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1. Effect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort studyResearch in context

Author

Elisabetta Zucchi, Umberto Maria Musazzi, Guido Fedele, Ilaria Martinelli, Giulia Gianferrari, Cecilia Simonini, Nicola Fini, Andrea Ghezzi, Maria Caputo, Elisabetta Sette, Veria Vacchiano, Lucia Zinno, Pietro Anceschi, Elena Canali, Marco Vinceti, Salvatore Ferro, Jessica Mandrioli, Laura Ferri, Annalisa Gessani, Rocco Liguori, Pietro Cortelli, Roberto Michelucci, Fabrizio Salvi, Ilaria Bartolomei, Anna Maria Borghi, Andrea Zini, Rita Rinaldi, Valeria Tugnoli, Maura Pugliatti, Luca Codeluppi, Franco Valzania, Filippo Stragliati, Andi Nuredini, Sonia Romano, Alessandro D'Orsi, Liborio Parrino, Doriana Medici, Giovanna Pilurzi, Emilio Terlizzi, Donata Guidetti, Silvia De Pasqua, Mario Santangelo, Paola De Massis, Matteo Gizzi, Mario Casmiro, Pietro Querzani, Simonetta Morresi, Maria Vitiello, Marco Longoni, Alberto Patuelli, Susanna Malagù, Francesca Bianchi, Marco Currò Dossi, and Cristiana Ganino

Subjects
Amyotrophic lateral sclerosis, Tauroursodeoxycholic acid, Real-world evidence, Propensity score matching, Survival, Medicine (General), R5-920
Abstract

Summary: Background: Oral tauroursodeoxycholic acid (TUDCA) is a commercial drug currently tested in patients with amyotrophic lateral sclerosis (ALS) both singly and combined with sodium phenylbutyrate. This retrospective study aimed to investigate, in a real-world setting, whether TUDCA had an impact on the overall survival of patients with ALS who were treated with this drug compared to those patients who received standard care only. Methods: This propensity score–matched study was conducted in the Emilia Romagna Region (Italy), which has had an ALS regional registry since 2009. Out of 627 patients with ALS diagnosed from January 1st, 2015 to June 30th, 2021 and recorded in the registry with available information on death/tracheostomy, 86 patients took TUDCA and were matched in a 1:2 ratio with patients who received only usual care according to age at onset, sex, phenotype, diagnostic latency, ALS Functional Rating Scale-Revised (ALSFRS-R) at first visit, disease progression rate at first visit, and BMI at diagnosis. The primary outcome was survival difference (time from onset of symptoms to tracheostomy/death) between TUDCA exposed and unexposed patients. Findings: A total of 86 patients treated with TUDCA were matched to 172 patients who did not receive treatment. TUDCA-exposed patients were stratified based on dosage (less than or equal to 1000 mg/day or greater) and duration (less than or equal to 12 months or longer) of treatment. The median overall survival was 49.6 months (95% CI 41.7–93.5) among those treated with TUDCA and 36.2 months (95% CI 32.7–41.6) in the control group, with a reduced risk of death observed in patients exposed to a higher dosage (defined as ≥ 1000 mg/day) of TUDCA (HR 0.56; 95% CI 0.38–0.83; p = 0.0042) compared to both the control group and those with lower TUDCA dosages (defined as

Published
2023
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2. Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study

Author

Giulia Gianferrari, Ilaria Martinelli, Cecilia Simonini, Elisabetta Zucchi, Nicola Fini, Maria Caputo, Andrea Ghezzi, Annalisa Gessani, Elena Canali, Mario Casmiro, Patrizia De Massis, Marco Curro’ Dossi, Silvia De Pasqua, Rocco Liguori, Marco Longoni, Doriana Medici, Simonetta Morresi, Alberto Patuelli, Maura Pugliatti, Mario Santangelo, Elisabetta Sette, Filippo Stragliati, Emilio Terlizzi, Veria Vacchiano, Lucia Zinno, Salvatore Ferro, Amedeo Amedei, Tommaso Filippini, Marco Vinceti, ERRALS GROUP, and Jessica Mandrioli

Subjects
amyotrophic lateral sclerosis, elderly ALS, epidemiology, phenotype, prognosis, survival, Science
Abstract

Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient’s prognosis, it should be more extensively applied to this fragile group of patients.

Published
2023
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3. Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy

Author

Giulia Gianferrari, Ilaria Martinelli, Elisabetta Zucchi, Cecilia Simonini, Nicola Fini, Marco Vinceti, Salvatore Ferro, Annalisa Gessani, Elena Canali, Franco Valzania, Elisabetta Sette, Maura Pugliatti, Valeria Tugnoli, Lucia Zinno, Salvatore Stano, Mario Santangelo, Silvia De Pasqua, Emilio Terlizzi, Donata Guidetti, Doriana Medici, Fabrizio Salvi, Rocco Liguori, Veria Vacchiano, Mario Casmiro, Pietro Querzani, Marco Currò Dossi, Alberto Patuelli, Simonetta Morresi, Marco Longoni, Patrizia De Massis, Rita Rinaldi, Annamaria Borghi, ERRALS GROUP, Amedeo Amedei, and Jessica Mandrioli

Subjects
amyotrophic lateral sclerosis, epidemiology, population-based registry, incidence, clinical features, genetics, Biology (General), QH301-705.5
Abstract

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.

