Publications by authors named "Giorgio Silvestrelli"

60 Publications

Age-dependent effect of susceptibility factors on the risk of intracerebral haemorrhage: Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy).

J Neurol Neurosurg Psychiatry 2021 Jul 12. Epub 2021 Jul 12.

Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.

Objective: To investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH).

Methods: We performed a case-control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1-Q4).

Results: We analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively).

Conclusions: Our findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH.
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http://dx.doi.org/10.1136/jnnp-2020-325648DOI Listing
July 2021

SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

J Neurol 2021 May 24. Epub 2021 May 24.

Department of Neurology and Stroke Unit, Carlo Poma Hospital, ASST Mantova, Mantova, Italy.

Objective: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients.

Methods: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19.

Results: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death.

Conclusions: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.
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http://dx.doi.org/10.1007/s00415-021-10620-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142879PMC
May 2021

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

J Neurol 2021 Mar 8. Epub 2021 Mar 8.

Department of Neurology and Stroke Unit, Carlo Poma Hospital, ASST Mantova, Mantua, Italy.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.
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http://dx.doi.org/10.1007/s00415-021-10497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937781PMC
March 2021

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

Eur Stroke J 2020 Dec 22;5(4):374-383. Epub 2020 Jul 22.

Internal Medicine, San Giuseppe Hospital, Empoli, Italy.

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing.

Materials And Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke.

Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80).

Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events.

Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
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http://dx.doi.org/10.1177/2396987320937116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856592PMC
December 2020

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

PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis.

Eur Neurol 2020 13;83(6):566-575. Epub 2020 Nov 13.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Background: In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH).

Methods: Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo.

Results: PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29-2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03-2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43-1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17-1.60), and in mortality (OR 0.85; 95% CI 0.64-1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31-3.04).

Conclusions: In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.
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http://dx.doi.org/10.1159/000511574DOI Listing
May 2021

Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation.

Stroke 2020 08 10;51(8):2347-2354. Epub 2020 Jul 10.

Internal Medicine, Santa Maria Nuova Hospital, Firenze, Italy (V. Vannucchi, L.M.).

Background And Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention.

Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features.

Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]).

Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.
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http://dx.doi.org/10.1161/STROKEAHA.120.030143DOI Listing
August 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

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

Stroke 2019 08 25;50(8):2168-2174. Epub 2019 Jun 25.

Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.).

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHADS-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHADS-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHADS-VASc score were associated with increased risk of cerebrovascular events.
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http://dx.doi.org/10.1161/STROKEAHA.119.025350DOI Listing
August 2019

Anticoagulation After Stroke in Patients With Atrial Fibrillation.

Stroke 2019 08 21;50(8):2093-2100. Epub 2019 Jun 21.

Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Italy (A. Pezzini, L.P., A. Padovani).

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
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http://dx.doi.org/10.1161/STROKEAHA.118.022856DOI Listing
August 2019

Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.

Eur Stroke J 2019 Mar 25;4(1):55-64. Epub 2018 Jul 25.

Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy.

Background: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear.

Purpose: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation.

Methods: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke.

Results: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)).

Conclusions: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.
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http://dx.doi.org/10.1177/2396987318785853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533867PMC
March 2019

The clinical spectrum of reversible cerebral vasoconstriction syndrome: The Italian Project on Stroke at Young Age (IPSYS).

Cephalalgia 2019 Sep 6;39(10):1267-1276. Epub 2019 May 6.

28 Neurologia d'Urgenza and Stroke Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano-Milano, Italy.

Introduction: To describe clinical, neuroimaging, and laboratory features of a large cohort of Italian patients with reversible cerebral vasoconstriction syndrome.

