Publications by authors named "Loris Poli"

44 Publications

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

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

Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions.

J Neurol Neurosurg Psychiatry 2021 07 6;92(7):751-756. Epub 2020 Nov 6.

Unit of Neurology, ASST Valcamonica, Esine (Bs), Italy.

Objective: Single cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19.

Methods: GBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered.

Results: Incidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002).

Conclusions: This study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.
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http://dx.doi.org/10.1136/jnnp-2020-324837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650204PMC
July 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

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

Neurology 2020 08 22;95(7):e910-e920. Epub 2020 May 22.

From the Neurology Unit (A.B., A. Pilotto, I.L., M.G., E.B., S.B., M.C., S.C.P., V.C., A.I., M. Locatelli, S.M., B.R., L.R., A.S., F.S.d.C., N.Z., B.B., A. Pezzini, A. Padovani), Department of Clinical and Experimental Sciences, University of Brescia; Neurology Unit (A.B., A. Pilotto, C.A., A.A., S.C., E.C., M.F., S. Gipponi, P.L., L.P., R.R., L.R., I.V., B.B., A. Pezzini, A. Padovani), Vascular Neurology Unit (E.P., A.C., I.D., M.G., N.G., R.S., V.V., M.M.), and Neurophysiology Unit (S. Gazzina, U.L.), Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia; Neurology Unit (M.B.), University of Bologna; Department of Neuroimmunology and Neuromuscular Diseases (L.B.) and Neurology (M. Leonardi), Public Health and Disability Unit, Foundation IRCCS Neurological Institute Carlo Besta, Milan; and Neurology Unit (P.I.), Fondazione Poliambulanza Hospital, Brescia, Italy.

Objective: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19).

Methods: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period.

Results: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, = 0.009) on admission.

Conclusions: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.
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http://dx.doi.org/10.1212/WNL.0000000000009848DOI Listing
August 2020

Subarachnoid Extension Predicts Lobar Intracerebral Hemorrhage Expansion.

Stroke 2020 05 23;51(5):1470-1476. Epub 2020 Mar 23.

Dipartimento di Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Neuroradiologia, Università degli Studi di Firenze, Ospedale Universitario Careggi, Firenze, Italia (G.B., E.F.).

Background and Purpose- We investigated whether subarachnoid extension (SAHE) of intracerebral hemorrhage (ICH) is associated with hematoma expansion (HE). Methods- Retrospective analysis of patients with primary spontaneous ICH admitted at 3 academic hospitals in Italy. The study population was divided into a development and a replication cohort. SAHE was rated on baseline noncontrast computed tomography by investigators blinded to clinical data. The main outcome of interest was HE, defined as ICH growth >33% mL and/or >6 mL. Predictors of HE were explored with multivariable logistic regression stratified by ICH location (lobar versus nonlobar). Results- A total of 360 and 192 patients were included in the development and replication cohort, respectively. SAHE was identified with good interrater reliability (=0.82), and its frequency was 27.8% in the development and 24.5% in the replication cohort. In univariate analysis, HE was more common in patients with SAHE (52.0% versus 27.3%; <0.001). When controlling for confounders in logistic regression, SAHE was an independent predictor of lobar HE (odds ratio, 6.00 [95% CI, 2.16-16.64]; =0.001) whereas there was no association with HE in nonlobar ICH (odds ratio, 0.55 [95% CI, 0.17-1.84]; =0.334). The increased risk of HE in lobar ICH with SAHE was confirmed in the replication cohort (odds ratio, 3.46 [95% CI, 1.07-11.20]; =0.038). Conclusions- SAHE predicts HE in lobar ICH. This may improve the stratification of HE risk in clinical practice or future trials targeting HE. Further research is needed to confirm our findings and characterize the underlying biological mechanisms.
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http://dx.doi.org/10.1161/STROKEAHA.119.028338DOI Listing
May 2020

History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS).

J Stroke 2019 09 30;21(3):324-331. Epub 2019 Sep 30.

Department of Clinical and Experimental Sciences, Neurological Clinic, University of Brescia, Brescia, Italy.

Background And Purpose: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated.

Methods: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status.

Results: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54).

Conclusion: s These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.
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http://dx.doi.org/10.5853/jos.2019.00332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780016PMC
September 2019

Validation and Comparison of Noncontrast CT Scores to Predict Intracerebral Hemorrhage Expansion.

