Publications by authors named "Andrea Morotti"

95 Publications

Vessel wall magnetic resonance imaging in COVID-19-associated cryptogenic ischemic stroke.

Eur J Neurol 2021 Sep 27. Epub 2021 Sep 27.

Neurology Unit, Department of Neurological Sciences and Vision, ASST- Spedali Civili, Brescia, Italy.

Background And Purpose: Acute ischemic stroke (AIS) is a common complication of coronavirus disease 2019 (COVID-19), but the underlying biological mechanisms remain unclear. We aimed to describe the prevalence of vessel wall alterations in patients with cryptogenic stroke through vessel wall magnetic resonance imaging (vwMRI).

Methods: All consecutive patients admitted for AIS and COVID-19 to a single neuro-COVID unit from 10 November to 31 December 2020 were prospectively evaluated and underwent a complete etiologic workup for AIS. In patients with cryptogenic stroke, the diagnostic workup was completed with vwMRI study.

Results: After the exclusion of four patients ineligible for MRI, a total of 10 patients were included (median age = 78 years, 50% males), of whom four (40%) had a cryptogenic stroke. vwMRI showed vascular changes consistent with inflammation of intracranial artery walls in three subjects (75%). Two patients had focal and one multifocal involvement.

Conclusions: vwMRI detected signs of vascular inflammation in the majority of patients with cryptogenic AIS, leading to an etiologic definition with potential therapeutical implications. Our findings are best interpreted as hypothesis-generating, suggesting the possibility of expanding the diagnostic workup of cryptogenic stroke with vessel wall imaging.
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http://dx.doi.org/10.1111/ene.15128DOI Listing
September 2021

Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial.

Neurocrit Care 2021 Jul 22. Epub 2021 Jul 22.

Department of Neurology J. P. Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial.

Methods: We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139 mm Hg versus 140-179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days.

Results: Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions.

Conclusions: Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 ).
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http://dx.doi.org/10.1007/s12028-021-01254-9DOI Listing
July 2021

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

J Neurol Neurosurg Psychiatry 2021 Oct 12;92(10):1068-1071. Epub 2021 Jul 12.

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

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

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

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

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

CD163 as a Potential Biomarker of Monocyte Activation in Ischemic Stroke Patients.

Int J Mol Sci 2021 Jun 23;22(13). Epub 2021 Jun 23.

IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy.

In ischemic stroke patients, a higher monocyte count is associated with disease severity and worse prognosis. The complex correlation between subset phenotypes and functions underscores the importance of clarifying the role of monocyte subpopulations. We examined the subtype-specific distribution of the CD163+ and CD80+ circulating monocytes and evaluated their association with the inflammatory status in 26 ischemic stroke patients and 16 healthy controls. An increased percentage of CD163+/CD16+ and CD163+/CD14++ events occurred 24 and 48 h after a stroke compared to the controls. CD163+ expression was more pronounced in CD16+ non-classical and intermediate monocytes, as compared to CD14+ classical subtype, 24 h after stroke. Conversely, the percentage of CD80+/CD16+ events was unaffected in patients; meanwhile, the percentage of CD80+/CD14+ events significantly increased only 24 h after stroke. Interleukin (IL)-1beta, TNF-alpha, and IL-4 mRNA levels were higher, while IL-10 mRNA levels were reduced in total monocytes from patients versus controls, at either 24 h or 48 h after stroke. The percentage of CD163+/CD16+ events 24 h after stroke was positively associated with NIHSS score and mRS at admission, suggesting that stroke severity and disability are relevant triggers for CD163+ expression in circulating CD16+ monocytes.
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http://dx.doi.org/10.3390/ijms22136712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268853PMC
June 2021

Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage Related to Different Oral Anticoagulants.

J Clin Med 2021 May 21;10(11). Epub 2021 May 21.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.

Background: There is a need to examine the effects of different types of oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) on perihematomal edema (PHE), which is gaining considerable appeal as a biomarker for secondary brain injury and clinical outcome.

Methods: In a large multicenter approach, computed tomography-derived imaging markers for PHE (absolute PHE, relative PHE (rPHE), edema expansion distance (EED)) were calculated for patients with OAC-ICH and NON-OAC-ICH. Exploratory analysis for non-vitamin-K-antagonist OAC (NOAC) and vitamin-K-antagonists (VKA) was performed. The predictive performance of logistic regression models, employing predictors of poor functional outcome (modified Rankin scale 4-6), was explored.