Methods: In the setting of the multicenter Italian Project on Stroke at Young Age (IPSYS), we retrospectively enrolled patients with a diagnosis of definite reversible cerebral vasoconstriction syndrome according to the International Classification of Headache Disorders (ICHD)-3 beta criteria (6.7.3 Headache attributed to reversible cerebral vasoconstriction syndrome, imaging-proven). Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of reversible cerebral vasoconstriction syndrome without typical causes ("idiopathic reversible cerebral vasoconstriction syndrome") were compared with those of reversible cerebral vasoconstriction syndrome related to putative causative factors ("secondary reversible cerebral vasoconstriction syndrome").

Results: A total of 102 patients (mean age, 47.2 ± 13.9 years; females, 85 [83.3%]) qualified for the analysis. Thunderclap headache at presentation was reported in 69 (67.6%) patients, and it typically recurred in 42 (60.9%). Compared to reversible cerebral vasoconstriction syndrome cases related to putative etiologic conditions (n = 21 [20.6%]), patients with idiopathic reversible cerebral vasoconstriction syndrome (n = 81 [79.4%]) were significantly older (49.2 ± 13.9 vs. 39.5 ± 11.4 years), had more frequently typical thunderclap headache (77.8% vs. 28.6%) and less frequently neurological complications (epileptic seizures, 11.1% vs. 38.1%; cerebral infarction, 6.1% vs. 33.3%), as well as concomitant reversible brain edema (25.9% vs. 47.6%).

Conclusions: Clinical manifestations and putative etiologies of reversible cerebral vasoconstriction syndrome in our series are slightly different from those observed in previous cohorts. This variability might be partly related to the coexistence of precipitating conditions with a putative etiologic role on disease occurrence.
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http://dx.doi.org/10.1177/0333102419849013DOI Listing
September 2019

Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

J Am Heart Assoc 2018 11;7(22):e010133

13 Department of Clinical and Experimental Sciences Neurology Unit University of Brescia Italy.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.
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http://dx.doi.org/10.1161/JAHA.118.010133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404429PMC
November 2018

Migraine improvement after spontaneous cervical artery dissection the Italian Project on Stroke in Young Adults (IPSYS).

Neurol Sci 2019 Jan 21;40(1):59-66. Epub 2018 Sep 21.

Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1,, 25123, Brescia, Italy.

Objective: Whether migraine modifies after spontaneous cervical artery dissection (sCeAD) more than after other stroke etiologic subtypes has never been adequately investigated.

Methods: In the setting of the Italian Project on Stroke in Young Adults (IPSYS), we compared the course of migraine before and after acute brain infarct in a group of migraine patients with sCeAD and a group of migraine patients whose ischemia was due to a cause other than CeAD (non-CeAD IS), matched by sex, age (± 3 years), and migraine subtype.We applied linear mixed models to evaluate pre-event vs post-event changes and differences between sCeAD and non-CeAD IS patients.

Results: Eighty-seven patients per group (migraine without aura/migraine with aura, 67/20) qualified for the analysis. After the acute event, migraine headaches disappeared in 14.0% of CeAD patients vs 0.0% of non-CeAD IS patients (p ≤ 0.001). Migraine frequency (patients suffering at least 1 attack, from 93.1 to 80.5%, p = 0.001), pain intensity (from 6.7 ± 1.7 to 4.6 ± 2.6 in a 0 to 10 pain scale, p ≤ 0.001), and use of acute anti-migraine medications (patients taking at least 1 preparation, from 81.6 to 64.4%, p = 0.007) also improved significantly after CeAD as opposed to that observed after non-CeAD IS.

Conclusion: The spontaneous improvement of migraine after sCeAD reinforces the hypothesis of a pathogenic link between the two conditions.
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http://dx.doi.org/10.1007/s10072-018-3578-9DOI Listing
January 2019

Alcohol intake and the risk of intracerebral hemorrhage in the elderly: The MUCH-Italy.

Neurology 2018 07 13;91(3):e227-e235. Epub 2018 Jun 13.

