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5. Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing

Author

Coppola, A, Krithika, S, Iacomino, M, Bobbili, D, Balestrini, S, Bagnasco, I, Bilo, L, Buti, D, Casellato, S, Cuccurullo, C, Ferlazzo, E, Leu, C, Giordano, L, Gobbi, G, Hernandez-Hernandez, L, Lench, N, Martins, H, Meletti, S, Messana, T, Nigro, V, Pinelli, M, Pippucci, T, Bellampalli, R, Salis, B, Sofia, V, Striano, P, Striano, S, Tassi, L, Vignoli, A, Vaudano, AE, Viri, M, Scheffer, IE, May, P, Zara, F, Sisodiya, SM, Coppola, A, Krithika, S, Iacomino, M, Bobbili, D, Balestrini, S, Bagnasco, I, Bilo, L, Buti, D, Casellato, S, Cuccurullo, C, Ferlazzo, E, Leu, C, Giordano, L, Gobbi, G, Hernandez-Hernandez, L, Lench, N, Martins, H, Meletti, S, Messana, T, Nigro, V, Pinelli, M, Pippucci, T, Bellampalli, R, Salis, B, Sofia, V, Striano, P, Striano, S, Tassi, L, Vignoli, A, Vaudano, AE, Viri, M, Scheffer, IE, May, P, Zara, F, and Sisodiya, SM

Abstract

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. A

Published
2024

6. Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients with COVID-19 Infected with Pre-Omicron Variants

Author

Beretta, S, Cristillo, V, Camera, G, Morotti Colleoni, C, Pellitteri, G, Viti, B, Bianchi, E, Gipponi, S, Grimoldi, M, Valente, M, Guttmann, S, Cotelli, M, Palumbo, P, Gelosa, G, Meletti, S, Schenone, C, Ottaviani, D, Filippi, M, Zini, A, Basilico, P, Tancredi, L, Cortelli, P, Braga, M, De Giuli, V, Servidei, S, Paolicelli, D, Verde, F, Caproni, S, Pisani, A, Lo Re, V, Massacesi, L, Roccatagliata, D, Manganotti, P, Spitaleri, D, Formenti, A, Piccoli, M, Marino, S, Polverino, P, Aguglia, U, Ornello, R, Perego, E, Siciliano, G, Merlo, P, Capobianco, M, Pantoni, L, Lugaresi, A, Angelocola, S, De Rosa, A, Sessa, M, Beghi, E, Agostoni, E, Monaco, S, Padovani, A, Priori, A, Silani, V, Tedeschi, G, Ferrarese, C, Beretta S., Cristillo V., Camera G., Morotti Colleoni C., Pellitteri G., Viti B., Bianchi E., Gipponi S., Grimoldi M., Valente M., Guttmann S., Cotelli M. S., Palumbo P., Gelosa G., Meletti S., Schenone C., Ottaviani D., Filippi M., Zini A., Basilico P., Tancredi L., Cortelli P., Braga M., De Giuli V., Servidei S., Paolicelli D., Verde F., Caproni S., Pisani A., Lo Re V., Massacesi L., Roccatagliata D. V., Manganotti P., Spitaleri D., Formenti A., Piccoli M., Marino S., Polverino P., Aguglia U., Ornello R., Perego E., Siciliano G., Merlo P., Capobianco M., Pantoni L., Lugaresi A., Angelocola S., De Rosa A., Sessa M., Beghi E., Agostoni E. C., Monaco S., Padovani A., Priori A., Silani V., Tedeschi G., Ferrarese C., Beretta, S, Cristillo, V, Camera, G, Morotti Colleoni, C, Pellitteri, G, Viti, B, Bianchi, E, Gipponi, S, Grimoldi, M, Valente, M, Guttmann, S, Cotelli, M, Palumbo, P, Gelosa, G, Meletti, S, Schenone, C, Ottaviani, D, Filippi, M, Zini, A, Basilico, P, Tancredi, L, Cortelli, P, Braga, M, De Giuli, V, Servidei, S, Paolicelli, D, Verde, F, Caproni, S, Pisani, A, Lo Re, V, Massacesi, L, Roccatagliata, D, Manganotti, P, Spitaleri, D, Formenti, A, Piccoli, M, Marino, S, Polverino, P, Aguglia, U, Ornello, R, Perego, E, Siciliano, G, Merlo, P, Capobianco, M, Pantoni, L, Lugaresi, A, Angelocola, S, De Rosa, A, Sessa, M, Beghi, E, Agostoni, E, Monaco, S, Padovani, A, Priori, A, Silani, V, Tedeschi, G, Ferrarese, C, Beretta S., Cristillo V., Camera G., Morotti Colleoni C., Pellitteri G., Viti B., Bianchi E., Gipponi S., Grimoldi M., Valente M., Guttmann S., Cotelli M. S., Palumbo P., Gelosa G., Meletti S., Schenone C., Ottaviani D., Filippi M., Zini A., Basilico P., Tancredi L., Cortelli P., Braga M., De Giuli V., Servidei S., Paolicelli D., Verde F., Caproni S., Pisani A., Lo Re V., Massacesi L., Roccatagliata D. V., Manganotti P., Spitaleri D., Formenti A., Piccoli M., Marino S., Polverino P., Aguglia U., Ornello R., Perego E., Siciliano G., Merlo P., Capobianco M., Pantoni L., Lugaresi A., Angelocola S., De Rosa A., Sessa M., Beghi E., Agostoni E. C., Monaco S., Padovani A., Priori A., Silani V., Tedeschi G., and Ferrarese C.

Abstract

Background and ObjectivesA variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome.MethodsThe Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death.ResultsAmong 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling s

Published
2023

7. Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report.

Author

MAZZOLI, M., RICCI, A., VAUDANO, A. E., MARCACCI, M., MARCHINI, S., BERGONZINI, P., DI PIERRO, E., PISCHIK, E., IUGHETTI, L., PIETRANGELO, A., MELETTI, S., and VENTURA, P.

Abstract

BACKGROUND: We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering RNA that drastically decreases delta-aminolevulinic acid production and reduces porphyric attacks' recurrence. CASE REPORT: A 12-year-old male patient with refractory acute intermittent porphyria and severe porphyric neuropathy was followed prospectively for 12 months after givosiran initiation (subcutaneous, 2.5 mg/kg monthly). Serial neurological, structural, and resting-state functional magnetic resonance imaging (MRI) evaluations were performed, including clinical scales and neurophysiological tests. Delta-aminolevulinic acid urinary levels dropped drastically during treatment. In parallel, all the administered neurological rating scales and neurophysiological assessments showed improvement in all domains. Moreover, an improvement in central motor conduction parameters and resting-state functional connectivity in the sensory-motor network was noticed. At the end of the follow-up, the patient could walk unaided after using a wheelchair for 5 years. CONCLUSIONS: A clear beneficial effect of givosiran was demonstrated in our patient with both clinical and peripheral nerve neurophysiologic outcome measures. Moreover, we first reported a potential role of givosiran in recovering central motor network impairment in acute intermittent porphyria (AIP), which was previously unknown. This study provides Class IV evidence that givosiran improves chronic porphyric neuropathy. [ABSTRACT FROM AUTHOR]

Published
2024

8. The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase Methylation Status in Glioblastoma Patients: The Female Power

Author

Baruzzi, A., Albani, F., Calbucci, F., D'Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, E., Biasini, C., Cavanna, L., Guidetti, D., Marcello, N., Pisanello, A., Cremonini, A.M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall'Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall'Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Faedi, M., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A.R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, M., Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M.R., Urbini, B., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E.M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., Franceschi, Enrico, Tosoni, Alicia, Minichillo, Santino, Depenni, Roberta, Paccapelo, Alexandro, Bartolini, Stefania, Michiara, Maria, Pavesi, Giacomo, Urbini, Benedetta, Crisi, Girolamo, Cavallo, Michele A., Tosatto, Luigino, Dazzi, Claudio, Biasini, Claudia, Pasini, Giuseppe, Balestrini, Damiano, Zanelli, Francesca, Ramponi, Vania, Fioravanti, Antonio, Giombelli, Ermanno, De Biase, Dario, Baruzzi, Agostino, and Brandes, Alba A.

