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6. Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity

Author

Bartolini, E., Borgogni, E., Bruttini, M., Muzzi, A., Giuliani, M., Iozzi, S., Petracca, R., Martinelli, M., Bonacci, S., Marchi, S., Brettoni, C., Donati, C., Torricelli, G., Guidotti, S., Domina, M., Beninati, C., Teti, G., Felici, F., Rappuoli, R., Castellino, F., Del Giudice, G., Masignani, V., Pizza, M., and Maione, D.

Published
2020
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12. 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

13. 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

14. Efficacy of Sofosbuvir/Ledipasvir in Adolescents with Chronic Hepatitis C Genotypes 1, 3, and 4: A Real-world Study

Author

Serranti, D, Nebbia, G, Cananzi, M, Nicastro, E, Dato, F, Nuti, F, Garazzino, S, Silvestro, E, Giacomet, V, Forlanini, F, Pinon, M, Calvo, P, Riva, S, Dodi, I, Cangelosi, A, Antonucci, R, Ricci, S, Bartolini, E, Mastrangelo, G, Trapani, S, Lenge, M, Gaio, P, Vajro, P, Iorio, R, D'Antiga, L, Indolfi, G, Serranti D., Nebbia G., Cananzi M., Nicastro E., Dato F. D., Nuti F., Garazzino S., Silvestro E., Giacomet V., Forlanini F., Pinon M., Calvo P. L., Riva S., Dodi I., Cangelosi A. M., Antonucci R., Ricci S., Bartolini E., Mastrangelo G., Trapani S., Lenge M., Gaio P., Vajro P., Iorio R., D'Antiga L., Indolfi G., Serranti, D, Nebbia, G, Cananzi, M, Nicastro, E, Dato, F, Nuti, F, Garazzino, S, Silvestro, E, Giacomet, V, Forlanini, F, Pinon, M, Calvo, P, Riva, S, Dodi, I, Cangelosi, A, Antonucci, R, Ricci, S, Bartolini, E, Mastrangelo, G, Trapani, S, Lenge, M, Gaio, P, Vajro, P, Iorio, R, D'Antiga, L, Indolfi, G, Serranti D., Nebbia G., Cananzi M., Nicastro E., Dato F. D., Nuti F., Garazzino S., Silvestro E., Giacomet V., Forlanini F., Pinon M., Calvo P. L., Riva S., Dodi I., Cangelosi A. M., Antonucci R., Ricci S., Bartolini E., Mastrangelo G., Trapani S., Lenge M., Gaio P., Vajro P., Iorio R., D'Antiga L., and Indolfi G.

Abstract

Objectives: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA)for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to <18 years old) with CHC in the real-world setting. Methods: Prospective, open-label, multicentre study involving 12 Italian centres. Patients received the fixed-dose combination of SOF/LDV (400/90 mg) once daily-ribavirin as per EMA approval and recommendations. The key efficacy endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) as per intention-to-treat analysis. Safety was assessed by adverse events and clinical/laboratory data. Results: Seventy-eight consecutive adolescents (median age 15.2 years, range 12-17.9; girls 53.8%) were enrolled and treated between June 2018 and December 2019. Genotype distribution was as follows: Genotype 1 (82.1%), 3 (2.5%), and 4 (15.4%). Seventy-six (97.4%) patients completed treatment and follow-up. Overall, SVR12 was 98.7%. One patient was lost to follow-up after 4 weeks of treatment; 1 patient completed treatment and missed the follow-up visit. No virological breakthrough or relapse were observed. No patient experienced grade 3 to 4 adverse event or serious adverse event. Conclusions: The results of this real-world study confirmed the high efficacy and the optimal safety profile of SOF/LDV for treatment of CHC in adolescents.

