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101. Digital therapeutics in neurology

Author

Abbadessa, G., primary, Brigo, F., additional, Clerico, M., additional, De Mercanti, S., additional, Trojsi, F., additional, Tedeschi, G., additional, Bonavita, S., additional, and Lavorgna, L., additional

Published
2021
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104. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS)

Author

Patti, F., Visconti, A., Capacchione, A., Roy, S., Trojano, M., Amato, M. P., Cocco, E., Danni, M. C., Filippi, M., Gasperini, C., Inglese, M., Luca, G. D., Lus, G., Mallucci, G., Marfia, G. A., Pesci, I., Petruzzo, M., Pozzilli, C., Tedeschi, G., and Zaffaroni, M.

Subjects
Pediatrics, medicine.medical_specialty, effectiveness, cladribine tablets, registry, multiple sclerosis, lcsh:RC346-429, long-term data, 03 medical and health sciences, 0302 clinical medicine, secondary progressive MS, medicine, In patient, 030212 general & internal medicine, Cladribine, clinically isolated syndrome, real-world data, real-world evidence, relapsing-remitting MS, lcsh:Neurology. Diseases of the nervous system, Original Research, Pharmacology, Clinically isolated syndrome, business.industry, Multiple sclerosis, medicine.disease, Term (time), Neurology, Long term data, Neurology (clinical), Previously treated, business, Real world data, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Methods: Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLE-MS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model. Results: Time span under observation in the Italian MS Registry was 1–137 (median 80.3) months. In the total Italian patient population ( n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5–39.5) months. Conclusion: CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2.

Published
2020

106. Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells

Author

Tripodi, F, Badone, B, Vescovi, M, Milanesi, R, Nonnis, S, Maffioli, E, Bonanomi, M, Gaglio, D, Tedeschi, G, Coccetti, P, Tripodi, Farida, Badone, Beatrice, Vescovi, Marta, Milanesi, Riccardo, Nonnis, Simona, Maffioli, Elisa, Bonanomi, Marcella, Gaglio, Daniela, Tedeschi, Gabriella, Coccetti, Paola, Tripodi, F, Badone, B, Vescovi, M, Milanesi, R, Nonnis, S, Maffioli, E, Bonanomi, M, Gaglio, D, Tedeschi, G, Coccetti, P, Tripodi, Farida, Badone, Beatrice, Vescovi, Marta, Milanesi, Riccardo, Nonnis, Simona, Maffioli, Elisa, Bonanomi, Marcella, Gaglio, Daniela, Tedeschi, Gabriella, and Coccetti, Paola

Abstract

Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti‐cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP‐activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.

Published
2020

107. Behavioral and psychological effects of coronavirus disease-19 quarantine in patients with dementia

Author

Cagnin, A., Di Lorenzo, R., Marra, C., Bonanni, L., Cupidi, C., Lagana, V., Rubino, E., Vacca, A., Provero, P., Isella, V., Vanacore, N., Agosta, F., Appollonio, I., Caffarra, P., Pettenuzzo, I., Sambati, R., Quaranta, D., Guglielmi, V., Logroscino, G., Filippi, M., Tedeschi, G., Ferrarese, C., Rainero, I., Bruni, A. C., Gallo, E., Grassini, A., Marcinno, A., Roveta, F., De Martino, P., Frangipane, F., Puccio, G., Colao, R., Mirabelli, M., Martellacci, N., Lino, F., Mozzetta, S., Busse, C., Camporese, G., Sacco, S., Lechiara, M. C., Carrarini, C., Russo, M., Casalena, A., Sucapane, P., Tiraboschi, P., Caroppo, P., Redaelli, V., Di Fede, G., Coppa, D., Peluso, L., Insarda, P., De Bartolo, M., Esposito, S., Iavarone, A., Orsini, A. V. M., Salvatore, E., Criscuolo, C., Sambati, L., Santoro, R., Gragnaniello, D., Pedriali, I., Ludovico, L., Chiari, A., Fabbo, A., Bevilacqua, P., Galli, C., Magarelli, S., Perini, M., Spalletta, G., Banaj, N., Porcari, D. E., Caruso, G., Cipollini, V., Casini, A. R., Ursini, F., Bruno, G., Rozzini, R., Brambilla, M., Magnani, G., Caso, F., Spinelli, E. G., Ramusino, M. C., Perini, G., Luzzi, S., Cacchio, G., Angeloni, R., Giuli, C., Fabi, K., Guidi, M., Paci, C., Castellano, A., Carapelle, E., Petrucci, R., Accogli, M., Calabrese, G., Trevisi, G. N., Coluccia, B., Giuliano, A. V., Caggiula, M., Da Re, F., Milia, A., Pilia, G., Mascia, M. G., Putzu, V., Piccoli, T., Cuffaro, L., Monastero, R., Battaglia, A., Blandino, V., Lupo, F., Cumbo, E., Antonina, L., Caravaglios, G., Vezzosi, A., Bessi, V., Tognoni, G., Calsolaro, V., Mossello, E., Amici, S., Trequattrini, A., Pezzuto, S., Mecocci, P., Fichera, G., Pradelli, S., Formilan, M., Coin, A., Detogni, L., Sala, F., Sandri, G., Gallucci, M., Mazzarolo, A. P., Bergamelli, C., Marra C. (ORCID:0000-0003-3994-4044), Cagnin, A., Di Lorenzo, R., Marra, C., Bonanni, L., Cupidi, C., Lagana, V., Rubino, E., Vacca, A., Provero, P., Isella, V., Vanacore, N., Agosta, F., Appollonio, I., Caffarra, P., Pettenuzzo, I., Sambati, R., Quaranta, D., Guglielmi, V., Logroscino, G., Filippi, M., Tedeschi, G., Ferrarese, C., Rainero, I., Bruni, A. C., Gallo, E., Grassini, A., Marcinno, A., Roveta, F., De Martino, P., Frangipane, F., Puccio, G., Colao, R., Mirabelli, M., Martellacci, N., Lino, F., Mozzetta, S., Busse, C., Camporese, G., Sacco, S., Lechiara, M. C., Carrarini, C., Russo, M., Casalena, A., Sucapane, P., Tiraboschi, P., Caroppo, P., Redaelli, V., Di Fede, G., Coppa, D., Peluso, L., Insarda, P., De Bartolo, M., Esposito, S., Iavarone, A., Orsini, A. V. M., Salvatore, E., Criscuolo, C., Sambati, L., Santoro, R., Gragnaniello, D., Pedriali, I., Ludovico, L., Chiari, A., Fabbo, A., Bevilacqua, P., Galli, C., Magarelli, S., Perini, M., Spalletta, G., Banaj, N., Porcari, D. E., Caruso, G., Cipollini, V., Casini, A. R., Ursini, F., Bruno, G., Rozzini, R., Brambilla, M., Magnani, G., Caso, F., Spinelli, E. G., Ramusino, M. C., Perini, G., Luzzi, S., Cacchio, G., Angeloni, R., Giuli, C., Fabi, K., Guidi, M., Paci, C., Castellano, A., Carapelle, E., Petrucci, R., Accogli, M., Calabrese, G., Trevisi, G. N., Coluccia, B., Giuliano, A. V., Caggiula, M., Da Re, F., Milia, A., Pilia, G., Mascia, M. G., Putzu, V., Piccoli, T., Cuffaro, L., Monastero, R., Battaglia, A., Blandino, V., Lupo, F., Cumbo, E., Antonina, L., Caravaglios, G., Vezzosi, A., Bessi, V., Tognoni, G., Calsolaro, V., Mossello, E., Amici, S., Trequattrini, A., Pezzuto, S., Mecocci, P., Fichera, G., Pradelli, S., Formilan, M., Coin, A., Detogni, L., Sala, F., Sandri, G., Gallucci, M., Mazzarolo, A. P., Bergamelli, C., and Marra C. (ORCID:0000-0003-3994-4044)