Published
2018
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9. Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis

Author

Tabaee Damavandi, P, Fabin, N, Giossi, R, Matricardi, S, Del Giovane, C, Striano, P, Meletti, S, Brigo, F, Trinka, E, Lattanzi, S, Tabaee Damavandi, Payam, Fabin, Natalia, Giossi, Riccardo, Matricardi, Sara, Del Giovane, Cinzia, Striano, Pasquale, Meletti, Stefano, Brigo, Francesco, Trinka, Eugen, Lattanzi, Simona, Tabaee Damavandi, P, Fabin, N, Giossi, R, Matricardi, S, Del Giovane, C, Striano, P, Meletti, S, Brigo, F, Trinka, E, Lattanzi, S, Tabaee Damavandi, Payam, Fabin, Natalia, Giossi, Riccardo, Matricardi, Sara, Del Giovane, Cinzia, Striano, Pasquale, Meletti, Stefano, Brigo, Francesco, Trinka, Eugen, and Lattanzi, Simona

Abstract

Introduction: Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy. Methods: We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome. Results: Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73–11.54) and 4.71 (95% CI 0.57–39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33–5.02) and 0.50 (95% CI 0.031–7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89–3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and pl

Published
2023

10. ICHOSA (Intra Cerebral Hemorrage and Obstructive Sleep Apnea) project: first results

Author

Picchetto, L., primary, Pizza, F., additional, Bigliardi, G., additional, Giacobazzi, L., additional, Dell'Acqua, M., additional, Vandelli, L., additional, Ciolli, L., additional, Vandelli, G., additional, Rosafio, F., additional, Ricceri, R., additional, Galli, C., additional, Vitetta, F., additional, Zini, A., additional, Meletti, S., additional, and Plazzi, G., additional

Published
2022
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13. Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy

Author

Baldin, Elisa, Testoni, Stefania, de Pasqua, Silvia, Ferro, Salvatore, Albani, Fiorenzo, Baruzzi, Agostino, D’Alessandro, Roberto, Baruzzi, A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Cavallo, M., Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, E., Biasini, C., Cavanna, L., Guidetti, D., Marcello, N., Pisanello, A., Cremonini, A. M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Faedi, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Fallica, E., Granieri, E., Latini, F., Lelli, G., Monetti, C., Saletti, A., Schivalocchi, R., Seraceni, S., Tola, M. R., Urbini, B., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., and On behalf of PERNO study group

Published
2017
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14. OS02.6.A Lacosamide in monotherapy in brain tumour-related epilepsy (BTRE): results from an Italian multicentre retrospective study

Author

Bruno, F, primary, Mo, F, additional, Meletti, S, additional, Belcastro, V, additional, Quadri, S, additional, Napolitano, M, additional, Bello, L, additional, Dainese, F, additional, Scarpelli, M, additional, Florindo, I, additional, Mascia, A, additional, Pauletto, G, additional, Pellerino, A, additional, Giovannini, G, additional, Polosa, M, additional, Sessa, M, additional, Conti Nibali, M, additional, Di Gennaro, G, additional, Gigli, G, additional, Cavallieri, F, additional, Pisanello, A, additional, and Rudà, R, additional

Published
2022
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15. Intravenous brivaracetam in status epilepticus: A multicentric retrospective study in Italy

Author

Orlandi, N, Bartolini, E, Audenino, D, Moja, M, Urso, L, D'Orsi, G, Pauletto, G, Nilo, A, Zinno, L, Cappellani, R, Zummo, L, Giordano, A, Dainese, F, Nazerian, P, Pescini, F, Beretta, S, Dono, F, Gaudio, L, Ferlisi, M, Marino, D, Piccioli, M, Renna, R, Rosati, E, Rum, A, Strigaro, G, Giovannini, G, Meletti, S, Cavalli, S, Contento, M, Cottone, S, Di Claudio, M, Florindo, I, Guadagni, M, Kiferle, L, Lazzaretti, D, Lazzari, M, Coco, D, Pradella, S, Rikani, K, Rodorigo, D, Sabetta, A, Sicurella, L, Tontini, V, Turchi, G, Vaudano, A, Zanoni, T, Orlandi N., Bartolini E., Audenino D., Moja M. C., Urso L., d'Orsi G., Pauletto G., Nilo A., Zinno L., Cappellani R., Zummo L., Giordano A., Dainese F., Nazerian P., Pescini F., Beretta S., Dono F., Gaudio L. D., Ferlisi M., Marino D., Piccioli M., Renna R., Rosati E., Rum A., Strigaro G., Giovannini G., Meletti S., Cavalli S. M., Contento M., Cottone S., Di Claudio M. T., Florindo I., Guadagni M., Kiferle L., Lazzaretti D., Lazzari M., Coco D. L., Pradella S., Rikani K., Rodorigo D., Sabetta A., Sicurella L., Tontini V., Turchi G., Vaudano A. E., Zanoni T., Orlandi, N, Bartolini, E, Audenino, D, Moja, M, Urso, L, D'Orsi, G, Pauletto, G, Nilo, A, Zinno, L, Cappellani, R, Zummo, L, Giordano, A, Dainese, F, Nazerian, P, Pescini, F, Beretta, S, Dono, F, Gaudio, L, Ferlisi, M, Marino, D, Piccioli, M, Renna, R, Rosati, E, Rum, A, Strigaro, G, Giovannini, G, Meletti, S, Cavalli, S, Contento, M, Cottone, S, Di Claudio, M, Florindo, I, Guadagni, M, Kiferle, L, Lazzaretti, D, Lazzari, M, Coco, D, Pradella, S, Rikani, K, Rodorigo, D, Sabetta, A, Sicurella, L, Tontini, V, Turchi, G, Vaudano, A, Zanoni, T, Orlandi N., Bartolini E., Audenino D., Moja M. C., Urso L., d'Orsi G., Pauletto G., Nilo A., Zinno L., Cappellani R., Zummo L., Giordano A., Dainese F., Nazerian P., Pescini F., Beretta S., Dono F., Gaudio L. D., Ferlisi M., Marino D., Piccioli M., Renna R., Rosati E., Rum A., Strigaro G., Giovannini G., Meletti S., Cavalli S. M., Contento M., Cottone S., Di Claudio M. T., Florindo I., Guadagni M., Kiferle L., Lazzaretti D., Lazzari M., Coco D. L., Pradella S., Rikani K., Rodorigo D., Sabetta A., Sicurella L., Tontini V., Turchi G., Vaudano A. E., and Zanoni T.

Abstract

Purpose: to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). Methods: a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration. Results: 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed. Conclusion: BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.

Published
2021

16. Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis

Author

Lattanzi, S, De Maria, G, Rosati, E, Didato, G, Chiesa, V, Ranzato, F, Canafoglia, L, Cesnik, E, Anzellotti, F, Meletti, S, Pauletto, G, Nilo, A, Bartolini, E, Marino, D, Tartara, E, Luisi, C, Bonanni, P, Marrelli, A, Stokelj, D, Dainese, F, Foschi, N, Cagnetti, C, Gazzina, S, Contento, M, Biggi, M, Magliani, M, Di Giacomo, R, Pastori, C, Canevini, M, Zambrelli, E, Billo, G, Casazza, M, Fallica, E, Rosa, G, Dono, F, Speranza, R, Cioclu, C, Vaudano, A, Kiferle, L, Galli, R, Guadagni, M, Galimberti, C, Kassabian, B, Ferreri, F, Osanni, E, Ciuffini, R, Badioni, V, Beretta, S, Lattanzi S., De Maria G., Rosati E., Didato G., Chiesa V., Ranzato F., Canafoglia L., Cesnik E., Anzellotti F., Meletti S., Pauletto G., Nilo A., Bartolini E., Marino D., Tartara E., Luisi C., Bonanni P., Marrelli A., Stokelj D., Dainese F., Foschi N., Cagnetti C., Gazzina S., Contento M., Biggi M., Magliani M., Di Giacomo R., Pastori C., Canevini M. P., Zambrelli E., Billo G., Casazza M., Fallica E., Rosa G., Dono F., Speranza R., Cioclu C., Vaudano A. E., Kiferle L., Galli R., Guadagni M., Galimberti C. A., Kassabian B., Ferreri F., Osanni E., Ciuffini R., Badioni V., Beretta S., Lattanzi, S, De Maria, G, Rosati, E, Didato, G, Chiesa, V, Ranzato, F, Canafoglia, L, Cesnik, E, Anzellotti, F, Meletti, S, Pauletto, G, Nilo, A, Bartolini, E, Marino, D, Tartara, E, Luisi, C, Bonanni, P, Marrelli, A, Stokelj, D, Dainese, F, Foschi, N, Cagnetti, C, Gazzina, S, Contento, M, Biggi, M, Magliani, M, Di Giacomo, R, Pastori, C, Canevini, M, Zambrelli, E, Billo, G, Casazza, M, Fallica, E, Rosa, G, Dono, F, Speranza, R, Cioclu, C, Vaudano, A, Kiferle, L, Galli, R, Guadagni, M, Galimberti, C, Kassabian, B, Ferreri, F, Osanni, E, Ciuffini, R, Badioni, V, Beretta, S, Lattanzi S., De Maria G., Rosati E., Didato G., Chiesa V., Ranzato F., Canafoglia L., Cesnik E., Anzellotti F., Meletti S., Pauletto G., Nilo A., Bartolini E., Marino D., Tartara E., Luisi C., Bonanni P., Marrelli A., Stokelj D., Dainese F., Foschi N., Cagnetti C., Gazzina S., Contento M., Biggi M., Magliani M., Di Giacomo R., Pastori C., Canevini M. P., Zambrelli E., Billo G., Casazza M., Fallica E., Rosa G., Dono F., Speranza R., Cioclu C., Vaudano A. E., Kiferle L., Galli R., Guadagni M., Galimberti C. A., Kassabian B., Ferreri F., Osanni E., Ciuffini R., Badioni V., and Beretta S.

