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1. Do patients’ and referral centers’ characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register

Author

Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Aguglia, U., Amato, M. P., Ancona, A. L., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bergamaschi, R., Bertora, P., Bianchi, M., Bramanti, P., Morra, V. Brescia, Brichetto, G., Brioschi, A. M., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capobianco, M., Capone, F., Capone, L., Cargnelutti, D., Carrozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M. G., Clerici, R., Clerico, M., Cocco, E., Confalonieri, P., Coniglio, M. G., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M. C., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Corte, M. Della, Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M. T., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M. F., Grasso, M. G., Grimaldi, L. M. E., Iaffaldano, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Luezzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G. T., Marfia, G. A., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Meucci, G., Mirabella, M., Montepietra, S., Nasuelli, D., Nicolao, P., Passantino, F., Patti, F., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Romeo, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Santuccio, G., Sarchielli, P., Sinisi, L., Sola, P., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Tonietti, S., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Ulivelli, M., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., Zarbo, R., Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Mosconi, Paola, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, Bergamaschi, Roberto, and Comi, Giancarlo

Published
2022
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2. Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Author

Mosconi, P., Guerra, T., Paletta, P., D’Ettorre, A., Ponzio, M., Battaglia, M. A., Amato, M. P., Bergamaschi, R., Capobianco, M., Comi, G., Gasperini, C., Patti, F., Pugliatti, M., Ulivelli, M., Trojano, M., Lepore, V., Aguglia, U., Amato, M., Ancona, A., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bertora, P., Bianchi, M., Bramanti, P., Brescia Morra, V., Brichetto, G., Brioschi, A., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capone, F., Capone, L., Cargnelutti, D., Carozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M., Clerici, R., Clerico, M., Cocco, E., Torri Clerici, V., Coniglio, M., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Della Corte, M., Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M., Grimaldi, L., Iaffaldano, P., Immovilli, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Leuzzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G., Marfia, G., Margari, L., Marinelli, F., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Fioretti, C., Mirabella, Massimiliano, Montepietra, S., Nasuelli, D., Nicolao, P., Pasquali, L., Passantino, F., Pecori, C., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Filippi, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Leone, A., Sarchielli, P., Sinisi, L., Ferraro, D., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Santuccio, G., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Turano, G., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., and Zarbo, R.

Subjects
Multiple sclerosis, Settore MED/26 - NEUROLOGIA, Real world data, Quality control, Quality indicators, Register
Published
2023