Abstract

Background: In March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of neuropsychiatric symptoms during quarantine in patients with dementia and their caregivers. Methods: This is a sub-study of a multicenter nation-wide survey. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VD), followed regularly at 87 Italian memory clinics. Variations in behavioral and psychological symptoms (BPSD) were collected after 1 month since quarantine declaration and associations with disease type, severity, gender, and caregiver’s stress burden were analyzed. Results: A total of 4,913 caregivers participated in the survey. Increased BPSD was reported in 59.6% of patients as worsening of preexisting symptoms (51.9%) or as new onset (26%), and requested drug modifications in 27.6% of these cases. Irritability, apathy, agitation, and anxiety were the most frequently reported worsening symptoms and sleep disorder and irritability the most frequent new symptoms. Profile of BPSD varied according to dementia type, disease severity, and patients’ gender. Anxiety and depression were associated with a diagnosis of AD (OR 1.35, CI: 1.12–1.62), mild to moderate disease severity and female gender. DLB was significantly associated with a higher risk of worsening hallucinations (OR 5.29, CI 3.66–7.64) and sleep disorder (OR 1.69, CI 1.25–2.29), FTD with wandering (OR 1.62, CI 1.12–2.35), and change of appetite (OR 1.52, CI 1.03–2.25). Stress-related symptoms were experienced by two-thirds of caregiv

Published
2020

109. Lifestyle and Mediterranean diet adherence in a cohort of Southern Italian patients with Multiple Sclerosis

Author

Esposito, S., primary, Sparaco, M., additional, Maniscalco, G.T., additional, Signoriello, E., additional, Lanzillo, R., additional, Russo, C., additional, Carmisciano, L., additional, Cepparulo, S., additional, Lavorgna, L., additional, Gallo, A., additional, Trojsi, F., additional, Brescia Morra, V., additional, Lus, G., additional, Tedeschi, G., additional, Saccà, F., additional, Signori, A., additional, and Bonavita, S., additional

Published
2021
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113. Conclusioni

Author

Nocentini, U., primary, Tedeschi, G., additional, and Caltagirone, C., additional

Published
2011
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117. Towards the standardization of mitochondrial proteomics: the Italian mt-HPP initiative

