Publications by authors named "Guido Bigliardi"

25 Publications

  • Page 1 of 1

"Don't call me from the left side…": ischemic stroke in a patient with uncommon vertebral artery dissection.

Neurol Sci 2021 Jun 5. Epub 2021 Jun 5.

Neurology Clinic, Department of Neuroscience, University Hospital of Modena, via Giardini 1355 Baggiovara, ZIP 41100, Modena, Italy.

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http://dx.doi.org/10.1007/s10072-021-05369-xDOI Listing
June 2021

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

Neurology 2021 Jun 4. Epub 2021 Jun 4.

Department of Clinical Neuroscience, Karolinska Institutet.

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

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

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

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

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

TeleNeurological evaluation and Support for the Emergency Department (TeleNS-ED): protocol for an open-label clinical trial.

BMJ Open 2021 05 19;11(5):e048293. Epub 2021 May 19.

Neurology Unit, Azienda Ospedaliero-Universitaria di Modena Ospedale Civile di Baggiovara, Modena, Italy

Introduction: The COVID-19 pandemic compelled health systems to protect patients and medical personnel during transit in hospitals by minimising transfers, prompting the use of telehealth systems. In the field of neurology, telemedicine has been used in emergency settings for acute stroke management between spoke and hub hospital networks, where good outcomes have been achieved. However, data on the use of telemedicine in non-stroke acute neurological conditions accessing the emergency department (ED) are currently missing.

Methods And Analyses: This is an interventional, open-label trial on the use of teleconsultation in the ED for neurological diseases other than stroke. The study aims to develop a remote consultancy system (TeleNeurological Evaluation and Support, TeleNS) for patients with acute neurological symptoms referred to hospital facilities without a 24-hour availability of a neurologist consultant (spoke hospitals). The study population will include 100 ED patients referred to two spoke hospitals in 6 months, who will be asked to perform teleconsultation instead of inperson visits. As a control group, retrospectively available data from patients admitted to the ED of spoke hospitals during the same time period over the last 2 years will be evaluated. The primary objective is to assess whether a TeleNS for the ED guarantees a faster but qualitatively non-inferior diagnostic/therapeutic work-up if compared with inperson examination, assuring the availability of all the necessary examinations and treatments with consistent time-saving.

Ethics And Dissemination: The trial was designed following the national guidelines on clinical investigation on telemedicine provided by the Italian Ministry of Health and according to the Standard Protocol Items for Randomized Trials statement guidelines. This research protocol was approved by Comitato Etico Area Vasta Emilia Nord in September 2020 (number/identification: 942/2020/DISP/AOUMO SIRER ID 805) and was written without patient involvement. Patients' associations will be involved in the dissemination of study design and results. The results of the study will be presented during scientific symposia or published in scientific journals.

Trial Registration Number: NCT04611295.
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http://dx.doi.org/10.1136/bmjopen-2020-048293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137206PMC
May 2021

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

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

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

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

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

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

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

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

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

Stroke Unit, Spedali Civili, Brescia, Italy.

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

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

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

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

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

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

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

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

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

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

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

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

Middle cerebral artery ischemic stroke and COVID-19: a case report.

J Neurovirol 2020 12 8;26(6):967-969. Epub 2020 Sep 8.

Stroke Unit - Neurology Clinic, Department of Neuroscience, Ospedale Civile di Baggiovara, Azienda Ospedaliera Universitaria di Modena, Modena, Italy.

We present a clinical case of a patient with SARS-CoV-2 infection and respiratory symptoms, complicated with a pro-thrombotic state involving multiple vascular territories and concomitant interleukin-6 increase. This case underlines the possibility to develop a COVID-19-related coagulopathy.
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http://dx.doi.org/10.1007/s13365-020-00898-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478241PMC
December 2020

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

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

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

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

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

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

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

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

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

Azienda Ospedaliero-Univeristaria, Padua, Italy.

Background: Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT.

Methods: A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT).