Abstract

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P =.002). The number of prior antiseizure medications (adjusted hazard ratio [adjHR] = 1.07, 95% CI = 1.02-1.13, P =.009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001-1.008, P =.028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

Published
2021

17. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author

Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Enia G., Giussani G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., Lattanzi S., La N. A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F. G. S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., Bravar G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Enia G., Giussani G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., Lattanzi S., La N. A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F. G. S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., and Bravar G.

Abstract

Objective: The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods: This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results: Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of

Published
2021

18. International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) incl. Febrile Infection-Related Epilepsy Syndrome (FIRES): Statements and Supporting Evidence

Author

Wickstrom, R., Taraschenko, O., Dilena, R., Payne, E. T., Specchio, N., Nabbout, R., Koh, S., Gaspard, N., Hirsch, L. J., Auvin, S., van Baalen, A., Beghi, E., Benseler, S. M., Bergin, P., Bleck, T., Brunklaus, A., Caraballo, R. H., Cervenka, M., Costello, D., Drislane, F., Farias-Moeller, R., Gallantine, W., Gilmore, E., Gofton, T., Jimenez, M. A. P., Hocker, S., Kaliakatsos, M., Kellogg, M., Lee, J. W., Loddenkemper, T., Meletti, S., Mizugushi, M., Muscal, E., Riviello, J. J., Rosenthal, E. S., Rossetti, A. O., Ruegg, S., Said, R., Sculier, C., Schmitt, S., Schuele, S., Stredny, C., Trinka, E., Wainwright, M., Vanhaerents, S., Wells, E., Wirrell, E., and Zuberi, S. M.

Subjects
status epilepticus, pediatric, Neurology, ketogenic diet, adult, refractory status epilepticus, epilepsy, antiseizure medication, immunotherapy, Neurology (clinical), Delphi
Abstract

To develop consensus-based recommendations for the management of adult and paediatric patients with NORSE/FIRES based on best evidence and experience.The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater or equal to 7, and inappropriate if the median score was less than or equal to 3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey.Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article.This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.

Published
2022

19. International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) including Febrile Infection-Related Epilepsy Syndrome (FIRES): Summary and Clinical Tools

Author

Wickstrom, R., Taraschenko, O., Dilena, R., Payne, E. T., Specchio, N., Nabbout, R., Koh, S., Gaspard, N., Hirsch, L. J., Auvin, S., van Baalen, A., Beghi, E., Benseler, S. M., Bergin, P., Bleck, T., Brunklaus, A., Caraballo, R. H., Cervenka, M., Costello, D., Drislane, F., Farias-Moeller, R., Gallantine, W., Gilmore, E. J., Gofton, T., Jimenez, M. A. P., Hocker, S., Kaliakatsos, M., Kellogg, M., Lee, J. W., Loddenkemper, T., Meletti, S., Mizugushi, M., Muscal, E., Riviello, J. J., Rosenthal, E. S., Rossetti, A. O., Ruegg, S., Said, R., Sculier, C., Schmitt, S., Schuele, S., Stredny, C., Trinka, E., Wainwright, M., Vanhaerents, S., Wells, E., Wirrell, E., and Zuberi, S. M.

Subjects
refractory, status epilepticus, pediatric, Neurology, ketogenic diet, adult, anti-seizure medication, Delphi, epilepsy, immunotherapy, Neurology (clinical)
Abstract

To develop consensus-based recommendations for the management of adult and pediatric patients with NORSE/FIRES based on best available evidence and expert opinion.The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater than or equal to 7, and inappropriate if the median score was less than or equal to 3.Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. These are summarized in this article along with two practical clinical flowsheets: one for diagnosis and evaluation and one for acute treatment. A corresponding evidence-based analysis of all 85 recommendations alongside responses by the Delphi panel is presented in a companion article.The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.

Published
2022

20. The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study

Author

Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Giussani G., Enia G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., La Neve A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F., Galletta S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., Bravar G., Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Giussani G., Enia G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., La Neve A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F., Galletta S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., and Bravar G.

Abstract

Purpose: The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods: In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results: Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion: Patients and physicians' priorities in the mana

Published
2020

21. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author

Park, B.-y., Larivière, S., Rodríguez-Cruces, R., Royer, J., Tavakol, S., Wang, Y., Caciagli, L., Caligiuri, M.E., Gambardella, A., Concha, L., Keller, S.S., Cendes, F., Alvim, M.K.M., Yasuda, C., Bonilha, L., Gleichgerrcht, E., Focke, N.K., Kreilkamp, B.A.K., Domin, M., Podewils, F. von, Langner, S., Rummel, C., Rebsamen, M., Wiest, R., Martin, P., Kotikalapudi, R., Bender, B., O’Brien, T.J., Law, M., Sinclair, B., Vivash, L., Kwan, P., Desmond, P.M., Malpas, C.B., Lui, E., Alhusaini, S., Doherty, C.P., Cavalleri, G.L., Delanty, N., Kälviäinen, R., Jackson, G.D., Kowalczyk, M., Mascalchi, M., Semmelroch, M., Thomas, R.H., Soltanian-Zadeh, H., Davoodi-Bojd, E., Zhang, J., Lenge, M., Guerrini, R., Bartolini, E., Hamandi, K., Foley, S., Weber, B., Depondt, C., Absil, J., Carr, S.J.A., Abela, E., Richardson, M.P., Devinsky, O., Severino, M., Striano, P., Parodi, C., Tortora, D., Hatton, S.N., Vos, S.B., Duncan, J.S., Galovic, M., Whelan, C.D., Bargalló, N., Pariente, J., Conde-Blanco, E., Vaudano, A.E., Tondelli, M., Meletti, S., Kong, X.Z., Francks, C., Fisher, S.E., Caldairou, B., Ryten, M., Labate, A., Sisodiya, S.M., Thompson, P.M., McDonald, C.R., Bernasconi, A., Bernasconi, N., Bernhardt, B.C., Park, B.-y., Larivière, S., Rodríguez-Cruces, R., Royer, J., Tavakol, S., Wang, Y., Caciagli, L., Caligiuri, M.E., Gambardella, A., Concha, L., Keller, S.S., Cendes, F., Alvim, M.K.M., Yasuda, C., Bonilha, L., Gleichgerrcht, E., Focke, N.K., Kreilkamp, B.A.K., Domin, M., Podewils, F. von, Langner, S., Rummel, C., Rebsamen, M., Wiest, R., Martin, P., Kotikalapudi, R., Bender, B., O’Brien, T.J., Law, M., Sinclair, B., Vivash, L., Kwan, P., Desmond, P.M., Malpas, C.B., Lui, E., Alhusaini, S., Doherty, C.P., Cavalleri, G.L., Delanty, N., Kälviäinen, R., Jackson, G.D., Kowalczyk, M., Mascalchi, M., Semmelroch, M., Thomas, R.H., Soltanian-Zadeh, H., Davoodi-Bojd, E., Zhang, J., Lenge, M., Guerrini, R., Bartolini, E., Hamandi, K., Foley, S., Weber, B., Depondt, C., Absil, J., Carr, S.J.A., Abela, E., Richardson, M.P., Devinsky, O., Severino, M., Striano, P., Parodi, C., Tortora, D., Hatton, S.N., Vos, S.B., Duncan, J.S., Galovic, M., Whelan, C.D., Bargalló, N., Pariente, J., Conde-Blanco, E., Vaudano, A.E., Tondelli, M., Meletti, S., Kong, X.Z., Francks, C., Fisher, S.E., Caldairou, B., Ryten, M., Labate, A., Sisodiya, S.M., Thompson, P.M., McDonald, C.R., Bernasconi, A., Bernasconi, N., and Bernhardt, B.C.