4. The Italian multiple sclerosis register

Author

Trojano, M, Bergamaschi, R, Amato, Mp, Comi, G, Ghezzi, A, Lepore, V, 7, Marrosu, Mg, Mosconi, P, Patti, F, Ponzio, M, Zaratin, P, Battaglia, Ma1, Acquistapace D, Italian Multiple Sclerosis Register Centers Group., Aguglia, U, Annunziata, P, Ardito, B, Avolio, C, Balgera, R, Bandini, F, Banfi, P, Barone, P, Bellantonio, P, Bertolotto, A, Bertora, P, Bombardi, R, Bosco Zimatore, G, Bossio, Rb, Bramanti, P, Brescia Morra, V, Brioschi, Am, Bruzzone, M, Buccafusca, M, Busillo, V, Caneve, G, Caniatti, Lm, Capone, L, Capone, F, Cappellani, A, Cargnelutti, D, Cavaletti, G, Cavalla, P, Celani, Mg, Centonze, D, Chiveri, L, Clerici, R, Clerico, M, Cocco, E, Comi, C, Coniglio, Mg, Cordera, S, Corea, F, Cortese, A, Costantino, G, Cottone, S, Crociani, P, D'Andrea, F, Danni, Mc, De Luca, G, de Pascalis, D, De Robertis, F, De Stefano, N, Di Battista, G, Di Napoli, M, Falcini, M, Fausto, F, Ferrò, Mt, Florio, C, Fortunato, M, Frittelli, C, Galgani, S, Gallo, P, Gatto, M, Gazzola, P, Geda, C, Giordano, A, Granella, F, Grasso, Mg, Grimaldi, Lme, Imperiale, D, Lo Russo, L, Logullo, Fo, Lugaresi, A, Lus, G, Maccarrone, G, Maimone, D, Malagù, S, Marconi, R, Maritato, P, Massacesi, L, Mazzoni, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Neri, W, Orefice, G, Parodi, S, Pasquali, L, Passarella, B, Peresson, M, Perla, F, Pesci, I, Piantadosi, C, Piras, Ml, Pizio, Nr, Pozzilli, C, Protti, A, Pugliatti, M, Quatrale, R, Ragno, M, Rezzonico, M, Ribizzi, G, Riva, M, Ronzoni, M, Rosso, Mg, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santangelo, M, Santangelo, G, Santuccio, G, Sarchielli, P, Scarpini, E, Sechi, Gp, Severi, S, Sinisi, L, Sola, P, Spitaleri, D, Tassinari, T, Tedeschi, G, Tonietti, S, Torri Clerici, V, Totaro, R, Traccis, S, Turla, M, Uccelli, A, Ulivelli, M, Valentino, P, Valeriani, M, Venturi, S, Vianello, M, Zaffaroni, M., Trojano M., Bergamaschi R., Amato M.P., Comi G., Ghezzi A., Lepore V., Marrosu M.G., Mosconi P., Patti F., Ponzio M., Zaratin P., Battaglia M.A., Acquistapace D., Aguglia U., Annunziata P., Ardito B., Avolio C., Balgera R., Bandini F., Banfi P., Barone P., Bellantonio P., Bertolotto A., Bertora P., Bombardi R., Bosco Zimatore G., Bossio R.B., Bramanti P., Brescia Morra V., Brioschi A.M., Bruzzone M., Buccafusca M., Busillo V., Caneve G., Caniatti L.M., Capone L., Capone F., Cappellani A., Cargnelutti D., Cavaletti G., Cavalla P., Celani M.G., Centonze D., Chiveri L., Clerici R., Clerico M., Cocco E., Comi C., Coniglio M.G., Cordera S., Corea F., Cortese A., Costantino G., Cottone S., Crociani P., D'Andrea F., Danni M.C., De Luca G., de Pascalis D., De Robertis F., De Stefano N., Di Battista G., Di Napoli M., Falcini M., Fausto F., Ferro M.T., Florio C., Fortunato M., Frittelli C., Galgani S., Gallo P., Gatto M., Gazzola P., Geda C., Giordano A., Granella F., Grasso M.G., Grimaldi L.M.E., Imperiale D., Lo Russo L., Logullo F.O., Lugaresi A., Lus G., Maccarrone G., Maimone D., Malagu S., Marconi R., Maritato P., Massacesi L., Mazzoni M., Meucci G., Mirabella M., Montepietra S., Nasuelli D., Neri W., Orefice G., Parodi S., Pasquali L., Passarella B., Peresson M., Perla F., Pesci I., Piantadosi C., Piras M.L., Pizio N.R., Pozzilli C., Protti A., Pugliatti M., Quatrale R., Ragno M., Rezzonico M., Ribizzi G., Riva M., Ronzoni M., Rosso M.G., Rottoli M., Rovaris M., Salemi G., Salvetti M., Santangelo M., Santangelo G., Santuccio G., Sarchielli P., Scarpini E., Sechi G.P., Severi S., Sinisi L., Sola P., Spitaleri D., Tassinari T., Tedeschi G., Tonietti S., Torri Clerici V., Totaro R., Traccis S., Turla M., Uccelli A., Ulivelli M., Valentino P., Valeriani M., Venturi S., Vianello M., Zaffaroni M., Trojano M, Bergamaschi R, Amato M.P, Comi G, Ghezzi A, Lepore V, Marrosu M.G, Mosconi P, Patti F, Ponzio M, Zaratin P, Battaglia M.A, Acquistapace