Results: Of 811 retrospectively enrolled patients, 212 (26.14%) had an OAC-ICH. Mean rPHE and mean EED were significantly lower in patients with OAC-ICH compared to NON-OAC-ICH, -value 0.001 and 0.007; whereas, mean absolute PHE did not differ, -value 0.091. Mean EED was also significantly lower in NOAC compared to NON-OAC-ICH, -value 0.05. Absolute PHE was an independent predictor of poor clinical outcome in NON-OAC-ICH (OR 1.02; 95%CI 1.002-1.028; -value 0.027), but not in OAC-ICH (-value 0.45).

Conclusion: Quantitative markers of early PHE (rPHE and EED) were lower in patients with OAC-ICH compared to those with NON-OAC-ICH, with significantly lower levels of EED in NOAC compared to NON-OAC-ICH. Increase of early PHE volume did not increase the likelihood of poor outcome in OAC-ICH, but was independently associated with poor outcome in NON-OAC-ICH. The results underline the importance of etiology-specific treatment strategies. Further prospective studies are needed.
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http://dx.doi.org/10.3390/jcm10112234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196746PMC
May 2021

Association between perihematomal perfusion and intracerebral hemorrhage shape.

Neuroradiology 2021 Sep 14;63(9):1563-1567. Epub 2021 Apr 14.

Neuroradiology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Purpose: The pathophysiological determinants of irregular intracerebral hemorrhage (ICH) shape are unclear. We aimed at characterizing the relationship between perihematomal perfusion and ICH shape.

Methods: A single-center cohort of patients with primary ICH was analyzed. Patients underwent computed tomography perfusion within 6 h from onset. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated in the manually outlined perihematomal low-density region. ICH shape was rated on baseline non-contrast CT following international consensus criteria, and predictors of irregular shape were explored with logistic regression.

Results: A total of 150 patients were included, of whom 66 (44%) had irregular shape. Perihematomal CBF was lower in irregular ICH (median 23 vs 35 mL/100 g/min, p<0.001). CBF<20 mL/100 g/min was independently associated with irregular shape (odds ratio 9.67, 95% CI 2.42-38.69, p=0.001).

Conclusion: Our findings suggest that perihematomal hypoperfusion may contribute to the CT appearance of acute ICH.
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http://dx.doi.org/10.1007/s00234-021-02709-8DOI Listing
September 2021

Neuroimaging of Acute Intracerebral Hemorrhage.

J Clin Med 2021 Mar 5;10(5). Epub 2021 Mar 5.

ASST Valcamonica, UOSD Neurology, Esine (BS), 25040 Brescia, Italy.

Intracerebral hemorrhage (ICH) accounts for 10% to 20% of all strokes worldwide and is associated with high morbidity and mortality. Neuroimaging is clinically important for the rapid diagnosis of ICH and underlying etiologies, but also for identification of ICH expansion, often as-sociated with an increased risk for poor outcome. In this context, rapid assessment of early hema-toma expansion risk is both an opportunity for therapeutic intervention and a potential hazard for hematoma evacuation surgery. In this review, we provide an overview of the current literature surrounding the use of multimodal neuroimaging of ICH for etiological diagnosis, prediction of early hematoma expansion, and prognostication of neurological outcome. Specifically, we discuss standard imaging using computed tomography, the value of different vascular imaging modalities to identify underlying causes and present recent advances in magnetic resonance imaging and computed tomography perfusion.
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http://dx.doi.org/10.3390/jcm10051086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962049PMC
March 2021

Hematoma Expansion in Intracerebral Hemorrhage With Unclear Onset.

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

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

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

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

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

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

Imaging-Based Outcome Prediction of Acute Intracerebral Hemorrhage.

Transl Stroke Res 2021 Feb 6. Epub 2021 Feb 6.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