Abstract

Contains fulltext : 252489.pdf (Publisher’s version ) (Open Access)

Published
2022

22. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author

Park, B-Y, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Tavakol, S, Wang, Y, Caciagli, L, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Alvim, MKM, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Kreilkamp, BAK, Domin, M, von Podewils, F, Langner, S, Rummel, C, Rebsamen, M, Wiest, R, Martin, P, Kotikalapudi, R, Bender, B, O'Brien, TJ, Law, M, Sinclair, B, Vivash, L, Kwan, P, Desmond, PM, Malpas, CB, Lui, E, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Parodi, C, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Galovic, M, Whelan, CD, Bargallo, N, Pariente, J, Conde-Blanco, E, Vaudano, AE, Tondelli, M, Meletti, S, Kong, X-Z, Francks, C, Fisher, SE, Caldairou, B, Ryten, M, Labate, A, Sisodiya, SM, Thompson, PM, McDonald, CR, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Park, B-Y, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Tavakol, S, Wang, Y, Caciagli, L, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Alvim, MKM, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Kreilkamp, BAK, Domin, M, von Podewils, F, Langner, S, Rummel, C, Rebsamen, M, Wiest, R, Martin, P, Kotikalapudi, R, Bender, B, O'Brien, TJ, Law, M, Sinclair, B, Vivash, L, Kwan, P, Desmond, PM, Malpas, CB, Lui, E, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Parodi, C, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Galovic, M, Whelan, CD, Bargallo, N, Pariente, J, Conde-Blanco, E, Vaudano, AE, Tondelli, M, Meletti, S, Kong, X-Z, Francks, C, Fisher, SE, Caldairou, B, Ryten, M, Labate, A, Sisodiya, SM, Thompson, PM, McDonald, CR, Bernasconi, A, Bernasconi, N, and Bernhardt, BC

Abstract

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine ou

Published
2022

23. A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies

Author

Altmann, A, Ryten, M, Di Nunzio, M, Ravizza, T, Tolomeo, D, Reynolds, RH, Somani, A, Bacigaluppi, M, Iori, V, Micotti, E, Di Sapia, R, Cerovic, M, Palma, E, Ruffolo, G, Botia, JA, Absil, J, Alhusaini, S, Alvim, MKM, Auvinen, P, Bargallo, N, Bartolini, E, Bender, B, Bergo, FPG, Bernardes, T, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Blackmon, K, Braga, B, Caligiuri, ME, Calvo, A, Carlson, C, Carr, SJA, Cavalleri, GL, Cendes, F, Chen, J, Chen, S, Cherubini, A, Concha, L, David, P, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP, Domin, M, Focke, NK, Foley, S, Franca, W, Gambardella, A, Guerrini, R, Hamandi, K, Hibar, DP, Isaev, D, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kowalczyk, MA, Kuzniecky, R, Kwan, P, Labate, A, Langner, S, Lenge, M, Liu, M, Martin, P, Mascalchi, M, Meletti, S, Morita-Sherman, ME, O'Brien, TJ, Pariente, JC, Richardson, MP, Rodriguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Striano, P, Thesen, T, Thomas, RH, Tondelli, M, Tortora, D, Vaudano, AE, Vivash, L, Podewils, F, Wagner, J, Weber, B, Wiest, R, Yasuda, CL, Zhang, G, Zhang, J, Leu, C, Avbersek, A, Thom, M, Whelan, CD, Thompson, P, McDonald, CR, Vezzani, A, Sisodiya, SM, Altmann, A, Ryten, M, Di Nunzio, M, Ravizza, T, Tolomeo, D, Reynolds, RH, Somani, A, Bacigaluppi, M, Iori, V, Micotti, E, Di Sapia, R, Cerovic, M, Palma, E, Ruffolo, G, Botia, JA, Absil, J, Alhusaini, S, Alvim, MKM, Auvinen, P, Bargallo, N, Bartolini, E, Bender, B, Bergo, FPG, Bernardes, T, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Blackmon, K, Braga, B, Caligiuri, ME, Calvo, A, Carlson, C, Carr, SJA, Cavalleri, GL, Cendes, F, Chen, J, Chen, S, Cherubini, A, Concha, L, David, P, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP, Domin, M, Focke, NK, Foley, S, Franca, W, Gambardella, A, Guerrini, R, Hamandi, K, Hibar, DP, Isaev, D, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kowalczyk, MA, Kuzniecky, R, Kwan, P, Labate, A, Langner, S, Lenge, M, Liu, M, Martin, P, Mascalchi, M, Meletti, S, Morita-Sherman, ME, O'Brien, TJ, Pariente, JC, Richardson, MP, Rodriguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Striano, P, Thesen, T, Thomas, RH, Tondelli, M, Tortora, D, Vaudano, AE, Vivash, L, Podewils, F, Wagner, J, Weber, B, Wiest, R, Yasuda, CL, Zhang, G, Zhang, J, Leu, C, Avbersek, A, Thom, M, Whelan, CD, Thompson, P, McDonald, CR, Vezzani, A, and Sisodiya, SM

Abstract

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Published
2022

24. The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Author

Sisodiya, SM, Whelan, CD, Hatton, SN, Huynh, K, Altmann, A, Ryten, M, Vezzani, A, Caligiuri, ME, Labate, A, Gambardella, A, Ives-Deliperi, V, Meletti, S, Munsell, BC, Bonilha, L, Tondelli, M, Rebsamen, M, Rummel, C, Vaudano, AE, Wiest, R, Balachandra, AR, Bargallo, N, Bartolini, E, Bernasconi, A, Bernasconi, N, Bernhardt, B, Caldairou, B, Carr, SJA, Cavalleri, GL, Cendes, F, Concha, L, Desmond, PM, Domin, M, Duncan, JS, Focke, NK, Guerrini, R, Hamandi, K, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kowalczyk, MA, Kreilkamp, BAK, Kwan, P, Lariviere, S, Lenge, M, Lopez, SM, Martin, P, Mascalchi, M, Moreira, JCV, Morita-Sherman, ME, Pardoe, HR, Pariente, JC, Raviteja, K, Rocha, CS, Rodriguez-Cruces, R, Seeck, M, Semmelroch, MKHG, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Thomopoulos, SI, Velakoulis, D, Vivash, L, Weber, B, Yasuda, CL, Zhang, J, Thompson, PM, McDonald, CR, Sisodiya, SM, Whelan, CD, Hatton, SN, Huynh, K, Altmann, A, Ryten, M, Vezzani, A, Caligiuri, ME, Labate, A, Gambardella, A, Ives-Deliperi, V, Meletti, S, Munsell, BC, Bonilha, L, Tondelli, M, Rebsamen, M, Rummel, C, Vaudano, AE, Wiest, R, Balachandra, AR, Bargallo, N, Bartolini, E, Bernasconi, A, Bernasconi, N, Bernhardt, B, Caldairou, B, Carr, SJA, Cavalleri, GL, Cendes, F, Concha, L, Desmond, PM, Domin, M, Duncan, JS, Focke, NK, Guerrini, R, Hamandi, K, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kowalczyk, MA, Kreilkamp, BAK, Kwan, P, Lariviere, S, Lenge, M, Lopez, SM, Martin, P, Mascalchi, M, Moreira, JCV, Morita-Sherman, ME, Pardoe, HR, Pariente, JC, Raviteja, K, Rocha, CS, Rodriguez-Cruces, R, Seeck, M, Semmelroch, MKHG, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Thomopoulos, SI, Velakoulis, D, Vivash, L, Weber, B, Yasuda, CL, Zhang, J, Thompson, PM, and McDonald, CR

Abstract

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

Published
2022

25. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Author

Lariviere, S, Royer, J, Rodriguez-Cruces, R, Paquola, C, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, CL, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Lui, E, Vaudano, AE, Meletti, S, Tondelli, M, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Winston, GP, Griffin, A, Singh, A, Tiwari, VK, Kreilkamp, BAK, Lenge, M, Guerrini, R, Hamandi, K, Foley, S, Ruber, T, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Kaestner, E, Hatton, SN, Vos, SB, Caciagli, L, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, Bernhardt, BC, Lariviere, S, Royer, J, Rodriguez-Cruces, R, Paquola, C, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, CL, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Lui, E, Vaudano, AE, Meletti, S, Tondelli, M, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Winston, GP, Griffin, A, Singh, A, Tiwari, VK, Kreilkamp, BAK, Lenge, M, Guerrini, R, Hamandi, K, Foley, S, Ruber, T, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Kaestner, E, Hatton, SN, Vos, SB, Caciagli, L, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, and Bernhardt, BC

Abstract

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Published
2022

26. Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, RealWorld Study

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Cerulli Irelli, E., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Di Gennaro, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Gangitano, M., La Neve, A., Mecarelli, O., Montalenti, E., Morano, A., Piazza, F., Pizzanelli, C., Pulitano, P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Giacomo, R., Di Liberto, A., Domina, E., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fisco, G., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giallonardo, A. T., Giorgi, F. S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Milano, C., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quarato, P. P., Quintas, R., Renna, R., Rizzo, G. R., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Vaudano, A. E., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi, Simona, Canafoglia, Laura, Canevini, Maria Paola, Casciato, Sara, Cerulli Irelli, Emanuele, Chiesa, Valentina, Dainese, Filippo, De Maria, Giovanni, Didato, Giuseppe, Di Gennaro, Giancarlo, Falcicchio, Giovanni, Fanella, Martina, Ferlazzo, Edoardo, Gangitano, Massimo, La Neve, Angela, Mecarelli, Oriano, Montalenti, Elisa, Morano, Alessandra, Piazza, Federico, Pizzanelli, Chiara, Pulitano, Patrizia, Ranzato, Federica, Rosati, Eleonora, Tassi, Laura, and Di Bonaventura, Carlo

Subjects
Antiseizure medication, Focal seizures, Brivaracetam, Epilepsy, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), Settore MED/26, Settore MED/39 - Neuropsichiatria Infantile
Abstract

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications. Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p

Published
2022

27. Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1

Author

Ballotta D., Talami F., Pizza F., Vaudano A. E., Benuzzi F., Plazzi G., Meletti S., Ballotta D., Talami F., Pizza F., Vaudano A.E., Benuzzi F., Plazzi G., and Meletti S.