D., Aguglia U., Annunziata P., Ardito B., Avolio C., Balgera R., Bandini F., Banfi P., Barone P., Bellantonio P., Bertolotto A., Bertora P., Bombardi R., Bosco Zimatore G., Bossio R.B., Bramanti P., Brescia Morra V., Brioschi A.M., Bruzzone M., Buccafusca M., Busillo V., Caneve G., Caniatti L.M., Capone L., Capone F., Cappellani A., Cargnelutti D., Cavaletti G., Cavalla P., Celani M.G., Centonze D., Chiveri L., Clerici R., Clerico M., Cocco E., Comi C., Coniglio M.G., Cordera S., Corea F., Cortese A., Costantino G., Cottone S., Crociani P., D’Andrea F., Danni M.C., De Luca G., de Pascalis D., De Robertis F., De Stefano N., Di Battista G., Di Napoli M., Falcini M., Fausto F., Ferrò M.T., Florio C., Fortunato M., Frittelli C., Galgani S., Gallo P., Gatto M., Gazzola P., Geda C., Giordano A., Granella F., Grasso M.G., Grimaldi L.M.E., Imperiale D., Lo Russo L., Logullo F.O., Lugaresi A., Lus G., Maccarrone G., Maimone D., Malagù S., Marconi R., Maritato P., Massacesi L., Mazzoni M., Meucci G., Mirabella M., Montepietra S., Nasuelli D., Neri W., Orefice G., Parodi S., Pasquali L., Passarella B., Peresson M., Perla F., Pesci I., Piantadosi C., Piras M.L., Pizio N.R., Pozzilli C., Protti A., Pugliatti M., Quatrale R., Ragno M., Rezzonico M., Ribizzi G., Riva M., Ronzoni M., Rosso M.G., Rottoli M., Rovaris M., Salemi G., Salvetti M., Santangelo M., Santangelo G., Santuccio G., Sarchielli P., Scarpini E., Sechi G.P., Severi S., Sinisi L., Sola P, Spitaleri D., Tassinari T., Tedeschi G., Tonietti S., Torri Clerici V., Totaro R., Traccis S., Turla M., Uccelli A., Ulivelli M., Valentino P., Valeriani M., Venturi S., Vianello M., Zaffaroni M., Trojano, Maria, Bergamaschi, Roberto, Amato, Maria Pia, Comi, Giancarlo, Ghezzi, Angelo, Lepore, Vito, Marrosu, Maria Giovanna, Mosconi, Paola, Patti, Francesco, Ponzio, Michela, Zaratin, Paola, Battaglia, Mario Alberto, Acquistapace, D, Aguglia, U, Amato, Mp, Annunziata, P, Ardito, B, Avolio, C, Balgera, R, Bandini, F, Banfi, P, Barone, P, Bellantonio, P, Bergamaschi, R, Bertolotto, A, Bertora, P, Bombardi, R, Bosco Zimatore, G, Bossio, Rb, Bramanti, P, Brescia Morra, V, Brioschi, Am, Bruzzone, M, Buccafusca, M, Busillo, V, Caneve, G, Caniatti, Lm, Capone, L, Capone, F, Cappellani, A, Cargnelutti, D, Cavaletti, G, Cavalla, P, Celani, Mg, Centonze, D, Chiveri, L, Clerici, R, Clerico, M, Cocco, E, Comi, G, Comi, C, Coniglio, Mg, Cordera, S, Corea, F, Cortese, A, Costantino, G, Cottone, S, Crociani, P, D'Andrea, F, Danni, Mc, De Luca, G, de Pascalis, D, De Robertis, F, De Stefano, N, Di Battista, G, Di Napoli, M, Falcini, M, Fausto, F, Ferrò, Mt, Florio, C, Fortunato, M, Frittelli, C, Galgani, S, Gallo, P, Gatto, M, Gazzola, P, Geda, C, Giordano, A, Granella, F, Grasso, Mg, Grimaldi, Lme, Imperiale, D, Lo Russo, L, Logullo, Fo, Lugaresi, A, Lus, G, Maccarrone, G, Maimone, D, Malagù, S, Marconi, R, Maritato, P, Massacesi, L, Mazzoni, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Neri, W, Orefice, G, Parodi, S, Pasquali, L, Passarella, B, Patti, F, Peresson, M, Perla, F, Pesci, I, Piantadosi, C, Piras, Ml, Pizio, Nr, Pozzilli, C, Protti, A, Pugliatti, M, Quatrale, R, Ragno, M, Rezzonico, M, Ribizzi, G, Riva, M, Ronzoni, M, Rosso, Mg, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santangelo, M, Santangelo, G, Santuccio, G, Sarchielli, P, Scarpini, E, Sechi, Gp, Severi, S, Sinisi, L, Sola, P, Spitaleri, D, Tassinari, T, Tedeschi, G, Tonietti, S, Torri Clerici, V, Totaro, R, Traccis, S, Trojano, M, Turla, M, Uccelli, A, Ulivelli, M, Valentino, P, Valeriani, M, Venturi, S, Vianello, M, Zaffaroni, M., Amato, M, Ghezzi, A, Lepore, V, Marrosu, M, Mosconi, P, Ponzio, M, Zaratin, P, Battaglia, M, Bossio, R, Brioschi, A, Caniatti, L, Celani, M, Coniglio, M, D’Andrea, F, Danni, M, Ferrò, M, Grasso, M, Grimaldi, L, Logullo, F, Piras, M, Pizio, N, Rosso, M, Sechi, G, and Zaffaroni, M

