Publications by authors named "Andrea Zini"

101 Publications

Safety and Outcomes of Thrombectomy in Ischemic Stroke With vs Without Intravenous Thrombolysis.

Neurology 2021 Jun 4. Epub 2021 Jun 4.

Department of Clinical Neuroscience, Karolinska Institutet.

Objective: To test the hypothesis that intravenous thrombolysis (IVT) treatment prior to endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the SITS-International Stroke Thrombectomy Register (SITS-ISTR).

Methods: We identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014-19. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS 0-2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS-MOST. We performed propensity score matched (PSM) and multivariable logistic regression analyses.

Results: Of 6350 patients from 42 centers, 3944 (62.1%) received IVT. IVT+EVT treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure and pre-stroke disability. PSM analysis showed that IVT+EVT patients had a higher rate of functional independence than EVT alone patients (46.4% vs. 40.3%, p<0.001) and a lower rate of death at 3 months (20.3% vs. 23.3%, p=0.035). SICH rates (3.5% vs. 3.0%, p= 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM.

Interpretation: Pretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS Thrombectomy Registry. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding and possible residual confounding by indication.

Classification Of Evidence: This study provides Class II evidence that IVT prior to EVT increases the probability of functional independence at 3 months compared to EVT alone.
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http://dx.doi.org/10.1212/WNL.0000000000012327DOI Listing
June 2021

Bridging versus direct endovascular therapy in basilar artery occlusion.

J Neurol Neurosurg Psychiatry 2021 May 25. Epub 2021 May 25.

Neurovascular Interventional Unit, University Hospital Careggi, Firenze, Italy.

Background: We evaluated safety and efficacy of intravenous recombinant tissue Plasminogen Activator plus endovascular (bridging) therapy compared with direct endovascular therapy in patients with ischaemic stroke due to basilar artery occlusion (BAO).

Methods: From a national prospective registry of endovascular therapy in acute ischaemic stroke, we selected patients with BAO. We compared bridging and direct endovascular therapy evaluating vessel recanalisation, haemorrhagic transformation at 24-36 hours; procedural complications; and functional outcome at 3 months according to the modified Rankin Scale. We ran logistic and ordinal regression models adjusting for age, sex, National Institutes of Health Stroke Scale (NIHSS), onset-to-groin-puncture time.

Results: We included 464 patients, mean(±SD) age 67.7 (±13.3) years, 279 (63%) males, median (IQR) NIHSS=18 (10-30); 166 (35%) received bridging and 298 (65%) direct endovascular therapy. Recanalisation rates and symptomatic intracerebral haemorrhage were similar in both groups (83% and 3%, respectively), whereas distal embolisation was more frequent in patients treated with direct endovascular therapy (9% vs 3%; p=0.009). In the whole population, there was no difference between bridging and direct endovascular therapy regarding functional outcome at 3 months (OR=0.79; 95% CI=0.55 to 1.13). However, in patients with onset-to-groin-puncture time ≤6 hours, bridging therapy was associated with lower mortality (OR=0.53; 95% CI=0.30 to 0.97) and a shift towards better functional outcome in ordinal analysis (OR=0.65; 95% CI=0.42 to 0.98).

Conclusions: In ischaemic stroke due to BAO, when endovascular therapy is initiated within 6 hours from symptoms onset, bridging therapy resulted in lower mortality and better functional outcome compared with direct endovascular therapy.
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http://dx.doi.org/10.1136/jnnp-2020-325328DOI Listing
May 2021

Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion.