Subjects
Male, Brain Mapping, Adolescent, Computer applications to medicine. Medical informatics, R858-859.7, Amygdala, Functional connectivity, Hypothalamus, Narcolepsy, Resting-state fMRI, Regular Article, Magnetic Resonance Imaging, nervous system, Hypothalamu, Humans, Neurology. Diseases of the nervous system, RC346-429, Child, psychological phenomena and processes, Human
Abstract

Highlights • Hypothalamus and amygdala functional connectivity is altered in adolescents with NT1. • The hypothalamus shows reduced connectivity with the hippocampus and parietal cortex. • The amygdala showed both reduced and increased functional connectivity. • Reduced connectivity was observed between amygdala, sensorimotor and visual network. • Increased functional connectivity was present between amygdala and salience network., Introduction functional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcoleptic patients would influence both brain metabolism and perfusion and would cause reduction in cortical grey matter. Previous fMRI studies have mainly focused on cerebral functioning during emotional processing. The aim of the present study was to explore the hemodynamic behaviour of spontaneous BOLD fluctuation at rest in patients with Narcolepsy type 1 (NT1) close to disease onset. Methods Fifteen drug naïve children/adolescents with NT1 (9 males; mean age 11.7 ± 3 years) and fifteen healthy children/adolescents (9 males; mean age 12.4 ± 2.8 years) participated in an EEG-fMRI study in order to investigate the resting-state functional connectivity of hypothalamus and amygdala. Functional images were acquired on a 3 T system. Seed-based functional connectivity analyses were performed using SPM12. Regions of Interest were the lateral hypothalamus and the amygdala. Results compared to controls, NT1 patients showed decreased functional connectivity between the lateral hypothalamus and the left superior parietal lobule, the hippocampus and the parahippocampal gyrus. Decreased functional connectivity was detected between the amygdala and the post-central gyrus and several occipital regions, whereas it was increased between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen. Conclusion in NT1 patients the abnormal connectivity between the hypothalamus and brain regions involved in memory consolidation during sleep, such as the hippocampus, may be linked to the loss of orexin containing neurons in the dorsolateral hypothalamus. Moreover, also functional connectivity of the amygdala seems to be influenced by the loss of orexin-containing neurons. Therefore, we can hypothesize that dysfunctional interactions between regions subserving the maintenance of arousal, memory and emotional processing may contribute to the main symptom of narcolepsy.

Published
2021

28. Temporal Lobe Spikes Affect Distant Intrinsic Connectivity Networks

Author

Mirandola, L., Ballotta, D., Talami, F., Giovannini, G., Pavesi, G., Vaudano, A. E., and Meletti, S.

Subjects
TLE, genetic structures, fMRI, EEG-fMRI, behavioral disciplines and activities, BOLD, EEG, epilepsy, temporal lobe, nervous system, Neurology, psychological phenomena and processes, Original Research
Abstract

Objective: To evaluate local and distant blood oxygen level dependent (BOLD) signal changes related to interictal epileptiform discharges (IED) in drug-resistant temporal lobe epilepsy (TLE). Methods: Thirty-three TLE patients undergoing EEG–functional Magnetic Resonance Imaging (fMRI) as part of the presurgical workup were consecutively enrolled. First, a single-subject spike-related analysis was performed: (a) to verify the BOLD concordance with the presumed Epileptogenic Zone (EZ); and (b) to investigate the Intrinsic Connectivity Networks (ICN) involvement. Then, a group analysis was performed to search for common BOLD changes in TLE. Results: Interictal epileptiform discharges were recorded in 25 patients and in 19 (58%), a BOLD response was obtained at the single-subject level. In 42% of the cases, BOLD changes were observed in the temporal lobe, although only one patient had a pure concordant finding, with a single fMRI cluster overlapping (and limited to) the EZ identified by anatomo-electro-clinical correlations. In the remaining 58% of the cases, BOLD responses were localized outside the temporal lobe and the presumed EZ. In every patient, with a spike-related fMRI map, at least one ICN appeared to be involved. Four main ICNs were preferentially involved, namely, motor, visual, auditory/motor speech, and the default mode network. At the single-subject level, EEG–fMRI proved to have high specificity (above 65%) in detecting engagement of an ICN and the corresponding ictal/postictal symptom, and good positive predictive value (above 67%) in all networks except the visual one. Finally, in the group analysis of BOLD changes related to IED revealed common activations at the right precentral gyrus, supplementary motor area, and middle cingulate gyrus. Significance: Interictal temporal spikes affect several distant extra-temporal areas, and specifically the motor/premotor cortex. EEG–fMRI in patients with TLE eligible for surgery is recommended not for strictly localizing purposes rather it might be useful to investigate ICNs alterations at the single-subject level.

Published
2021

30. Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study

Author

Franceschi, Enrico, Depenni, Roberta, Paccapelo, Alexandro, Ermani, Mario, Faedi, Marina, Sturiale, Carmelo, Michiara, Maria, Servadei, Franco, Pavesi, Giacomo, Urbini, Benedetta, Pisanello, Anna, Crisi, Girolamo, Cavallo, Michele A., Dazzi, Claudio, Biasini, Claudia, Bertolini, Federica, Mucciarini, Claudia, Pasini, Giuseppe, Baruzzi, Agostino, Brandes, Alba A., Baruzzi, A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Cavallo, M., Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, E., Biasini, C., Cavanna, L., Guidetti, D., Marcello, N., Pisanello, A., Cremonini, A. M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., PastoreTrossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Faedi, M., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, M., Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M. R., Urbini, B., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., and The PERNO Study Group

Published
2017
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32. Topographic Divergence of Atypical Cortical Asymmetry and Regional Atrophy Patterns in Temporal Lobe Epilepsy: A Worldwide ENIGMA Study

Author

Colin P. Doherty, Boris C. Bernhardt, Graeme D. Jackson, Mariasavina Severino, Christian Rummel, Charles B Malpas, Esmaeil Davoodi-Bojd, Gianpiero L. Cavalleri, Angelo Labate, Sean N. Hatton, Soenke Langner, Magdalena A. Kowalczyk, Domenico Tortora, Barbara A. K. Kreilkamp, Manuela Tondelli, Clarissa L. Yasuda, Clyde Francks, Sara Larivière, Jose C. Pariente, Norman Delanty, Terence J. O'Brien, J Duncan, Roland Wiest, Emanuele Bartolini, Lorenzo Caciagli, Pasquale Striano, Saud Alhusaini, Jessica Royer, Ezequiel Gleichgerrcht, Lucy Vivash, Conde E, Paul M. Thompson, Raúl Rodríguez-Cruces, Neda Bernasconi, Elaine Lui, Renzo Guerrini, Antonio Gambardella, Xiangzhen Kong, Simon E. Fisher, Matteo Lenge, Leonardo Bonilha, Bernd Weber, Patricia Desmond, von Podewils F, Luis Concha, Andrea Bernasconi, Mark P. Richardson, Christopher D. Whelan, Benjamin Bender, Bo-yong Park, Khalid Hamandi, Julie Absil, Eugenio Abela, Hamid Soltanian-Zadeh, Marina K. M. Alvim, Benjamin Sinclair, Núria Bargalló, Pascal Martin, Anna Elisabetta Vaudano, Jinwei Zhang, Martin Domin, Sarah J. A. Carr, Meletti S, Sanjay M. Sisodiya, Carrie R. McDonald, Niels K. Focke, Mira Semmelroch, Devinsky O, Maria Eugenia Caligiuri, Parodi C, Chantal Depondt, Marian Galovic, Reetta Kälviäinen, Shahin Tavakol, Simon S. Keller, Micheal Rebsamen, Fernando Cendes, Yezhou Wang, Mario Mascalchi, Meng Law, Rhys H. Thomas, Sjoerd B. Vos, Raviteja Kotikalapudi, and Sonya Foley

Subjects
0303 health sciences, Neuropathology, Disease, Hippocampal formation, Grey matter, Biology, medicine.disease, Divergence, Temporal lobe, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, medicine.anatomical_structure, Atrophy, medicine, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Temporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

Published
2021

33. Mild to Severe Neurological Manifestations of COVID-19: Cases Reports

Author

Melegari, G., Rivi, V., Zelent, G., Nasillo, V., De Santis, E., Melegari, A., Bevilacqua, C., Zoli, M., Meletti, S., and Barbieri, A.