Subjects
Register (sociolinguistics), Adult, Male, Knowledge management, Databases, Factual, Epidemiology, media_common.quotation_subject, Disease epidemiology, Multiple sclerosis, Quality of care, Register, Longitudinal Studie, Dermatology, NO, Cohort Studies, Databases, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosi, Humans, Quality (business), Longitudinal Studies, 030212 general & internal medicine, Registries, Epidemiology, Multiple sclerosis, Quality of care, Register, Adult, Cohort Studies, Data Collection, Databases, Factual, Female, Humans, Italy, Longitudinal Studies, Male, Multiple Sclerosis, Registries, Factual, media_common, Data collection, business.industry, Data Collection, Correction, Female, Italy, Multiple Sclerosis, General Medicine, Register data, Psychiatry and Mental Health, Observational study, Original Article, Settore MED/26 - Neurologia, Business, Neurology (clinical), Cohort Studie, 030217 neurology & neurosurgery, 2708, Human
Abstract

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups. The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups.

Published
2019

6. Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia

Author

Nemni, R, Sanvito, L, Quattrini, A, Santuccio, G, Camerlingo, M, and Canal, N

Subjects
Polyneuropathies -- Diagnosis, Cryoglobulinemia -- Physiological aspects -- Diagnosis, Hepatitis C virus -- Physiological aspects -- Analysis, Statistics -- Analysis -- Physiological aspects, Diseases -- Causes and theories of causation, Health, Psychology and mental health, Diagnosis, Physiological aspects, Analysis
Abstract

Objectives: Hepatitis C virus (HCV) infection is often associated with cryoglobulinaemia (CG). Peripheral neuropathy (PN) is a comparatively common complication of CG associated with HCV infection and it is thought [...]

Published
2003

8. No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML

Author

Landi, Doriana, De Rossi, Nicola, Zagaglia, Sara, Scarpazza, Cristina, Prosperini, Luca, Albanese, Maria, Buttari, Fabio, Mori, Francesco, Marfia, Girolama Alessandra, Sormani, Maria Pia, Capra, Ruggero, Centonze, Diego, the Italian PML Study group Amato, Maria Pia, Bandini, F, Bertolotto, Antonio, Brescia-Morra, Vincenzo, Cavaletti, G, Cavalla, Paola, Capobianco, Marco, Clerico, Marinella, D'Aleo, G, De Riz, M, Deotto, L, Durelli, Luca, Falcini, M, Ferrari, E, Fusco, ML, Gasperini, C, Gerevini, S, Ghezzi, A, Grimaldi, L, Guidotti, M, Lugaresi, A, Naldi, P, Moiola, Lucia, Perrone, P, Pizzorno, M, Pozzilli, C, Rezzonico, M, Rovaris, M, Salemi, G, Salvetti, M, Santuccio, G, Scarpini, E, Sessa, E, Solaro, C, Tabiadon, G, Tortorella, C, Trojano M., Landi, Doriana, De Rossi, Nicola, Zagaglia, Sara, Scarpazza, Cristina, Prosperini, Luca, Albanese, Maria, Buttari, Fabio, Mori, Francesco, Marfia, Girolama Alessandra, Sormani, Maria Pia, Capra, Ruggero, Centonze, Diego, Brescia Morra, Vincenzo, the Italian PML Study group Amato, Maria Pia, Bandini, F, Bertolotto, Antonio, Brescia-Morra, Vincenzo, Cavaletti, G, Cavalla, Paola, Capobianco, Marco, Clerico, Marinella, D'Aleo, G, De Riz, M, Deotto, L, Durelli, Luca, Falcini, M, Ferrari, E, Fusco, ML, Gasperini, C, Gerevini, S, Ghezzi, A, Grimaldi, L, Guidotti, M, Lugaresi, A, Naldi, P, Moiola, Lucia, Perrone, P, Pizzorno, M, Pozzilli, C, Rezzonico, M, Rovaris, M, Salemi, G, Salvetti, M, Santuccio, G, Scarpini, E, Sessa, E, Solaro, C, Tabiadon, G, Tortorella, C, Trojano M., Landi, D, De Rossi, N, Zagaglia, S, Scarpazza, C, Prosperini, L, Albanese, M, Buttari, F, Mori, F, Marfia, G, Sormani, M, Capra, R, Centonze, D, Amato, M, Bertolotto, A, Brescia Morra, V, Cavalla, P, Capobianco, M, Clerico, M, de Riz, M, Durelli, L, Fusco, M, Moiola, L, and Trojano, M

