% CI, p = 0.012). The propensity score analysis of two groups matched for age, sex, and NIHSS at admission yielded the same results.ConclusionMT is safe and effective in HF patients with AIS. Patients with HF and AIS suffered from higher 3-month mortality and unfavourable outcome regardless of acute treatments.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014–15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524–1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215–14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064–6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095–0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009–0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006–0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011–0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395–89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

IntroductionThe aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation.Patients and methodsPatients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed.ResultsAmong the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173–3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579–12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378–22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310–11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0–1 (72.1% versus 69.1%), mRS score 0–2 (79.6% versus 79%), and death (6.2% versus 6.1%).ConclusionsCompared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24 h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24 h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion.

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88–1.79, p  = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40–0.93, p  = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 %, p  = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86–1.54), p  = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p  = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00–3.03, p  = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

BackgroundThe benefit, safety, and time intervals of mechanical thrombectomy (MT) in patients with in-hospital stroke (IHS) are unclear. We sought to evaluate the outcomes and treatment times for IHS patients compared with out-of-hospital stroke (OHS) patients receiving MT.MethodsWe analyzed data from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) between 2015 and 2019. We compared the functional outcomes (modified Rankin Scale (mRS) scores) at 3 months, recanalization rates, and symptomatic intracranial hemorrhage (sICH) after MT. Time intervals from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were recorded for both groups, as were door-to-imaging and door-to-groin for OHS. A multivariate analysis was performed.ResultsOf 5619 patients, 406 (7.2%) had IHS. At 3 months, IHS patients had a lower rate of mRS 0–2 (39% vs 48%, P<0.001) and higher mortality (30.1% vs 19.6%, P<0.001). Recanalization rates and sICH were similar. Time intervals (min, median (IQR)) from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were favorable for IHS (60 (34–106) vs 123 (89–188.5); 150 (105–220) vs 220 (168–294); 227 (164–303) vs 293 (230–370); all P<0.001), whereas OHS had lower door-to-imaging and door-to-groin times compared with stroke onset-to-imaging and onset-to-groin for IHS (29 (20–44) vs 60 (34–106), P<0.001; 113 (84–151) vs 150 (105–220); P<0.001). After adjustment, IHS was associated with higher mortality (aOR 1.77, 95% CI 1.33 to 2.35, P<0.001) and a shift towards worse functional outcomes in the ordinal analysis (aOR 1.32, 95% CI 1.06 to 1.66, P=0.015).ConclusionDespite favorable time intervals for MT, IHS patients had worse functional outcomes than OHS patients. Delays in IHS management were detected.

Background Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. Methods A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy ( n  = 486, absolute exclusion criteria for IVT alone; n  = 384, absolute in combination with relative exclusion criteria for IVT; n  = 777, relative exclusion criteria for IVT alone; n  = 635, non-exclusion criteria for IVT). Results After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042–2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014–1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014–1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039–1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0–2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count < 100,000/mm 3 (OR: 4.798), bacterial endocarditis (OR: 15.069), neoplasm with increased hemorrhagic risk (OR: 6.046), and severe liver disease (OR: 6.124). Conclusions Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.