Published
2022
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4. Intravenous Thrombolysis for Acute Ischemic Stroke in the Elderly: An Italian Cohort Study in a 'Real World' Setting

Author

Paolo Immovilli, Eugenia Rota, Nicola Morelli, Paola De Mitri, Fabiola Magnifico, Andrea Mascolo, Emilio Terlizzi, Ilaria Iafelice, Andrea Magnacavallo, Emanuele Michieletti, and Donata Guidetti

Subjects
cerebrovascular disease, elderly patients, intravenous thrombolysis, rt-PA, stroke, Geriatrics, RC952-954.6
Abstract

Background: Thrombolysis in the elderly is still a matter of debate. Recently, the Third International Stroke Trial (IST-3) suggested that recombinant tissue plasminogen activator (rt-PA) improves functional outcome, without a substantial absolute increase in symptomatic intracranial hemorrhage, even in older patients. The aim of the current prospective study is to describe safety and functional outcome in a cohort of patients treated by intravenous rt-PA in an Italian stroke unit “real world setting”. Methods: All the consecutive patients treated with rt-PA between 2006 and 2010 in an Italian province with 290,000 inhabitants were enrolled. Total and symptomatic (associated with a 4-point worsening on the National Institutes of Health Stroke Scale [NIHSS] score) hemorrhages were evaluated, as safety measures, along with disability (at 3-month modified Rankin scale) as effectiveness measure. Results: One hundred and eighty-seven patients were treated with rt-PA; 90 males (48.1%); average age 75.1 (±11.9) years; 79 (42.2%) patients aged ≥80 years. Patients aged ≥80 years had a higher NIHSS score at stroke onset (13.5 vs. 10.9). No significant difference was found between patients aged

Published
2015
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5. ‘Possessed’: Acute Confusional Migraine in an Adolescent, Prevented by Topiramate

Author

Eugenia Rota, Nicola Morelli, Paolo Immovilli, Paola De Mitri, Fabiola Magnifico, Emilio Terlizzi, Lucia Mazza, Barbara Sala, Giacomo Biasucci, and Donata Guidetti

Subjects
Acute confusional migraine, Migraine, Migraine prophylaxis, Topiramate, Neurology. Diseases of the nervous system, RC346-429
Abstract

Acute confusional migraine (ACM) is recognized as a rare, but highly disabling migraine equivalent, mostly reported in children and adolescents. Herein we describe the case of a 12-year-old girl admitted to hospital for an acute confusional state and severe psychomotor agitation, associated with a pulsating headache and nausea, which turned out to be a manifestation of ACM. The girl was discharged on topiramate prophylaxis, titrated up to 75 mg/die; no recurrence of confusional and/or headache episodes has been reported over the last 14 months to date. Due to the rarity of this clinical entity, only anecdotal reports about acute and prophylactic treatment of ACM are available in the literature. The case reported herein suggests that topiramate seems to be effective in ACM prophylaxis, although a longer observation period in our patient and more cases are needed to confirm any long-term clinical benefit.

Published
2012
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6. Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study

Author

Mandrioli, Giulia Gianferrari, Ilaria Martinelli, Cecilia Simonini, Elisabetta Zucchi, Nicola Fini, Maria Caputo, Andrea Ghezzi, Annalisa Gessani, Elena Canali, Mario Casmiro, Patrizia De Massis, Marco Curro’ Dossi, Silvia De Pasqua, Rocco Liguori, Marco Longoni, Doriana Medici, Simonetta Morresi, Alberto Patuelli, Maura Pugliatti, Mario Santangelo, Elisabetta Sette, Filippo Stragliati, Emilio Terlizzi, Veria Vacchiano, Lucia Zinno, Salvatore Ferro, Amedeo Amedei, Tommaso Filippini, Marco Vinceti, ERRALS GROUP ERRALS GROUP, and Jessica

Subjects
amyotrophic lateral sclerosis, elderly ALS, epidemiology, phenotype, prognosis, survival
Abstract

Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient’s prognosis, it should be more extensively applied to this fragile group of patients.

Published
2023
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7. A 'Post-mortem' of COVID-19-associated stroke: a case-control study

Author

Paolo Immovilli, Elena Marchesi, Chiara Terracciano, Nicola Morelli, Veronica Bazzurri, Fabiola Magnifico, Domenica Zaino, Emilio Terlizzi, Paola De Mitri, Stefano Vollaro, Nicola Mometto, and Donata Guidetti

Subjects
Stroke, SARS-CoV-2, Case-Control Studies, Rehabilitation, Humans, COVID-19, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, Pandemics, Communicable Diseases, Retrospective Studies
Abstract

To assess whether COVID-19 could be a concurrent factor in the genesis and/or worsening of stroke and to provide data on COVID-19 -associated stroke patients during the first pandemic wave and comparative data on COVID-19 negative stroke patients in the same period.This is a retrospective, observational, case-control, single centre study, carried out in a General Hospital in northern Italy. Sixty-three consecutive stroke patients were included, COVID-19-associated stroke was classified as cases and non COVID-19-associated stroke as controls.A total of 19/63 (28.8%) had a COVID-19-associated stroke, 11 /63 (17.5%) were haemorrhagic and 52/63 (82.5%) ischaemic. COVID-19-associated strokes were more severe (p-value 0.019) and had a higher risk of severe disability and/or death (OR 3.79, CI 95%: 1.21-11.93, p-value 0.19). The COVID-19-associated stroke patients with onset during hospitalization for COVID-19 had a more severe stroke than patients with COVID-19 onset during hospitalization for stroke (p-value 0.019).Although no relationship was observed between the stroke aetiology and COVID-19, intriguingly, COVID-associated stroke turned out to be more severe and disabling. Hopefully, further studies will provide more data and help in the management of this emerging population.