Subjects
Oncology, Male, JC virus, 030204 cardiovascular system & hematology, medicine.disease_cause, Leukoencephalopathy, Disability Evaluation, neurology (clinical), progressive multifocal leukoencephalopathy, reconstitution inflammatory syndrome, multiple-sclerosis, 0302 clinical medicine, Natalizumab, Immunologic Factor, Retrospective Studie, Multiple Sclerosi, Medicine, Plasmapheresi, Adult, Female, Humans, Immunologic Factors, Leukoencephalopathy, Progressive Multifocal, Middle Aged, Multiple Sclerosis, Plasmapheresis, PubMed, Retrospective Studies, Statistics, Nonparametric, Treatment Outcome, Progressive multifocal leukoencephalopathy, Statistics, Settore MED/26 - Neurologia, medicine.drug, Human, medicine.medical_specialty, Progressive Multifocal, 03 medical and health sciences, Immune reconstitution inflammatory syndrome, Internal medicine, Nonparametric, progressive multifocal leukoencephalopathy, multiple sclerosis, side effect, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Retrospective cohort study, medicine.disease, Immunology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective:To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)–associated progressive multifocal leukoencephalopathy (PML).Methods:The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution. The effects on survival and clinical outcome of PLEX, sex, age, country, pre-PML Expanded Disability Status Scale score, NTZ infusion number, prior immunosuppressant exposure, PML symptoms, PML lesion location at diagnosis, CSF JC virus status and copies, additional PML treatments and steroids, and PML immune reconstitution inflammatory syndrome (IRIS) development were investigated with both univariate and multivariate analyses.Results:A total of 219 NTZ-PML cases were analyzed, and 184 (84%) underwent PLEX, which did not reduce the mortality risk or the likelihood of poor vs favorable outcomes. Country was predictive of mortality and poor outcome, while PML-IRIS development was predictive of poor outcome.Conclusions:PLEX did not improve the survival or clinical outcomes of Italian or international patients with MS and NTZ-PML, suggesting that this treatment should be performed cautiously in the future.Classification of evidence:This study provides Class III evidence that for patients with NTZ-PML, PLEX does not improve survival. The study lacks the statistical precision to exclude an important benefit or harm of PLEX.

Published
2017

9. Cortical/Subcortical Disease Burden and Cognitive Impairment in Patients with Multiple Sclerosis

Author

marco rovaris, Filippi, M., Minicucci, L., Iannucci, G., Santuccio, G., Possa, F., Comi, G., Rovaris, M, Filippi, Massimo, Minicucci, L, Iannucci, G, Santuccio, G, Possa, F, and Comi, Giancarlo

Subjects
Adult, Cerebral Cortex, Male, Letter, Multiple Sclerosis, Brain, Middle Aged, Neuropsychological Tests, Image Enhancement, Magnetic Resonance Imaging, Radiography, Neurology, Humans, Female, Cognition Disorders, Technology, Radiologic, Follow-Up Studies
Abstract

BACKGROUND AND PURPOSE: We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS). METHODS: Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis. RESULTS: All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment. CONCLUSION: The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.

Published
2000

12. Evoked potentials in diagnosis and monitoring of multiple sclerosis

Author

Comi, G., Letizia Leocani, Medaglini, S., Locatelli, T., Martinelli, V., Santuccio, G., Rossi, P., Comi, G, Leocani, ANNUNZIATA MARIA LETIZIA, Medaglini, S, Locatelli, T, Martinelli, V, Santuccio, G, and Rossi, P.

Subjects
Multiple Sclerosis, Evoked Potentials, Somatosensory, Humans, Evoked Potentials, Motor
Published
1999

13. Evidence of interferon beta-1a dose response in relapsing-remitting MS - The OWIMS study

Author

Ebers, G., Lee, D., Rice, G., Lesaux, J., Kennedy, K., Sanders, Eacm, Versteylen, Rj, Andel, Jd, Story, Jp, Milliano, M., O Connor, P., Cheung, G., Houston, P., Hall, J., Comi, G., Massimo Filippi, Martinelli, V., Santuccio, G., Poggi, A., Gironi, M., Moiola, L., Duquette, P., Bourgouin, P., Pepin, G., Poirer, J., Bernier, G., Dubois, R., Metz, L., Diamond, Rt, Bell, R., Mcgowan, D., Demchuk, A., Harris, E., Yeung, M., Murphy, A., Murray, Tj, Vandorpe, R., Bhan, V., Maxner, C., Weldon, P., Armstrong, L., Bouchard, Jp, Grondin, P., Gosselin, F., Thibaut, M., Kirouac, L., Morin, A., Abramsky, O., Gomori, Jm, Karussis, D., Karni, A., Mor, M., Freedman, Ms, Avruch, L., Nelson, R., Christie, S., Rabinovitch, H., Freedman, C., Benavente, M., Pelletier, J., Levrier, O., Bensa, P., Dalesky, A., Paty, D., Li, D., Rhodes, B., Riddehough, A., Zhao, G., Wang, X., Chang, Y., Abdul-Ahad, A., Ammoury, N., Dupont, F., Francis, G., Furcha, R., Galazka, A., Hyde, R., Olson, M., Pernin, Mo, Shah, S., Freedman, M., Murray, J., Ebers, G, Lee, D, Rice, G, Lesaux, J, Kennedy, K, Sanders, Eacm, Versteylen, Rj, van Andel, Jd, Story, Jp, de Milliano, M, O'Connor, P, Cheung, G, Houston, P, Hall, J, Comi, G, Filippi, Massimo, Martinelli, V, Santuccio, G, Poggi, A, Gironi, M, Moiola, L, Duquette, P, Bourgouin, P, Pepin, G, Poirer, J, Bernier, G, Dubois, R, Metz, L, Diamond, Rt, Bell, R, Mcgowan, D, Demchuk, A, Harris, E, Yeung, M, Murphy, A, Murray, Tj, Vandorpe, R, Bhan, V, Maxner, C, Weldon, P, Armstrong, L, Bouchard, Jp, Grondin, P, Gosselin, F, Thibaut, M, Kirouac, L, Morin, A, Abramsky, O, Gomori, Jm, Karussis, D, Karni, A, Mor, M, Freedman, M, Avruch, L, Nelson, R, Christie, S, Rabinovitch, H, Freedman, C, Benavente, M, Pelletier, J, Levrier, O, Bensa, P, Dalesky, A, Paty, D, Li, D, Rhodes, B, Riddehough, A, Zhao, G, Wang, X, Chang, Y, Abdul Ahad, A, Ammoury, N, Dupont, F, Francis, G, Furcha, R, Galazka, A, Hyde, R, Olson, M, Pernin, Mo, Shah, S, Murray, J, and Francis, G.