N Engl J Med 2021 05;384(20):1910-1920

From the Departments of Radiology (L.C.M.L., E.J.R.J.H., J.-A.V.) and Neurology (W.J.S.), St. Antonius Hospital, Nieuwegein, the Departments of Neurology (D.W.J.D.) and Radiology and Nuclear Medicine (A.L., P.-J.D.), Erasmus University Medical Center, Rotterdam, the Departments of Radiology (R.T.H.L.) and Neurology (L.J.K.) and the Department of Neurology and Neurosurgery, Brain Center, and the Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht, and Utrecht University (A.A.), Utrecht, the Departments of Neurology (J.B.) and Radiology (G.J.L.N.), Haaglanden Medical Center, and the Department of Neurology, Haga Hospital (K.F.L.), The Hague, the Departments of Neurology (J.S.) and Radiology and Nuclear Medicine (W.H.Z.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Departments of Neurology (P.J.N.) and Radiology (C.B.L.M.M., B.J.E.), Amsterdam University Medical Center, Amsterdam, the Department of Neurology, Rijnstate Hospital, Arnhem, and the Department of Clinical Neurophysiology, University of Twente, Enschede (J.H.), the Departments of Neurology (M.J.H.W.) and Radiology (A.C.G.M.E.), Leiden University Medical Center, Leiden, and the Department of Neurology, Amphia Hospital, Breda (M.J.M.R.) - all in the Netherlands; the Interventional Neuroradiology Service (F.J.A.M.) and the Neurology Service (J.J.F.C., F.O.L.), Hospital Geral de Fortaleza, Fortaleza, the Department of Neurology, Federal University of Rio Grande do Sul and Hospital de Clinicas de Porto Alegre, Porto Alegre (S.O.M.), and the Stroke Service, Neurology Division, Department of Neuroscience and Behavioral Sciences (F.A.D., O.M.P.-N.), and the Interventional Neuroradiology Service, Department of Medical Imaging, Hematology and Oncology (D.G.A.), Ribeirão Preto Medical School, University of São Paulo, São Paulo - all in Brazil; the Institute of Neuroradiology (J.C.G.) and the Department of Neurology (V.P.), Dresden Neurovascular Center, University Hospital Carl Gustav Carus, and Medizinische Fakultät Carl Gustav Carus (H.S.), Technische Universität Dresden, Dresden, the Department of Neurology and Center for Stroke Research, Charité Universitätsmedizin Berlin, Berlin (C.H.N., H.J.A.), the Department of Neurology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim (K.S.), the Department of Neurology, University Hospital Augsburg, Augsburg (H.S.), and the Department of Neurology, Oberschwabenklinik, Ravensburg (C.M.R.) - all in Germany; Rothschild Foundation Hospital, INSERM Unité 1148, University of Paris, Paris (M.M., M.P.); the IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna (A.Z.), and the Neuroradiology Unit, Department of Neuroscience, Ospedale Civile S. Agostino-Estense, Modena University Hospital, Modena (S.V.) - both in Italy; the Texas Stroke Institute, Fort Worth (A.J.Y.); and the Stroke Center, Neurology Service, Lausanne University Hospital, Lausanne, Switzerland (P.M.).

Background: The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.

Methods: We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days.

Results: A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12).

Conclusions: Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.).
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http://dx.doi.org/10.1056/NEJMoa2030297DOI Listing
May 2021

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome.

J Stroke Cerebrovasc Dis 2021 Jul 5;30(7):105800. Epub 2021 May 5.

Stroke Unit, Neurology Unit, Department of Neuroscience, Ospedale Civile, Azienda Ospedaliera Universitaria di Modena, Via Giardini 1355, Modena, Emilia Romagna 41126, Italy. Electronic address:

Objectives: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting.

Materials And Methods: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors.

Results: We included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 - 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 - 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 - 203.14).

Conclusion: We found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105800DOI Listing
July 2021

Angioedema after rt-PA infusion led to airway emergency: a case report of rescue treatment with fresh frozen plasma.

Braz J Anesthesiol 2021 Apr 28. Epub 2021 Apr 28.

Ospedale Maggiore, Intensive Care and Prehospital Emergency Service, Department of Anesthesia, Bologna, Italy.

The authors report the case of a 71-year-old woman presented to the Emergency Department with acute ischemic stroke. She was treated with rt-PA and interventional endovascular revascularization and developed rapidly progressing angioedema that led to emergency intubation. The standard treatment was not very effective and the swelling improved after infusion of fresh frozen plasma. Angioedema after rt-PA infusion could be a life-threatening emergency that requires quick airway management by skilled professionals. As this condition is triggered by several factors, such as unregulated histamine and bradykinin production, the traditional treatment recommended by the guidelines may not be sufficient and the use of FFP can be considered as a safe and valuable aid.
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http://dx.doi.org/10.1016/j.bjane.2021.04.023DOI Listing
April 2021

Hematoma Expansion in Intracerebral Hemorrhage With Unclear Onset.

Neurology 2021 05 1;96(19):e2363-e2371. Epub 2021 Apr 1.

