Publications by authors named "Anna Cavallini"

88 Publications

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

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

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

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

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

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

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

Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

Dev Psychopathol 2021 Jul 2:1-9. Epub 2021 Jul 2.

Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.
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http://dx.doi.org/10.1017/S0954579421000766DOI Listing
July 2021

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

J Neurol 2021 May 24. Epub 2021 May 24.

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

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

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

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

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

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

J Neurol Sci 2021 Jul 5;426:117479. Epub 2021 May 5.

Neurological Department, "Alessandro Manzoni" Hospital, ASST Lecco, Via dell'Eremo 9/11, 23900 Lecco, Italy.

Introduction: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection.

Method: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH.

Results: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2).

Discussion: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.
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http://dx.doi.org/10.1016/j.jns.2021.117479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096523PMC
July 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

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

J Neurol 2021 Mar 8. Epub 2021 Mar 8.

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

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

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

Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE): study protocol for a multicentric longitudinal project.

BMJ Open 2020 12 31;10(12):e044585. Epub 2020 Dec 31.

Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy.

Introduction: COVID-19 is a highly infectious respiratory disease that rapidly emerged as an unprecedented epidemic in Europe, with a primary hotspot in Northern Italy during the first months of 2020. Its high infection rate and rapid spread contribute to set the risk for relevant psychological stress in citizens. In this context, mother-infant health is at risk not only because of potential direct exposure to the virus but also due to high levels of stress experienced by mothers from conception to delivery. Prenatal stress exposure associates with less-than-optimal child developmental outcomes, and specific epigenetic mechanisms (eg, DNA methylation) may play a critical role in mediating this programming association.

Methods And Analysis: We present the methodological protocol for a longitudinal, multicentric study on the behavioural and epigenetic effects of COVID-19-related prenatal stress in a cohort of mother-infant dyads in Northern Italy. The dyads will be enrolled at 10 facilities in Northern Italy. Saliva samples will be collected at birth to assess the methylation status of specific genes linked with stress regulation in mothers and newborns. Mothers will provide retrospective data on COVID-19-related stress during pregnancy. At 3, 6 and 12 months, mothers will provide data on child behavioural and socioemotional outcomes, their own psychological status (stress, depressive and anxious symptoms) and coping strategies. At 12 months, infants and mothers will be videotaped during semistructured interaction to assess maternal sensitivity and infant's relational functioning.

Ethics And Dissemination: This study was approved by the Ethics Committee (Pavia). Results will be published in peer-reviewed journals and presented at national and international scientific conferences.

Trial Registration Number: NCT04540029; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-044585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780424PMC
December 2020

European Multicenter Study of ET-COVID-19.

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

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

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

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

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

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

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

Early Parenting Intervention - Biobehavioral Outcomes in infants with Neurodevelopmental Disabilities (EPI-BOND): study protocol for an Italian multicentre randomised controlled trial.

BMJ Open 2020 07 21;10(7):e035249. Epub 2020 Jul 21.

Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy.

Introduction: Neurodevelopmental disability (ND) represents an adverse condition for infants' socio-emotional and behavioural development as well as for caregiving (eg, parental sensitivity) and mother-infant interaction. Adverse exposures are associated with altered neuroendocrine hormones concentrations (eg, oxytocin and cortisol) and epigenetic regulation (eg, methylation of stress-related genes), which in turn may contribute to less-than-optimal mother-infant interaction. Parental sensitivity is a protective factor for childrens' development and early parental interventions (eg, video-feedback intervention) can promote parental caregiving and better developmental outcomes in children. The present multi-centric and longitudinal randomised controlled trial aims to assess if and to which extent early VFI could benefit both infants and mothers in terms of behavioural outcomes as well as neuroendocrine and epigenetic regulation.

Methods And Analysis: Dyads will be randomly assigned to the video-feedback Intervention Group or Control Group ('dummy' intervention: telephone calls). Infants with ND aged 3 to 18 months will be recruited from three major child neuropsychiatric units in northern Italy. A multi-layer approach to intervention effects will include videotapes of mother-infant interaction, maternal reports as well as saliva samples for hormones concentrations and target-gene methylation analysis (eg, , , ) that will be obtained at each of the four assessment sessions: T, baseline; T, post-intervention; T, short-term follow-up (3 month); T, long-term follow-up (6 month). Primary effectiveness measures will be infant socio-emotional behaviour and maternal sensitivity. Neuroendocrine hormones concentrations and DNA methylation status of target genes will be secondary outcomes. Feasibility, moderation and confounding variables will be measured and controlled between the two groups.