From U.O. Neurologia (P.C.), Istituto Ospedaliero Poliambulanza, Brescia; Dipartimento di Scienze Cliniche e Sperimentali (A. Pezzini, L.P., V.D.G., F.C., A. Padovani), Clinica Neurologica, Università degli Studi di Brescia; Dipartimento di Scienze del Sistema Nervoso e del Comportamento (M. Grassi), Unità di Statistica Medica e Genomica, Università di Pavia; Laboratorio di Epidemiologia Molecolare e Nutrizionale (L.I., A.D.C., G.d.G.), Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli; S.C. Neurologia (M.Z.), Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia; Neurologia d'Urgenza and Stroke Unit (S.M.), IRCCS Istituto Clinico Humanitas, Rozzano-Milano; Stroke Unit (G.S.), Dipartimento di Neuroscienze, Ospedale Carlo Poma, Mantova; Unità di Neurologia (M.L.D.), Ospedale di Circolo, Università dell'Insubria, Varese; U.O. Neurologia (M.S.), Istituti Ospedalieri di Cremona, Cremona; Stroke Unit (A.Z.), Clinica Neurologica, Nuovo Ospedale Civile, "S. Agostino Estense," AUSL Modena; Stroke Unit and Divisione di Medicina Cardiovascolare (M.P., G.A.), Università di Perugia; Stroke Unit (C.A., A.D.V.), Divisione di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria di Ferrara; Stroke Unit (M. Gamba), Neurologia Vascolare, Spedali Civili di Brescia; Unità di Neurologia (M.D.S.), E.O. Ospedali Galliera, Genova; U.O.C. Neurologia (A.T., N.P.), A.O. Universitaria "San Giovanni di Dio e Ruggi d'Aragona," Salerno; Dipartimento di Neuroscienze (C.G.), Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova; U.O. Neurologia (D.M.B.), Azienda Ospedaliera "Cà Foncello," Treviso; Stroke Unit (R.T., G.M.), AOU Senese, Siena; Stroke Unit (A. Cavallini, A.M.), IRCCS Fondazione Istituto Neurologico Nazionale "C. Mondino," Pavia; Neurologia (A. Chiti), Azienda Ospedaliero Universitaria Pisana, Pisa; Istituto di Ricovero e Cura a Carattere Scientifico (R.S.C.), Centro Neurolesi Bonino-Pulejo, Messina; Dipartimento di Neuroscienze (F.G.), Scienze Psichiatriche e Anestesiologiche Clinica Neurologica, Università di Messina; USD Stroke Unit (P.B., G.T.), DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata Verona; Centro Trombosi (C.L.), IRCCS Istituto Clinico Humanitas, Rozzano-Milano; Divisione di Biologia e Genetica (M.R., M.C.), Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia; and Dipartimento di Specialità Medico-Chirurgiche (C.C.), Scienze Radiologiche e Sanità Pubblica, Clinica Neurochirurgica, Università degli Studi di Brescia, Italy.

Objective: To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding.

Methods: We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH.

Results: We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32).

Conclusions: In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH.
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http://dx.doi.org/10.1212/WNL.0000000000005814DOI Listing
July 2018

Anticoagulants Resumption after Warfarin-Related Intracerebral Haemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy).

Thromb Haemost 2018 03 12;118(3):572-580. Epub 2018 Feb 12.

S.C. Neurologia, IRCCS - Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.