From UO Neurologia (A.M.), Azienda Socio-Sanitaria Territoriale (ASST) Valcamonica, Esine, Italy; Neuroradiology Department (G. Boulouis), Centre Hospitalier Sainte-Anne, Paris, France; J.P. Kistler Stroke Research Center, Department of Neurology (A. Charidimou, Q.L., A.D.W., C.D.A., M.E.G., A.B., A.V., S.M.G., J.R., J.N.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica (L.P., A. Pezzini, A. Padovani), Università degli Studi di Brescia; UO di Neurologia (P.C.), Istituto Clinico Fondazione Poliambulanza, Brescia; UOC Neurologia (V.D.G.), ASST Cremona; UC Malattie Cerebrovascolari e Stroke Unit (E.L., F.M., A. Cavallini) and UC Neurologia d'Urgenza (E.L., F.M., G.M.), IRCCS Fondazione Mondino, Pavia; Dipartimento di Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Neuroradiologia, Università degliStudi di Firenze (G. Busto, E.F.), and Stroke Unit (F.A., A.Z.), Ospedale Universitario Careggi, Firenze; UOC Neurologia e Rete Stroke, Metropolitana (L.B., S.G.), and Unità di Neuroradiologia (L.S.), IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Maggiore; Clinica Neurologica, Dipartimento di Scienze Biomediche e Chirurgico Specialistiche (M.L., I.C.), Università degli studi diFerrara, Ospedale Universitario S. Anna, Ferrara; Neurologia e Stroke Unit (E.C.), Ospedale di Circolo, ASST Settelaghi, Varese; Stroke Unit (M.G., M.M.), Neurologia Vascolare, ASST Spedali Civili, Brescia, Italy; Division of Neurocritical Care and Emergency Neurology, Department of Neurology (C.D.A., J.R., J.N.G.), Harvard Medical School, Henry and Allison McCance Center for Brain Health (C.D.A., J.R., J.N.G.), and Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Boston.

Objective: To investigate the prevalence, predictors, and prognostic effect of hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) with unclear symptom onset (USO).

Methods: We performed a retrospective analysis of patients with primary spontaneous ICH admitted at 5 academic medical centers in the United States and Italy. HE (volume increase >6 mL or >33% from baseline to follow-up noncontrast CT [NCCT]) and mortality at 30 days were the outcomes of interest. Baseline NCCT was also analyzed for presence of hypodensities (any hypodense region within the hematoma margins). Predictors of HE and mortality were explored with multivariable logistic regression.

Results: We enrolled 2,165 participants, 1,022 in the development cohort and 1,143 in the replication cohort, of whom 352 (34.4%) and 407 (35.6%) had ICH with USO, respectively. When compared with participants having a clear symptom onset, patients with USO had a similar frequency of HE (25.0% vs 21.9%, = 0.269 and 29.9% vs 31.5%, = 0.423). Among patients with USO, HE was independently associated with mortality after adjustment for confounders (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.43-4.89, = 0.002). This finding was similar in the replication cohort (OR 3.46, 95% CI 1.86-6.44, < 0.001). The presence of NCCT hypodensities in patients with USO was an independent predictor of HE in the development (OR 2.59, 95% CI 1.27-5.28, = 0.009) and replication (OR 2.43, 95% CI 1.42-4.17, = 0.001) population.

Conclusion: HE is common in patients with USO and independently associated with worse outcome. These findings suggest that patients with USO may be enrolled in clinical trials of medical treatments targeting HE.
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http://dx.doi.org/10.1212/WNL.0000000000011895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166446PMC
May 2021

Clinical Features of Patients With Cervical Artery Dissection and Fibromuscular Dysplasia.

Stroke 2021 Mar 28;52(3):821-829. Epub 2021 Jan 28.

UO Neurologia, Ospedale Villa Sofia, Palermo, Italy (V.T.).

Background And Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated.

Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-).

Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis.

Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.
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http://dx.doi.org/10.1161/STROKEAHA.120.031579DOI Listing
March 2021

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale: Results From RE-SPECT ESUS.

Stroke 2021 Mar 28;52(3):1065-1068. Epub 2021 Jan 28.

Department of Neurology, Miller School of Medicine, University of Miami, FL (R.L.S.).

Background And Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed.

Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS.

Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43-1.14]) for ischemic stroke.

Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120.
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http://dx.doi.org/10.1161/STROKEAHA.120.031237DOI Listing
March 2021

Different endovascular procedures for stroke with isolated M2-segment MCA occlusion: a real-world experience.

J Thromb Thrombolysis 2021 May 24;51(4):1157-1162. Epub 2021 Jan 24.