Neurocrit Care 2020 06;32(3):804-811

Stroke Unit, IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino, Pavia, Italy.

Background And Purpose: The BAT, BRAIN, and HEP scores have been proposed to predict hematoma expansion (HE) with noncontrast computed tomography (NCCT). We sought to validate these tools and compare their diagnostic performance.

Methods: We retrospectively analyzed two cohorts of patients with primary intracerebral hemorrhage. HE expansion was defined as volume growth > 33% or > 6 mL. Two raters analyzed NCCT scans and calculated the scores, blinded to clinical and imaging data. The inter-rater reliability was assessed with the interclass correlation statistic. Discrimination and calibration were calculated with area under the curve (AUC) and Hosmer-Lemeshow χ statistic, respectively. AUC comparison between different scores was explored with DeLong test. We also calculated the sensitivity, specificity, positive, and negative predictive values of the dichotomized scores with cutoffs identified with the Youden's index.

Results: A total of 230 subjects were included, of whom 86 (37.4%) experienced HE. The observed AUC for HE were 0.696 for BAT, 0.700 for BRAIN, and 0.648 for HEP. None of the scores had a significantly superior AUC compared with the others (all p > 0.4). All the scores had good calibration (all p > 0.3) and good-to-excellent inter-rater reliability (interclass correlation > 0.8). BAT ≥ 3 showed the highest specificity (0.81), whereas BRAIN ≥ 6 had the highest sensitivity (0.76).

Conclusions: The BAT, BRAIN, and HEP scores can predict HE with acceptable discrimination and require just a baseline NCCT scan. These tools may be used to stratify the risk of HE in clinical practice or randomized controlled trials.
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http://dx.doi.org/10.1007/s12028-019-00797-2DOI Listing
June 2020

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

Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results.

BMC Neurol 2019 May 29;19(1):103. Epub 2019 May 29.

Stroke Unit, Neurologia Vascolare, ASST Spedali Civili di Brescia, Piazzale Spedali Civili 1, Brescia 25123, Brescia, Italy.

Background: endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients remains unclear. The present study aims to investigate whether IVT followed by ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS with LVO.

Methods: we achieved a single center retrospective study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. Functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up brain CT scan infarct volume (EFIV) (for recanalized patients only), symptomatic intracerebral hemorrhage (sICH) and 3-month mortality were the outcomes of interests. Independent predictors of the outcomes were explored with multivariable logistic regression.

Results: 145 subjects were included in the study, of whom 70 underwent direct ET and 75 were treated with CoT. Functional independence at 3-months was more frequent in CoT subjects compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P < 0.001. mRS score 0-2: 67.1% vs 37.3%; P < 0.001); CoT patients had also higher first-pass success rate (62.7% vs 38.6%, P < 0.05), higher recanalization rate (84.3% vs 65.3%; P = 0.009) and, in recanalized subjects, smaller EFIV (16.4 ml vs 62.3 ml; P = 0.003). Mortality and intracranial bleeding did not differ between the two groups. In multivariable regression analysis, low baseline NIHSS score (P < 0.05), vessel recanalization (P = 0.05) and CoT (P = 0.03) were independent predictors of favorable outcome at three months.

Conclusions: CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.
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http://dx.doi.org/10.1186/s12883-019-1341-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540520PMC
May 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

Acute Stroke.

Semin Neurol 2019 02 11;39(1):61-72. Epub 2019 Feb 11.

U.O. di Neurologia, Istituto Clinico Fondazione Poliambulanza, Brescia, Italy.

Stroke remains one of the leading determinants of death and severe disability worldwide. It is a medical emergency with a narrow window for recognition and administration of outcome-modifying treatment in the emergency department. Ischemic stroke accounts for the majority of cerebrovascular events and revascularization therapies such as intravenous thrombolysis and endovascular thrombectomy are the mainstays of treatment in carefully selected patients. Intracerebral hemorrhage is less common but remains the deadliest type of stroke. Blood pressure reduction and hemostatic treatment in case of coagulopathy are the cornerstones of acute intracerebral hemorrhage treatment. Admission to dedicated stroke units is associated with improved outcome in patients suffering from acute stroke.
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http://dx.doi.org/10.1055/s-0038-1676992DOI Listing
February 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

Short-term outcome of carotid dissecting pseudoaneurysm: is it always benign?