Results: After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042-2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014-1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014-1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039-1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0-2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count < 100,000/mm (OR: 4.798), bacterial endocarditis (OR: 15.069), neoplasm with increased hemorrhagic risk (OR: 6.046), and severe liver disease (OR: 6.124).

Conclusions: Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.
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http://dx.doi.org/10.1007/s00415-020-10098-wDOI Listing
December 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Relation Between Aortic Arch Branching Types and the Laterality of Cardio-Embolic Stroke.

J Stroke Cerebrovasc Dis 2020 Jul 13;29(7):104917. Epub 2020 May 13.

Department of Neuroscience, Stroke Unit - Neurology Clinic, Ospedale Civile di Baggiovara, AOU di Modena, Italy; Faculty of Medicine, Department of Neurology, Mansoura University, Mansoura 35511, Egypt. Electronic address:

Background And Purpose: The trajectory of cardiogenic emboli could be affected by anatomical and flow characteristics of the aortic arch. We aimed to study the relation between the different aortic arch patterns and the laterality of cardiogenic emboli.

Methods: 192 cardioembolic strokes were classified into 3 groups according to the type of the aortic arch; type 1 (n = 69), type 2 (n = 49), type 3 (n = 74). The side and site of the cerebral vessels occlusion were divided into anterior and posterior circulation strokes, and anterior strokes were further subdivided into right or left internal carotid, middle or anterior cerebral arteries occlusion.

Results: Overall, the anterior circulation embolic occlusions were more common than the posterior, and middle cerebral artery more commonly affected than internal carotid artery. The left side propensity was higher either in the total patients' pool or after segregation into atrial fibrillation (AF) and non AF cardio-embolic cases in all types of aortic arch except for type 1 aortic arch in the non AF cases. This propensity tended to get higher with advancement of the aortic arch types but failed to show statistically significant difference between the 3 arch types, however combination of type 2 and 3 arches into a single group showed statistically significant rise in the left side propensity in the total cardioembolic cases (P = 0.039) and in the non AF cardioembolic cases (P = 0.029). The bovine arch also showed increased left side propensity.

Conclusion: Cardioemboli tends to have left anterior cerebrovascular predilection especially with AF. Different geometrical patterns of aortic arch branching seem to affect the laterality of cardioemboli and increase its left side predilection.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104917DOI Listing
July 2020

Novel pathogenic TGFBR1 and SMAD3 variants identified after cerebrovascular events in adult patients with Loeys-dietz syndrome.

Eur J Med Genet 2019 Oct 18;62(10):103727. Epub 2019 Jul 18.

Stroke Unit, Neurology Clinic, Department of Neuroscience, Ospedale Civile "S. Agostino-Estense", Modena University Hospital, University of Modena and Reggio Emilia, Modena, Italy.

Introduction: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder due to heterozygous pathogenic variants in transforming growth factor beta (TGFβ) signaling-related genes. LDS types 1-6 are distinguished depending on the involved gene. LDS is characterized by multiple arterial aneurysms and dissections in addition to variable neurological and systemic manifestations. Patient 1: a 68-year-old man was admitted due to an aphasic transient ischemic attack (TIA). Brain CT-scan and CT angiography revealed a chronic and asymptomatic right vertebral artery dissection. Stroke diagnostic panel was unremarkable. His history showed mild stroke familiarity. At age of 49, he was treated for dissecting-aneurysm of the ascending aorta and started anticoagulation therapy. Seven years later, he underwent surgery for dissecting aneurysm involving aortic arch, descending-thoracic aorta, left subclavian artery, and both iliac arteries. Patient 2: a 47-year-old man presented a left hemiparesis due to right middle cerebral artery (MCA) and anterior cerebral artery (ACA) occlusion caused by right internal carotid artery (ICA) dissection after sport activity. Despite i.v. thrombolysis and mechanical thrombectomy, he developed malignant cerebral infarction and underwent decompressive hemicraniectomy. Digital subtraction angiography showed bilateral carotid and vertebral kinking, aneurysmatic dilatation on both common iliac arteries and proximal ectasia of the descending aorta. His father and his uncle died because of an ischemic stroke and a cerebral aneurysm rupture with a subarachnoid hemorrhage (SAH), respectively.