Sapienza University Hospital, Rome, Italy.

Acute ischemic stroke with isolated occlusion of the M2-segment middle cerebral artery (MCA) has not been a focus of trials on mechanical thrombectomy (MT) thus far. We aimed to assess outcomes in stroke patients treated with different endovascular procedures versus direct MT alone for isolated M2-MCA occlusion. We conducted a cohort study on data from 506 stroke patients with isolated M2-MCA occlusion who were enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort. We calculated odds ratio (OR) with confidence interval (CI) of different endovascular procedures (vs direct MT alone) for outcomes after adjustment for age, enrollment period, pre-stroke mRS score, NIHSS score, ASPECT score, onset-to-groin time, and procedure time. Endovascular procedures were direct MT alone (n = 156), intravenous thrombolysis (IVT) plus MT (n = 266), MT plus intra-arterial thrombolysis (IAT) (n = 43), and IAT alone (n = 41). MT plus IAT was associated with higher rates of TICI 2b/3 (OR 3.281, 95% CI 1.006-10.704), 3-month mRS 0-1 (OR 4.153, 95% CI 1.267-13.612), and 3-month mRS 0-2 (OR 4.497, 95% CI 1.485-13.617). IAT alone was associated with lower rates of TICI 3 (OR 0.348, 95% CI 0.139-0.874) and TICI 2b/3 (OR 0.369, 95% CI 0.144-0.948). IVT plus MT was associated with higher rate of asymptomatic ICH (OR 2.526, 95% CI 1.145-5.571). No significant difference was found between different endovascular procedures and direct MT alone as regards symptomatic ICH and 3-month death. In stroke patients with isolated M2-MCA occlusion, MT plus IAT was associated with better outcomes as compared with direct MT alone.
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http://dx.doi.org/10.1007/s11239-021-02378-7DOI Listing
May 2021

Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: A systematic review and meta-analysis.

Eur J Neurol 2021 Jan 11. Epub 2021 Jan 11.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Neurology and Metropolitan Stroke Center, "C.A. Pizzardi" Maggiore Hospital, Bologna, Italy.

Background And Purpose: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease-2019 (COVID-19).

Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases to identify cases of COVID-19-associated CVT. The search period spanned 1 January 2020 to 1 December 2020, and the review protocol (PROSPERO-CRD42020214327) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were evaluated for bias using the Newcastle-Ottawa scale. A proportion meta-analysis was performed to estimate the frequency of CVT among hospitalized COVID-19 patients.

Results: We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, and the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37%, and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS-CoV-2 infection were present in 31%. In-hospital mortality was 40%. Using data from 34,331 patients, the estimated frequency of CVT among patients hospitalized for SARS-CoV-2 infection was 0.08% (95% confidence interval [CI]: 0.01-0.5). In an inpatient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID-19 (cohort of 406 patients, 95% CI: 1.47-11.39).

Conclusions: Cerebral venous thrombosis in the context of SARS-CoV-2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, because the diagnosis of this potentially life-threatening condition in COVID-19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID-19-associated CVT.
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http://dx.doi.org/10.1111/ene.14727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014715PMC
January 2021

Mechanical Thrombectomy for Acute Intracranial Carotid Occlusion with Patent Intracranial Arteries : The Italian Registry of Endovascular Treatment in Acute Stroke.

Clin Neuroradiol 2021 Mar 10;31(1):21-29. Epub 2020 Dec 10.

Stroke Unit, Spedali Civili, Brescia, Italy.

Purpose: Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion.

Methods: A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3‑month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated.

Results: Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome.

Conclusion: Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3‑month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome.
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http://dx.doi.org/10.1007/s00062-020-00980-5DOI Listing
March 2021

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke.

Int J Stroke 2020 12 6:1747493020976681. Epub 2020 Dec 6.

Department of Translational Research and New Technologies in Medicine and Surgery, 9310University of Pisa, Pisa, Italy.

Background: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes.

Aims: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications.

Methods: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected.

Results: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21-2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13-8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66-12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31-0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97-0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19-0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6-0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02-1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02-1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25-2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26-3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08-2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55-0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up.

Conclusions: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits.
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http://dx.doi.org/10.1177/1747493020976681DOI Listing
December 2020

European Multicenter Study of ET-COVID-19.

Stroke 2021 01 23;52(1):31-39. Epub 2020 Nov 23.