Whether to resume antithrombotic treatment after oral anticoagulant-related intracerebral haemorrhage (OAC-ICH) is debatable. In this study, we aimed at investigating long-term outcome associated with OAC resumption after warfarin-related ICH, in comparison with secondary prevention strategies with platelet inhibitors or antithrombotic discontinuation. Participants were patients who sustained an incident ICH during warfarin treatment (2002-2014) included in the Multicenter Study on Cerebral Hemorrhage in Italy. Primary end-point was a composite of ischemic stroke/systemic embolism (SE) and all-cause mortality. Secondary end-points were ischemic stroke/SE, all-cause mortality and major recurrent bleeding. We computed individual propensity score (PS) as the probability that a patient resumes OACs or other agents given his pre-treatment variables, and performed Cox multivariable analysis using Inverse Probability of Treatment Weighting (IPTW) procedure. A total of 244 patients qualified for the analysis. Unlike antiplatelet agents, OAC resumption was associated with a lower rate of the primary end-point (weighted hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09-0.45), as well as of overall mortality (weighted HR, 0.17; 95% CI, 0.06-0.45) and ischemic stroke/SE (weighted HR, 0.19; 95% CI, 0.06-0.60) with no significant increase of major bleeding in comparison with patients receiving no antithrombotics. In the subgroup of patients with atrial fibrillation, OACs resumption was also associated with a reduction of the primary end-point (weighted HR, 0.22; 95% CI, 0.09-0.54), and the secondary end-point ischemic stroke/SE (weighted HR, 0.09; 95% CI, 0.02-0.40). In conclusion, in patients who have an ICH while receiving warfarin, resuming anticoagulation results in a favorable trade-off between bleeding susceptibility and thromboembolic risk.
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http://dx.doi.org/10.1055/s-0038-1627454DOI Listing
March 2018

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study.

J Am Heart Assoc 2017 Nov 29;6(12). Epub 2017 Nov 29.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Italy.

Background: The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.

Methods And Results: Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHADS-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.

Conclusions: In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
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http://dx.doi.org/10.1161/JAHA.117.007034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779022PMC
November 2017

Association Between Migraine and Cervical Artery Dissection: The Italian Project on Stroke in Young Adults.

JAMA Neurol 2017 05;74(5):512-518

Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.

Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS).

Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD.

Design, Setting, And Participants: A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine.

Main Outcomes And Measures: Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS.

Results: Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P < .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainous patients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P > .99).

Conclusions And Relevance: In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.
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http://dx.doi.org/10.1001/jamaneurol.2016.5704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822194PMC
May 2017

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

Stroke 2017 03 9;48(3):726-732. Epub 2017 Feb 9.