Published
1999

14. Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis

Author

Rovaris, M., Comi, G., Maria A Rocca, Cercignani, M., Colombo, B., Santuccio, G., Filippi, M., Rovaris, M, Comi, G, Rocca, Ma, Cercignani, M, Colombo, B, Santuccio, G, and Filippi, M

Subjects
Adult, Male, Multiple Sclerosis, Recurrence, Disease Progression, Brain, Humans, Female, Middle Aged, Magnetic Resonance Imaging, Aged
Abstract

BACKGROUND AND PURPOSE: Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures. METHODS: Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS). RESULTS: Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1–22); their median load was 1.4 mL (range, 0.05–12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense lesions shown by fast FLAIR imaging were significantly higher in patients with secondary progressive MS. Significant correlations were found between Expanded Disability Status Scale scores and MR lesion load. A multivariate analysis showed that only the presence of hypointense lesions on fast FLAIR images significantly separated cases of relapsing-remitting MS from cases of secondary progressive MS (relative risk, 7.1; 95% confidence interval, 2.0–25.9). CONCLUSION: The presence of hypointense lesions on fast FLAIR images was a strong predictor of disease severity in cases of MS, although the low sensitivity of this approach might limit its use for the assessment of MS evolution.

Published
1999

20. Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis.

Author

Rovaris, M, Bozzali, M, Santuccio, G, Iannucci, G, Sormani, M P, Colombo, B, Comi, G, and Filippi, M

Abstract

Objective: To assess (a) the correlations between magnetisation transfer ratio (MTR) histogram derived measures of the brain and the cervical cord from patients with different multiple sclerosis phenotypes and (b) the correlation between these metrics and clinical disability. Magnetisation transfer imaging is sensitive to the most destructive aspects of multiple sclerosis pathology. Magnetisation transfer ratio histogram analysis encompasses the macroscopic and the microscopic lesion burdens.Methods: Seventy seven patients with multiple sclerosis were studied (40 relapsing-remitting (RR), 28 secondary progressive (SP), and nine primary progressive (PP)). For the brain, we obtained dual echo, T1 weighted, and gradient echo (GE) scans (with and without an MT saturation pulse). For the cervical cord, fast short tau inversion recovery (STIR) and GE scans (with and without an MT saturation pulse) were obtained. Brain T2 and T1 weighted lesion volumes (LVs) were measured. The number and length of cord lesions on fast STIR scans were assessed. Magnetisation transfer ratio maps were created from GE images and MTR histograms of the entire brain and cervical cord were obtained.Results: Brain T1 LV, and number and size of cord lesions were significantly higher and brain MTR histogram peak location was significantly lower in patients with SPMS than those with RRMS or PPMS. Cord MTR histogram peak location was also significantly lower in patients with SPMS than in those with RRMS. The univariate correlations between MTR histogram derived metrics obtained from the brain and the cervical cord were all non-significant, with the exception of that between average brain MTR and cord MTR histogram peak location. On a multivariable analysis, both increasing brain T2 LV and decreasing cord MTR histogram peak location values were significantly associated with a higher probability for patients to have SPMS or to have locomotor disability.Conclusions: This study shows that the extent and severity of tissue damage in the brain and cervical cord are both relevant to determine disability in multiple sclerosis and that the assessment of brain and cord pathology provides complementary information. [ABSTRACT FROM AUTHOR]

Published
2000
Full Text
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21. Measuring evoked responses in multiple sclerosis.