Interventional Neuroradiology Department, CHRU Colmar, France (F.B., P.A.L.).

Background And Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19.

Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality.

Secondary Outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage.

Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH).

Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.
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http://dx.doi.org/10.1161/STROKEAHA.120.031514DOI Listing
January 2021

Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke.

Front Neurol 2020 19;11:587226. Epub 2020 Oct 19.

Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.

Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.
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http://dx.doi.org/10.3389/fneur.2020.587226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604480PMC
October 2020

The stroke mothership model survived during COVID-19 era: an observational single-center study in Emilia-Romagna, Italy.

Neurol Sci 2020 Dec 8;41(12):3395-3399. Epub 2020 Oct 8.

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.

Introduction: A reduction of the hospitalization and reperfusion treatments was reported during COVID-19 pandemic. However, high variability in results emerged, potentially due to logistic paradigms adopted. Here, we analyze stroke code admissions, hospitalizations, and stroke belt performance for ischemic stroke patients in the metropolitan Bologna region, comparing temporal trends between 2019 and 2020 to define the impact of COVID-19 on the stroke network.

Methods: This retrospective observational study included all people admitted at the Bologna Metropolitan Stroke Center in timeframes 1 March 2019-30 April 2019 (cohort-2019) and 1 March 2020-30 April 2020 (cohort-2020). Diagnosis, treatment strategy, and timing were compared between the two cohorts to define temporal trends.

Results: Overall, 283 patients were admitted to the Stroke Center, with no differences in demographic factors between cohort-2019 and cohort-2020. In cohort-2020, transient ischemic attack (TIA) was significantly less prevalent than 2019 (6.9% vs 14.4%, p = .04). Among 216 ischemic stroke patients, moderate-to-severe stroke was more represented in cohort-2020 (17.8% vs 6.2%, p = .027). Similar proportions of patients underwent reperfusion (45.9% in 2019 vs 53.4% in 2020), although a slight increase in combined treatment was detected (14.4% vs 25.4%, p = .05). Door-to-scan timing was significantly prolonged in 2020 compared with 2019 (28.4 ± 12.6 vs 36.7 ± 14.6, p = .03), although overall timing from stroke to treatment was preserved.

Conclusion: During COVID-19 pandemic, TIA and minor stroke consistently reduced compared to the same timeframe in 2019. Longer stroke-to-call and door-to-scan times, attributable to change in citizen behavior and screening at hospital arrival, did not impact on stroke-to-treatment time. Mothership model might have minimized the effects of the pandemic on the stroke care organization.
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http://dx.doi.org/10.1007/s10072-020-04754-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541754PMC
December 2020

The domino effect of acephalgic spontaneous intracranial hypotension.

Neurol Sci 2021 Jan 29;42(1):309-312. Epub 2020 Sep 29.

Department of Neurology and Stroke Center, Maggiore Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna, Largo Nigrisoli 2, 40133, Bologna, Italy.

Spontaneous intracranial hypotension results from a spinal CSF leak and usually presents with orthostatic headache, although acephalgic presentations have anecdotally been reported. The underlying low CSF volume, rarely, leads to serious complications such as cerebral venous thrombosis and coma. We report a patient presenting with cerebral venous thrombosis secondary to acephalgic spontaneous intracranial hypotension. An epidural blood patch was performed; nonetheless, the patient intracracal condition deteriorated to coma and neuroimages showed a deep brain swelling with midbrain distortion, subsequently complicated by intracranial pontine hemorrhage.
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http://dx.doi.org/10.1007/s10072-020-04755-1DOI Listing
January 2021

Qualitative versus automatic evaluation of CT perfusion parameters in acute posterior circulation ischaemic stroke.

Neuroradiology 2021 Mar 19;63(3):317-330. Epub 2020 Aug 19.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.

Purpose: To compare the diagnostic accuracy (ACC) in the detection of acute posterior circulation strokes between qualitative evaluation of software-generated colour maps and automatic assessment of CT perfusion (CTP) parameters.

Methods: Were retrospectively collected 50 patients suspected of acute posterior circulation stroke who underwent to CTP (GE "Lightspeed", 64 slices) within 24 h after symptom onset between January 2016 and December 2018. The Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was used for quantifying the extent of ischaemic areas on non-contrast (NC)CT and colour-coded maps generated by CTP4 (GE) and RAPID (iSchemia View) software. Final pc-ASPECTS was calculated on follow-up NCCT and/or MRI (Philips Intera 3.0 T or Philips Achieva Ingenia 1.5 T). RAPID software also elaborated automatic quantitative mismatch maps.