From the Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Italy (M.P., G. Agnelli, V.C., C.B., N.F., A.A., M.V., M. Acciarresi, C.D., M.G.M., L.A.C., A. Procopio); Department of Neurology, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (G.T., K.V.); International Clinic Research Center, St Anne's University Hospital Brno, Czech Republic (G.T.); Second Department of Neurology, "Attikon" Hospital, University of Athens, School of Medicine, Greece (G.T., C.L., M. Chondrogianni); Division of Stroke and Cerebrovascular Diseases, Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI (K.L.F., P.T., S.Y.); Neurology Unit, Stroke Unit, Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia, Italy (M.Z.); Medical School and Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., K.R.L.); Unità Semplice Dipartimentale (USD) Stroke Unit, DAI di Neuroscienze, AOUI Verona, Italy (P.B., M. Carletti, A.R., M. Cappellari); Department of Neurology, Helsinki University Central Hospital, Finland (J.P., L.T., T. Tatlisumak); Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg and Department of Neurology, Sahlgrenska University Hospital, Sweden (T. Tatlisumak); Department of Neurology, Ospedale San Paolo, Savona, Italy (F.B.); Neurologia d'urgenza e Stroke Unit, Istituto Clinico Humanitas, Rozzano, Milano, Italy (S. Marcheselli); Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Italy (A. Pezzini, L.P., A. Padovani); Internal Medicine, Santa Maria Nuova Hospital, Firenze, Italy (L.M., V. Vannucchi); Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea (S.-I.S.); Stroke Unit, AOU Senese, Siena, Italy (G.L.); SC Medicina e Chirurgia d'Accettazione e d'Urgenza, Pontedera o Volterra, Azienda USL Toscana Nord Ovest, Italy (R.T., F. Guideri, M. Acampa, G. Martini); Department of Medicine, University of Thessaly, Larissa, Greece (G.N., E.K., G. Athanasakis, K.M.); Department of Internal Medicine, Ospedale Civile di Livorno, Italy (N.M.); Stroke Unit, Jazzolino Hospital, Vibo Valentia, Italy (D.C., F. Galati); Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Italy (S.S., A. Carolei, C.T.); UO Gravi Cerebrolesioni, San Giovanni Battista Hospital, Foligno (F.C.); Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy (W.A., M.B., G.C.); S.C. di Neurologia e S.S. di Stroke Unit, ASST di Mantova, Mantova, Italy (G.S., A. Ciccone); Stroke Unit, Neuroscience Department, University of Parma, Italy (U.S.); Stroke Unit, Dipartimento Geriatrico Riabilitativo, University of Parma, Italy (L.D.); Clinica Neurologica, Azienda Ospedaliero-Universitaria, Pisa, Italy (M. Mancuso, M. Maccarrone, G.O., N.G., G.G., A. Chiti); Neurologia, Ospedale Apuano, Massa Carrara, Italy (G.O., M.G.); Stroke Unit, Department of Neurology, Santa Corona Hospital, Pietra Ligure (Savona), Italy (T. Tassinari); Stroke Unit, Department of Neurology, Insubria University, Varese, Italy (M.L. D.L., G.B.); Abteilung für Neurologie, Oberschwabenklinik gGmbH, Ravensburg, Germany (C.R.); Stroke Unit, Ospedale di Portogruaro, Portogruaro (Venice), Italy (A.B., S.D.); Department of Neurology and Psychiatry, Sapienza University of Rome, Italy (D.T., F.L., A. Pieroni); U.O. Neurologia Stroke Unit, Ospedale SM delle Croci, Ravenna, Italy (E.M.L.); Stroke and Neurorehabilitation Unit, MC 'Universal Clinic 'Oberig' Kyiv, Ukraine (Y.F.); Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); 2nd Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece (T.K.); Stroke Unit, Ospedale Civico, Palermo, Italy (S. Monaco, M.M.B.); Stroke Unit, University of Debrecen, Hungary (L.C., L.S.); Stroke Unit, Department of Neurology, Sant'Andrea Hospital, La Spezia, Italy (A. Chiti, E.G., M.D.S.); Divisione di Neurologia, Ospedale Galliera, Genoa, Italy (M.D.S.); Department of Internal Medicine, Ospedale Civile di Piacenza, Italy (D.I., D.Z.); City Hospital No. 1, Novosibirsk State Medical University, Russia (B.D., V. Volodina); Centre Cérébrovasculaire, Service de Neurologie, Département des Neurosciences Cliniques Centre Hopitalier Universitaire Vaudois, Lausanne (Switzerland) (P.M.); Department of Neurology, Born Bunge Institute, Antwerp University Hospital, Antwerp, Belgium (P.V.); Department of Neurology, Dresden University Stroke Center, Germany (K.B., L.-P.P., J.K., U.B., J.G.); Neurology, Hamad Medical Corporation, Doha, Qatar (D.D., G. Melikyan, F.I., N.A.); and Department of Neurology, Evangelismos Hospital, Athens (V.G.).

Background And Purposes: This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.

Methods: The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; =0.10) for major bleedings.

Results: The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; =0.009) for ischemic outcome events and 0.407 (0.275-0.540; =0.14) for hemorrhagic outcome events.

Conclusions: In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.
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http://dx.doi.org/10.1161/STROKEAHA.116.015770DOI Listing
March 2017

Propensity Score-Based Analysis of Percutaneous Closure Versus Medical Therapy in Patients With Cryptogenic Stroke and Patent Foramen Ovale: The IPSYS Registry (Italian Project on Stroke in Young Adults).