Published
2022

8. Identifying and predicting amyotrophic lateral sclerosis clinical subgroups: a population-based machine-learning study

Author

Faraz Faghri, Fabian Brunn, Anant Dadu, Elisabetta Zucchi, Ilaria Martinelli, Letizia Mazzini, Rosario Vasta, Antonio Canosa, Cristina Moglia, Andrea Calvo, Michael A Nalls, Roy H Campbell, Jessica Mandrioli, Bryan J Traynor, Adriano Chiò, Umberto Manera, Francesca Palumbo, Alessandro Bombaci, Maurizio Grassano, Maura Brunetti, Federico Casale, Giuseppe Fuda, Paolina Salamone, Barbara Iazzolino, Laura Peotta, Paolo Cugnasco, Giovanni De Marco, Maria Claudia Torrieri, Salvatore Gallone, Marco Barberis, Luca Sbaiz, Salvatore Gentile, Alessandro Mauro, Fabiola De Marchi, Lucia Corrado, Sandra D'Alfonso, Antonio Bertolotto, Daniele Imperiale, Marco De Mattei, Salvatore Amarù, Cristoforo Comi, Carmelo Labate, Fabio Poglio, Luigi Ruiz, Lucia Testa, Eugenia Rota, Paolo Ghiglione, Nicola Launaro, Alessia Di Sapio, Nicola Fini, Giulia Gianferrari, Cecilia Simonini, Stefano Meletti, Rocco Liguori, Veria Vacchiano, Fabrizio Salvi, Ilaria Bartolomei, Roberto Michelucci, Pietro Cortelli, Rita Rinaldi, Anna Maria Borghi, Andrea Zini, Elisabetta Sette, Valeria Tugnoli, Maura Pugliatti, Elena Canali, Luca Codeluppi, Franco Valzania, Lucia Zinno, Giovanni Pavesi, Doriana Medici, Giovanna Pilurzi, Emilio Terlizzi, Donata Guidetti, Silvia De Pasqua, Mario Santangelo, Patrizia De Massis, Martina Bracaglia, Mario Casmiro, Pietro Querzani, Simonetta Morresi, Marco Longoni, Alberto Patuelli, Susanna Malagù, Marco Currò Dossi, Simone Vidale, Salvatore Ferro, Faghri F., Brunn F., Dadu A., Chio A., Calvo A., Moglia C., Canosa A., Manera U., Vasta R., Palumbo F., Bombaci A., Grassano M., Brunetti M., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M.C., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., D'Alfonso S., Bertolotto A., Imperiale D., De Mattei M., Amaru S., Comi C., Labate C., Poglio F., Ruiz L., Testa L., Rota E., Ghiglione P., Launaro N., Di Sapio A., Mandrioli J., Fini N., Martinelli I., Zucchi E., Gianferrari G., Simonini C., Meletti S., Liguori R., Vacchiano V., Salvi F., Bartolomei I., Michelucci R., Cortelli P., Rinaldi R., Borghi A.M., Zini A., Sette E., Tugnoli V., Pugliatti M., Canali E., Codeluppi L., Valzania F., Zinno L., Pavesi G., Medici D., Pilurzi G., Terlizzi E., Guidetti D., De Pasqua S., Santangelo M., De Massis P., Bracaglia M., Casmiro M., Querzani P., Morresi S., Longoni M., Patuelli A., Malagu S., Curro Dossi M., Vidale S., Ferro S., Nalls M.A., Campbell R.H., and Traynor B.J.

Subjects
Cohort Studies, Machine Learning, Health Information Management, Amyotrophic Lateral Sclerosis, Medicine (miscellaneous), Cluster Analysis, Humans, Decision Sciences (miscellaneous), Health Informatics, ALS, population based study, Article, United States, Retrospective Studies
Abstract