Author

Comi, G., Leocani, L., Medaglini, S., Locatelli, T., Martinelli, V., Santuccio, G., and Rossi, P.

Subjects
MULTIPLE sclerosis treatment, EVOKED potentials (Electrophysiology), MAGNETIC resonance imaging, PROGNOSIS
Abstract

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
1999
Full Text
View/download PDF

24. MS Italian patients manifesting natalizumab-related PML between 2009 and 2014. Report of the Italian group for MS-PML study

Author

Rossi, N., Cordioli, C., simonetta gerevini, Amato, M. P., Bandini, F., Cavalla, P., Clerico, M., Capobianco, M., Deotto, L., Riz, M. A., Ferrari, E., Scarpazza, C., Fusco, M. L., Ghezzi, A., Grimaldi, L., Lugaresi, A., Moiola, L., Perrone, P., Prosperini, L., Rezzonico, M., Rovaris, M., Salemi, G., Salvetti, M., Santuccio, G., Solaro, C., Tortorella, C., and Capra, R.

28. The still under-investigated role of cognitive deficits in PML diagnosis

Author

Scarpazza, Cristina, De Rossi, Nicola, Moiola, Lucia, Gerevini, Simonetta, Cosottini, Mirco, Capra, Ruggero, Mattioli, Flavia, Amato, Maria Pia, Artusi, Carlo Alberto, Bandini, Fabio, Barcella, Valeria, Bertolotto, Antonio, Bresciamorra, Vincenzo, Capobianco, Marco, Cavaletti, Guido, Cavalla, Paola, Centonze, Diego, Clerico, Marinella, Cordioli, Cinzia, D'Aleo, Giangaetano, de Riz, Marilena, Deotto, Luciano, Durelli, Luca, Falcini, Mario, Ferrari, Ernesta, Fusco, Maria Luisa, Gasperini, Claudio, Ghezzi, Angelo, Grimaldi, Luigi, Guidotti, Mario, Laroni, Alice, Lugaresi, Alessandra, Naldi, Paola, Pane, Chiara, Perrone, Patrizia, Pizzorno, Matteo, Pozzilli, Carlo, Prosperini, Luca, Rezzonico, Monica, Rovaris, Marco, Salemi, Giuseppe, Salvetti, Marco, Santuccio, Giuseppe, Scarpini, Elio, Sessa, Edoardo, Solaro, Claudio, Tabiadon, Giulia, Tortorella, Carla, Trojano, Maria, Valentino, Paola, Scarpazza C, De Rossi N, Gerevini S, Cosottini M, Capra R, Mattioli F, Amato MP, Artusi CA, Bandini F, Barcella V, Bertolotto A, Bresciamorra V, Capobianco M, Cavaletti G, Cavalla P, Centonze D, Clerico M, Cordioli C, D’Aleo G, de Riz M, Deotto L, Durelli L, Falcini M, Ferrari E, Fusco ML, Gasperini C, Ghezzi A, Grimaldi L, Guidotti M, Laroni A, Lugaresi A, Naldi P, Pane C, Perrone P, Pizzorno M, Pozzilli C, Prosperini L, Rezzonico M, Rovaris M, Salemi G, Salvetti M, Santuccio G, Scarpini E, Sessa E, Solaro C, Tabiadon G, Tortorella C, Trojano M, Valentino P., Scarpazza, C, De Rossi, N, Moiola, L, Gerevini, S, Cosottini, M, Capra, R, Mattioli, F, Amato, M, Artusi, C, Bandini, F, Barcella, V, Bertolotto, A, Bresciamorra, V, Capobianco, M, Cavaletti, G, Cavalla, P, Centonze, D, Clerico, M, Cordioli, C, D'Aleo, G, de Riz, M, Deotto, L, Durelli, L, Falcini, M, Ferrari, E, Fusco, M, Gasperini, C, Ghezzi, A, Grimaldi, L, Guidotti, M, Laroni, A, Lugaresi, A, Naldi, P, Pane, C, Perrone, P, Pizzorno, M, Pozzilli, C, Prosperini, L, Rezzonico, M, Rovaris, M, Salemi, G, Salvetti, M, Santuccio, G, Scarpini, E, Sessa, E, Solaro, C, Tabiadon, G, Tortorella, C, Trojano, M, and Valentino, P

Subjects
0301 basic medicine, cognition, medicine.medical_specialty, Pediatrics, italian database, natalizumab, neuropsychological impairment, progressive multifocal leukoencephalopathy, neurology (clinical), neurology, immunology, immunology and allergy, Neurology, Settore MED/17 - Malattie Infettive, Asymptomatic, Apraxia, 03 medical and health sciences, 0302 clinical medicine, medicine, Dementia, Psychiatry, Cognitive deficit, Progressive multifocal leukoencephalopathy, Neuropsychology, Cognition, Progressive multifocal leukoencephalopathy Natalizumab Cognition Neuropsychological impairment Italian database, medicine.disease, 030104 developmental biology, Italian database, Natalizumab, Neuropsychological impairment, Cognition, Italian database, Natalizumab, Neuropsychological impairment, Progressive multifocal leukoencephalopathy, Immunology and Allergy, Immunology, Neurology (clinical), Settore MED/26 - Neurologia, medicine.symptom, Psychology, 030217 neurology & neurosurgery
Abstract

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment.