Author

Alberio, T., Pieroni, L., Ronci, M., Banfi, C., Bongarzone, I., Bottoni, P., Brioschi, M., Caterino, M., Chinello, C., Cormio, A., Cozzolino, F., Cunsolo, V., FONTANA, Simona, Garavaglia, B., Giusti, L., Greco, V., Lucacchini, A., Maffioli, E., Magni, F., Monteleone, Francesca, Monti, M., Monti, V., Musicco, C., Petrosillo, G., Porcelli, V., Saletti, R., Scatena, R., Soggiu, A., Tedeschi, G., Zilocchi, M., Roncada, P., Urbani, A., Fasano, M., Alberio, T, Pieroni, L, Ronci, M, Banfi, C, Bongarzone, I, Bottoni, P, Brioschi, M, Caterino, M, Chinello, C, Cormio, A, Cozzolino, F, Cunsolo, V, Fontana, S, Garavaglia, B, Giusti, L, Greco, V, Lucacchini, A, Maffioli, E, Magni, F, Monteleone, F, Monti, M, Monti, V, Musicco, C, Petrosillo, G, Porcelli, V, Saletti, R, Scatena, R, Soggiu, A, Tedeschi, G, Zilocchi, M, Roncada, P, Urbani, A, Fasano, M, Alberio, T., Pieroni, L., Ronci, M., Banfi, C., Bongarzone, I., Bottoni, P., Brioschi, M., Caterino, M., Chinello, C., Cormio, A., Cozzolino, F., Cunsolo, V., Fontana, S., Garavaglia, B., Giusti, L., Greco, V., Lucacchini, A., Maffioli, E., Magni, F., Monteleone, F., Monti, M., Monti, V., Musicco, C., Petrosillo, G., Porcelli, V., Saletti, R., Scatena, R., Soggiu, A., Tedeschi, G., Zilocchi, M., Roncada, P., Urbani, A., and Fasano, M.

Subjects
itlian mt-HPP iniziative, Mitochondria, standardization, enrichment protocol, Mitochondrial Human Proteome Project, mitochondrial proteomic, BIO/10 - BIOCHIMICA, proteomic
Abstract

The mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed datasets were analysed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and sub-mitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted nodes of this network but with a different ability in co-isolating mitochondria-associated structures for each enrichment protocol/cell line pair.

Published
2017

118. Three years of experience: the Italian registry and safety data update

Author

Mancardi, G. L., Tedeschi, G., Amato, M. P., D’Alessandro, R., Drago, F., Milanese, C., Popoli, P., Rossi, P., Savettieri, G., Tola, M. R., Comi, G., Pozzilli, C., Bertolotto, A., Marrosu, M. G., Grimaldi, L. M. E., Laroni, A., Vanacore, N., Covezzoli, A., De Rosa, M., Piccinni, C., Montanaro, N., Periotto, L., Iommelli, R., Tomino, C., and Provinciali, L.

Published
2011
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123. The pharmacovigilance program on natalizumab in Italy: 2 years of experience

Author

Tedeschi, G., Amato, M. P., D’Alessandro, R., Drago, F., Milanese, C., Popoli, P., Rossi, P., Savettieri, G., Tola, M. R., Vanacore, N., Covezzoli, A., De Rosa, M., Comi, G., Pozzilli, Carlo, Bertolotto, Antonio, Marrosu, Maria Giovanna, Grimaldi, Luigi M. E., Piccinni, C., Montanaro, N., Periotto, Laura, Iommelli, Rosamaria, Addis, Antonio, Martini, Nello, Provinciali, L., and Mancardi, G. L.

Published
2009
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127. An exploration of anger phenomenology in multiple sclerosis

Author

Nocentini, U., Tedeschi, G., Migliaccio, R., Dinacci, D., Lavorgna, L., Bonavita, S., Bresciamorra, V., Comanducci, G., Coniglio, G., Livrea, P., Mannu, R., Orefice, G., Paciello, M., Patti, F., Quattrone, A., Salemi, G., Savettieri, G., Simone, I.L., Valentino, P., Zappia, M., Bonavita, V., Musicco, M., and Caltagirone, C.

Published
2009
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128. Disability assessment in the Google Maps era: a pilot study

Author

Lavorgna, L., Laffaldano, P., Abbadessa, G., Lanzillo, R., Esposito, S., Ippolito, D., Sparaco, M., Cepparulo, S., Lus, G., Viterbo, R., Marinella CLERICO, Ragonese, P., Borriello, G., Signoriello, E., Trojano, M., Tedeschi, G., and Bonavita, S.