Amyotrophic lateral sclerosis (ALS) is known to represent a collection of overlapping syndromes. Various classification systems based on empirical observations have been proposed, but it is unclear to what extent they reflect ALS population substructures. We aimed to use machine-learning techniques to identify the number and nature of ALS subtypes to obtain a better understanding of this heterogeneity, enhance our understanding of the disease, and improve clinical care.In this retrospective study, we applied unsupervised Uniform Manifold Approximation and Projection [UMAP]) modelling, semi-supervised (neural network UMAP) modelling, and supervised (ensemble learning based on LightGBM) modelling to a population-based discovery cohort of patients who were diagnosed with ALS while living in the Piedmont and Valle d'Aosta regions of Italy, for whom detailed clinical data, such as age at symptom onset, were available. We excluded patients with missing Revised ALS Functional Rating Scale (ALSFRS-R) feature values from the unsupervised and semi-supervised steps. We replicated our findings in an independent population-based cohort of patients who were diagnosed with ALS while living in the Emilia Romagna region of Italy.Between Jan 1, 1995, and Dec 31, 2015, 2858 patients were entered in the discovery cohort. After excluding 497 (17%) patients with missing ALSFRS-R feature values, data for 42 clinical features across 2361 (83%) patients were available for the unsupervised and semi-supervised analysis. We found that semi-supervised machine learning produced the optimum clustering of the patients with ALS. These clusters roughly corresponded to the six clinical subtypes defined by the Chiò classification system (ie, bulbar, respiratory, flail arm, classical, pyramidal, and flail leg ALS). Between Jan 1, 2009, and March 1, 2018, 1097 patients were entered in the replication cohort. After excluding 108 (10%) patients with missing ALSFRS-R feature values, data for 42 clinical features across 989 patients were available for the unsupervised and semi-supervised analysis. All 1097 patients were included in the supervised analysis. The same clusters were identified in the replication cohort. By contrast, other ALS classification schemes, such as the El Escorial categories, Milano-Torino clinical staging, and King's clinical stages, did not adequately label the clusters. Supervised learning identified 11 clinical parameters that predicted ALS clinical subtypes with high accuracy (area under the curve 0·982 [95% CI 0·980-0·983]).Our data-driven study provides insight into the ALS population substructure and confirms that the Chiò classification system successfully identifies ALS subtypes. Additional validation is required to determine the accuracy and clinical use of these algorithms in assigning clinical subtypes. Nevertheless, our algorithms offer a broad insight into the clinical heterogeneity of ALS and help to determine the actual subtypes of disease that exist within this fatal neurodegenerative syndrome. The systematic identification of ALS subtypes will improve clinical care and clinical trial design.US National Institute on Aging, US National Institutes of Health, Italian Ministry of Health, European Commission, University of Torino Rita Levi Montalcini Department of Neurosciences, Emilia Romagna Regional Health Authority, and Italian Ministry of Education, University, and Research.For the Italian and German translations of the abstract see Supplementary Materials section.

Published
2022

9. Epidemiological effects in Amyotrophic Lateral Sclerosis from the application of a DTCP

Author

Elena Braghieri, Emilio Terlizzi, Michela Benvenuti, Maria Teresa Pinotti, Roberto Antenucci, Marcello Sartori, Massimo Esposito, and Rossella Raggi

Subjects
medicine.medical_specialty, business.industry, Epidemiology, medicine, Amyotrophic lateral sclerosis, Bioinformatics, medicine.disease, business
Abstract

This article introduces the report on the difference occurred in management of ALS patients by an italian Public Health Care Service through 15 years with-and without DTCP (Diagnostic and Therapeutic Care Pathway) during three timeframes. The article illustrates Demography, Provenance and Territorial context of the patients in charge. The formalization of the staging-based ALS DTCP appears to have increased and improved the possibility of clinical taking in charge of patients.

Published
2021
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10. A sight into the elderly ALS patients in Emilia Romagna region: Epidemiological and clinical features of late onset ALS in a prospective population-based study

Author

Silvia Depasqua, Elisabetta Canali, Fabrizio Salvi, Lucia Zinno, Jessica Mandrioli, Cecilia Simonini, Simonetta Morresi, Doriana Medici, Marco Vinceti, Marco Curròdossi, Elisabetta Zucchi, Giulia Gianferrari, Maura Pugliatti, Rocco Liguori, Ilaria Martinelli, Mario Santangelo, Alberto Patuelli, Nicola Fini, Emilio Terlizzi, Veria Vacchiano, Elisabetta Sette, and M. Casmiro

Subjects
Population based study, Pediatrics, medicine.medical_specialty, Neurology, business.industry, Epidemiology, medicine, Late onset, Neurology (clinical), business
Published
2021
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11. Stroke in COVID-19 patients—A case series from Italy

Author

Domenica Zaino, Paola De Mitri, Donata Guidetti, Chiara Terracciano, Emanuele Michieletti, Nicola Morelli, Davide Colombi, Paolo Immovilli, Elena Marchesi, Stefano Vollaro, Fabiola Magnifico, and Emilio Terlizzi

Subjects
Male, 2019-20 coronavirus outbreak, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Cohort Studies, Betacoronavirus, medicine, Humans, Viral therapy, Pandemics, Stroke, Viral etiology, Aged, Aged, 80 and over, Series (stratigraphy), SARS-CoV-2, business.industry, COVID-19, medicine.disease, Italy, Neurology, Female, Coronavirus Infections, business, Cohort study
Published
2020
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12. Intravenous Thrombolysis for Acute Ischemic Stroke in the Elderly: An Italian Cohort Study in a 'Real World' Setting

Author

Andrea Magnacavallo, Ilaria Iafelice, Paola De Mitri, Donata Guidetti, Emilio Terlizzi, Paolo Immovilli, Fabiola Magnifico, Andrea Mascolo, Emanuele Michieletti, Nicola Morelli, and Eugenia Rota