We hypothesized that imaging-only-based machine learning algorithms can analyze non-enhanced CT scans of patients with acute intracerebral hemorrhage (ICH). This retrospective multicenter cohort study analyzed 520 non-enhanced CT scans and clinical data of patients with acute spontaneous ICH. Clinical outcome at hospital discharge was dichotomized into good outcome and poor outcome using different modified Rankin Scale (mRS) cut-off values. Predictive performance of a random forest machine learning approach based on filter- and texture-derived high-end image features was evaluated for differentiation of functional outcome at mRS 2, 3, and 4. Prediction of survival (mRS ≤ 5) was compared to results of the ICH Score. All models were tuned, validated, and tested in a nested 5-fold cross-validation approach. Receiver-operating-characteristic area under the curve (ROC AUC) of the machine learning classifier using image features only was 0.80 (95% CI [0.77; 0.82]) for predicting mRS ≤ 2, 0.80 (95% CI [0.78; 0.81]) for mRS ≤ 3, and 0.79 (95% CI [0.77; 0.80]) for mRS ≤ 4. Trained on survival prediction (mRS ≤ 5), the classifier reached an AUC of 0.80 (95% CI [0.78; 0.82]) which was equivalent to results of the ICH Score. If combined, the integrated model showed a significantly higher AUC of 0.84 (95% CI [0.83; 0.86], P value <0.05). Accordingly, sensitivities were significantly higher at Youden Index maximum cut-offs (77% vs. 74% sensitivity at 76% specificity, P value <0.05). Machine learning-based evaluation of quantitative high-end image features provided the same discriminatory power in predicting functional outcome as multidimensional clinical scoring systems. The integration of conventional scores and image features had synergistic effects with a statistically significant increase in AUC.
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http://dx.doi.org/10.1007/s12975-021-00891-8DOI Listing
February 2021

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

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

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

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

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

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

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

Hemorrhage Expansion After Pediatric Intracerebral Hemorrhage.

Stroke 2021 Jan 11;52(2):588-594. Epub 2021 Jan 11.

GHU Paris Psychiatrie et Neurosciences, Hospitalier Sainte Anne, Service d'imagerie Morphologique et Fonctionnelle, Institut de Psychiatrie et Neurosciences de Paris, Unité mixte de recherche S1266, Institut National de la Santé Et de la Recherche Médicale, Université de Paris, Paris, France (G.B., J.-F.H., B.K., F.G., L.G., O.N.).

Background And Purpose: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children.

Methods: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King's Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5.

Results: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; =0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04-217]; =0.048). sHE was independently associated with poor outcome (King's Outcome Scale for Childhood Head Injury <5A, odds ratio, 5.77 [95% CI, 1.01-38.95]; =0.043).

Conclusions: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.
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http://dx.doi.org/10.1161/STROKEAHA.120.030592DOI Listing
January 2021

Tenecteplase vs Alteplase Before Endovascular Therapy in Basilar Artery Occlusion.

Neurology 2021 03 6;96(9):e1272-e1277. Epub 2021 Jan 6.

From the Department of Medicine and Neurology (F. Alemseged, G.S., L.C., B.Y., M.W.P., S.M.D., P.J.M., N.Y. B.C.V.C.), University of Melbourne, and Department of Radiology (C.W., S.B., R.D.), Royal Melbourne Hospital, Parkville, Australia; Stroke Unit (F. Alemseged, A.R., F.S., M.D.) and Department of Biomedicine and Prevention (F.D.), University Hospital of Tor Vergata, Rome, Italy; Department of Neurology (F.C.N.), Austin Health, Melbourne, Australia; Department of Neurology (V.P.), Institute of Neuroradiology (D.K.), and Dresden Neurovascular Center (V.P., D.K.), University of Technology Dresden, Germany; Department of Interventional Neuroradiology (G.B.), Sainte-Anne-Hospital, Paris, France; Department of Neurology (T.J.K.), Royal Adelaide Hospital, Australia; Department of Neurology (T.Y.W.), Christchurch Hospital, New Zealand; Division of Medicine (D.S.), Princess Alexandra Hospital, Brisbane, Australia; NEUROFARBA Department (F. Arba), Careggi University Hospital, Florence; ASST Valcamonica (A.M.), Department of Neurology, Esine, Italy; Department of Neurosciences (H.M.D.), Eastern Health, Melbourne; Department of Neurology (P.B.), Gold Coast University Hospital, Queensland; Department of Neurology (B.O.), Gosford Hospital, New South Wales; and Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

Objective: To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO).

Methods: To determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated.

Results: We included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7-32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3-12; = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40-71] minutes) vs alteplase-treated patients (110 [IQR 51-185] minutes; = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; = 0.9).

Conclusions: TNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted.

Clinicaltrialsgov Identifiers: NCT02388061 and NCT03340493.

Classification Of Evidence: This study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.
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http://dx.doi.org/10.1212/WNL.0000000000011520DOI Listing
March 2021

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study.

Neurology 2021 01 3;96(3):e343-e351. Epub 2020 Nov 3.