Results: By qualitative evaluation of colour-coded maps, MTT-CTP4D and Tmax-RAPID showed the highest sensitivity (SE) (88.6% and 90.9%, respectively) and ACC (84% and 88%, respectively) compared with the other perfusion parameters (CBV, CBF). Baseline NCCT and CBF provided by RAPID quantitative perfusion mismatch maps had the lowest SE (29.6% and 6.8%, respectively) and ACC (38% and 18%, respectively). CBF and Tmax assessment provided by quantitative RAPID perfusion mismatch maps showed significant lower SE and ACC than qualitative evaluation. No significant differences were found between the pc-ASPECTSs assessed on colour-coded MTT and Tmax maps neither between the scores assessed on colour-coded CBV-CTP4D and CBF-RAPID maps.

Conclusion: Qualitative analysis of colour-coded maps resulted more sensitive and accurate in the detection of ischaemic changes than automatic quantitative analysis.
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http://dx.doi.org/10.1007/s00234-020-02517-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880970PMC
March 2021

Coverage of the requirements of first and second level stroke unit in Italy.

Neurol Sci 2021 Mar 31;42(3):1073-1079. Epub 2020 Jul 31.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova and IRCCS ICS Maugeri, Genova, Pavia, Italy.

Background And Aim: In the scientific literature, there is unanimous consensus that hospitalization in stroke unit (SU) is the most important treatment for stroke patients. In this regard, the Act number 70/2015 by the Italian government identified specific skills that contribute to a classification of SU and outlined a "hub and spoke" stroke network. The aim of our study was to check the coverage of requirements of first and second level SU in the national territory and to shed light on any deficit or misdistribution of resources.

Material And Methods: In 2019, a survey on the current situation related to stroke care in Italy was carried out by the Italian Society of Neurology (SIN), The Italian Stroke Organization (ISO), and the Association for the Fight against Stroke (A.L.I.Ce).

Results: First level SU was found to be 58 against a requirement, according to the Act 70/2015, of 240. Second level SU was found to be 52 compared with an expected requirement of 60. Neurointerventionists were 280 nationally, with a requirement of 240. A misdistribution of resources within individual regions was often seen.

Conclusions: The survey demonstrated a severe shortage of beds dedicated to cerebrovascular diseases, mainly because of lack of first level SU, especially in central and southern Italy. It also suggests that the current hub and spoke system is not yet fully implemented across the country and that resources should be better distributed in order to ensure uniform and fair care for all stroke patients on the whole territory.
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http://dx.doi.org/10.1007/s10072-020-04616-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870770PMC
March 2021

Direct thrombectomy for stroke in the presence of absolute exclusion criteria for thrombolysis.

J Neurol 2020 Dec 25;267(12):3731-3740. Epub 2020 Jul 25.

Azienda Ospedaliero-Univeristaria, Padua, Italy.

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 (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.
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http://dx.doi.org/10.1007/s00415-020-10098-wDOI Listing
December 2020

Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients.

Eur Stroke J 2020 Jun 13;5(2):138-147. Epub 2019 Nov 13.

Stroke Center and Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.

Introduction: Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous.

Patients And Methods: In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3-6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: <12 g/dl; male: <13 g/dl) and polyglobulia (female: >15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male: <11 g/dl). Normal haemoglobin level (female: 12.0-15.5 g/dl, male: 13.0-17.0 g/dl) served as reference group. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated with logistic regression models.

Results: Among 6866 intravenous thrombolysis-treated stroke patients, 5448 (79.3%) had normal haemoglobin level, 1232 (17.9%) anaemia - of those 903 (13.2%) had mild and 329 (4.8%) moderate/severe anaemia - and 186 (2.7%) polyglobulia. Anaemia was associated with poor outcome (OR 1.25 (1.05-1.48)) and mortality (OR 1.58 (1.27-1.95)). In anaemia subgroups, both mild and moderate/severe anaemia independently predicted poor outcome (OR 1.29 (1.07-1.55) and 1.48 (1.09-2.02)) and mortality (OR 1.45 (1.15-1.84) and OR 2.00 (1.46-2.75)). Each haemoglobin level decrease by 1 g/dl independently increased the risk of poor outcome (OR 1.07 (1.02-1.11)) and mortality (OR 1.08 (1.02-1.15)). Anaemia was not associated with occurrence of symptomatic intracranial haemorrhage. Polyglobulia did not change any outcome.