Subjects
medicine.medical_specialty, medicine.medical_treatment, lcsh:Geriatrics, elderly patients, law.invention, Randomized controlled trial, law, Modified Rankin Scale, Internal medicine, medicine, intravenous thrombolysis, rt-PA, Prospective cohort study, Acute ischemic stroke, Stroke, business.industry, Thrombolysis, medicine.disease, stroke, cerebrovascular disease, lcsh:RC952-954.6, Cohort, Physical therapy, Geriatrics and Gerontology, business, Cohort study
Abstract

Background: Thrombolysis in the elderly is still a matter of debate. Recently, the Third International Stroke Trial (IST-3) suggested that recombinant tissue plasminogen activator (rt-PA) improves functional outcome, without a substantial absolute increase in symptomatic intracranial hemorrhage, even in older patients. The aim of the current prospective study is to describe safety and functional outcome in a cohort of patients treated by intravenous rt-PA in an Italian stroke unit “real world setting”. Methods: All the consecutive patients treated with rt-PA between 2006 and 2010 in an Italian province with 290,000 inhabitants were enrolled. Total and symptomatic (associated with a 4-point worsening on the National Institutes of Health Stroke Scale [NIHSS] score) hemorrhages were evaluated, as safety measures, along with disability (at 3-month modified Rankin scale) as effectiveness measure. Results: One hundred and eighty-seven patients were treated with rt-PA; 90 males (48.1%); average age 75.1 (±11.9) years; 79 (42.2%) patients aged ≥80 years. Patients aged ≥80 years had a higher NIHSS score at stroke onset (13.5 vs. 10.9). No significant difference was found between patients aged

Published
2015

13. ‘Possessed’: Acute Confusional Migraine in an Adolescent, Prevented by Topiramate

Author

Giacomo Biasucci, Paola De Mitri, Nicola Morelli, Emilio Terlizzi, Donata Guidetti, Fabiola Magnifico, Lucia Mazza, Barbara Sala, Eugenia Rota, and Paolo Immovilli

Subjects
Topiramate, Pediatrics, medicine.medical_specialty, Psychomotor agitation, Nausea, media_common.quotation_subject, Migraine prophylaxis, Observation period, Published online: December, 2012, lcsh:RC346-429, medicine, Girl, lcsh:Neurology. Diseases of the nervous system, Migraine, media_common, Acute Confusional Migraine, business.industry, Acute confusional migraine, medicine.disease, Anesthesia, Neurology (clinical), medicine.symptom, business, medicine.drug, Prophylactic treatment
Abstract

Acute confusional migraine (ACM) is recognized as a rare, but highly disabling migraine equivalent, mostly reported in children and adolescents. Herein we describe the case of a 12-year-old girl admitted to hospital for an acute confusional state and severe psychomotor agitation, associated with a pulsating headache and nausea, which turned out to be a manifestation of ACM. The girl was discharged on topiramate prophylaxis, titrated up to 75 mg/die; no recurrence of confusional and/or headache episodes has been reported over the last 14 months to date. Due to the rarity of this clinical entity, only anecdotal reports about acute and prophylactic treatment of ACM are available in the literature. The case reported herein suggests that topiramate seems to be effective in ACM prophylaxis, although a longer observation period in our patient and more cases are needed to confirm any long-term clinical benefit.