From the Department of Neuroradiology (P.B.S., M.-N.P., A.B.), Clinic for Radiology & Nuclear Medicine, University Hospital Basel, Switzerland; Department of Diagnostic and Interventional Neuroradiology (P.B.S., U.H., G.B., J.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Departments of Pediatrics (R.S.), and Neurology (J.M.), University Hospital of Muenster; Department of Neuroradiology (R.C.), Alfried-Krupp Hospital, Essen; Department of Neuroradiology (H.H., E.H.), Klinikum Stuttgart, Germany; Department of Neuroradiology (A.G.), Medical University of Innsbruck, Austria; Department for Diagnostic and Interventional Neuroradiology (F.D.), University of Munich (LMU), Campus Grosshadern; Department of Neuroradiology (O.N., M.W.), RWTH Aachen University; Diagnostic and Interventional Neuroradiology (G.B.), Eberhard Karls University Tuebingen; Department of Radiology and Neuroradiology (A.W.), University Hospital Knappschaftskrankenhaus Bochum Langendreer; Department of Neuroradiology (D.K.), University Hospital Carl Gustav Carus, Dresden7; Department of Neuroradiology (U.Y.), Saarland University Hospital, Homburg, Germany; ASST Valcamonica (A.M.), Ospedale di Esine, UOSD Neurologia, Esine, Italy; Division of Neuroradiology and Musculoskeletal Radiology (W.M.), Department of Biomedical Imaging and Image-Guided Therapy, and Department of Biomedical Imaging and Image-Guided Therapy (R.N.), Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Austria; Department of Radiology and Neuroradiology (U.J.-K.), University Hospital of Schleswig-Holstein, Kiel; Section of Neuroradiology (M.B.), University of Ulm, Guenzburg; Department for Neuroradiology (S.S.), University Hospital Leipzig; Department of Neuroradiology (O.B.), University Hospital of Magdeburg; Department of Diagnostic and Interventional Neuroradiology (F.G.), Hannover Medical School, Germany; Institute of Neuroradiology (J.T.), Kepler University Hospital, Johannes Kepler University Linz, Austria; Institute of Neuroradiology (B.T.), University Hospital Duesseldorf; Department of Neuroradiology at Heidelberg University Hospital (M.M.); Department of Radiology (C.W.), University Hospital Regensburg; Department of Neuroradiology (P.S., A. Kemmling), University Hospital of Luebeck, Germany; Department of Neurology (P.L.M.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Child Neurology (S.L.), Department of Neurology, Stanford University, CA; Department of Neuroradiology (M.S.), University Hospital of Cologne; Department of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), University Hospital Essen, University of Duisburg-Essen; Institute of Epidemiology and Social Medicine (A. Karch, N.R.), University of Muenster; and Department of Radiology, University of Munich (LMU) (M.W.), Campus Grosshadern, Germany.

Objective: To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct.

Methods: A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct.

Results: Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population.

Conclusions: Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct.

Classification Of Evidence: This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.
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http://dx.doi.org/10.1212/WNL.0000000000011107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884981PMC
January 2021

Characterization of CB2 Receptor Expression in Peripheral Blood Monocytes of Acute Ischemic Stroke Patients.

Transl Stroke Res 2021 08 22;12(4):550-558. Epub 2020 Sep 22.

IRCCS Mondino Foundation, Via Mondino, 2, 27100, Pavia, Italy.

Both preclinical and clinical evidence supports the involvement of the endocannabinoid system in the pathobiology of cerebral ischemia. Selective cannabinoid-2 (CB2) receptor agonists exert significant neuroprotection in animal models of focal brain ischemia through a robust anti-inflammatory effect, involving both resident and peripheral immune cells. Nevertheless, no definitive studies demonstrating the relevance of CB2 receptors in human stroke exist.Using rtPCR and flow cytometry assays, we investigated CB2 receptor expression in circulating monocytes from 26 acute ischemic stroke patients and 16 age-matched healthy controls (CT). We also evaluated miR-665 expression, as potential CB2 receptor regulator. The median mRNA levels of CB2 were significantly (p < 0.0001) increased in total monocytes 24 h and 48 h after stroke as compared with CT. This was paralleled by elevation of miR-665 levels in monocytes collected from patients 24 h (p < 0.05 vs CT) and 48 h (p < 0.05 vs CT and p < 0.0001 vs 24 h) after ischemic stroke. Furthermore, an increased percentage of CB2+/CD16+ events, but not CB2+/CD14+ events, was found 24 h [20.17% (IQR, 17.22-23.58)] and 48 h [18.61% (IQR, 15.44-22.06)] after ischemic stroke when compared with CT [10.96% (IQR, 9.185-13.32)]. The percentage of CB2+/CD16+ events in monocytes was positively correlated with NIHSS score at entrance (r = 0.4327, p = 0.027). The potential beneficial functions of CD16+ intermediate and nonclassical monocytes in stroke and the elevated expression of CB2 receptor in these subsets strongly suggest that CB2 receptor agonists can be exploited for the treatment of ischemic stroke patients.
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http://dx.doi.org/10.1007/s12975-020-00851-8DOI Listing
August 2021

Noncontrast CT markers of intracerebral hemorrhage expansion and poor outcome: A meta-analysis.