Discussion: in both cases, considering the family history and the multiple dissections and aneurysms, LDS molecular analysis was performed. In patient 1, the novel NM_005902.3 (SMAD3): c.840T > G; p.(Asn280Lys) likely pathogenic variant was identified, thus leading to a diagnosis of LDS type 3. In patient 2, the novel NM_004612.2 (TGFBR1): c.1225T > G; p.(Trp409Gly) likely pathogenic variant was found, allowing for a diagnosis of LDS type 1.

Conclusion: LDS is characterized by genetic and clinical variability. Our report suggests that this genetically-determined connective tissue disorder is probably underestimated, as it might firstly show up with cerebrovascular events, although mild systemic manifestations. These findings could lead to identify people at risk of severe vascular complications (i.e., through genetic consult on asymptomatic relatives), in order to perform adequate vascular assessments and follow-up to prevent complications such as stroke.
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http://dx.doi.org/10.1016/j.ejmg.2019.103727DOI Listing
October 2019

Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment.

Adv Clin Exp Med 2019 Feb;28(2):219-222

Stroke Unit, Neurology Clinic, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, University of Modena and Reggio Emilia, Modena, Italy.

Background: Post-thrombotic intracerebral hemorrhage (ICH) is experienced by 6-8% of stroke patients and is associated with multiple factors, including acquired coagulopathy induced by the thrombolytic drug.

Objectives: The objective of this study was to assess the outcome of the intravenous (IV) administration of fibrinogen concentrate in a series of acute stroke patients who developed iatrogenic fibrinogen critical depletion after IV thrombolysis.

Material And Methods: Of the 39 ischemic stroke patients treated with IV thrombolysis with a severe hypofibrinogenemia requiring infusion with IV fibrinogen concentrate, 30 patients were treated with 2 g of IV recombinant tissue plasminogen activator (rt-PA), followed by further doses until the fibrinogen level reached 200 mg/dL in hemorrhagic patients or 100 mg/dL in non-hemorrhagic patients, and 9 were treated with IV rt-PA followed by endovascular thrombectomy.

Results: Preand post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) scores were statistically different for the Cochran-Mantel-Haenszel test overall (p = 0.0002), at 24-hour evaluation (p = 0.0455) and at 7-day assessment (p = 0.0006). Within the first 7 days post-thrombolysis, the brain computed tomography (CT) scans showed that 20/39 (51.28%) patients had ICH. Of the whole sample, 25.6% of the ICH patients had symptomatic intracerebral hemorrhage (SICH), according to National Institute of Neurological Disorders and Stroke (NINDS) classification. After rt-PA treatment, the median pre-thrombolysis fibrinogenemia of 332 mg/dL significantly dropped to 133 mg/dL (p < 0.0001). After the fibrinogen concentrate infusion, the median level of fibrinogenemia rose to 160 mg/dL, which was significantly higher than the median postthrombolysis levels (p < 0.0001). Recanalization was observed in 25/28 patients (89.29%): complete in 18 and partial in 7 patients. After fibrinogen IV infusion, no thrombotic complications were seen in 37 out of 39 patients (94.77%); 2/39 (0.05%) patients experienced a pulmonary embolism, 1 of them a segmental one.

Conclusions: This study showed the clinical safety of administering IV fibrinogen concentrate in order to increase plasma fibrinogen levels in a series of acute stroke patients with iatrogenic fibrinogen depletion after IV thrombolysis.
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http://dx.doi.org/10.17219/acem/84936DOI Listing
February 2019

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial).

Stroke 2017 12 3;48(12):3316-3322. Epub 2017 Nov 3.