Ethics And Dissemination: Ethics approval has been obtained in all three participating units. Results of the main trial and each of the secondary endpoints will be submitted for publication in peer-reviewed journals and international conferences.

Trial Registration Number: NCT03853564; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-035249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375429PMC
July 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

UO Neurologia, Ospedale Villa Sofia, Palermo, Italy.

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

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

Understanding the role and function of maternal touch in children with neurodevelopmental disabilities.

Infant Behav Dev 2020 02 3;58:101420. Epub 2020 Feb 3.

Scientific Institute, IRCCS E. Medea, 0-3 Center for the at-Risk Infant, Bosisio Parini, Lecco, Italy. Electronic address:

During the first years of life, maternal touch can serve different functions including facilitation of child's gaze orientation to faces which is a key precursor for social attention. Although children with neurodevelopmental disability (ND) may have reduced social skills, the role of maternal touch in contributing to gaze orientation to maternal face has not been explored in previous research. In the present study, we investigate the functions of maternal touch in dyads of mothers and children with ND, compared to dyads of children with typical development (TD). Micro-analytic 2-s coding of maternal touch (i.e., affectionate, playful, facilitating, holding, no touch) and children's gaze orientation (i.e., mother-oriented, object-oriented, non-oriented) occurred during 5-minute interactions between mothers and their 12-to-24-month-old ND and TD children. Dyads were paired for children chronological age and sex. Mothers of children with ND used more touch - especially facilitating and holding types -, compared to mothers of TD peers. Children with ND exhibited more non-orientated gaze compared to TD counterparts. Playful touch associated with increased mother-oriented gaze in children with ND, whereas affectionate and holding touch associated with greater mother-oriented gaze in TD children. Findings suggest that specific types of touch support children's attention to social partners.
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http://dx.doi.org/10.1016/j.infbeh.2020.101420DOI Listing
February 2020

Haploinsufficiency of AKT3 gene causing microcephaly and psychomotor delay in a patient with 1q43q44 microdeletion.

Clin Dysmorphol 2020 Apr;29(2):97-100

Pediatric Unit.

Deletion of the 1q43q44 chromosomal region has been related to a clinical syndrome characterized by neurodevelopmental delay, intellectual disability, microcephaly, congenital abnormality of the corpus callosum, and epilepsy and dysmorphic features. A wide variability of the clinical features have been linked to the contiguous deleted genes and incomplete penetrance has been observed too. Here, we report a 4-years-old boy with microcephaly, neurodevelopmental delay, and cardiac atrial septal defect, who had a de-novo 117 Kb 1q43-q44 microdeletion. The deleted chromosomal region encompassed the two genes SDCCAG8 and AKT3. The characteristics of the deletion and the clinical condition of the patient suggest a pathogenic role of the 1q43-q44 deletion, supporting a pivotal role of AKT3 gene in the expression of the clinical phenotype.
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http://dx.doi.org/10.1097/MCD.0000000000000313DOI Listing
April 2020

The importance of design in nanoarchitectonics: multifractality in MACE silicon nanowires.

Beilstein J Nanotechnol 2019 31;10:2094-2102. Epub 2019 Oct 31.

Department of Physics and Astronomy, University of Bologna, Viale Berti Pichat 6/2, 40127 Bologna, Italy.