Neurology 2020 10 26;95(14):632-643. Epub 2020 Aug 26.

Neurology Unit (A.M.), ASST Valcamonica, Esine, Brescia; Stroke Unit (F.A.), Careggi University Hospital, Florence, Italy; Neuroradiology Department (G.B.), Centre Hospitalier Sainte-Anne, Paris, France; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.

Objective: To provide precise estimates of the association between noncontrast CT (NCCT) markers, hematoma expansion (HE), and functional outcome in patients presenting with intracerebral hemorrhage (ICH) through a systematic review and meta-analysis.

Methods: We searched PubMed for English-written observational studies or randomized controlled trials reporting data on NCCT markers of HE and outcome in spontaneous ICH including at least 50 subjects. The outcomes of interest were HE (hematoma growth >33%, >33% and/or >6 mL, >33% and/or >12.5 mL), poor functional outcome (modified Rankin Scale 3-6 or 4-6) at discharge or at 90 days, and mortality. We pooled data in random-effects models and extracted cumulative odds ratio (OR) for each NCCT marker.

Results: We included 25 eligible studies (n = 10,650). The following markers were associated with increased risk of HE and poor outcome, respectively: black hole sign (OR = 3.70, 95% confidence interval [CI] = 1.42-9.64 and OR = 5.26, 95% CI = 1.75-15.76), swirl sign (OR = 3.33, 95% CI = 2.42-4.60 and OR = 3.70; 95% CI = 2.47-5.55), heterogeneous density (OR = 2.74; 95% CI = 1.71-4.39 and OR = 2.80; 95% CI = 1.78-4.39), blend sign (OR = 3.49; 95% CI = 2.20-5.55 and OR = 2.21; 95% CI 1.16-4.18), hypodensities (OR = 3.47; 95% CI = 2.18-5.50 and OR = 2.94; 95% CI = 2.28-3.78), irregular shape (OR = 2.01, 95% CI = 1.27-3.19 and OR = 3.43; 95% CI = 2.33-5.03), and island sign (OR = 7.87, 95% CI = 2.17-28.47 and OR = 6.05, 95% CI = 4.44-8.24).

Conclusion: Our results suggest that multiple NCCT ICH shape and density features, with different effect size, are important markers for HE and clinical outcome and may provide useful information for future randomized controlled trials.
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http://dx.doi.org/10.1212/WNL.0000000000010660DOI Listing
October 2020

Clinical and Imaging Characteristics in Patients with SARS-CoV-2 Infection and Acute Intracranial Hemorrhage.

J Clin Med 2020 Aug 6;9(8). Epub 2020 Aug 6.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, 20251 Hamburg, Germany.

Background And Purpose: Intracranial hemorrhage has been observed in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19), but the clinical, imaging, and pathophysiological features of intracranial bleeding during COVID-19 infection remain poorly characterized. This study describes clinical and imaging characteristics of patients with COVID-19 infection who presented with intracranial bleeding in a European multicenter cohort.

Methods: This is a multicenter retrospective, observational case series including 18 consecutive patients with COVID-19 infection and intracranial hemorrhage. Data were collected from February to May 2020 at five designated European special care centers for COVID-19. The diagnosis of COVID-19 was based on laboratory-confirmed diagnosis of SARS-CoV-2. Intracranial bleeding was diagnosed on computed tomography (CT) of the brain within one month of the date of COVID-19 diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy and outcomes in COVID-19 patients presenting with intracranial bleeding were analyzed.

Results: Eighteen patients had evidence of acute intracranial bleeding within 11 days (IQR 9-29) of admission. Six patients had parenchymal hemorrhage (33.3%), 11 had subarachnoid hemorrhage (SAH) (61.1%), and one patient had subdural hemorrhage (5.6%). Three patients presented with intraventricular hemorrhage (IVH) (16.7%).