Published
2012

14. Risk of Guillain-Barré syndrome after 2010–2011 influenza vaccination

Author

Galeotti F, Massari M, Beghi E, Chiò A, Logroscino G, Filippini G, Benedetti MD, Pugliatti M, Santuccio C, Raschetti R, The ITANG study Group [Clinical research assistants: Sara Marconi, Giorgia Giussani, Enrica Bersano, Umberto Manera, Stefano Zoccolella, Antonio Leo, Roberta Barki, Marco Turatti, Stefania Leoni, Steering committee of the study: Ettore Beghi, Maria Donata Benedetti, Andrea Calvo, Adriano Chiò, Roberto D’Alessandro, Fernanda Ferrazin, Graziella Filippini, Giancarlo Logroscino, Giampiero Mazzaglia, Maura Pugliatti, Roberto Raschetti, Carmela Santuccio, Loriana Tartaglia, Francesco Trotta, Clinical centers, co investigators: E. Romagna: Roberto MICHELUCCI, Patrizia RIGUZZI, Tommaso SACQUEGNA, Anna Maria BORGHI, Vittoria MUSSUTO, Patrizia DE MASSIS, Rita Rinaldi, Walter NERI, Carlo GUIDI, Maria Rosaria TOLA, Enrico GRANIERI, Valentina SIMIONI, Paolo NICHELLI, Jessica MANDRIOLI, Donata GUIDETTI, Emilio TERLIZZI, Mario Giovanni TERZANO, Giovanni PAVESI, Fabrizio RASI, Claudio CALLEGARINI, Norina MARCELLO, Massimo BONDAVALLI, Alessandro RAVASIO, Marco CURRÒ DOSSI, Annamaria MAURO, Chiara MINARDI, Gabriele GRECO, Stefano AMIDEI, Enrico MONTANARI, Doriana MEDICI, Lombardy: Tommaso RICCARDI, Elisabetta D’ADDA, Luigi BETTONI, Luciano ABRUZZI, Elio AGOSTONI, Francesco BASSO, Andrea MAGNONI, Vittorio CRESPI, Maria REPACI, Antonella CHELDI, Mariagrazia BELLOTTI, Carlo FERRARESE, Natale Augusto CURTÒ, Giovanni MEOLA, Giuseppe ROTONDO, Eduardo NOBILE ORAZIO, Fabrizia TERENGHI, Franco SASANELLI, Alessio GALBUSSERA, Marco MATTIOLI, Marco TIRITICCO, Caterina NASCIMBENE, Alessandra VANOTTI, Stefano JANN, Luisa DE TONI FRANCESCHINI, Vincenzo SILANI, Nicola TICOZZI, Giancarlo COMI, Raffaella FAZIO, Patrizia PERRONE, Andrea GIORGETTI, Alessandro ROMORINI, Pietro BASSI, Domenico SANTORO, Nereo BRESOLIN, Simone TONIETTI, Massimo SUARDELLI, Giacomo BEZZI, Daria BALDINI, Angelo Maurizio CLERICI, Giuseppina CAFASSO, Daniele PORAZZI, Isidoro LA SPINA, Giampiero GRAMPA, Davide ZARCONE, Michele PERINI, Marco POLONI, Emanuela AGAZZI, Massimiliano FILOSTO, Alessandro PADOVANI, Renato BESANA, Edoardo DONATI, Eugenio MAGNI, Marco ARNABOLDI, Vincenzo BELCASTRO, Mario GUIDOTTI, Raffaella CLERICI, Maurizio RIVA, Eugenio VITELLI, Paolo PREVIDI, Giuseppe MICIELI, Elisa CANDELORO, Carlo DALLOCCHIO, Carla ARBASINO, Piedmont: Andrea CALVO: Scdu Neurologia 4—AOU S. Giovanni Battista, Cristina MOGLIA: Scdu Neurologia 4—AOU S. Giovanni Battista, Marco VERCELLINO, Bruno FERRERO, Pietro PIGNATTA, Enrico ODDENINO, Daniele IMPERIALE, Daniela LEOTTA, Maurizio GIONCO, Carlo RAVETTI, Roberto CAVALLO, Nicoletta Di Vito, Claudio GEDA, Simona BORTOLOTTO, Emilio LUDA DI CORTEMIGLIA, Giovanna LIOTTA, Emilio URSINO, Mario PALERMO, Luca AMBROGIO, Piero MEINERI, Michele DOTTA, Paolo GHIGLIONE, Joseph MAISTRELLI, Susana ONORATO, Maurizio LEONE, Diego Maria PAPURELLO, Angelo VILLANI, Roberto CONTI, Franco COPPO, Fabiana TESSER, Lucia Testa, Silvia Isabella Cattaneo, Maria Teresa Penza, Graziano Gusmaroli, Katia Savio, Franco Perla, Fabrizio Pisano, Fabio Poglio, Luca Pradotto, Valle d’Aosta: Edo Fausto BOTTACCHI, Puglia: Paolo LIVREA, Francesco FEDERICO, Maria TROJANO, Vito COVELLI, Bruno MAGGIO, Vito SANTAMATO, Bruno PASSARELLA, Giovanni ZIMATORE, Giorgio TRIANNI, Gerardo CIARDO, Salvatore INTERNO’, Veneto: Corrado MARCHINI, Sandro ZAMBITO MARSALA, Giorgio MICHIELI, Carlo BORSATO, Giuseppe DIDONÈ, Emma FRASSON, Alberto POLO, Vincenza ARGENTIERO, Vincenzo ROMEO, Novenia PERLOTTO, Roberto L’ERARIO, Gianfranco MICAGLIO, Tiziana ROSSO, Sandro BRUNO, Bruno GIOMETTO, Mirco SERENA, Rocco QUATRALE, Ernesto GASTALDO, Francesco PERINI, Michele DILEONE, Alessandro CASANO, Lauretta SILVESTRI, Alessandro BURLINA, Virginia MUNERATI, Sebastiano D’Anna, Flavio SANSON, Valeria SARTORI, Giuseppe MORETTO, Giovanna SQUINTANI, Salvatore MONACO, Maria Donata BENEDETTI, Simone FUSINA, Claudio BIANCONI, Fabiana PIMAZZONI, Angela BONOMETTI, Giampietro ZANETTE, Marco TURATTI, Sardinia: Stefania LEONI, Giuseppe MURA, Anna TICCA, Piernicola MARCHI, Davide MANCA], D'ALESSANDRO, ROBERTO, CIRIGNOTTA, FABIO, Galeotti F, Massari M, D'Alessandro R, Beghi E, Chiò