Circ Cardiovasc Interv 2016 09;9(9)

From the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Italia (A.Pezzini, P. Costa, L.P. A.M., V.D.G., S.B., A. Padovani); Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Italia (M. Grassi, D.G.); Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (C.L., P.F.); Stroke Unit, Azienda Ospedaliera Sant'Andrea, Università "La Sapienza," Roma, Italia (R.P., A.S., M.R., S.L.S.); Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Italia (C.G., D.M.); Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense," AUSL Modena, Italia (A.Z., A.M.S.); Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia (M.L.D.); Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia (M.P., C.D.); Unità di Neurologia, Ospedale Galliera, Genova, Italia (M.D.S.); U.O.C. Neurologia, A.O Universitaria "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italia (A.T.); Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche, Clinica Neurologica, Università di Messina, Italia (R.M.); IRCCS, Centro Neurolesi Bonino-Pulejo, Messina, Italia (R.S.C.); UO Neurologia, Azienda Ospedaliera-Universitaria Borgo Trento, Verona, Italia (P.B., G.T.); Stroke Center, Dipartimento di Neurologia, Ospedale Sacro Cuore Negrar, Verona, Italia (A.A.); Stroke Unit, Dipartimento di Neuroscienze, Azienda Ospedaliera Carlo Poma, Mantova, Italia (G.S.); U.O Neurologia, Istituti Ospitalieri, Cremona, Italia (M.S.); Stroke Unit, IRCCS Fondazione Istituto "C. Mondino," Pavia, Italia (A. Cavallini); Neurologia d'Urgenza e Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (S.M.); Stroke Unit, U.O Neurologia, Ospedale "S. Chiara," Trento, Italia (D.M.B.); U.O.C Neurologia, Ospedale Vald

Background: We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study.

Methods And Results: Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39-1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33-1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04-0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05-0.68; P=0.011).

Conclusions: PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.115.003470DOI Listing
September 2016

Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

Stroke 2016 08 21;47(8):2141-3. Epub 2016 Jun 21.

From the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica (A.M., P.C., L.P., V.D.G., A. Padovani, A. Pezzini) and Sezione di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale (M.R., M.C.), Università degli Studi di Brescia, Brescia, Italy; Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italy (M.P., V.C., G.A.); Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense", AUSL Modena, Modena, Italy (A.Z., A.M.S., M.L.D.A.); S.C. di Neurologia e S.S. di Stroke Unit, ASST di Mantova, Mantova, Italy (G.S., A.L., A.C.); U.O. di Recupero e Rieducazione Funzionale, IRCCS Fondazione Don Gnocchi, Rovato, Italy (E.D.Z.); Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italy (M.G.); Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli, Italy (A.D.C., L.I., G.d.G.); and Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italy (M.G.).

Background And Purpose: Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level.

Methods: Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression.

Results: During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17; P<0.001). Conversely, dICH cases were more likely to be hypertensive (OR, 1.87; P<0.001), excessive alcohol consumers (OR, 1.70; P=0.001), and more frequently under treatment with warfarin (OR, 2.05; P=0.010) and statins (OR, 3.10; P<0.001). Hypercholesterolemia, diabetes mellitus, and antiplatelet treatment were not associated with a specific small vessel disease manifestation.

Conclusions: The risk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level.
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http://dx.doi.org/10.1161/STROKEAHA.116.013722DOI Listing
August 2016

Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).

J Neurol Neurosurg Psychiatry 2016 09 21;87(9):924-9. Epub 2016 Mar 21.

Stroke Unit, AOU Senese, Siena, Italia.

Objective: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated.

Methods: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH.

Results: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones.

Conclusions: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions.
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http://dx.doi.org/10.1136/jnnp-2015-312736DOI Listing
September 2016

Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study.

J Neurol 2015 Feb 2;262(2):459-68. Epub 2014 Dec 2.

Stroke Unit and Division of Internal and Cardiovascular Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Via G. Dottori 1, 06100, Perugia, Italy,

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.
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http://dx.doi.org/10.1007/s00415-014-7550-1DOI Listing
February 2015

Determinants of premature familial arterial thrombosis in patients with juvenile ischaemic stroke. The Italian Project on Stroke in Young Adults (IPSYS).

Thromb Haemost 2015 Mar 20;113(3):641-8. Epub 2014 Nov 20.