From the Geriatrics Ward-Stroke Care Section, (L.D., A.A.), Research and Innovation Unit (C.C., B.M., E.I.), and Stroke Care Program (U.S., P.C., C.Z.), University Hospital of Parma, Italy; Stroke Unit, Nuovo Ospedale Civile S Agostino Estense, University Hospital of Modena, Italy (A.Z., M.B., L. Vaghi, S.O., F.B., G.B., L. Vandelli); Stroke Unit, Neurology Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy (G.M., M.L.Z., E.P., D.M.); Department of Neurology, Guglielmo da Saliceto Hospital, Piacenza, Italy (D.G., I.I.); Neurology Unit, Vaio Fidenza Hospital, Italy (E.M., A.G.); Department of Oncology and Hemato-oncology, University of Milan, Italy (S.R.); and Institute of Communication and Health, University of Svizzera Italiana, Lugano, Switzerland (P.J.S.).

Background And Purpose: Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay.

Methods: According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends.

Results: We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60-1.08; =0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (=0.07).

Conclusions: Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.
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http://dx.doi.org/10.1161/STROKEAHA.117.018135DOI Listing
December 2017

Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study.

J Stroke Cerebrovasc Dis 2017 Aug 30;26(8):1864-1873. Epub 2017 May 30.

Stroke Unit, Neurology Clinic, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, University Hospital of Modena, Modena, Italy. Electronic address:

Background: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms.

Methods: A total of 624 stroke patients on antiplatelet therapy were included. Two different groups were identified: "non-naive patients", and "naive patients". Platelet function was measured with multiple electrode aggregometry, and genotyping assays were used to determine CYP2C19 polymorphisms.

Results: Aspirin (ASA) responsiveness was significantly more frequent in naive patients compared with non-naive patients (94.9% versus 82.6%, P < .0010). A better responsiveness to ASA compared with Clopidogrel or combination therapy was found in the entire population (P < .0010), in non-naive patients (P < .0253), and in naive patients (P < .0010). Multivariate analysis revealed a strong effect of Clopidogrel as a possible "risk factor" for unresponsiveness (odds ratio 3.652, P < .0001). No difference between etiological subgroups and no correlations between responsiveness and CYP2C19 polymorphisms were found.

Conclusion: In our opinion, platelet function testing could be potentially useful in monitoring the biological effect of antiplatelet agents. A substantial proportion of patients with stroke on ASA were "resistant", and the treatment with Clopidogrel was accompanied by even higher rates of unresponsiveness. Longitudinal studies are needed to assess whether aggregometry might supply individualized prognostic information and whether it can be considered a valid tool for future prevention strategies.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.04.023DOI Listing
August 2017

Usefulness of Thromboelastography in the Detection and Management of Tissue Plasminogen Activator-Associated Hyperfibrinolysis.

J Stroke Cerebrovasc Dis 2017 Feb 23;26(2):e29-e31. Epub 2016 Nov 23.

Stroke Unit, Department of Neuroscience, University of Modena and Reggio Emilia, NOCSAE, AUSL Modena, Baggiovara, Modena, Italy. Electronic address:

Rotation thromboelastometry is a viscoelastometric method that provides a rapid assessment of a patient's hemostatic processes in emergency settings, allowing prompt identification of specific coagulation abnormalities. Its results thus might guide targeted replacement therapy in hemorrhagic conditions, in case of platelet or coagulation factor deficiency, or hyperfibrinolysis, which is difficult to identify otherwise. Although currently used in emergency and traumatic surgery, there are limited data about thromboelastometry in ischemic stroke, particularly in monitoring the coagulative response to recombinant tissue plasminogen activator after intravenous thrombolysis (IVT). Here we report a case of ischemic stroke complicated by a remote asymptomatic intracranial hemorrhage after IVT and additional endovascular therapy that has been successfully treated with intravenous infusion of tranexamic acid after the detection of the status of hyperfibrinolysis provided by thromboelastometry. Further studies are needed to provide the potential usefulness of thromboelastometry and tranexamic acid in ischemic stroke complicated by intracranial bleeding.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.10.039DOI Listing
February 2017

Familial paraganglioma syndrome: a rare cause of carotid artery occlusion.

J Neurol 2016 Dec 20;263(12):2544-2546. Epub 2016 Oct 20.