Acta Neurol Belg 2018 Dec 10;118(4):537-539. Epub 2018 Apr 10.

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

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http://dx.doi.org/10.1007/s13760-018-0917-9DOI Listing
December 2018

Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers.

Stroke 2018 03 19;49(3):573-578. Epub 2018 Feb 19.

From the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica (A.P., L.P., F.C., V.D.G., A.P.) and Sezione di Neuroradiologia, Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica (R.G.), Università degli Studi di Brescia, Italia; Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Struttura Operativa Dipartimentale di Radiodiagnostica 2 (G.B., S.C.) and Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Struttura Operativa Dipartimentale di Neuroradiologia (E.F.), Università degli Studi di Firenze, Azienda Ospedaliero-Universitaria Careggi, Italia; Unità di Neurologia, Stroke Unit (M.Z.) and Unità di Neuroradiologia (R.P.), Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italia; Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Italia (M.G.); Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile S. Agostino Estense, AUSL Modena, Italia (A.Z., A.M.S.); and Unità di Neurologia, Dipartimento di Scienze Biologiche, Psichiatriche e Psicologiche, Università di Ferrara, Italia (M.P.).

Background And Purpose: Cerebral hyperexcitability in migraine experiencers might sensitize brain tissue to ischemia. We investigated whether a personal history of migraine is associated with vulnerability to brain ischemia in humans.

Methods: Multicenter cohort study of patients with acute ischemic stroke who underwent a brain computed tomography perfusion and were scheduled to undergo reperfusion therapy. In a case-control design, we compared the proportion of subjects with no-mismatch, the volume of penumbra salvaged, as well as the final infarct size in a group of patients with migraine and a group of patients with no history of migraine.

Results: We included 61 patients with migraine (34 [55.7%] men; mean age, 52.2±15.1 years; migraine without aura/migraine with aura, 44/17) and 61 patients with no history of migraine. The proportion of no-mismatch among migraineurs was significantly higher than among nonmigraineurs (17 [27.9%] versus 7 [11.5%]; =0.039) and was more prominent among patients with migraine with aura (6 [35.3%]; =0.030) while it was nonsignificantly increased in patients with migraine without aura (11 [25.0%]; =0.114). Migraine, especially migraine with aura, was independently associated with a no-mismatch pattern (odds ratio, 2.65; 95% CI, 0.95-7.41 for migraine; odds ratio, 5.54; 95% CI, 1.28-23.99 for migraine with aura), and there was a linear decrease of the proportion of patients with migraine with aura with increasing quartiles of mismatch volumes. Patients with migraine with aura had also smaller volumes of salvaged penumbra (9.8±41.2 mL) compared with patients with migraine without aura (36.4±54.1 mL) and patients with no migraine (45.1±55.0 mL; =0.056). Conversely, there was no difference in final infarct size among the 3 migraine subgroups (=0.312).

Conclusions: Migraine is likely to increase individual vulnerability to ischemic stroke during the process of acute brain ischemia and might represent, therefore, a potential new therapeutic target against occurrence and progression of the ischemic damage.
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http://dx.doi.org/10.1161/STROKEAHA.118.020554DOI Listing
March 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

Arterial tortuosity in patients with spontaneous cervical artery dissection.

Neuroradiology 2017 Jun 11;59(6):571-575. Epub 2017 May 11.

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

Purpose: The aim of this study was to test the hypothesis that patients with spontaneous cervical artery dissection (CeAD) have increased arterial tortuosity, and the objective quantification of such a tortuosity may aid in the identification of subjects at increased risk of disease.

Methods: In the setting of a hospital-based, case-control study, we used the vertebral tortuosity index (VTI) measured on magnetic resonance angiography, a validated method for the assessment and quantification of arterial tortuosity, to compare the degree of tortuosity in a series of consecutive patients with spontaneous CeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) and stroke-free subjects.