Conclusion: This study represents the largest case series of patients with intracranial hemorrhage diagnosed with COVID-19 based on key European countries with geospatial hotspots of SARS-CoV-2. Isolated SAH along the convexity may be a predominant bleeding manifestation and may occur in a late temporal course of severe COVID-19.
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http://dx.doi.org/10.3390/jcm9082543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464657PMC
August 2020

Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome.

Ann Rheum Dis 2020 10 30;79(10):1286-1289. Epub 2020 Jul 30.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Lombardia, Italy.

Objectives: The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC).

Methods: In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction).

Results: Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk.

Conclusion: This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.
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http://dx.doi.org/10.1136/annrheumdis-2020-217712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509521PMC
October 2020

Response by Morotti and Fainardi to Letter Regarding Article, "Subarachnoid Extension Predicts Lobar Intracerebral Hemorrhage Expansion".

Stroke 2020 08 2;51(8):e162. Epub 2020 Jul 2.

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

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http://dx.doi.org/10.1161/STROKEAHA.120.030415DOI Listing
August 2020

Sexual dimorphism in the cerebrospinal fluid total protein content.

Clin Chem Lab Med 2020 10;58(11):1885-1890

Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.

Objectives Cerebrospinal fluid (CSF) is a clear, colorless body fluid filling the central nervous system. The determination of the CSF total protein (TP) content represents an important screening test of various pathologies. We aimed to address the effect of sex and age on CSF-TP content and the use of the current upper reference limits (URLs). Methods CSF-TP content was analysed in a selected population of 1,252 patients (648 women and 604 men; age 18-89 years) who underwent lumbar puncture as a part of the diagnostic work-up. Samples presenting (i) more than 5 white blood cells (WBC)/µL, (ii) discolorations and (iii) reduced glucose were not included. Results The CSF-TP content median values were significantly higher in men than in women (46 vs. 37 mg/dL) even after adjusting for age and different hospital inpatients. CSF-TP content positively correlated with age both in men and in women with a constant difference between sexes of 8.5 mg/dL. Applying the most used URLs (mainly 45 and 50 mg/dL, but also 60 mg/dL), men received a laboratory report suggestive of altered CSF-TP content more frequently than women. The use of age- and sex-calibrated CSF-TP URLs reduced, but not eliminated, this sex-gap. Conclusions Using the current URLs, a condition of "elevated CSF-TP content" may be overestimated in men or, conversely, underestimated in women, regardless of the age and of the diagnosis. These results highlighted the need to apply CSF-TP URLs values ​​normalized for both sex and age.
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http://dx.doi.org/10.1515/cclm-2020-0419DOI Listing
October 2020

Ultra-Early Blood Pressure Reduction Attenuates Hematoma Growth and Improves Outcome in Intracerebral Hemorrhage.

Ann Neurol 2020 08 1;88(2):388-395. Epub 2020 Jul 1.

Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Objective: The aim was to investigate whether intensive blood pressure treatment is associated with less hematoma growth and better outcome in intracerebral hemorrhage (ICH) patients who received intravenous nicardipine treatment ≤2 hours after onset of symptoms.

Methods: A post-hoc exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial was performed. This was a multicenter, international, open-label, randomized clinical trial, in which patients with primary ICH were allocated to intensive versus standard blood pressure treatment with nicardipine ≤4.5 hours after onset of symptoms. We have included 913 patients with complete imaging and follow-up data in the present analysis.

Results: Among the 913 included patients, 354 (38.7%) had intravenous nicardipine treatment initiated within 2 hours. In this subgroup of patients treated within 2 hours, the frequency of ICH expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group (p = 0.02). Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma growth (odds ratio, 0.56; 95% confidence interval [CI], 0.34-0.92; p = 0.02), higher rate of functional independence (odds ratio, 2.17; 95% CI, 1.28-3.68; p = 0.004), and good outcome (odds ratio, 1.68; 95% CI, 1.01-2.83; p = 0.048) at 90 days. Ultra-early intensive blood pressure reduction was associated with a favorable shift in modified Rankin Scale score distribution at 3 months (p = 0.04).

Interpretation: In a subgroup of ICH patients with elevated blood pressure given intravenous nicardipine ≤2 hours after onset of symptoms, intensive blood pressure reduction was associated with reduced hematoma growth and improved functional outcome. ANN NEUROL 2020;88:388-395.
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http://dx.doi.org/10.1002/ana.25793DOI Listing
August 2020

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

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

UO Neurologia, Ospedale Villa Sofia, Palermo, Italy.

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

Prognostic Value of Non-Contrast CT Markers and Spot Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage under Oral Anticoagulation.