Discussion: The more severe the anaemia, the higher the probability of poor outcome and death. Severe anaemia might be a target for interventions in hyperacute stroke.

Conclusion: Anaemia on admission, but not polyglobulia, is a strong and independent predictor of poor outcome and mortality in intravenous thrombolysis-treated stroke patients.
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http://dx.doi.org/10.1177/2396987319889468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313367PMC
June 2020

Association of prestroke metformin use, stroke severity, and thrombolysis outcome.

Neurology 2020 07 29;95(4):e362-e373. Epub 2020 Jun 29.

From the Department of Neurology (L.P.W., R.W., A.R.L., S.W.), University Hospital Zurich; Epidemiology, Biostatistics and Prevention Institute, Department of Biostatistics (U.H., K.S.), University of Zurich, Switzerland; Department of Neurology (C.H., P.R.), University Hospital Heidelberg, Germany; Department of Neurology (S.C., N.M.-M., M.T.), University of Helsinki and Helsinki University Hospital, Finland; Department of Neurology and Center for Stroke Research (C.H.N., J.F.S., H.E.), Charité University Hospital, Berlin, Germany; Stroke Center and Neurology (A.A.P., C.T., H.G., S.T.E.), University Hospital Basel and University Basel; Department of Neurology (A.E., P.M.), University Hospital Lausanne; Department of Neurology (M.R.H., M.A.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Stroke Center (A.Z.), IRCCS Istituto delle Scienze Neurologiche di Bologna, Maggiore Hospital; Stroke Unit (L.V.), Department of Neuroscience, S'Agostino-Estense Hospital, Modena University Hospital, Italy; Department of Neurology (J.M.C., A.E.G., P.N.), Amsterdam University Medical Centers (AUMC), Location AMC, University of Amsterdam, the Netherlands; Neurology Clinic Belgrade (V.P., D.R.J.), Clinical Centre of Serbia; Medical Faculty (D.R.J.), University of Belgrade, Serbia; Department of Neurology (Y.B., C.B.), University Hospital of Dijon, University of Burgundy; Department of Neurology (G.T., P.S.), Sainte-Anne Hospital, Paris, France; Department of Clinical and Experimental Sciences (A.P.), Neurology Clinic, University of Brescia; Stroke Unit (M.M.), ASST Spedali Civili, Brescia, Italy; Department of Neurology (D.L., S.G.), University Hospital of Lille, France; Department of Neurology (M.J.S., G.K.), St. Gallen Cantonal Hospital, Switzerland; Department of Neurology (T.T.), Sahlgrenska University Hospital; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation Basel, Felix Platter Hospital, University of Basel, Switzerland.

Objective: To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis.

Methods: Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET.

Results: Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0-4.0] vs 3 [IQR 1.0-4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups.

Conclusions: Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.
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http://dx.doi.org/10.1212/WNL.0000000000009951DOI Listing
July 2020

Endovascular Thrombectomy for Acute Ischemic Stroke Beyond 6 Hours From Onset: A Real-World Experience.

Stroke 2020 07 17;51(7):2051-2057. Epub 2020 Jun 17.

Stroke Unit and Neurosonology Lab (A.P.), Padua University Hospital.

Background And Purpose: To evaluate outcome and safety of endovascular treatment beyond 6 hours of onset of ischemic stroke due to large vessel occlusion in the anterior circulation, in routine clinical practice.

Methods: From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke of known onset beyond 6 hours. Additional inclusion criteria were prestroke modified Rankin Scale score ≤2 and ASPECTS score ≥6. Patients were selected on individual basis by a combination of CT perfusion mismatch (difference between total hypoperfusion and infarct core sizes) and CT collateral score. The primary outcome measure was the score on modified Rankin Scale at 90 days. Safety outcomes were 90-day mortality and the occurrence of symptomatic intracranial hemorrhage. Data were compared with those from patients treated within 6 hours.