Subjects
encephalitis thrombosis, COVID-19 outbreak, SARS-CoV-2, Anosmia, lcsh:R, COVID-19, lcsh:Medicine, Case Report, intensive care unit, Encephalitis thrombosis, Intensive care unit, Humans, Intracranial Hemorrhages, Nervous System Diseases, Stroke, anosmia
Abstract

The main focus of Coronavirus disease 2019 (COVID-19) infection is pulmonary complications through virus-related neurological manifestations, ranging from mild to severe, such as encephalitis, cerebral thrombosis, neurocognitive (dementia-like) syndrome, and delirium. The hospital screening procedures for quickly recognizing neurological manifestations of COVID-19 are often complicated by other coexisting symptoms and can be obscured by the deep sedation procedures required for critically ill patients. Here, we present two different case-reports of COVID-19 patients, describing neurological complications, diagnostic imaging such as olfactory bulb damage (a mild and unclear underestimated complication) and a severe and sudden thrombotic stroke complicated with hemorrhage with a low-level cytokine storm and respiratory symptom resolution. We discuss the possible mechanisms of virus entrance, together with the causes of COVID-19-related encephalitis, olfactory bulb damage, ischemic stroke, and intracranial hemorrhage.

Published
2021

34. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 35, 12, (1289-1301), 10.1007/s40263-021-00856-3)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.

Published
2021

35. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 10.1007/s40263-021-00856-3)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.

Published
2021

36. Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi S., Canafoglia L., Canevini M.P., Casciato S., Chiesa V., Dainese F., De Maria G., Didato G., Falcicchio G., Fanella M., Ferlazzo E., Fisco G., Gangitano M., Giallonardo A.T., Giorgi F.S., La Neve A., Mecarelli O., Montalenti E., Piazza F., Pulitano P., Quarato P.P., Ranzato F., Rosati E., Tassi L., and Di Bonaventura C.

Subjects
medicine.medical_specialty, business.industry, Context (language use), Brivaracetam, medicine.disease, Discontinuation, law.invention, Psychiatry and Mental health, Epilepsy, Randomized controlled trial, Tolerability, focal epilepsy, add-on therapy, seizure, law, Concomitant, Internal medicine, Medicine, Pharmacology (medical), Neurology (clinical), Levetiracetam, Original Research Article, business, medicine.drug
Abstract

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp

Published
2021

37. Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study

Author

Gleichgerrcht, E, Munsell, BC, Alhusaini, S, Alvim, MKM, Bargallo, N, Bender, B, Bernasconi, A, Bernasconi, N, Bernhardt, B, Blackmon, K, Caligiuri, ME, Cendes, F, Concha, L, Desmond, PM, Devinsky, O, Doherty, CP, Domin, M, Duncan, JS, Focke, NK, Gambardella, A, Gong, B, Guerrini, R, Hatton, SN, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kreilkamp, BAK, Labate, A, Langner, S, Lariviere, S, Lenge, M, Lui, E, Martin, P, Mascalchi, M, Meletti, S, O'Brien, TJ, Pardoe, HR, Pariente, JC, Rao, JX, Richardson, MP, Rodriguez-Cruces, R, Ruber, T, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Vaudano, AE, Vivash, L, von Podewills, F, Vos, SB, Weber, B, Yao, Y, Yasuda, CL, Zhang, J, Thompson, PM, Sisodiya, SM, McDonald, CR, Bonilha, L, Gleichgerrcht, E, Munsell, BC, Alhusaini, S, Alvim, MKM, Bargallo, N, Bender, B, Bernasconi, A, Bernasconi, N, Bernhardt, B, Blackmon, K, Caligiuri, ME, Cendes, F, Concha, L, Desmond, PM, Devinsky, O, Doherty, CP, Domin, M, Duncan, JS, Focke, NK, Gambardella, A, Gong, B, Guerrini, R, Hatton, SN, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kreilkamp, BAK, Labate, A, Langner, S, Lariviere, S, Lenge, M, Lui, E, Martin, P, Mascalchi, M, Meletti, S, O'Brien, TJ, Pardoe, HR, Pariente, JC, Rao, JX, Richardson, MP, Rodriguez-Cruces, R, Ruber, T, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Vaudano, AE, Vivash, L, von Podewills, F, Vos, SB, Weber, B, Yao, Y, Yasuda, CL, Zhang, J, Thompson, PM, Sisodiya, SM, McDonald, CR, and Bonilha, L

Abstract

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.

Published
2021

38. Erratum to: Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy

Author

Baldin, Elisa, Testoni, Stefania, de Pasqua, Silvia, Ferro, Salvatore, Albani, Fiorenzo, Baruzzi, Agostino, D’Alessandro, Roberto, Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Cerasoli, S., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Visani, M., Dall’Agata, M., Faedi, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Fallica, E., Granieri, E., Latini, F., Lelli, G., Monetti, C., Saletti, A., Schivalocchi, R., Seraceni, S., Tola, M. R., Urbini, B., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., and On behalf of PERNO study group

Published
2017
Full Text
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39. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author

Enia, G., Giussani, G., Bianchi, E., Mecarelli, O., Beghi, E., Pulitano, P., Cagnetti, C., Baldinelli, S., Lattanzi, S., La Neve, A., Tappata, M., Francavilla, T., De Maria, G., Sofia, V., Giuliano, L., Mainieri, G., Fatuzzo, D., Belcastro, V., Elia, M., D'Orsi, G., Lalla, A., Salmaggi, A., Brigo, F., Magaudda, A., Pisani, F., Galletta, S., Pisani, L. R., Raffaele, M., Cosenza, D., Villani, F. S., Quintas, R. M. M., Cervellione, R., Borroni, S., Meletti, S., Ferrarese, C., Barbella, G., Di Francesco, J., Bogliun, G., Beretta, S., Galimberti, C. A., Cantisani, T. A., Cecconi, M., Celani, M. G., Papetti, R., Giorgi, F. S., Aguglia, U., Gasparini, S., Ferlazzo, E., Manganotti, P., Crichiutti, G., Bravar, G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, and Bravar, G

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Concordance, Need, Disease, Epilepsy, Needs, Patients, Physicians, Priorities, Newly diagnosed epilepsy, Young Adult, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Seizures, Anticonvulsant, medicine, Humans, 030212 general & internal medicine, Young adult, Aged, Aged, 80 and over, Patient, Prioritie, business.industry, Middle Aged, Caregiver, medicine.disease, Seizure, Clinical Practice, Caregivers, Italy, Neurology, Physician, Recurrent seizures, Family medicine, Population study, Anticonvulsants, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract

Objective The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients. Significance Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.

Published
2021

40. Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

Author

Ferraro, D., primary, Trovati, A., additional, Bedin, R., additional, Natali, P., additional, Franciotta, D., additional, Santangelo, M., additional, Camera, V., additional, Vitetta, F., additional, Varani, M., additional, Trenti, T., additional, Gastaldi, M., additional, De Biasi, S., additional, Nasi, M., additional, Pinti, M., additional, Meletti, S., additional, and Sola, P., additional

Published
2019
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43. Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study (Journal of Neuro-Oncology, (2016), 128, 1, (157-162), 10.1007/s11060-016-2093-1)

Author

Franceschi, Enrico, Depenni, Roberta, Paccapelo, Alexandro, Ermani, Mario, Faedi, Marina, Sturiale, Carmelo, Michiara, Maria, Servadei, Franco, Pavesi, Giacomo, Urbini, Benedetta, Pisanello, Anna, Crisi, Girolamo, Cavallo, Michele A., Dazzi, Claudio, Biasini, Claudia, Bertolini, Federica, Mucciarini, Claudia, Pasini, Giuseppe, Baruzzi, Agostino, Brandes, Alba A., Baruzzi, A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Cavallo, Marino, Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, Enrico, Biasini, C., Cavanna, L., Guidetti, D., Marcello, Norina, Pisanello, A., Cremonini, A. M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, Stefano, Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, Vincenzo, Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Faedi, M., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, Giuseppe, Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, Mario, Pasquini, Elena, Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, Greta, Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, Corrado, Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, Margherita, Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M. R., Urbini, B., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., and Nobile, C.