Published
2021

15. Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group

Author

Di Giorgio, A, Bartolini, E, Calvo, P, Cananzi, M, Cirillo, F, Della Corte, C, Dionisi-Vici, C, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Nebbia, G, Nicastro, E, Pinon, M, Ranucci, G, Sciveres, M, Vajro, P, D'Antiga, L, Di Giorgio A., Bartolini E., Calvo P. L., Cananzi M., Cirillo F., Della Corte C., Dionisi-Vici C., Indolfi G., Iorio R., Maggiore G., Mandato C., Nebbia G., Nicastro E., Pinon M., Ranucci G., Sciveres M., Vajro P., D'Antiga L., Di Giorgio, A, Bartolini, E, Calvo, P, Cananzi, M, Cirillo, F, Della Corte, C, Dionisi-Vici, C, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Nebbia, G, Nicastro, E, Pinon, M, Ranucci, G, Sciveres, M, Vajro, P, D'Antiga, L, Di Giorgio A., Bartolini E., Calvo P. L., Cananzi M., Cirillo F., Della Corte C., Dionisi-Vici C., Indolfi G., Iorio R., Maggiore G., Mandato C., Nebbia G., Nicastro E., Pinon M., Ranucci G., Sciveres M., Vajro P., and D'Antiga L.

Abstract

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Published
2021

16. 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

17. 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

18. 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

19. 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

22. European Multicentre Tics in Children Studies (EMTICS)

Author

Schrag, A, Martino, D, Apter, A, Ball, J, Bartolini, E, Benaroya-Milshtein, N, Buttiglione, M, Cardona, F, Creti, R, Efstratiou, A, Gariup, M, Georgitsi, M, Hedderly, T, Heyman, I, Margarit, I, Mir, P, Moll, N, Morer, A, Müller, N, Müller-Vahl, K, Münchau, A, Orefici, G, Plessen, Kj, Porcelli, C, Paschou, P, Rizzo, R, Roessner, V, Schwarz, Mj, Steinberg, T, Tagwerker Gloor, F, Tarnok, Z, Walitza, S, Dietrich, A, Hoekstra, Pj, Zacharias, Anastasiou, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga, Pablo, Mir, Astrid, Morer, Nanette Mol Debes, Natalie, Moll, Norbert Mu ̈ller, Peter, Nagy, Kerstin Jessica Plessen, Cesare, Porcelli, Renata, Rizzo, Veit, Roessner, Jaana, Schnell, Liselotte, Skov, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Baglioni, Valentina, Juliane, Ball, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Maria Cristina Ferro, Carolin, Fremer, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Anna, Marotta, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Tamar, Steinberg, Friederike Tagwerker Gloor, Elif, Weidinger, EMTICS Collaborative Group, Anastasiou, Z., Apter, A., Baglioni, V., Ball, J., Bartolini, E., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Buttiglione, M., Cardona, F., Correa Vela, M., Creti, R., Dietrich, A., Debes, N.M., Efstratiou, A., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gariup, M., Georgitsi, M., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Imperi, M., Karagiannidis, I., Laviola, G., Macri, S., Madruga-Garrido, M., Margarit, I., Marotta, A., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Müller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Orefici, G., Paschou, P., Pellico, A., Petruzzelli, O., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roazzi, P., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schütze, G.A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Stöber, S., Gloor, F.T., Tallon, M., Tarnok, Z., Turner, V.L., Walitza, S., Weidinger, E., Woods, M.L., European Commission, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), University College London, NHS Foundation Trust, GlaxoSmithKline, German Research Foundation, Instituto de Biomedicina de Sevilla (IBIS), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, Pediatrics, Tic disorder, BLOOD, Tourette syndrome, Obsessive–compulsive disorder, Cohort Studies, 0302 clinical medicine, Risk Factors, QUALITY-OF-LIFE, Obsessive-compulsive disorder, Developmental and Educational Psychology, Genetics, Longitudinal, Streptococcal infection, Stress, Prospective cohort study, Child, GENE-EXPRESSION, education.field_of_study, HAIR CORTISOL, 05 social sciences, A STREPTOCOCCAL INFECTIONS, Original Contribution, General Medicine, 3. Good health, Europe, Psychiatry and Mental health, LA-TOURETTE SYNDROME, Child, Preschool, NEUROPSYCHIATRIC DISORDERS, Cohort, Female, 050104 developmental & child psychology, Cohort study, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Tics, Adolescent, PSYCHOSOCIAL STRESS, Population, 03 medical and health sciences, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Genetic Predisposition to Disease, education, Tic Disorders/complications, Tic Disorders/diagnosis, Tic Disorders/pathology, business.industry, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, 030227 psychiatry, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, Tic Disorders, Pediatrics, Perinatology and Child Health, Chronic Tic Disorder, business, human activities
Abstract

EMTICS Collaborative Group., Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive–compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3–10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3–16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host’s immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders., This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant agreement no. 278367. Schrag was supported by the National Institute for Health Research UCLH Biomedical Research Centre, and Müller, Burger, Schnell and Weidinger by Stiftung Immunität und Seele. This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (Heyman); partially sponsored by GSK Vaccines (Margarit, Bartolini); and Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1 (Münchau).