Stroke Unit, Department of Neuroscience, Neurology Clinic, University of Modena and Reggio Emilia, Nuovo Ospedale Civile "S.Agostino-Estense", AUSL Modena, Via Giardini 1355 Baggiovara, 41100, Modena, Italy.

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http://dx.doi.org/10.1007/s00415-016-8317-7DOI Listing
December 2016

"Opening the Unopenable": Endovascular Treatment in a Patient with Three Months' Internal Carotid Artery Occlusion and Hemispheric Symptomatic Hypoperfusion.

J Stroke Cerebrovasc Dis 2016 Aug 27;25(8):2016-8. Epub 2016 May 27.

Stroke Unit-Neurology Clinic, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, AUSL Modena, Modena, Italy.

Background: Internal carotid artery occlusion (ICAO) is defined as "untouchable" by all specialists; no treatment is indicated because intervention risks (carotid endarterectomy (CEA) or endovascular treatment) are usually much more than benefits.(1,2) We report the case of a patient admitted to our hospital with an atherothrombotic ischemic stroke due to symptomatic acute ICAO, who developed a recurrent stroke with hemispheric hypoperfusion and was treated in the emergency department with ICAO revascularization after 60 days of occlusion finding.

Case Description: D.G., a 62-year-old man, came to our attention for a transient episode of left weakness and hypoesthesia. The electrocardiogram revealed a new diagnosis of atrial fibrillation. CT angiography showed right ICAO; computed tomography and magnetic resonance imaging studies with perfusion imaging revealed a severe hemispheric hypoperfusion. Full anticoagulation therapy was started, and antihypertensive therapy was reduced to help collateral circulation. Some weeks later, the patient was readmitted to the stroke unit for 2 episodes of left-hand weakness. Cerebral angiography confirmed right ICAO from the proximal tract to the siphon. After some days, the patient suffered a femoral hemorrhagic lesion, with active bleeding, and was treated with surgical intervention. On the following day, the patient presented with left hemiplegia with hemianesthesia (National Institutes of Health Stroke Scale score = 14). The patient was treated in the emergency department with a complex endovascular treatment with complete recanalization of ICAO by positioning 3 stents through the intravenous infusion of abciximab. After intensive rehabilitation, at the 3- and 6-month follow-up evaluations, the patient regained autonomy.

Conclusion: In literature, treatment of chronic ICAO is not indicated. Endovascular recanalization may be beneficial to patients with chronic cerebral hypoperfusion due to ICAO, when all conservative medical therapies have failed.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.04.019DOI Listing
August 2016

Fibrinogen decrease after intravenous thrombolysis in ischemic stroke patients is a risk factor for intracerebral hemorrhage.

J Stroke Cerebrovasc Dis 2015 Feb 11;24(2):394-400. Epub 2014 Dec 11.

Stroke Unit, Department of Neuroscience, University of Modena and Reggio Emilia, Nuovo Ospedale Civile S. Agostino-Estense, AUSL Modena, Modena, Italy. Electronic address:

Background: Intravenous thrombolysis is an effective treatment in acute stroke patients, but it increases the risk of intracerebral hemorrhages. Our aim is to establish if fibrinogen depletion increases the risk of intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke.

Methods: In 104 ischemic stroke patients, treated with intravenous thrombolysis, we assessed the rate of intracerebral hemorrhages documented by computed tomographic scan at 24 hours and within 7 days post-treatment. Fibrinogen levels were determined at 2 hours after therapy: patients were classified as belonging to "low fibrinogen group" if levels decreased to less than 2 g/L and/or by 25% or more. Fibrinogen levels and other known hemorrhagic risk factors were studied using univariate and multivariate analyses.

Results: During the first 7 days, an intracerebral hemorrhage was detected in 24 patients (23.1%), and only 6 of these (5.8%) experienced symptomatic bleeding; 41 patients were included in the low fibrinogen group. Among the 24 hemorrhages, 18 occurred in the low fibrinogen group and 6 in the "normal fibrinogen group": the bleeding rate in the low fibrinogen group was significantly higher (43.9%) than that in the normal fibrinogen group (9.5%; odds ratio [OR] 7.43, P < .001). Univariate and multivariate analyses revealed that only clinical severity (OR 1.15, P < .001) and hypofibrinogenemia (OR 7.47, P < .001) were significantly associated with brain bleeding at 7 days and at 24 hours (P = .008).