A, Logroscino G, Filippini G, Benedetti MD, Pugliatti M, Santuccio C, Raschetti R, The ITANG study Group [Clinical research assistants: Sara Marconi, Giorgia Giussani, Enrica Bersano and Umberto Manera, Stefano Zoccolella and Antonio Leo, Roberta Barki, Marco Turatti, Stefania Leoni, Steering committee of the study: Ettore Beghi, Maria Donata Benedetti, Andrea Calvo and Adriano Chiò, Roberto D’Alessandro, Fernanda Ferrazin, Graziella Filippini, Giancarlo Logroscino, Giampiero Mazzaglia, Maura Pugliatti, Roberto Raschetti, Carmela Santuccio, Loriana Tartaglia and Francesco Trotta, Clinical centers and co-investigators: E. Romagna: Roberto MICHELUCCI, Patrizia RIGUZZI, Tommaso SACQUEGNA, Anna Maria BORGHI, Vittoria MUSSUTO, Patrizia DE MASSIS, Fabio CIRIGNOTTA, Rita Rinaldi, Walter NERI, Carlo GUIDI, Maria Rosaria TOLA, Enrico GRANIERI, Valentina SIMIONI, Paolo NICHELLI, Jessica MANDRIOLI, Donata GUIDETTI, Emilio TERLIZZI, Mario Giovanni TERZANO, Giovanni PAVESI, Fabrizio RASI, Claudio CALLEGARINI, Norina MARCELLO, Massimo BONDAVALLI, Alessandro RAVASIO, Marco CURRÒ DOSSI, Annamaria MAURO, Chiara MINARDI, Gabriele GRECO, Stefano AMIDEI, Enrico MONTANARI, Doriana MEDICI, Lombardy: Tommaso RICCARDI, Elisabetta D’ADDA, Luigi BETTONI, Luciano ABRUZZI, Elio AGOSTONI, Francesco BASSO, Andrea MAGNONI, Vittorio CRESPI, Maria REPACI, Antonella CHELDI, Mariagrazia BELLOTTI, Carlo FERRARESE, Natale Augusto CURTÒ, Giovanni MEOLA, Giuseppe ROTONDO, Eduardo NOBILE-ORAZIO, Fabrizia TERENGHI, Franco SASANELLI, Alessio GALBUSSERA, Marco MATTIOLI, Marco TIRITICCO, Caterina NASCIMBENE, Alessandra VANOTTI, Stefano JANN, Luisa DE TONI FRANCESCHINI, Vincenzo SILANI, Nicola TICOZZI, Giancarlo COMI, Raffaella FAZIO, Patrizia PERRONE, Andrea GIORGETTI, Alessandro ROMORINI, Pietro BASSI, Domenico SANTORO, Nereo BRESOLIN, Simone TONIETTI, Massimo SUARDELLI, Giacomo BEZZI, Daria BALDINI, Angelo Maurizio CLERICI, Giuseppina CAFASSO, Daniele PORAZZI, Isidoro LA SPINA, Giampiero GRAMPA, Davide ZARCONE, Michele PERINI, Marco POLONI, Emanuela AGAZZI, Massimiliano FILOSTO, Alessandro PADOVANI, Renato BESANA, Edoardo DONATI, Eugenio MAGNI, Marco ARNABOLDI, Vincenzo BELCASTRO, Mario GUIDOTTI, Raffaella CLERICI, Maurizio RIVA, Eugenio VITELLI, Paolo PREVIDI, Giuseppe MICIELI, Elisa CANDELORO, Carlo DALLOCCHIO, Carla ARBASINO, Piedmont: Andrea CALVO: Scdu Neurologia 4—AOU S. Giovanni Battista, Cristina MOGLIA: Scdu Neurologia 4—AOU S. Giovanni Battista, Marco VERCELLINO, Bruno FERRERO, Pietro PIGNATTA, Enrico ODDENINO, Daniele IMPERIALE, Daniela LEOTTA, Maurizio GIONCO, Carlo RAVETTI, Roberto CAVALLO, Nicoletta Di Vito, Claudio GEDA, Simona BORTOLOTTO, Emilio LUDA DI CORTEMIGLIA, Giovanna LIOTTA, Emilio URSINO, Mario PALERMO, Luca AMBROGIO, Piero MEINERI, Michele DOTTA, Paolo GHIGLIONE, Joseph MAISTRELLI, Susana ONORATO, Maurizio LEONE, Diego Maria PAPURELLO, Angelo VILLANI, Roberto CONTI, Franco COPPO, Fabiana TESSER, Lucia Testa, Silvia Isabella Cattaneo, Maria Teresa Penza, Graziano Gusmaroli, Katia Savio, Franco Perla, Fabrizio Pisano, Fabio Poglio, Luca Pradotto, Valle d’Aosta: Edo Fausto BOTTACCHI, Puglia: Paolo LIVREA, Francesco FEDERICO, Maria TROJANO, Vito COVELLI, Bruno MAGGIO, Vito SANTAMATO, Bruno PASSARELLA, Giovanni ZIMATORE, Giorgio TRIANNI, Gerardo CIARDO, Salvatore INTERNO’, Veneto: Corrado MARCHINI, Sandro ZAMBITO MARSALA, Giorgio MICHIELI, Carlo BORSATO, Giuseppe DIDONÈ, Emma FRASSON, Alberto POLO, Vincenza ARGENTIERO, Vincenzo ROMEO, Novenia PERLOTTO, Roberto L’ERARIO, Gianfranco MICAGLIO, Tiziana ROSSO, Sandro BRUNO, Bruno GIOMETTO, Mirco SERENA, Rocco QUATRALE, Ernesto GASTALDO, Francesco PERINI, Michele DILEONE, Alessandro CASANO, Lauretta SILVESTRI, Alessandro BURLINA, Virginia MUNERATI, Sebastiano D’Anna, Flavio SANSON, Valeria SARTORI, Giuseppe MORETTO, Giovanna SQUINTANI, Salvatore MONACO, Maria Donata BENEDETTI, Simone FUSINA, Claudio BIANCONI, Fabiana PIMAZZONI, Angela BONOMETTI, Giampietro ZANETTE, Marco TURATTI, Sardinia: Stefania LEONI, Giuseppe MURA, Anna TICCA, Piernicola MARCHI, Davide MANCA], Galeotti, F, Massari, M, D'Alessandro, R, Beghi, E, Chiò, A, Logroscino, G, Filippini, G, Benedetti, M, Pugliatti, M, Santuccio, C, Raschetti, R, Ferrarese, C, Benedetti, Md, ITANG study, Group, and Giometto, B