Published
2019
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23. 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

25. Presenza-assenza o ascolto autentico. La dipendenza ontologica in Heidegger commentatore di Eraclito

Author

Bartolini, E and Bartolini, E

Subjects
Freedom, Filosofia e psicologia, Ontology, Heidegger, Eraclito, logos, Heidegger, Logos, Heraclitus
Abstract

Commenting on some Heraclitean fragments, Heidegger examines the meaning of Being as λόγος, affirming the possibility to have access to it through an authentic hearkening. The most interesting aspect about this analysis is that it is outlined a tight ontological dependence — a sort of belonging that comes to be translated as obedience — of the human being with respect to Being. However, the German philosopher doesn’t explicitly provide for human agency. This paper aims to give an account of the reading on Heraclitus that Heidegger presents in the ‘40s and ’50, underlying its critical elements in terms of their implications.

Published
2021

27. Shortened 8-Week Course of Sofosbuvir/Ledipasvir Therapy in Adolescents With Chronic Hepatitis C Infection

Author

Serranti, D, Dodi, I, Nicastro, E, Cangelosi, A, Riva, S, Ricci, S, Bartolini, E, Trapani, S, Mastrangelo, G, Vajro, P, D'Antiga, L, Resti, M, Indolfi, G, Serranti D., Dodi I., Nicastro E., Cangelosi A. M., Riva S., Ricci S., Bartolini E., Trapani S., Mastrangelo G., Vajro P., D'Antiga L., Resti M., Indolfi G., Serranti, D, Dodi, I, Nicastro, E, Cangelosi, A, Riva, S, Ricci, S, Bartolini, E, Trapani, S, Mastrangelo, G, Vajro, P, D'Antiga, L, Resti, M, Indolfi, G, Serranti D., Dodi I., Nicastro E., Cangelosi A. M., Riva S., Ricci S., Bartolini E., Trapani S., Mastrangelo G., Vajro P., D'Antiga L., Resti M., and Indolfi G.

Abstract

Treatment-naïve, noncirrhotic adults with chronic hepatitis C virus genotype 1 infection and with viremia levels <6 million IU/mL could be effectively treated with sofosbuvir/ledipasvir for 8 weeks. The aim of this pilot, prospective, open-label, multicenter study was to evaluate the efficacy and safety of this shortened treatment course in adolescents (≥12 years). The efficacy endpoint was sustained virological response 12 weeks after the end of treatment. Safety was assessed by adverse events and clinical/laboratory data. Fourteen consecutive adolescents (median age 16.5 years, Q1 14.1-Q3 17.4; female 57.1%), vertically infected, were enrolled and treated (June 2018-January 2019). Overall, the end of treatment response and sustained virological response 12 weeks after the end of treatment were 100%. No grade 3 to 4 adverse event or a serious adverse event was observed. Further studies are needed to confirm the optimal efficacy of the shortened 8-week treatment with sofosbuvir/ledipasvir for treatment-naïve, noncirrhotic adolescents with chronic hepatitis C virus genotype 1 infection and pretreatment viremia level < 6 million IU/mL.

Published
2019

33. Climate change and epilepsy: insights from clinical and basic science studies

Author

Gulcebi, M., Bartolini, E., Lee, O., Panagiotis Lisgaras, C., Onat, F., Mifsud, J., Striano, P., Vezzani, A., Hildebrand, M.S., Jimenez-Jimenez, D., Junck, L., Lewis-Smith, D., Scheffer, I.E., Thijs, R.D., Zuberi, S.M., Blenkinsop, S., Fowler, H.J., Foley, Aideen, and Sisodiya, S.M.

Subjects
geog
Abstract

Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, complex, and often indirect, which makes predictions difficult. We need more data on possible climate-driven altered risks for seizures, epilepsy, and epileptogenesis, to identify underlying mechanisms at systems, cellular, and molecular levels for better understanding of the impact of climate change on epilepsy. Further focussed data would help us to develop evidence for mitigation methods to do more to protect people with epilepsy from the effects of climate change.