Subjects
Cancer Research, Oncology, Neurology, Neurology (clinical)
Published
2018

44. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Author

Whelan, Cd, Altmann, A, Botía, Ja, Jahanshad, N, Hibar, Dp, Absil, J, Alhusaini, S, Alvim, Mkm, Auvinen, P, Bartolini, E, Bergo, Fpg, Bernardes, T, Blackmon, K, Braga, B, Caligiuri, Me, Calvo, A, Carr, Sj, Chen, J, Chen, S, Cherubini, A, David, P, Domin, M, Foley, S, França, W, Haaker, G, Isaev, D, Keller, Ss, Kotikalapudi, R, Kowalczyk, Ma, Kuzniecky, R, Langner, S, Lenge, M, Leyden, Km, Liu, M, Loi, Rq, Martin, P, Mascalchi, M, Morita, Me, Pariente, Jc, Rodríguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, Mk, Severino, M, Thomas, Rh, Tondelli, M, Tortora, D, Vaudano, AE39, Vivash, L40, von Podewils F42, Wagner, J43, Weber, B43, Yao, Y46, Yasuda, CL7, Zhang, G47, Bargalló, N15, Bender, B26, Bernasconi, N, Bernasconi, A, Bernhardt, Bc, Blümcke, I, Carlson, C, Cavalleri, Gl, Cendes, F, Concha, L, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP51, Focke, Nk, Gambardella, A, Guerrini, R, Hamandi, K, Jackson, Gd, Kälviäinen, R, Kochunov, P, Kwan, P, Labate, A, McDonald, Cr, Meletti, S, O'Brien, Tj, Ourselin, S, Richardson MP Striano, P, Thesen, T, Wiest, R, Zhang, J, Vezzani, A, Ryten, M, Thompson, Pm, and Sisodiya, Sm.

Subjects
MRI, epilepsy, precentral gyrus, thalamus
Published
2018

46. Erratum to: Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy

Author

Baldin, E, Testoni, S, de Pasqua, S, Ferro, S, Albani, F, Baruzzi, A, D'Alessandro, R, PERNO study group Participants: Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Cerasoli, S., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., (Bologna), Visani M., Dall’Agata, M., Faedi, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A. ., (ForlI´-Cesena), Strumia S., Casmiro, M., Gamboni, A., (Faenza, Rasi F., RA), (Lugo, Cruciani G., Cenni, P., Dazzi, C., Guidi, A. R., (Ravenna), Zumaglini F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., (Rimini), Viti B., (Cattolica, Sintini M., RN), Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., (Modena), Zunarelli E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., (Carpi, Stucchi C., MO), Iaccarino, C, Ragazzi, M., Rizzi, R., (Reggio Emilia), Zuccoli G., Api, P., Cartei, F., Fallica, E., Granieri, E., Latini, F., Lelli, G., Monetti, C., Saletti, A., Schivalocchi, R., Seraceni, S., Tola, M. R., (Ferrara), Urbini B., Giorgi, C., (Fidenza, Montanari E., PR), Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, Em., (Parma), Torelli P., Immovilli, P., Morelli, N., (Piacenza), Vanzo C., Nobile, C. (Padova)., Elisa Baldin, Stefania Testoni, Silvia de Pasqua, Salvatore Ferro, Fiorenzo Albani, Agostino Baruzzi, Roberto D’Alessandro, On behalf of PERNO study group, ELENA BONORA, and DARIO DE BIASE

Subjects
Psychiatry and Mental Health, Dermatology, General Medicine, Neurology (clinical)
Abstract

Unfortunately, some of the participants of the PERNO Study Group are missing in the original publication of the article. The correct details are given below: Participants: Agati R., Ambrosetto G., Bacci A., Baldin E., Baldrati A., Barbieri E., Bartolini S., Bellavista E., Bisulli F., Bonora E., Bunkheila F., Carelli V., Cerasoli S., Crisci M., Dall’Occa P., de Biase D., Ferro S., Franceschi C., Frezza G., GrassoV., Leonardi M., Marucci G., Morandi L., Mostacci B., Palandri G., Pasini E., Pastore Trossello M., Pession A., Poggi R., Riguzzi P., Rinaldi R., Rizzi S., Romeo G., Spagnolli F., Tinuper P., Trocino C., Visani M. (Bologna), Dall’Agata M., Faedi M., Frattarelli M., Gentili G., Giovannini A., Iorio P., Pasquini U., Galletti G., Guidi C., Neri W., Patuelli A.., Strumia S. (ForlÍ-Cesena), Casmiro M., Gamboni A., Rasi F. (Faenza, RA), Cruciani G. (Lugo, RA), Cenni P., Dazzi C., Guidi A.R., Zumaglini F. (Ravenna), Amadori A., Pasini G., Pasquinelli M., Pasquini E., Polselli A., Ravasio A., Viti B. (Rimini), Sintini M. (Cattolica, RN), Ariatti A., Bertolini F., Bigliardi G., Carpeggiani P., Cavalleri F., Meletti S., Nichelli P., Pettorelli E., Pinna G., Zunarelli E. (Modena), Artioli F., Bernardini I., Costa M., Greco G., Guerzoni R., Stucchi C. (Carpi, MO), Iaccarino C., Ragazzi M., Rizzi R., Zuccoli G. (Reggio Emilia), Api P., Cartei F., Fallica E., Granieri E., Latini F., Lelli G., Monetti C., Saletti A., Schivalocchi R., Seraceni S., Tola M.R., Urbini B. (Ferrara), Giorgi C., Montanari E. (Fidenza, PR), Cerasti D., Crafa P., Dascola I., Florindo I., Giombelli E., Mazza S., Ramponi V., Servadei F., Silini EM., Torelli P. (Parma), Immovilli P., Morelli N., Vanzo C. (Piacenza), Nobile C. (Padova).

Published
2017

47. New-onset refractory status epilepticus with claustrum damage: Definition of the clinical and neuroimaging features

Author

Meletti, S. Giovannini, G. d'Orsi, G. Toran, L. Monti, G. Guha, R. Kiryttopoulos, A. Pascarella, M.G. Martino, T. Alexopoulos, H. Spilioti, M. Slonkova, J.

Abstract

New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic-clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases,extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies. © 2017 Meletti, Giovannini, d'Orsi, Toran, Monti, Guha, Kiryttopoulos, Pascarella, Martino, Alexopoulos, Spilioti and Slonkova.

Published
2017

48. Erratum to: Survival prediction in high-grade gliomas using CT perfusion imaging [J Neurooncol (2015) 123, 93-102, DOI 10.1007/s11060-015-1766-5]