Subjects
Male, Epidemiology, Pharmaco-Epidemiology, medicine.disease_cause, MED/26 Neurologia, Influenza A Virus, H1N1 Subtype, Risk Factors, Influenza A virus, Odds Ratio, influenza vaccination, Guillain-Barré Syndrome, Case–control study, self controlled case series, Prospective Studies, Case-control study, Guillain-Barrè Syndrome, Influenza vaccination, Self controlled case series, Aged, 80 and over, Guillain-Barre syndrome, Respiratory tract infections, Incidence (epidemiology), Incidence, Middle Aged, Vaccination, Guillain-Barrè, epidemic risk , gastrointestinal and respiratory infections, Italy, Influenza Vaccines, Population Surveillance, Regression Analysis, Female, Settore MED/26 - Neurologia, Adult, medicine.medical_specialty, Guillain-Barre Syndrome, Mass Vaccination, NO, Internal medicine, Influenza, Human, medicine, Humans, Pandemics, Aged, business.industry, Odds ratio, medicine.disease, Relative risk, Case-Control Studies, Immunology, Attributable risk, business
Abstract

Influenza vaccination has been implicated in Guillain Barre Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.

Published
2013

15. Ulnar entrapment neuropathy in patients with type 2 diabetes mellitus: an electrodiagnostic study

Author

Emilio Terlizzi, Nicola Morelli, Paola De Mitri, Paolo Immovilli, Donata Guidetti, Donatella Zavaroni, Letizia Parietti, Eugenia Rota, and Ilaria Iafelice

Subjects
Male, medicine.medical_specialty, Diabetic neuropathy, Endocrinology, Diabetes and Metabolism, Elbow, Neural Conduction, Nerve conduction velocity, Ulnar neuropathy, Diagnosis, Differential, Polyneuropathies, Endocrinology, Internal Medicine, medicine, Humans, Ulnar nerve, Carpal tunnel syndrome, Ulnar Nerve, Retrospective Studies, business.industry, Electrodiagnosis, General Medicine, Middle Aged, medicine.disease, Ulnar Nerve Compression Syndromes, Surgery, body regions, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Entrapment Neuropathy, Female, business, Polyneuropathy, Follow-Up Studies
Abstract

Aims This study aimed to assess the prevalence and electrophysiological features of ulnar entrapment neuropathy in patients with type 2 diabetes mellitus (DM). Methods Nerve conduction studies (NCS) were performed in a sample of consecutive diabetic patients aged 25–75 years, referred by the Diabetology Unit. NCS of the median, ulnar, radial, peroneal and sural nerves were performed on the non-dominant side. Median entrapment neuropathy at the wrist (MNW) and ulnar neuropathy at the elbow (UNE) and wrist (UNW) were diagnosed according to standard electrodiagnostic criteria. Results Sixty-four patients were enrolled, 28 male (44%), average age 61, average DM duration 14.5 years. Polyneuropathy was diagnosed in 45 subjects (70%). UNE was detected in 22 patients (34%) (4 did not have polyneuropathy), in the abductor digiti minimi in 16, the first interosseus in 14 and in both in 8. UNW was detected in 7 (11%) subjects and MNW in 40 (63%). NCS alterations consistent with ulnar neuropathy were detected in a high proportion of patients (45%), suggesting that the ulnar nerve is very susceptible to focal entrapment in DM. Conclusions Upper limb sensory and motor NCS, including motor conduction velocity across the elbow, should be considered in the staging of DM patients.

Published
2013

17. Parenchymal Hematoma as Hemorrhagic Transformation of Ischemic Stroke Secondary to Spontaneous Internal Carotid Artery Dissection

Author

Paola De Mitri, Emilio Terlizzi, Donata Guidetti, Fabiola Magnifico, Nicola Morelli, Eugenia Rota, and Paolo Immovilli

Subjects
medicine.medical_specialty, Internal carotid artery dissection, business.industry, medicine.disease, Endovascular therapy, Surgery, Carotid artery dissection, Hematoma, Neurology, Neuroimaging, Parenchyma, Ischemic stroke, medicine, Right basal ganglia, cardiovascular diseases, Neurology (clinical), business
Abstract

The authors have no conflicts of interest to disclose. Dear Sir, Hemorrhagic transformation has rarely been reported in the evolution of ischemic stroke caused by carotid artery dissection [1] . Herein, we report the neuroimaging of a patient admitted to the hospital for a parenchymal hematoma over the right basal ganglia which, after an extensive neuroimaging workup, turned out to be the hemorrhagic transformation of an ischemic stroke secondary to spontaneous internal carotid artery dissection. This case was not treated with r-TPA or endovascular therapy. Received: November 15, 2011 Accepted: February 27, 2012 Published online: June 20, 2012

Published
2012
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