Published
2019

131. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Author

Bandres‐Ciga, S, Noyce, AJ, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Arosio, A, Barberis, M, Bartolomei, I, Battistini, S, Benigni, M, Borghero, G, Brunetti, M, Cammarosano, S, Cannas, A, Canosa, A, Capasso, M, Caponnetto, C, Caredda, C, Carrera, P, Casale, F, Cavallaro, S, Chiò, A, Colletti, T, Conforti, FL, Conte, A, Corrado, L, Costantino, E, D'Alfonso, S, Fasano, A, Femiano, C, Ferrarese, C, Fini, N, Floris, G, Fuda, G, Giannini, F, Grassano, M, Ilardi, A, La Bella, V, Lattante, S, Logroscino, G, Logullo, FO, Loi, D, Lunetta, C, Mancardi, G, Mandich, P, Mandrioli, J, Manera, U, Marangi, G, Marinou, K, Marrali, G, Marrosu, MG, Mazzini, L, Melis, M, Messina, S, Moglia, C, Monsurro, MR, Mosca, L, Occhineri, P, Origone, P, Pani, C, Penco, S, Petrucci, A, Piccirillo, G, Pirisi, A, Pisano, F, Pugliatti, M, Restagno, G, Ricci, C, Rita Murru, M, Riva, N, Sabatelli, M, Salvi, F, Santarelli, M, Sideri, R, Simone, I, Spataro, R, Tanel, R, Tedeschi, G, Tranquilli, S, Tremolizzo, L, Trojsi, F, Volanti, P, Zollino, M, Abramzon, Y, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Chia, R, Cooper‐Knock, J, Cusi, D, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, Faghri, F, Feldman, E, Kay Floeter, M, Fratta, P, Geiger, JT, Gerhard, G, Gibbs, JR, Gibson, SB, Glass, JD, Hardy, J, Harms, MB, Heiman‐Patterson, TD, Hernandez, DG, Jansson, L, Kamel, F, Kirby, J, Kowall, NW, Laaksovirta, H, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering‐Brown, S, Pioro, E, Pliner, HA, Pulst, SM, Ravits, JM, Renton, AE, Rivera, A, Robbrecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Salvi, E, Scholz, SW, Sendtner, M, Shaw, PJ, Sidle, KC, Simmons, Z, Singleton, AB, Stone, DC, Sulkava, R, Tienari, PJ, Traynor, BJ, Trojanowski, JQ, Troncoso, JC, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Stone, DJ, Bandres-Ciga, Sara, Noyce, Alastair J., Hemani, Gibran, Nicolas, Aude, Calvo, Andrea, Mora, Gabriele, Arosio, Alessandro, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Benigni, Michele, Borghero, Giuseppe, Brunetti, Maura, Cammarosano, Stefania, Cannas, Antonino, Canosa, Antonio, Capasso, Margherita, Caponnetto, Claudia, Caredda, Carla, Carrera, Paola, Casale, Federico, Cavallaro, Sebastiano, Chiò, Adriano, Colletti, Tiziana, Conforti, Francesca L., Conte, Amelia, Corrado, Lucia, Costantino, Emanuela, D'Alfonso, Sandra, Fasano, Antonio, Femiano, Cinzia, Ferrarese, Carlo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Giannini, Fabio, Grassano, Maurizio, Ilardi, Antonio, La Bella, Vincenzo, Lattante, Serena, Logroscino, Giancarlo, Logullo, Francesco O., Loi, Daniela, Lunetta, Christian, Mancardi, Gianluigi, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Marangi, Giuseppe, Marinou, Kalliopi, Marrali, Giuseppe, Marrosu, Maria Giovanna, Mazzini, Letizia, Melis, Maurizio, Messina, Sonia, Moglia, Cristina, Monsurro, Maria Rosaria, Mosca, Lorena, Occhineri, Patrizia, Origone, Paola, Pani, Carla, Penco, Silvana, Petrucci, Antonio, Piccirillo, Giovanni, Pirisi, Angelo, Pisano, Fabrizio, Pugliatti, Maura, Restagno, Gabriella, Ricci, Claudia, Rita Murru, Maria, Riva, Nilo, Sabatelli, Mario, Salvi, Fabrizio, Santarelli, Marialuisa, Sideri, Riccardo, Simone, Isabella, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Volanti, Paolo, Zollino, Marcella, Abramzon, Yevgeniya, Arepalli, Sampath, Baloh, Robert H., Bowser, Robert, Brady, Christopher B., Brice, Alexi, Broach, Jame, Campbell, Roy H., Camu, William, Chia, Ruth, Cooper-Knock, John, Cusi, Daniele, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Eicher, John D., Faghri, Faraz, Feldman, Eva, Kay Floeter, Mary, Fratta, Pietro, Geiger, Joshua T., Gerhard, Glenn, Gibbs, J. Raphael, Gibson, Summer B., Glass, Jonathan D., Hardy, John, Harms, Matthew B., Heiman-Patterson, Terry D., Hernandez, Dena G., Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J. L., Maragakis, Nicholas J., Mouzat, Kevin, Murphy, Natalie A., Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik, Pliner, Hannah A., Pulst, Stefan M., Ravits, John M., Renton, Alan E., Rivera, Alberto, Robbrecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D., Salvi, Erika, Scholz, Sonja W., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Singleton, Andrew B., Stone, David C., Sulkava, Raimo, Tienari, Pentti J., Traynor, Bryan J., Trojanowski, John Q., Troncoso, Juan C., Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Stone, David J., Van Damme, P, Bandres-Ciga, S, Noyce, A, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Tienari, P, Stone, D, Nalls, M, Singleton, A, Chiò, A, Traynor, Bryan, J, Tremolizzo, L, Department of Neurosciences, Neurologian yksikkö, Clinicum, HUS Neurocenter, Translational neuroradiology unit [Bethesda], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada, Spain, Partenaires INRAE, Queen Mary University of London (QMUL), University College of London [London] (UCL), University of Bristol [Bristol], Département de Physique, Université de Genève, Université de Genève (UNIGE), Università degli studi di Torino (UNITO), University G. d'Annunzio, Chieti, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Department of Health Sciences, UPO University, UPO University, Dipartimento di Matematica 'Ulisse Dini', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Neurology, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Department of Neuroscience, University of Siena, Siena, Università cattolica del Sacro Cuore [Roma] (Unicatt), Università degli studi di Bari Aldo Moro (UNIBA), Istituto di Genetica Medica, Centro Sclerosi Multipla, Ospedale Binaghi, Via Is Guadazzonis 2, Cagliari, Italy, University of Novara, IRCCS-Istituti Clinici Scientifici Maugeri, University of Milan, Milan, Italy, Department of Biomedical and Specialty Surgical Sciences, Università degli Studi di Ferrara (UniFE), S. Anna Hospital, Department of Neuroscience, Catholic University, Roma, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Medical Genetics, Catholic University, Rome, Italy, Department of Clinical Genetics, Department of Pathology University of Pittsburgh School of Medicine, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Princeton University, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Milano [Milano] (UNIMI), Laboratory of Neurogenetics, National Institute of Aging, Tel Aviv Sourasky Medical Center [Te Aviv], University of New Haven [Connecticut], Emory University [Atlanta, GA], UCL Institute of neurology, UCL Institute of Neurology, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Boston University [Boston] (BU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California-University of California, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Johns Hopkins University, School of Medicine, Department of Medicine, Surgery, and Dentistry, University of Milano, Institute for Clinical Neurobiology, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Penn State Hershey Medical Center, Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System-Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Metacohorts Consortium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Helsinki, Merck Research Laboratories, National Institutes of Health [Bethesda] (NIH), Center for Neuroscience and Regenerative Medicine [Bethesda] (CNRM), and Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM)