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), 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

36. 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

37. 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

38. Climate change and epilepsy: Insights from clinical and basic science studies

Author

Gulcebi, M, Bartolini, E, Lee, O, Lisgaras, CP, Onat, F, Mifsud, J, Striano, P, Vezzani, A, Hildebrand, MS, Jimenez-Jimenez, D, Junck, L, Lewis-Smith, D, Scheffer, IE, Thijs, RD, Zuberi, SM, Blenkinsop, S, Fowler, HJ, Foley, A, Sisodiya, SM, Balestrini, S, Berkovic, S, Cavalleri, G, Correa, DJ, Custodio, HM, Galovic, M, Guerrini, R, Henshall, D, Howard, O, Hughes, K, Katsarou, A, Koeleman, BPC, Krause, R, Lowenstein, D, Mandelenaki, D, Marini, C, O'Brien, TJ, Pace, A, De Palma, L, Perucca, P, Pitkanen, A, Quinn, F, Selmer, KK, Steward, CA, Swanborough, N, Thijs, R, Tittensor, P, Trivisano, M, Weckhuysen, S, Zara, F, Gulcebi, M, Bartolini, E, Lee, O, Lisgaras, CP, Onat, F, Mifsud, J, Striano, P, Vezzani, A, Hildebrand, MS, Jimenez-Jimenez, D, Junck, L, Lewis-Smith, D, Scheffer, IE, Thijs, RD, Zuberi, SM, Blenkinsop, S, Fowler, HJ, Foley, A, Sisodiya, SM, Balestrini, S, Berkovic, S, Cavalleri, G, Correa, DJ, Custodio, HM, Galovic, M, Guerrini, R, Henshall, D, Howard, O, Hughes, K, Katsarou, A, Koeleman, BPC, Krause, R, Lowenstein, D, Mandelenaki, D, Marini, C, O'Brien, TJ, Pace, A, De Palma, L, Perucca, P, Pitkanen, A, Quinn, F, Selmer, KK, Steward, CA, Swanborough, N, Thijs, R, Tittensor, P, Trivisano, M, Weckhuysen, S, and Zara, F

Abstract

Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, compl

Published
2021

42. Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study

Author

Lariviere, S, Rodriguez-Cruces, R, Royer, J, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, C, 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, 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, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, Bernhardt, BC, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, C, 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, 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, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, and Bernhardt, BC

Abstract

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

Published
2020

45. Il futuro dell'antico. Filosofia antica e mondo contemporaneo.

Author

Indelicato, A, Daddi, I, Bartolini, E, Indelicato, A, Daddi, I, and Bartolini, E

Abstract

Atti del Convegno di Studi «Il futuro dell'antico. Filosofia antica e mondo contemporaneo», 27-28 Marzo 2019. Moderatori: Claudia Baracchi, Luca Grecchi. Discussant: Giulia Angelini, Selene I. S. Brumana, Federica Piangerelli, Elena Bartolini, Alessandra Filannino Indelicato, Andrea Ignazio Daddi.

Published
2020

46. Phytoestrogens and Colon Cancer

Author

Pampaloni, B., primary, Mavilia, C., additional, Bartolini, E., additional, Tonelli, F., additional, Brandi, M.L., additional, and DAst, Federica, additional

Published
2013
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47. Human as ζοον λόγον ἔχον and in-der-Welt-sein. Seeking gathering, the one always in relation

Author

Bartolini, E and Bartolini, E

Subjects
logos, linguaggio, ontologia, Heidegger, essere umano
Abstract

Una delle definizioni più note dell’essere umano è fornita da Aristotele nella Politica. In tale contesto, egli afferma che l’uomo è ζῷον λόγον ἔχον. Solitamente, traducendo λόγος con “linguaggio”, l’uomo viene identificato con l’animale che possiede il linguaggio. Tuttavia, considerando l’etimologia del termine, sarà possibile fornire una spiegazione differente di tale definizione, concependo l’umano nella sua abilità di vedere le relazioni che lo circondano ed essendo in grado di crearne di nuove.

Published
2018

49. Phytoestrogens: Food or Drug?

Author

Bacciottini, L, primary, Falchetti, A, additional, Pampaloni, B, additional, Bartolini, E, additional, Carossino, A, additional, and Brandi, M, additional

Published
2006
Full Text
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