Alessandro Pezzini, Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italia, Tel: +39.030.3384086, Fax: +39.030. 3384086, E-mail:

Factors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18-45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] < 45 years in proband's first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n = 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21-3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21-6.06). Smoking (OR, 2.48; 95 % CI, 1.20-5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31-10.10), and the A20210 mutation in the prothrombin gene (OR, 8.40; 95 % CI 3.35-21.05) were associated with FH of premature stroke (n = 33), while circulating anti-phospholipids to FH of premature myocardial infarction (n = 45; OR, 3.48; 95 % CI, 1.61-7.51). Mean follow-up time was 46.6 ± 38.6 months. Recurrent events occurred more frequently in the subgroup of patients with FH of premature stroke [19.4 %); p = 0.051] compared to patients without such a FH. In conclusion, young IS patients with FH of premature arterial thrombosis exhibit a distinct risk-factor profile, an underlying procoagulant state and have worse vascular prognosis than those with no FH of juvenile thrombotic events.
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http://dx.doi.org/10.1160/TH14-06-0566DOI Listing
March 2015

Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

Circulation 2014 Apr 7;129(16):1668-76. Epub 2014 Feb 7.

Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia (A. Pezzini, P.C., L.P., A.M., V.D.G., A. Padovani; Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italia (M.G.); Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (C.L., P.F.); Stroke Unit, Azienda Ospedaliera Sant'Andrea, Roma, Italia (R.P., A.S., M.R.); Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Genova, Italia (C.G., D.M.); Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense", AUSL Modena, Italia (A.Z., A.M.S.); Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia (M.L.D.); Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia (M.P.); Unità di Neurologia, Ospedale S. Andrea, La Spezia, Italia (M.D.S.); U.O.C. Neurologia, A.O Universitaria "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italia (A.T.); Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche, Clinica Neurologica, Università di Messina, Messina, Italia (R.M.); Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Messina, Italia (R.S.C.); UO Neurologia, Azienda Ospedaliera-Universitaria Borgo Trento, Verona, Italia (P.B.); Stroke Center, Dipartimento di Neurologia, Ospedale Sacro Cuore Negrar, Verona, Italia (A.A.); Stroke Unit, U.O Neurologia, Azienda Ospedaliera "C. Poma", Mantova, Italia (G.S.); Stroke Unit, U.O Neurologia, IRCCS Ospedale S. Raffaele, Milano, Italia (M.S., G.G.); U.C Malattie Cerebrovascolari e Stroke Unit (A.C.) and U.C Neurologia d'Urgenza (G.M.), IRCCS Fondazione Istituto Neurologico Nazionale "C. Mondino," Pavia, Italia; Neurologia d'Urgenza and Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (S.M.); Stroke Un

Background: Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited.

Methods And Results: We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65).

Conclusions: Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005663DOI Listing
April 2014

Antithrombotic medications and the etiology of intracerebral hemorrhage: MUCH-Italy.

Neurology 2014 Feb 15;82(6):529-35. Epub 2014 Jan 15.

From the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica (A. Pezzini, P.C., L.P., A.M., V.D.G., A. Padovani), and Divisione di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale (M.R., M.C.), Università degli Studi di Brescia; Dipartimento di Scienze del Sistema Nervoso e del Comportamento (M. Grassi, D.P.), Unità di Statistica Medica e Genomica, Università di Pavia; Stroke Unit and Divisione di Medicina Cardiovascolare (M.P., V.C., G.A.), Università di Perugia; Stroke Unit (A.Z., M.L.D., A.M.S.), Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense," AUSL Modena; U.O di Neurologia (G.S., A.L., A.C.), Ospedale "C. Poma," Mantova; U.O. di Recupero e Rieducazione Funzionale (E.D.Z.), IRCCS Fondazione Don Gnocchi, Rovato; U.O Neurologia (A.G., I.V.), Istituto Clinico "S. Anna," Brescia; and Stroke Unit (M. Gamba), Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italy.