Subjects
0301 basic medicine, Linkage disequilibrium, Multifactorial Inheritance, Multivariate analysis, LD SCORE REGRESSION, DYSLIPIDEMIA, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, PROTECTIVE FACTOR, Mendelian Randomization Analysis, 3. Good health, ALZHEIMERS-DISEASE, Settore MED/26 - NEUROLOGIA, risk factor, BIAS, Neurology, CARDIOVASCULAR-DISEASE, MENDELIAN RANDOMIZATION, Amyotrophic lateral Sclerosis, LD score regression, Mendelian randomization, amyotrophic lateral sclerosis, public resource, Life Sciences & Biomedicine, Clinical psychology, Human, Clinical Neurology, Biology, NO, 03 medical and health sciences, Humans, Genetic Predisposition to Disease, Mendelian Randomization Analysi, MESH: Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease / genetics, Genome-Wide Association Study / methods, Mendolian Randomization Analysis / methods, Exercise, Genetic association, Science & Technology, [SCCO.NEUR]Cognitive science/Neuroscience, Amyotrophic Lateral Sclerosis, 3112 Neurosciences, Neurosciences, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, CHOLESTEROL HOMEOSTASIS, Causal inference, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurosciences & Neurology, Neurology (clinical), Genome-Wide Association Study, ALS, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract

OBJECTIVE: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). METHODS: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. RESULTS: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. INTERPRETATION: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470-481. ispartof: ANNALS OF NEUROLOGY vol:85 issue:4 pages:470-481 ispartof: location:United States status: published

Published
2019

132. Effectiveness of Natalizumab on Multiple Sclerosis patients: the Italian registry experience

Author

Chisari, C., Comi, G., Zaffaroni, M., Morra, V. Brescia, Trojano, M., Iaffaldano, P., Cocco, E., Centonze, D., Uccelli, A., Pozzilli, C., Salemi, G., Luca, G., Cottone, S., Millefiorini, E., Salvetti, M., Aguglia, U., Costantino, G., Florio, C., Galgani, S., Pesci, I., Amato, M. P., Rovaris, M., Gazzola, P., Lus, G., Maimone, D., Grimaldi, L. M., Bergamaschi, R., Granella, F., Bertolotto, A., Totaro, R., Vianello, M., Bellantonio, P., Cavalla, P., Di Battista, G., Spitaleri, D., Tedeschi, G., Valzania, F., Scarpini, E., Gatto, M., Valentino, P., Renato Mantegazza, Rezzonico, M., Passarella, B., Avolio, C., Logullo, F. O., Cavalletti, G., Corea, F., Clerico, M., Lugaresi, A., and Patti, F.

Published
2019

134. Transparent and robust all-cellulose nanocomposite packaging materials prepared in a mixture of trifluoroacetic acid and trifluoroacetic anhydride

Author

Instituto de Ciencia de Materiales de Sevilla (ICMS), Guzman-Puyol, S., Ceseracciu, L., Tedeschi, G., Marras, S., Scarpellini, A., Benítez Jiménez, José Jesús, Athanassiou, Athanassia, Heredia Guerrero, José A., Instituto de Ciencia de Materiales de Sevilla (ICMS), Guzman-Puyol, S., Ceseracciu, L., Tedeschi, G., Marras, S., Scarpellini, A., Benítez Jiménez, José Jesús, Athanassiou, Athanassia, and Heredia Guerrero, José A.

Abstract

All-cellulose composites with a potential application as food packaging films were prepared by dissolving microcrystalline cellulose in a mixture of trifluoroacetic acid and trifluoroacetic anhydride, adding cellulose nanofibers, and evaporating the solvents. First, the effect of the solvents on the morphology, structure, and thermal properties of the nanofibers was evaluated by atomic force microscopy (AFM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA), respectively. An important reduction in the crystallinity was observed. Then, the optical, morphological, mechanical, and water barrier properties of the nanocomposites were determined. In general, the final properties of the composites depended on the nanocellulose content. Thus, although the transparency decreased with the amount of cellulose nanofibers due to increased light scattering, normalized transmittance values were higher than 80% in all the cases. On the other hand, the best mechanical properties were achieved for concentrations of nanofibers between 5 and 9 wt.%. At higher concentrations, the cellulose nanofibers aggregated and/or folded, decreasing the mechanical parameters as confirmed analytically by modeling of the composite Young’s modulus. Finally, regarding the water barrier properties, water uptake was not affected by the presence of cellulose nanofibers while water permeability was reduced because of the higher tortuosity induced by the nanocelluloses. In view of such properties, these materials are suggested as food packaging films.