Author

Yeung T. P. C., Wang Y., He W., Urbini B., Gafa R., Ulazzi L., Yartsev S., Bauman G., Lee T. -Y., Fainardi E., Baruzzi A., Albani F., Calbucci F., D'alessandro R., Michelucci R., Brandes A., Eusebi V., Ceruti S., Tamarozzi R., Emiliani E., Cavallo M., Franceschi E., Tosoni A., Fiorica F., Valentini A., Depenni R., Mucciarini C., Crisi G., Sasso E., Biasini C., Cavanna L., Guidetti D., Marcello N., Pisanello A., Cremonini A. M., Guiducci G., de Pasqua S., Testoni S., Agati R., Ambrosetto G., Bacci A., Baldin E., Baldrati A., Barbieri E., Bartolini S., Bellavista E., Bisulli F., Bonora E., Bunkheila F., Carelli V., Crisci M., Dall'occa P., de Biase D., Ferro S., Franceschi C., Frezza G., Grasso V., Leonardi M., Marucci G., Morandi L., Mostacci B., Palandri G., Pasini E., Pastore Trossello M., Pession A., Poggi R., Riguzzi P., Rinaldi R., Rizzi S., Romeo G., Spagnolli F., Tinuper P., Trocino C., Dall'agata M., Frattarelli M., Gentili G., Giovannini A., Iorio P., Pasquini U., Galletti G., Guidi C., Neri W., Patuelli A., Strumia S., Faedi M., Casmiro M., Gamboni A., Rasi F., Cruciani G., Cenni P., Dazzi C., Guidi A. R., Zumaglini F., Amadori A., Pasini G., Pasquinelli M., Pasquini E., Polselli A., Ravasio A., Viti B., Sintini M., Ariatti A., Bertolini F., Bigliardi G., Carpeggiani P., Cavalleri F., Meletti S., Nichelli P., Pettorelli E., Pinna G., Zunarelli E., Artioli F., Bernardini I., Costa M., Greco G., Guerzoni R., Stucchi C., Iaccarino C., Ragazzi M., Rizzi R., Zuccoli G., Api P., Cartei F., Colella M., Fallica E., Farneti M., Frassoldati A., Granieri E., Latini F., Monetti C., Saletti A., Schivalocchi R., Sarubbo S., Seraceni S., Tola M. R., Zini G., Giorgi C., Montanari E., Cerasti D., Crafa P., Dascola I., Florindo I., Giombelli E., Mazza S., Ramponi V., Servadei F., Silini E. M., Torelli P., Immovilli P., Morelli N., Vanzo C., Nobile C., Yeung T.P.C., Wang Y., He W., Urbini B., Gafa R., Ulazzi L., Yartsev S., Bauman G., Lee T.-Y., Fainardi E., Baruzzi A., Albani F., Calbucci F., D'alessandro R., Michelucci R., Brandes A., Eusebi V., Ceruti S., Tamarozzi R., Emiliani E., Cavallo M., Franceschi E., Tosoni A., Fiorica F., Valentini A., Depenni R., Mucciarini C., Crisi G., Sasso E., Biasini C., Cavanna L., Guidetti D., Marcello N., Pisanello A., Cremonini A.M., Guiducci G., de Pasqua S., Testoni S., Agati R., Ambrosetto G., Bacci A., Baldin E., Baldrati A., Barbieri E., Bartolini S., Bellavista E., Bisulli F., Bonora E., Bunkheila F., Carelli V., Crisci M., Dall'occa P., de Biase D., Ferro S., Franceschi C., Frezza G., Grasso V., Leonardi M., Marucci G., Morandi L., Mostacci B., Palandri G., Pasini E., Pastore Trossello M., Pession A., Poggi R., Riguzzi P., Rinaldi R., Rizzi S., Romeo G., Spagnolli F., Tinuper P., Trocino C., Dall'agata M., Frattarelli M., Gentili G., Giovannini A., Iorio P., Pasquini U., Galletti G., Guidi C., Neri W., Patuelli A., Strumia S., Faedi M., Casmiro M., Gamboni A., Rasi F., Cruciani G., Cenni P., Dazzi C., Guidi A.R., Zumaglini F., Amadori A., Pasini G., Pasquinelli M., Pasquini E., Polselli A., Ravasio A., Viti B., Sintini M., Ariatti A., Bertolini F., Bigliardi G., Carpeggiani P., Cavalleri F., Meletti S., Nichelli P., Pettorelli E., Pinna G., Zunarelli E., Artioli F., Bernardini I., Costa M., Greco G., Guerzoni R., Stucchi C., Iaccarino C., Ragazzi M., Rizzi R., Zuccoli G., Api P., Cartei F., Colella M., Fallica E., Farneti M., Frassoldati A., Granieri E., Latini F., Monetti C., Saletti A., Schivalocchi R., Sarubbo S., Seraceni S., Tola M.R., Zini G., Giorgi C., Montanari E., Cerasti D., Crafa P., Dascola I., Florindo I., Giombelli E., Mazza S., Ramponi V., Servadei F., Silini E.M., Torelli P., Immovilli P., Morelli N., Vanzo C., and Nobile C.

Subjects
PERNO, Gender, Glioblastoma, MGMT, Methylation
Abstract

Background: Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. Methods: We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. Results: A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival. Conclusions: Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor.

Published
2015

49. Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis.

Author

Ferraro, D., Trovati, A., Bedin, R., Natali, P., Franciotta, D., Santangelo, M., Camera, V., Vitetta, F., Varani, M., Trenti, T., Gastaldi, M., De Biasi, S., Nasi, M., Pinti, M., Meletti, S., and Sola, P.

Subjects
CEREBROSPINAL fluid, MULTIPLE sclerosis, SERUM albumin, DETECTION limit, BINDING sites
Abstract

Background and purpose: Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB‐negative patients with suspected MS. Methods: The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB‐negative patients with suspected/possible MS and in 54 OCB‐positive patients with MS. Results: The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut‐off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB‐negative MS (23/92) and in 98% of OCB‐positive patients with MS. Using a qualitative approach and a kappa index cut‐off of 5.9, based on literature data, we likewise found that 24% of OCB‐negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB‐negative patients without MS (P < 0.001). No reliable data could be obtained for the lambda index; lambda FLCs were below the detection limit (0.68 mg/L) in 90% of CSF samples. Conclusions: The kappa index could contribute to the identification of OCB‐negative patients with a high probability of an MS diagnosis. Using more sensitive techniques might even improve the diagnostic performance of the kappa index and better define the role of the lambda index. [ABSTRACT FROM AUTHOR]

Published
2020
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50. The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase Methylation Status in Glioblastoma Patients: The Female Power

Author

Franceschi, Enrico, primary, Tosoni, Alicia, additional, Minichillo, Santino, additional, Depenni, Roberta, additional, Paccapelo, Alexandro, additional, Bartolini, Stefania, additional, Michiara, Maria, additional, Pavesi, Giacomo, additional, Urbini, Benedetta, additional, Crisi, Girolamo, additional, Cavallo, Michele A., additional, Tosatto, Luigino, additional, Dazzi, Claudio, additional, Biasini, Claudia, additional, Pasini, Giuseppe, additional, Balestrini, Damiano, additional, Zanelli, Francesca, additional, Ramponi, Vania, additional, Fioravanti, Antonio, additional, Giombelli, Ermanno, additional, De Biase, Dario, additional, Baruzzi, Agostino, additional, Brandes, Alba A., additional, Baruzzi, A., additional, Albani, F., additional, Calbucci, F., additional, D'Alessandro, R., additional, Michelucci, R., additional, Brandes, A., additional, Eusebi, V., additional, Ceruti, S., additional, Fainardi, E., additional, Tamarozzi, R., additional, Emiliani, E., additional, Cavallo, M., additional, Franceschi, E., additional, Tosoni, A., additional, Fiorica, F., additional, Valentini, A., additional, Depenni, R., additional, Mucciarini, C., additional, Crisi, G., additional, Sasso, E., additional, Biasini, C., additional, Cavanna, L., additional, Guidetti, D., additional, Marcello, N., additional, Pisanello, A., additional, Cremonini, A.M., additional, Guiducci, G., additional, de Pasqua, S., additional, Testoni, S., additional, Agati, R., additional, Ambrosetto, G., additional, Bacci, A., additional, Baldin, E., additional, Baldrati, A., additional, Barbieri, E., additional, Bartolini, S., additional, Bellavista, E., additional, Bisulli, F., additional, Bonora, E., additional, Bunkheila, F., additional, Carelli, V., additional, Crisci, M., additional, Dall'Occa, P., additional, de Biase, D., additional, Ferro, S., additional, Franceschi, C., additional, Frezza, G., additional, Grasso, V., additional, Leonardi, M., additional, Marucci, G., additional, Morandi, L., additional, Mostacci, B., additional, Palandri, G., additional, Pasini, E., additional, Pastore Trossello, M., additional, Pession, A., additional, Poggi, R., additional, Riguzzi, P., additional, Rinaldi, R., additional, Rizzi, S., additional, Romeo, G., additional, Spagnolli, F., additional, Tinuper, P., additional, Trocino, C., additional, Dall'Agata, M., additional, Frattarelli, M., additional, Gentili, G., additional, Giovannini, A., additional, Iorio, P., additional, Pasquini, U., additional, Galletti, G., additional, Guidi, C., additional, Neri, W., additional, Patuelli, A., additional, Strumia, S., additional, Faedi, M., additional, Casmiro, M., additional, Gamboni, A., additional, Rasi, F., additional, Cruciani, G., additional, Cenni, P., additional, Dazzi, C., additional, Guidi, A.R., additional, Zumaglini, F., additional, Amadori, A., additional, Pasini, G., additional, Pasquinelli, M., additional, Pasquini, E., additional, Polselli, A., additional, Ravasio, A., additional, Viti, B., additional, Sintini, M., additional, Ariatti, A., additional, Bertolini, F., additional, Bigliardi, G., additional, Carpeggiani, P., additional, Cavalleri, F., additional, Meletti, S., additional, Nichelli, P., additional, Pettorelli, E., additional, Pinna, G., additional, Zunarelli, E., additional, Artioli, F., additional, Bernardini, I., additional, Costa, M., additional, Greco, G., additional, Guerzoni, R., additional, Stucchi, C., additional, Iaccarino, C., additional, Ragazzi, M., additional, Rizzi, R., additional, Zuccoli, G., additional, Api, P., additional, Cartei, F., additional, Colella, M., additional, Fallica, E., additional, Farneti, M., additional, Frassoldati, A., additional, Granieri, E., additional, Latini, F., additional, Monetti, C., additional, Saletti, A., additional, Schivalocchi, R., additional, Sarubbo, S., additional, Seraceni, S., additional, Tola, M.R., additional, Urbini, B., additional, Zini, G., additional, Giorgi, C., additional, Montanari, E., additional, Cerasti, D., additional, Crafa, P., additional, Dascola, I., additional, Florindo, I., additional, Giombelli, E., additional, Mazza, S., additional, Ramponi, V., additional, Servadei, F., additional, Silini, E.M., additional, Torelli, P., additional, Immovilli, P., additional, Morelli, N., additional, Vanzo, C., additional, and Nobile, C., additional

Published
2018
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