Objective: To test the hypothesis that the effect of antithrombotic medications on the risk of intracerebral hemorrhage (ICH) varies according to the location of the hematoma.

Methods: Consecutive patients with ICH were enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy). Multivariable logistic regression models served to examine whether risk factors for ICH and location of the hematoma (deep vs lobar) predict treatment-specific ICH subgroups (antiplatelets-related ICH and oral anticoagulants [OACs]-related ICH).

Results: A total of 870 (313 lobar ICH, 557 deep ICH) subjects were included. Of these, 223 (25.6%) were taking antiplatelets and 77 (8.8%) OACs at the time of stroke. The odds of antiplatelet-related ICH increased with aging (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.03-1.07) and hypertension (OR 1.86; 95% CI 1.22-2.85) but had no relation with the anatomical location of ICH. Conversely, lobar location of the hematoma was associated with the subgroup of OAC-related ICH (OR 1.70; 95% CI 1.03-2.81) when compared to the subgroup of patients taking no antithrombotic medications. Within the subgroup of patients taking OACs, international normalized ratio (INR) values were higher in those with lobar ICH as compared to those with deep ICH (2.8 ± 1.1 vs 2.2 ± 0.8; p = 0.011). The proportion of patients with lobar hematoma increased with increasing intensity of anticoagulation, with a ~2-fold increased odds of lobar compared to deep ICH (odds 2.17; p = 0.03) in those exposed to overanticoagulation (INR values >3.0).

Conclusions: OACs, as opposed to antiplatelets, predispose to lobar location of brain hematomas according to a dose-response relationship.
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http://dx.doi.org/10.1212/WNL.0000000000000108DOI Listing
February 2014

Obesity and the risk of intracerebral hemorrhage: the multicenter study on cerebral hemorrhage in Italy.

Stroke 2013 Jun 2;44(6):1584-9. Epub 2013 Apr 2.

Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italia.

Background And Purpose: The effect of obesity on the risk of intracerebral hemorrhage (ICH) may depend on the pathophysiology of vessel damage. To further address this issue, we investigated and quantified the correlations between obesity and obesity-related conditions in the causal pathways leading to ICH.

Methods: A total of 777 ICH cases ≥ 55 years of age (287 lobar ICH and 490 deep ICH) were consecutively enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy and compared with 2083 control subjects by a multivariate path analysis model. Separate analyses were conducted for deep and lobar ICH.

Results: Obesity was not independently associated with an increased risk of lobar ICH (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-1.01) or deep ICH (OR, 1.18; 95% CI, 0.95-1.45) when compared with control subjects. The path analysis confirmed the nonsignificant total effect of obesity on the risk of lobar ICH (OR, 0.77; 95% CI, 0.58-1.02) but demonstrated a significant indirect effect on the risk of deep ICH (OR, 1.28; 95% CI, 1.03-1.57), mostly determined by hypertension (OR, 1.07; 95% CI, 1.04-1.11) and diabetes mellitus (OR, 1.04; 95% CI, 1.01-1.07). Obesity was also associated with an increased risk of deep ICH when compared with lobar ICH (OR, 1.62; 95% CI, 1.14-2.31).

Conclusions: Obesity increases the risk of deep ICH, mostly through an indirect effect on hypertension and other intermediate obesity-related comorbidities, but has no major influence on the risk of lobar ICH. This supports the hypothesis of different, vessel-specific, biological mechanisms underlying the relationship between obesity and cerebral hemorrhage.
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http://dx.doi.org/10.1161/STROKEAHA.111.000069DOI Listing
June 2013

The THRombolysis and STatins (THRaST) study.

Neurology 2013 Feb 23;80(7):655-61. Epub 2013 Jan 23.

SSO Stroke Unit, U.O. Neurologia d.O., DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata, Italy.

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.

Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death.

Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007).

Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.
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http://dx.doi.org/10.1212/WNL.0b013e318281cc83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590058PMC
February 2013