Published
2019

135. Current and emerging evidence-based treatment options in chronic migraine: A narrative review

Author

Agostoni, E. C., Barbanti, P., Calabresi, Paolo, Colombo, B., Cortelli, P., Frediani, F., Geppetti, P., Grazzi, L., Leone, M., Martelletti, P., Pini, L. A., Prudenzano, M. P., Sarchielli, P., Tedeschi, G., Russo, A., Calabresi P. (ORCID:0000-0003-0326-5509), Agostoni, E. C., Barbanti, P., Calabresi, Paolo, Colombo, B., Cortelli, P., Frediani, F., Geppetti, P., Grazzi, L., Leone, M., Martelletti, P., Pini, L. A., Prudenzano, M. P., Sarchielli, P., Tedeschi, G., Russo, A., and Calabresi P. (ORCID:0000-0003-0326-5509)

Abstract

Background: Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment. Findings: Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment. Conclusions: Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Published
2019

136. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Author

Bandres-Ciga, S., Noyce, A. J., Hemani, G., Nicolas, A., Calvo, A., Mora, G., Arosio, A., Barberis, M., Bartolomei, I., Battistini, S., Benigni, M., Borghero, G., Brunetti, M., Cammarosano, S., Cannas, A., Canosa, A., Capasso, Monica, Caponnetto, C., Caredda, C., Carrera, P., Casale, F., Cavallaro, S., Chio, A., Colletti, T., Conforti, F. L., Conte, Amelia, Corrado, L., Costantino, E., D'Alfonso, Sandra, Fasano, Alfonso, Femiano, C., Ferrarese, C., Fini, N., Floris, G., Fuda, G., Giannini, F., Grassano, M., Ilardi, A., La Bella, V., Lattante, Serena, Logroscino, Giandomenico, Logullo, F. O., Loi, D., Lunetta, C., Mancardi, G., Mandich, P., Mandrioli, J., Manera, U., Marangi, Giuseppe, Marinou, K., Marrali, G., Marrosu, M. G., Mazzini, L., Melis, M., Messina, S., Moglia, C., Monsurro, M. R., Mosca, Luigi, Occhineri, P., Origone, P., Pani, C., Penco, S., Petrucci, A., Piccirillo, G., Pirisi, A., Pisano, F., Pugliatti, M., Restagno, G., Ricci, C., Rita Murru, M., Riva, N., Sabatelli, Mario, Salvi, F., Santarelli, M., Sideri, R., De Simone, Idor, Spataro, R., Tanel, R., Tedeschi, G., Tranquilli, S., Tremolizzo, L., Trojsi, F., Volanti, P., Zollino, Marcella, Abramzon, Y., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Cusi, D., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., Faghri, F., Feldman, E., Kay Floeter, M., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kamel, F., Kirby, J., Kowall, N. W., Laaksovirta, H., Landi, Francesco, Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robbrecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Salvi, E., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Stone, D. C., Sulkava, R., Tienari, P. J., Traynor, B. J., Trojanowski, J. Q., Troncoso, J. C., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Stone, D. J., Capasso M., Conte A., D'Alfonso S., Fasano A., Lattante S. (ORCID:0000-0003-2891-0340), Logroscino G. (ORCID:0000-0003-1301-5343), Marangi G. (ORCID:0000-0002-6898-8882), Mosca L. (ORCID:0000-0003-4641-0841), Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Landi F. (ORCID:0000-0002-3472-1389), Bandres-Ciga, S., Noyce, A. J., Hemani, G., Nicolas, A., Calvo, A., Mora, G., Arosio, A., Barberis, M., Bartolomei, I., Battistini, S., Benigni, M., Borghero, G., Brunetti, M., Cammarosano, S., Cannas, A., Canosa, A., Capasso, Monica, Caponnetto, C., Caredda, C., Carrera, P., Casale, F., Cavallaro, S., Chio, A., Colletti, T., Conforti, F. L., Conte, Amelia, Corrado, L., Costantino, E., D'Alfonso, Sandra, Fasano, Alfonso, Femiano, C., Ferrarese, C., Fini, N., Floris, G., Fuda, G., Giannini, F., Grassano, M., Ilardi, A., La Bella, V., Lattante, Serena, Logroscino, Giandomenico, Logullo, F. O., Loi, D., Lunetta, C., Mancardi, G., Mandich, P., Mandrioli, J., Manera, U., Marangi, Giuseppe, Marinou, K., Marrali, G., Marrosu, M. G., Mazzini, L., Melis, M., Messina, S., Moglia, C., Monsurro, M. R., Mosca, Luigi, Occhineri, P., Origone, P., Pani, C., Penco, S., Petrucci, A., Piccirillo, G., Pirisi, A., Pisano, F., Pugliatti, M., Restagno, G., Ricci, C., Rita Murru, M., Riva, N., Sabatelli, Mario, Salvi, F., Santarelli, M., Sideri, R., De Simone, Idor, Spataro, R., Tanel, R., Tedeschi, G., Tranquilli, S., Tremolizzo, L., Trojsi, F., Volanti, P., Zollino, Marcella, Abramzon, Y., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Cusi, D., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., Faghri, F., Feldman, E., Kay Floeter, M., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kamel, F., Kirby, J., Kowall, N. W., Laaksovirta, H., Landi, Francesco, Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robbrecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Salvi, E., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Stone, D. C., Sulkava, R., Tienari, P. J., Traynor, B. J., Trojanowski, J. Q., Troncoso, J. C., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Stone, D. J., Capasso M., Conte A., D'Alfonso S., Fasano A., Lattante S. (ORCID:0000-0003-2891-0340), Logroscino G. (ORCID:0000-0003-1301-5343), Marangi G. (ORCID:0000-0002-6898-8882), Mosca L. (ORCID:0000-0003-4641-0841), Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), and Landi F. (ORCID:0000-0002-3472-1389)

Abstract

Objective: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). Methods: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. Results: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. Interpretation: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470–481.