J Clin Med 2020 Apr 10;9(4). Epub 2020 Apr 10.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Introduction: In patients with spontaneous intracerebral hemorrhage (ICH), several non-contrast computed tomography (NCCT) markers and the spot sign (SS) in computed tomography (CT) angiography (CTA) have been established for the prediction of hematoma growth and neurological outcome. However, the prognostic value of these markers in patients under oral anticoagulation (ORAC) is unclear. We hypothesized that outcome prediction by these imaging markers may be significantly different between patients with and without ORAC. Therefore, we aimed to investigate the predictive value of NCCT markers and SS in patients with ICH under ORAC.

Methods: This is a retrospective study of the database for patients with ICH at a German tertiary stroke center. Inclusion criteria were (1) patients with ICH, (2) oral anticoagulation within the therapeutic range, and (3) NCCT and CTA performed on admission within 6 h after onset of symptoms. We defined a binary outcome: modified Rankin Scale (mRS) ≤ 3 = good outcome versus mRS > 3 = poor outcome at discharge. The predictive value of each sign was assessed in uni- and multivariable logistic regression models.

Results: Of 129 patients with ICH under ORAC, 76 (58.9%) presented with hypodensities within the hematoma in admission NCCT, 64 (52.7%) presented with an irregular shape of the hematoma, 60 (46.5%) presented with a swirl sign, 49 (38.0%) presented with a black hole sign, and 46 (35.7%) presented with a heterogeneous density of the hematoma. Moreover, 44 (34.1%) patients had a satellite sign, in 20 (15.5%) patients, an island sign was detected, 18 (14.0%) patients were blend-sign positive, and 14 (10.9%) patients presented with a CTA spot sign. Inter-rater agreement was very high for all included characteristics between the two readers. Multivariable logistic regression analysis identified the presence of black hole sign (odds ratio 10.59; < 0.001), swirl sign (odds ratio 14.06; < 0.001), and satellite sign (odds ratio 6.38; = 0.011) as independent predictors of poor outcome.

Conclusions: The distribution and prognostic value of several NCCT markers and CTA spot sign in ICH patients under ORAC is comparable to those with spontaneous ICH, even though these parameters are partly based on coagulant status. These findings suggest that a similar approach can be used for further research regarding outcome prediction in ICH patients under ORAC and those with spontaneous ICH.
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http://dx.doi.org/10.3390/jcm9041077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230516PMC
April 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

Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project.

Neurol Sci 2020 Aug 12;41(8):2193-2200. Epub 2020 Mar 12.

Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient's clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.
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http://dx.doi.org/10.1007/s10072-020-04306-8DOI Listing
August 2020

Pediatric ischemic stroke.

J Neurol 2020 04;267(4):1221-1222

Stroke Unit, IRCCS Fondazione Mondino, Pavia, Italia.

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http://dx.doi.org/10.1007/s00415-020-09779-3DOI Listing
April 2020

Does Device Selection Impact Recanalization Rate and Neurological Outcome?: An Analysis of the Save ChildS Study.

Stroke 2020 04 2;51(4):1182-1189. Epub 2020 Mar 2.

Institute of Neuroradiology, University Hospital Duesseldorf, Germany (B.T.).

Background and Purpose- The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods- The Save ChildS cohort study (January 2000-December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (<18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results- Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions- Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration- URL: https://www.drks.de/; Unique identifier: DRKS00016528.
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http://dx.doi.org/10.1161/STROKEAHA.119.028221DOI Listing
April 2020

Association Between Perihematomal Perfusion and Intracerebral Hemorrhage Outcome.

Neurocrit Care 2020 10;33(2):525-532

Neuroradiology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Background: The prognostic impact of perihematomal hypoperfusion in patients with acute intracerebral hemorrhage (ICH) remains unclear. We tested the hypothesis that perihematomal hypoperfusion predicts poor ICH outcome and explored whether hematoma growth (HG) is the pathophysiological mechanism behind this association.

Methods: A prospectively collected single-center cohort of consecutive ICH patients undergoing computed tomography perfusion on admission was analyzed. Cerebral blood flow (pCBF) was measured in the manually outlined perihematomal low-density area. pCBF was categorized into normal (40-55 mL/100 g/min), low (< 40 mL/100 g/min), and high (> 55 mL/100 g/min). HG was calculated as total volume increase from baseline to follow-up CT. A modified Rankin scale > 2 at three months was the outcome of interest. The association between cerebral perfusion and outcome was investigated with logistic regression, and potential mediators of this relationship were explored with mediation analysis.