Conclusions: An early fibrinogen reduction seems to increase the risk of intracerebral hemorrhage after rtPA treatment in ischemic stroke. Fibrinogen assessment could be a rapid, inexpensive, and widely available tool to help the identification of patients at higher risk of bleeding.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.09.005DOI Listing
February 2015

Isolated paroxysmal dysarthria caused by a single demyelinating midbrain lesion.

BMJ Case Rep 2013 Oct 16;2013. Epub 2013 Oct 16.

Department of Biomedical Science, Metabolism and Neuroscience, University of Modena and Reggio Emilia, Modena, Italy.

Paroxysmal dysarthria is an unusual condition characterised by brief episodes of dysarthria with the sudden onset and frequent recurrence. It has been mainly reported in multiple sclerosis and an association with midbrain lesions has been claimed; however, most of the reported patients had multiple brain alterations so it was difficult to associate this symptom with a specific lesion site. We illustrate the cases of two patients with an isolated demyelinating midbrain lesion presenting paroxysmal dysarthria as the only symptom; both participants had oligoclonal bands in the cerebrospinal fluid and an unremarkable follow-up. Both patients had benefit from carbamazepine treatment, similarly to previously reported cases. Our report confirms that a demyelinating midbrain lesion is sufficient to provoke paroxysmal dysarthria. It is noteworthy that an erroneous diagnosis of psychogenic disorders was initially made in both cases, highlighting the importance not to underestimate isolated paroxysmal symptoms in clinical practice.
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http://dx.doi.org/10.1136/bcr-2013-200777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822091PMC
October 2013

IV thrombolysis and renal function.

Neurology 2013 Nov 11;81(20):1780-8. Epub 2013 Oct 11.

From the Departments of Neurology (H.G., D.J.S., N.P., L.H.B., P.A.L., S.T.E.), University Hospital Basel, Switzerland; Academic Medical Center (S.M.Z., Y.B.R., P.J.N.), University of Amsterdam, the Netherlands; University of Heidelberg (P.R.), Germany; Helsinki University Central Hospital (V.A., J.P., E.H., T.T.), Finland; University Lille North de France (D.L., R.B.), UDSL (EA1046), France; Centre Hospitalier Universitaire Vaudois and University of Lausanne (P.M., C.O.), Switzerland; Municipal Hospital Altenburg (J.B.), Germany; University Hospital Bern (M.A., M.R.H., H.S.), Switzerland; AUSL Modena (A.Z., G.B.), Italy; Clinical Center (V.P.), School of Medicine, University of Belgrade, Serbia; University Hospital Brescia (A.P.), Italy; Swiss Tropical and Public Health Institute (C.S.), University of Basel, Switzerland; University Hospital Zurich (H.S.), Switzerland.

Objective: To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT).

Methods: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3-6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group.

Results: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m(2)). A GFR decrease by 10 mL/min/1.73 m(2) increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17-1.24]; ORadjusted 1.05 [1.01-1.09]), death (ORunadjusted 1.33 [1.28-1.38]; ORadjusted 1.18 [1.11-1.249]), and sICH (ORunadjusted 1.15 [1.01-1.22]; ORadjusted 1.11 [1.04-1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10-1.58]), death (ORadjusted 1.73 [1.39-2.14]), and sICH (ORadjusted 1.64 [1.21-2.23]) compared with normal GFR (60-120 mL/min/1.73 m(2)). Low GFR (ORadjusted 1.64 [1.21-2.23]) and stroke severity (ORadjusted 1.05 [1.03-1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41-2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63-0.94]).

Conclusion: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m(2) seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.
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http://dx.doi.org/10.1212/01.wnl.0000435550.83200.9eDOI Listing
November 2013