Published
2019

137. Theme 08 - CLINICAL IMAGING AND ELECTROPHYSIOLOGY.

Author

Bashford, J., Weddell, T., Wickham, A., Iniesta, R., Chen, M., Zhou, P., Drakakis, E., Boutelle, M., Mills, K., Shaw, C., D'Alvano, G., Trojsi, F., Di Nardo, F., Passaniti, C., Siciliano, M., Caiazzo, G., Canna, A., Esposito, F., Tedeschi, G., and Foucher, J.

Subjects
DIAGNOSTIC imaging, MAGNETIC resonance imaging, AMYOTROPHIC lateral sclerosis, ELECTROPHYSIOLOGY, MOTOR unit, TRANSCRANIAL magnetic stimulation
Abstract

Spinal cord imaging in amyotrophic lateral sclerosis: historical concepts - novel techniques. Integrated magnetic resonance imaging and [11 C]-PBR28 positron emission tomographic imaging in amyotrophic lateral sclerosis. 1 Bashford J, Mills K, Shaw C. The evolving role of surface electromyography in amyotrophic lateral sclerosis: a systematic review. Comparison of Two Clinical Upper Motor Neuron Burden Rating Scales in ALS Using Quantitative Brain Imaging. [Extracted from the article]

Published
2021
Full Text
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140. Management of pregnancy-related issues in multiple sclerosis patients: the need for an interdisciplinary approach

Author

Amato MP, Bertolotto A, Brunelli R, Cavalla P, Goretti B, Marrosu MG, Patti F, Pozzilli C, Provinciali L, Rizzo N, Strobelt N, Tedeschi G, Trojano M, Comi G., and Amato MP, Bertolotto A, Brunelli R, Cavalla P, Goretti B, Marrosu MG, Patti F, Pozzilli C, Provinciali L, Rizzo N, Strobelt N, Tedeschi G, Trojano M, Comi G.

Subjects
Treatment, Glatiramer acetate, Pregnancy, Multiple sclerosi, Interdisciplinary approach, Relapse
Abstract

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS), most probably autoimmune in origin, usually occurring in young adults with a female/male prevalence of approximately 3:1. Women with MS in the reproductive age may face challenging issues in reconciling the desire for parenthood with their condition, owing to the possible influence both on the ongoing or planned treatment with the possible consequences on the disease course and on the potential negative effects of treatments on foetal and pregnancy outcomes. At MS diagnosis, timely counselling should promote informed parenthood, while disease evolution should be assessed before making therapeutic decisions. Current guidelines advise the discontinuation of any treatment during pregnancy, with possible exceptions for some treatments in patients with very active disease. Relapses decline during pregnancy but are more frequent during puerperium, when MS therapy should be promptly resumed in most of the cases. First-line immunomodulatory agents, such as interferon-β (IFN-β) and glatiramer acetate (GA), significantly reduce the post-partum risk of relapse. Due to substantial evidence of safety with the use of GA during pregnancy, a recent change in European marketing authorization removed the pregnancy contraindication for GA. This paper reports a consensus of Italian experts involved in MS management, including neurologists, gynaecologists and psychologists. This consensus, based on a review of the available scientific evidence, promoted an interdisciplinary approach to the management of pregnancy in MS women.

Published
2017

142. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study

Author

Prosperini, L, Annovazzi, P, Boffa, L, Buscarinu, Mc, Gallo, A, Matta, M, Moiola, L, Musu, L, Perini, P, Avolio, C, Barcella, V, Bianco, A, Farina, D, Ferraro, E, Pontecorvo, S, Granella, F, Grimaldi, Lme, Laroni, A, Lus, G, Patti, F, Pucci, E, Pasca, M, Sarchielli, P, Ghezzi, A, Zaffaroni, M, Baroncini, D, Buttari, F, Centonze, D, Fornasiero, A, Salvetti, M, Docimo, R, Signoriello, E, Tedeschi, G, Bertolotto, A, Capobianco, M, Comi, G, Cocco, E, Gallo, P, Puthenparampil, M, Grasso, R, Di Francescantonio, V, Rottoli, Mr, Mirabella, M, Lugaresi, A, De Luca, G, Di Ioia, M, Di Tommaso, V, Mancinelli, L, Di Battista, G, Francia, A, Ruggieri, S, Pozzilli, C, Curti, E, Tsantes, E, Palmeri, B, Lapucci, C, Mancardi, Gl, Uccelli, A, Chisari, C, D'Amico, E, Cartechini, E, Repice, Am, Magnani, E, Massaccesi, L, Calabresi, P, Di Filippo, M, Di Gregorio, M, Italian Alemtuzumab Study, Group., Prosperini, Luca, Annovazzi, Pietro, Boffa, Laura, Buscarinu, Maria Chiara, Gallo, Antonio, Matta, Manuela, Moiola, Lucia, Musu, Luigina, Perini, Paola, Avolio, Carlo, Barcella, Valeria, Bianco, Assunta, Farina, Deborah, Ferraro, Elisabetta, Pontecorvo, Simona, Granella, Franco, Grimaldi, Luigi M E, Laroni, Alice, Lus, Giacomo, Patti, Francesco, Pucci, Eugenio, Pasca, Matteo, and Sarchielli, Paola

Subjects
Adult, Male, medicine.medical_specialty, Neurology, Outcome measurement, Relapsing-Remitting, Follow-Up Studie, Multiple sclerosis, 03 medical and health sciences, Immunologic Factor, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Alemtuzumab, Multiple sclerosis, Outcome measurement, Retrospective Studie, Alemtuzumab, Internal medicine, Medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Female, Follow-Up Studies, Magnetic Resonance Imaging, Retrospective Studies, Treatment Outcome, Neurology (clinical), Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Retrospective cohort study, Magnetic resonance imaging, Odds ratio, medicine.disease, alemtuzumab, multiple sclerosis, outcome measurement, neurology, Clinical trial, Settore MED/26 - NEUROLOGIA, business, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract

In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.