Mechanisms of self-assembly/self-organization are fundamental for the emergence of nanoarchitectonic systems composed by elemental units, and it is important to build a theoretical framework for them. Additionally, because the enhanced functionalities of these systems are related to their spatial morphologies, it is necessary to quantify the self-organized design through suited statistical analysis tools. We have investigated the self-assembly bundling process of nanowires fabricated by metal-assisted chemical etching (MACE). First, we have applied theoretical models in order to obtain a quantitative estimation of the driving forces leading to self-assembly. Then, we have studied the surfaces of the nanoarchitectures by means of multifractal analysis. We have found that these systems are not simple monofractals, but that the more complex paradigm of multifractality (different fractal dimensions across different scales) has to be applied to describe their morphology. The multifractal analysis approach has proven its ability to discriminate among different MACE nanoarchitectures. Additionally, it has demonstrated its capacity to measure the degree of homogeneity of these surfaces. Finally, a correlation between the growth conditions and the capacity dimension of the nanowires was obtained.
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http://dx.doi.org/10.3762/bjnano.10.204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839548PMC
October 2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adherence to recommendations and clinical outcomes of patients hospitalized for stroke: the role of the admission ward-a real-life investigation from Italy.

Neurol Sci 2019 Jul 2;40(7):1433-1442. Epub 2019 Apr 2.

National Centre for Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy.

Objective: To determine whether out-of-hospital healthcare and adverse outcomes are better in stroke patients admitted to a neurology ward compared with those admitted to general wards.

Methods: Beneficiaries of the National Health Service from the Italian Lombardy Region who were discharged alive after hospital admission during the year 2009 for ischemic stroke (9776 patients) or intracerebral or subarachnoid hemorrhage (1102 patients) entered into the cohort and were followed until 2012. Exposure of interest was the ward type where inpatients were admitted (neuro vs. general wards). Outcomes were out-of-hospital healthcare (i.e., drug prescriptions, diagnostic procedures, and laboratory clinical evaluations) and adverse clinical outcomes (i.e., all-cause death and hospital readmission). Exposure-outcome associations were investigated. High-dimensional propensity score methodology was used for taking into account confounders. Mediation analysis was used to verify whether the association between ward type and clinical outcomes is mediated by out-of-hospital adherence to healthcare.

Results: Better adherence to out-of-hospital healthcare received from patients discharged from neuro, rather than general, wards was observed being the proportions of adherent patients 42.4% and 39.5%, respectively. Compared with general wards, discharge from neuro was associated with reduced 3-year emergency admissions (from 50.1 to 47.5% among ischemic stroke patients) and reduced 3-year mortality (from 37.5 to 27.0% among hemorrhagic stroke patients). From 10 to 15% of outcome risk, reductions were mediated by better adherence to out-of-hospital healthcare.

Conclusions: For patients with acute ischemic and hemorrhagic stroke, admission to neuro vs. general wards is associated with better out-of-hospital healthcare and long-term adverse outcomes.
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http://dx.doi.org/10.1007/s10072-019-03867-7DOI Listing
July 2019

Functional Evaluation of Eating Difficulties Scale to predict oral motor skills in infants with neurodevelopmental disorders: a longitudinal study.

Dev Med Child Neurol 2019 07 5;61(7):813-819. Epub 2019 Feb 5.

Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.

Aim: To assess the predictive validity of the Functional Evaluation of Eating Difficulties Scale (FEEDS) on long-term eating developmental outcomes in infants with neurodevelopmental disorders.

Method: In total, 144 infants (69 females, 75 males) aged 0 to 12 months (mean [SD] 5.34mo [3.42]) with neurodevelopmental disorders and requiring enteral nutrition support, hospitalized between January 2004 and December 2017, were included. The FEEDS was administered at the onset of hospitalization. Follow-up evaluations of feeding modalities occurred at discharge and at 6 months, 12 months, and 24 months after discharge. FEEDS score was tested as a predictor of infants' feeding modality (percutaneous endoscopic gastrostomy, nasogastric tube, mixed, oral feeding) and time to autonomous oral feeding. Percentages of false-positive and negative cases were checked.

Results: Lower FEEDS scores significantly predicted infants' feeding modality (0.40≤R ≤0.61). A 1-point increase in FEEDS score was associated with increased risk (6%-14%; p<0.05) of being non-autonomous feeders at the different follow-up points in infants who had a FEEDS score above the clinical cut-off.

Interpretation: The FEEDS appears to be a clinically valid assessment to predict the presence of eating difficulties in infants with neurodevelopmental disabilities.