Results: Out of 3057 patients, 327 were treated beyond 6 hours. Their mean age was 66.8±14.9 years, the median baseline National Institutes of Health Stroke Scale 16, and the median onset to groin puncture time 430 minutes. The most frequent site of occlusion was middle cerebral artery (45.1%). Functional independence (90-day modified Rankin Scale score, 0-2) was achieved by 41.3% of cases. Symptomatic intracranial hemorrhage occurred in 6.7% of patients, and 3-month case fatality rate was 17.1%. The probability of surviving with modified Rankin Scale score, 0-2 (odds ratio, 0.58 [95% CI, 0.43-0.77]) was significantly lower in patients treated beyond 6 hours as compared with patients treated earlier No differences were found regarding recanalization rates and safety outcomes between patients treated within and beyond 6 hours. There were no differences in outcome between people treated 6-12 hours from onset (278 patients) and those treated 12 to 24 hours from onset (49 patients).

Conclusions: This real-world study suggests that in patients with large vessel occlusion selected on the basis of CT perfusion and collateral circulation assessment, endovascular treatment beyond 6 hours is feasible and safe with no increase in symptomatic intracranial hemorrhage.
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http://dx.doi.org/10.1161/STROKEAHA.119.027974DOI Listing
July 2020

General Anesthesia Versus Conscious Sedation and Local Anesthesia During Thrombectomy for Acute Ischemic Stroke.

Stroke 2020 07 10;51(7):2036-2044. Epub 2020 Jun 10.

Interventional Neuroradiology Unit and Stroke Unit, Azienda Ospedaliera-Universitaria, Padova, Italy (F.C., C.B.).

Background And Purpose: As numerous questions remain about the best anesthetic strategy during thrombectomy, we assessed functional and radiological outcomes in stroke patients treated with thrombectomy in presence of general anesthesia (GA) versus conscious sedation (CS) and local anesthesia (LA).

Methods: We conducted a cohort study on prospectively collected data from 4429 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke.

Results: GA was used in 2013 patients, CS in 1285 patients, and LA in 1131 patients. The rates of 3-month modified Rankin Scale score of 0-1 were 32.7%, 33.7%, and 38.1% in the GA, CS, and LA groups: GA versus CS: odds ratios after adjustment for unbalanced variables (adjusted odds ratio [aOR]), 0.811 (95% CI, 0.602-1.091); and GA versus LA: aOR, 0.714 (95% CI, 0.515-0.990). The rates of modified Rankin Scale score of 0-2 were 42.5%, 46.6%, and 52.4% in the GA, CS, and LA groups: GA versus CS: aOR, 0.902 (95% CI, 0.689-1.180); and GA versus LA: aOR, 0.769 (95% CI, 0.566-0.998). The rates of 3-month death were 21.5%, 19.7%, and 14.8% in the GA, CS, and LA groups: GA versus CS: aOR, 0.872 (95% CI, 0.644-1.181); and GA versus LA: aOR, 1.235 (95% CI, 0.844-1.807). The rates of parenchymal hematoma were 9%, 12.6%, and 11.3% in the GA, CS, and LA groups: GA versus CS: aOR, 0.380 (95% CI, 0.262-0.551); and GA versus LA: aOR, 0.532 (95% CI, 0.337-0.838). After model of adjustment for predefined variables (age, sex, thrombolysis, National Institutes of Health Stroke Scale, onset-to-groin time, anterior large vessel occlusion, procedure time, prestroke modified Rankin Scale score of <1, antiplatelet, and anticoagulant), differences were found also between GA versus CS as regards modified Rankin Scale score of 0-2 (aOR, 0.659 [95% CI, 0.538-0.807]) and GA versus LA as regards death (aOR, 1.413 [95% CI, 1.095-1.823]).

Conclusions: GA during thrombectomy was associated with worse 3-month functional outcomes, especially when compared with LA. The inclusion of an LA arm in future randomized clinical trials of anesthesia strategy is recommended.
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http://dx.doi.org/10.1161/STROKEAHA.120.028963DOI Listing
July 2020

Long-term outcome of cervical artery dissection : IPSYS CeAD: study protocol, rationale, and baseline data of an Italian multicenter research collaboration.

Neurol Sci 2020 Nov 12;41(11):3265-3272. Epub 2020 May 12.

UO Neurologia, Ospedale Villa Sofia, Palermo, Italy.

Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t) and then annually (t at 1 year, t at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.
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http://dx.doi.org/10.1007/s10072-020-04464-9DOI Listing
November 2020

"Minor" stroke: not a minor, still open question.

J Thromb Thrombolysis 2020 Jan;49(1):132-135

SC Neurologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy.

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http://dx.doi.org/10.1007/s11239-019-02001-wDOI Listing
January 2020