Results: A total of 155 subjects were included, of whom 55 (35.5%) had poor outcome. The rates of normal pCBF, low pCBF, and high pCBF were 17.4%, 68.4%, and 14.2%, respectively. After adjustment for confounders and keeping subjects with normal pCBF as reference, the risk of poor outcome was increased in patients with pCBF < 40 mL/100 g/min (odds ratio 6.11, 95% confidence interval 1.09-34.35, p = 0.040). HG was inversely correlated with pCBF (R = -0.292, p < 0.001) and mediated part of the association between pCBF and outcome (proportion mediated: 82%, p = 0.014).

Conclusion: Reduced pCBF is associated with poor ICH outcome in patients with mild-moderate severity. HG appears a plausible biological mediator but does not fully account for this association, and other mechanisms might be involved.
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http://dx.doi.org/10.1007/s12028-020-00929-zDOI Listing
October 2020

Increased age and male sex are independently associated with higher frequency of blood-cerebrospinal fluid barrier dysfunction using the albumin quotient.

Fluids Barriers CNS 2020 Feb 5;17(1):14. Epub 2020 Feb 5.

Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, Settore 1C3, 44124, Ferrara, Italy.

Background: The cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood-cerebrospinal fluid barrier (B-CSF-B) permeability. For years QAlb was considered only as an age-related parameter but recently it has also been associated to sex. The aim of the present study was to explore the impact of sex in the determination of B-CSF-B dysfunction.

Methods: The analysis was retrospectively conducted on subjects consecutively admitted to the neurological ward. CSF and serum albumin levels were measured by immunonephelometry and pathological QAlb thresholds were considered: 6.5 under 40 years, 8.0 in the age 40-60 and 9.0 over 60 years.

Results: 1209 subjects were included in the study. 718 females and 491 males (age: 15-88 years): 24.6% of patients had a diagnosis of multiple sclerosis, 23.2% suffered from other inflammatory neurological diseases, 24.6% were affected by non-inflammatory neurological diseases, and for 27.6% of patients the final neurological diagnosis could not be traced. Dysfunctional B-CSF-B was detected more frequently (44 vs. 20.1%, p < 0.0001) and median QAlb value were higher (7.18 vs. 4.87, p < 0.0001) in males than in females in the overall study population and in all disease subgroups. QAlb and age were positively correlated both in female (p < 0.0001) and male (p < 0.0001) patients, however the slopes of the two regression lines were not significantly different (p = 0.7149), while the difference between the elevations was extremely significant (p < 0.0001) with a gap of 2.2 units between the two sexes. Finally, in a multivariable linear regression analysis increased age and male sex were independently associated with higher QAlb in the overall study population (both p < 0.001) and after stratification by age and disease group.

Conclusions: Accordingly, identification and validation of sex-targeted QAlb thresholds should be considered as a novel tool in an effort to achieve more precision in the medical approach.
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http://dx.doi.org/10.1186/s12987-020-0173-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003357PMC
February 2020

Comparison of perihematomal perfusion in deep and lobar intracerebral hemorrhage.

Neuroradiology 2020 Feb 20;62(2):257-261. Epub 2019 Dec 20.

Neuroradiology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Purpose: Hypoperfusion in the perihematomal rim is common in acute intracerebral hemorrhage (ICH) but its determinants remain incompletely characterized. Despite known biological differences between deep and lobar ICH, the association between ICH location and cerebral perfusion has not been investigated. We tested the hypothesis that perihematomal perfusion differs between deep and lobar ICH.

Methods: Prospectively collected cohort of subjects with primary spontaneous ICH undergoing CT perfusion on admission. Cerebral blood flow (CBF), blood volume (CBV), and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. The association between perihematomal perfusion and ICH location was explored with multivariable linear regression.

Results: A total of 155 patients were enrolled (59 with a lobar bleeding). In univariate analysis, median perihematomal CBF and CBV were lower in lobar ICH compared with deep ICH (23.8 vs 33.4 mL/100 g/min, p = 0.001 and 1.7 vs 2.3 mL/100 g, p = 0.001, respectively). Lobar ICH location remained inversely associated with CBF (β = - 0.17, p = 0.038) and CBV (β = - 0.19, p = 0.023) after adjustment for confounders in linear regression.

Conclusion: Lobar ICH location is inversely related with perihematomal CBF and CBV. Further studies are needed to confirm this association and define the underlying biological mechanisms.
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http://dx.doi.org/10.1007/s00234-019-02331-9DOI Listing
February 2020
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