What This Paper Adds: Functional Evaluation of Eating Difficulties Scale (FEEDS) significantly predicted eating difficulties in infants with neurodevelopmental disabilities. Lower FEEDS score is significantly associated with autonomous feeding at the 24-month follow-up. FEEDS cut-off identified infants at low-risk and high-risk for eating disorder.
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http://dx.doi.org/10.1111/dmcn.14154DOI Listing
July 2019

Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.

World Neurosurg 2019 Jan 22. Epub 2019 Jan 22.

Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Polo Didattico "CesareBrusotti", Pavia, Italy.

Objective: To delineate the most recommendable treatment of spontaneous intracerebral hemorrhages and the indication for surgery, its timing, and the best surgical technique to be adopted case by case.

Methods: Based on PubMed/MEDLINE, Embase, and the Cochrane Library databases, a systematic review of the literature was performed using as keywords the terms "spontaneous intracerebral hemorrhage," "surgical management," "medical management," "supratentorial," and "infratentorial." Because of the highest level of evidence, only randomized and nonrandomized clinical trials, meta-analyses, and comparative cohort studies reported within the last 12 years were selected. An updated and evidence-based treatment algorithm was reported also.

Results: The search initially returned 255 articles. After application of the exclusion criteria, only 19 studies were selected. According to the site and volume of the hematoma, admission Glasgow Coma Scale (GCS) score, and progressive neurologic decline, specific subgroups were identified. Surgery must be considered in patients with an admission GCS score ranging between 5 and 12 and a hematoma volume >30 mL. The best time-window has been reported to be 7-24 hours after ictus. Endoscopic surgery is recommendable for patients with a supratentorial hematoma >60 mL and with a poor GCS score (4-8). Alternative techniques, such as minimally invasive puncture and thrombolysis, may be considered for deeper hematoma.

Conclusions: Careful selection of patients eligible for surgery is mandatory. The optimal timing falls into a time-window ranging between 7 and 24 hours after ictus. Minimal invasive techniques are valuable surgical options for patients in a poor GCS score or harboring large deep-seated hemorrhages.
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http://dx.doi.org/10.1016/j.wneu.2019.01.016DOI Listing
January 2019

Longitudinal Study on Low-Dose Aspirin versus Placebo Administration in Silent Brain Infarcts: The Silence Study.

Stroke Res Treat 2018 3;2018:7532403. Epub 2018 Oct 3.

Department of Human Neuroscience, "Sapienza" University of Rome, Rome, Italy.

Background: We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment.

Methods: We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment.

Results: Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-a [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence.

Conclusions: These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis. is registered with EudraCT Number: 2005-000996-16; Sponsor Protocol Number: 694/30.06.04.
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http://dx.doi.org/10.1155/2018/7532403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192130PMC
October 2018

The role of clinical and neuroimaging features in the diagnosis of CADASIL.

J Neurol 2018 Dec 11;265(12):2934-2943. Epub 2018 Oct 11.

AO Melegnano-Ospedale di Vizzolo Predabissi, Melegnano, Italy.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL.

Methods: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities.

Results: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity.

Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.
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http://dx.doi.org/10.1007/s00415-018-9072-8DOI Listing
December 2018

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

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

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

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

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

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

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

Leveraging semantic labels for multi-level abstraction in medical process mining and trace comparison.

J Biomed Inform 2018 07 21;83:10-24. Epub 2018 May 21.

DISIT, Computer Science Institute, Università del Piemonte Orientale, Viale Michel 11, I-15121 Alessandria, Italy. Electronic address:

Many medical information systems record data about the executed process instances in the form of an event log. In this paper, we present a framework, able to convert actions in the event log into higher level concepts, at different levels of abstraction, on the basis of domain knowledge. Abstracted traces are then provided as an input to trace comparison and semantic process discovery. Our abstraction mechanism is able to manage non trivial situations, such as interleaved actions or delays between two actions that abstract to the same concept. Trace comparison resorts to a similarity metric able to take into account abstraction phase penalties, and to deal with quantitative and qualitative temporal constraints in abstracted traces. As for process discovery, we rely on classical algorithms embedded in the framework ProM, made semantic by the capability of abstracting the actions on the basis of their conceptual meaning. The approach has been tested in stroke care, where we adopted abstraction and trace comparison to cluster event logs of different stroke units, to highlight (in)correct behavior, abstracting from details. We also provide process discovery results, showing how the abstraction mechanism allows to obtain stroke process models more easily interpretable by neurologists.
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http://dx.doi.org/10.1016/j.jbi.2018.05.012DOI Listing
July 2018

Predictors and outcomes of the Neonatal Oral Motor Assessment Scale (NOMAS) performance: a systematic review.