Results: The study group was composed of 102 patients with CeAD (mean age, 44.5 ± 7.8 years; 66.7% men), 102 with non-CEAD IS, and 102 stroke-free subjects. The VTI was higher in the group of patients with CeAD (median, 7.3; 25th-75th percentile, 10.2) compared with that of non-CeAD IS (median, 3.4; 25th-75th percentile, 4.4) and of stroke-free subjects (median, 4.0; 25th-75th percentile, 2.9; p ≤ 0.001), and was independently associated to the risk of CeAD (OR, 1.18; 95% CI, 1.09-1.29) in multivariable regression analysis. The degree of tortuosity also tended to be higher in CeAD patients who experienced short-term recurrence (5.8%; median, 20.2; 25th-75th percentile, 31.2) than in those without recurrent events (median, 7.2; 25th-75th percentile, 9.4; p = 0.074).

Conclusion: CeAD patients exhibit increased arterial tortuosity. This might have potential implications for better understanding of the pathophysiology of the disease as well as clinical utility in evaluation, prognostication, and decision-making of affected individuals.
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http://dx.doi.org/10.1007/s00234-017-1836-9DOI Listing
June 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

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation).

Eur Stroke J 2017 Mar 15;2(1):46-53. Epub 2016 Nov 15.

SSO Stroke Unit, UO Neurologia, DAI di Neuroscienze, AOUI Verona, Italy.

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes.

Methods: Data were analyzed from the "Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation" (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0-2 favorable outcome, 3-6 unfavorable outcome).

Results: Of the 1029 patients enrolled, 561 were women (54.5%) ( < 0.001) and younger ( < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke ( = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%,  = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women,  = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5,  < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men ( = 0.28 and  = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men ( < 0.001). Multivariate analysis did not confirm this significance.

Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes.
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http://dx.doi.org/10.1177/2396987316679577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377059PMC
March 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

Infective Endocarditis Presenting with Intracranial Bleeding.

J Emerg Med 2016 Jul 25;51(1):50-4. Epub 2016 May 25.

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

Background: Infective endocarditis (IE) can be complicated by intracranial bleeding (ICB) caused by different pathologic mechanisms. The occurrence of ICB in patients with IE significantly influences therapeutic decisions and has a negative impact on outcome.

Case Report: We describe the clinical courses of 3 patients with aortic prosthetic valve IE presenting with ICB. Patients 1 and 2 experienced subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), respectively, caused by rupture of an intracranial infectious aneurysm (IIA). Both underwent endovascular treatment of IIA with good outcome. In patient 3, ICB was the hemorrhagic conversion of an acute ischemic lesion from septic brain embolization. In the subacute phase of the disease, aortic valve replacement was performed, with excellent outcome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ICB is a relevant complication and sometimes the first clinical feature of IE. Imaging of brain vessels should be performed to investigate the pathologic mechanism underlying ICB. The prevalence of IIA is probably underestimated and may influence the therapeutic strategy. Cerebrovascular imaging may therefore also be considered in asymptomatic subjects with left-sided IE. Withdrawal of anticoagulant treatment and delay of cardiac surgery are recommended in all cases of IE complicated by ICB. Because of the impact of ICB on IE management and outcome, a high level of clinical suspicion and prompt recognition and treatment of this complication are necessary.
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http://dx.doi.org/10.1016/j.jemermed.2016.04.003DOI Listing
July 2016

Severe eosinophilia associated with cholangiocarcinoma.

J Community Support Oncol 2016 Apr;14(4):173-7

Department of Internal Medicine, Cervesi Hospital (AUSL Romagna), Cattolica, Italy.

It is widely recognized that eosinophils are found in tumor infiltrates and that their mechanism of action is associated with particular symptoms and prognosis. However, the causes of and reasons for this process remain unclear, as does the exact mechanism by which it occurs. We report on the case of a 71-year-old woman with cholangiocellar carcinoma (CCC) with a marked eosinophilia. When the patient presented at the hospital, she said she was suffering from fatigue, depression, and pain. That triad of symptoms, indicative of peripheral eosinophilia (TABE, or tumor-associated blood eosinophilia) and tissue eosinophilia (TATE, or tumor-associated tissue eosinophilia), are recurrent in oncology. We also conducted a structured review of literature on eosinophilia associated with biliary tumors to try to answer 3 questions: Is eosinophilia (TABE or TATE) associated with solid tumors, with particular reference to the tumor of the bile duct? Is eosinophilia in biliary tumors associated with specific symptoms? Does eosinophilia (TABE or TATE) predict a specific prognosis?
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http://dx.doi.org/10.12788/jcso.0223DOI Listing
April 2016