Published
2018

146. Discontinuation of teriflunomide and dimethyl fumarate in a large Italian multicentre population: a 24-month real-world experience

Author

D’Amico, E., primary, Zanghì, A., additional, Sciandra, M., additional, Borriello, G., additional, Callari, G., additional, Gallo, A., additional, Salemi, G., additional, Cottone, S., additional, Buccafusca, M., additional, Valentino, P., additional, Bossio, R. B., additional, Grimaldi, L. M. E., additional, Pozzilli, C., additional, Tedeschi, G., additional, Zappia, M., additional, and Patti, F., additional

Published
2018
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150. Assessing response to interferon-β in a multicenter dataset of patients with MS

Author

Sormani, Mp, Gasperini, C, Romeo, M, Rio, J, Calabrese, M, Cocco, E, Enzingher, C, Fazekas, F, Filippi, M, Gallo, A, Kappos, L, Marrosu, Mg, Martinelli, V, Prosperini, Luca, Rocca, Ma, Rovira, A, Sprenger, T, Stromillo, Ml, Tedeschi, G, Tintorè, M, Tortorella, C, Trojano, M, Montalban, X, Pozzilli, Carlo, Comi, G, De Stefano, N, MAGNIMS study group, Sormani, Maria Pia, Gasperini, Claudio, Romeo, Marzia, Rio, Jordi, Calabrese, Massimiliano, Cocco, Eleonora, Enzingher, Christian, Fazekas, Franz, Filippi, Massimo, Gallo, Antonio, Kappos, Ludwig, Marrosu, Maria Giovanna, Martinelli, Vittorio, Prosperini, Luca, Rocca, Maria Assunta, Rovira, Alex, Sprenger, Till, Stromillo, Maria Laura, Tedeschi, Gioacchino, Tintorè, Mar, Tortorella, Carla, Trojano, Maria, Montalban, Xavier, Pozzilli, Carlo, Comi, Giancarlo, De Stefano, Nicola, Sormani, Mp, Gasperini, C, Romeo, M, Rio, J, Calabrese, M, Cocco, E, Enzingher, C, Fazekas, F, Gallo, A, Kappos, L, Marrosu, Mg, Martinelli, V, Prosperini, L, Rocca, Ma, Rovira, A, Sprenger, T, Stromillo, Ml, Tedeschi, G, Tintorè, M, Tortorella, C, Trojano, M, Montalban, X, Pozzilli, C, and De Stefano, N.

Subjects
Time Factors, multiple sclerosis, interferon-β therapy, Magnetic Resonance Imaging, assessment, follow-up, risk of treatment failure, Expanded Disability Status Scale, relapse, worsening, Datasets as Topic, Kaplan-Meier Estimate, Relapsing-Remitting, Disability Evaluation, 0302 clinical medicine, Adolescent, Adult, Aged, Child, Europe, Follow-Up Studies, Humans, Immunologic Factors, Interferon-beta, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Risk, Treatment Failure, Young Adult, Neurology (clinical), 030212 general & internal medicine, Young adult, medicine.diagnostic_test, Hazard ratio, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Proportional hazards model, business.industry, Multiple sclerosis, Magnetic resonance imaging, Retrospective cohort study, medicine.disease, Confidence interval, multiple-sclerosis patients, treatment optimization, clinical-practice, ifn-beta, mri, recommendations, predictors, score, business, 030217 neurology & neurosurgery
Abstract

To provide new insights into the role of markers of response to interferon-β therapy in multiple sclerosis (MS) in a multicenter setting, focusing on the relevance of MRI lesions in combination with clinical variables.A large multicenter clinical dataset was collected within the Magnetic Resonance Imaging in MS (MAGNIMS) network. This included a large cohort of patients with relapsing-remitting MS on interferon-β treatment, MRI and clinical assessments during the first year of treatment, and clinical follow-up of at least 2 additional years. Heterogeneity among centers was assessed before pooling the data. The association of 1-year MRI or clinical relapses with the risk of treatment failure (defined as Expanded Disability Status Scale [EDSS] worsening or treatment switch for inefficacy) and of EDSS worsening alone was evaluated using multivariate Cox models.A pooled dataset of 1,280 patients with relapsing-remitting MS from 9 MAGNIMS centers was analyzed. The risk of failure had a relevant increase with 1 relapse (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.39-2.44, p0.001) and ≥3 new T2 lesions (HR 1.55, 95% CI 0.92-2.60, p = 0.09). In patients without relapses and less than 3 new T2 lesions, the 3-year risk of failure and EDSS worsening were 17% and 15%; in patients with 1 relapse or ≥3 new T2 lesions, the risks were 27% and 22%; in patients with both conditions or more than 1 relapse, the risks were 48% (p0.001) and 29% (p0.001).Substantial MRI activity, particularly if in combination with clinical relapses, during the first year of treatment with interferon-β indicates significant risk of treatment failure and EDSS worsening in the short term.

Published
2016

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