Eur J Pediatr 2018 May 21;177(5):665-673. Epub 2018 Mar 21.

Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute IRCCS Eugenio Medea, via Don Luigi Monza 20, 23842, Bosisio Parini, (LC), Italy.

The NOMAS is by far the most used tool to screen early oral-motor skills in newborns. Here we provide an updated review of scientific literature on the use of the Neonatal Oral Motor Assessment Scale (NOMAS) to screen early oral-motor skills in newborns. An integrative review has been carried out consistent with PRISMA guidelines and standardized qualitative appraisal. Data abstracting and synthesis were executed by two independent co-authors who solved disagreement in conference. Twenty records have been included and reviewed. The efficacy of the NOMAS in screening and identifying precocious oral-motor skills received inconsistent support. Moderate validity and low reliability emerged. Moreover, despite the NOMAS' adequately screen efficient and inefficient feeders, limited evidence emerged for predictive value of NOMAS score on feeding and psychomotor developmental trajectories during the first 2 years of age.

Conclusion: The present review highlights benefits and limitations of the NOMAS. Future research is needed to develop observational and clinically-relevant tools to better identify newborns which are at lower- and higher-risk of developing less-than-optimal feeding behaviors and to guide with greater precision the diagnostic and therapeutic journey of these newborns. What is Known: • The assessment of oral-motor skills in newborns and infants is critical for early intervention • The NOMAS is the most adopted tool to assess oral-motor skills in newborns and infants What is New: • The ability of the NOMAS to target newborn at risk for feeding disorders is confirmed • Nonetheless, the capacity to predict long-term developmental outcomes is limited.
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http://dx.doi.org/10.1007/s00431-018-3130-1DOI Listing
May 2018

The Functional Evaluation of Eating Difficulties Scale: Study Protocol and Validation in Infants with Neurodevelopmental Impairments and Disabilities.

Front Pediatr 2017 18;5:273. Epub 2017 Dec 18.

Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Italy.

Introduction: A reliable and accurate evaluation of oral-motor skills in newborns at risk for swallowing and feeding disorders is key to set the goals of effective early interventions. Although many tools are available to assess oral-motor skills in newborns, limited evidence exists for what pertains their reliability and their effectivity in predicting short- and long-term developmental outcomes in at-risk infants. The aim of the present study is to develop and provide a preliminary validation of a new clinically grounded tool [i.e., the Functional Evaluation of Eating Difficulties Scale (FEEDS)] specifically designed to be used with at-risk newborns and infants. The paper describes the steps of tool development and information on the reliability of the tool are provided.

Methods/analysis: The FEEDS has been developed according to clinical evidence and expertise by a multidisciplinary team of professionals dealing with feeding problems in at-risk infants diagnosed with neurodevelopmental impairments and disabilities. The steps of FEEDS development are reported, together with a detailed description of items, scoring procedure, and clinical cutoff. The FEEDS has been applied to a relatively large sample of 0- to 12-month-old infants ( = 136) with neurodevelopmental disability, enrolled consecutively between 2004 and 2016 at the Scientific Institute IRCCS Eugenio Medea (Bosisio Parini, Italy), which is the main rehabilitation hospital for children with neurodevelopmental disabilities in Italy. Internal consistency (Cronbach's alpha) and reliability (inter-rater agreement) have been assessed.

Ethics And Dissemination: All the procedures are consistent with the World Medical Association Declaration of Helsinki (2013) and the FEEDS has been approved by the clinical committee of the Scientific Institute IRCCS Eugenio Medea. Further psychometric characteristics and evidence of the predictive validity of the FEEDS will be obtained on a larger sample and they will be reported in future publications from this group.
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http://dx.doi.org/10.3389/fped.2017.00273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741606PMC
December 2017
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