Published
2017

29. Early diagnosis of progressive multifocal leucoencephalopathy: Longitudinal lesion evolution

Author

Scarpazza, Cristina, Signori, Alessio, Prosperini, Luca, Sormani, Maria Pia, Cosottini, Mirco, Capra, Ruggero, Gerevini, Simonetta, Altieri, Marta, Amato, Maria Pia, Artusi, Carlo Alberto, Bandini, Fabio, Barcella, Valeria, Bertolotto, Antonio, Morra, Vincenzo Brescia, Capobianco, Marco, Cavaletti, Guido, Cavalla, Paola, Centonze, Diego, Chiusole, Maurizia, Clerico, Marinella, Cordioli, Cinzia, D'Aleo, Giangaetano, De Luca, Giovanna, De Riz, Milena, De Rossi, Nicola, Deotto, Luciano, Durelli, Luca, Falcini, Mario, Ferrante, Claudio, Ferrari, Ernesta, Fusco, Maria Luisa, Gasperini, Claudio, Ghezzi, Angelo, Grimaldi, Luigi, Guidotti, Mario, Laroni, Alice, Lugaresi, Alessandra, Moiola, Lucia, Naldi, Paola, Pane, Chiara, Palmeri, Barbara, Perrone, Patrizia, Pizzorno, Matteo, Pozzilli, Carlo, Rezzonico, Monica, Rottoli, Maria Rosa, Rovaris, Marco, Salemi, Giuseppe, Salvetti, Marco, Santuccio, Giuseppe, Scarpini, Elio, Sessa, Edoardo, Solaro, Claudio, Stenta, Gianola, Tabiadon, Giulietta, Tortorella, Carla, Trojano, Maria, Valentino, Paola, Rottoli, Maira Rosa, Scarpazza, C, Signori, A, Prosperini, L, Sormani, M, Cosottini, M, Capra, R, Gerevini, S, Altieri, M, Amato, M, Artusi, C, Bandini, F, Barcella, V, Bertolotto, A, Morra, V, Capobianco, M, Cavaletti, G, Cavalla, P, Centonze, D, Chiusole, M, Clerico, M, Cordioli, C, D'Aleo, G, De Luca, G, De Riz, M, De Rossi, N, Deotto, L, Durelli, L, Falcini, M, Ferrante, C, Ferrari, E, Fusco, M, Gasperini, C, Ghezzi, A, Grimaldi, L, Guidotti, M, Laroni, A, Lugaresi, A, Moiola, L, Naldi, P, Pane, C, Palmeri, B, Perrone, P, Pizzorno, M, Pozzilli, C, Rezzonico, M, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santuccio, G, Scarpini, E, Sessa, E, Solaro, C, Stenta, G, Tabiadon, G, Tortorella, C, Trojano, M, and Valentino, P

Subjects
natalizumab treatment, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Surgery, Neurology (clinical), Psychiatry and Mental Health, natalizumab, progressive multifocal leucoencephalopathy, Progressive Multifocal, Lesion, Leukoencephalopathy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Psychiatry and Mental Health, progressive multifocal leucoencephalopathy, medicine, Humans, Immunologic Factors, Young adult, Progressive multifocal leucoencephalopathy, Retrospective Studies, medicine.diagnostic_test, business.industry, Multiple sclerosis, Natalizumab, Leukoencephalopathy, Progressive Multifocal, Magnetic resonance imaging, Retrospective cohort study, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Early Diagnosis, Female, Italy, Cohort, Settore MED/26 - Neurologia, Radiology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

ObjectiveEarly diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed a major priority by the regulatory agencies but has yet to become a reality. The current paper aims to: (1) investigate whether patients with NTZ-PML pass through a prolonged presymptomatic phase with MRI abnormalities, (2) estimate the longitudinal PML lesion volume increase during the presymptomatic phase and (3) estimate the presymptomatic phase length and its impact on therapy duration as a risk stratification parameter.MethodsAll Italian patients who developed NTZ-PML between 2009 and 2018 were included. The data of patients with available prediagnostic MRI were analysed (n=41). Detailed clinical and neuroradiological information was available for each participant.Results(1) PML lesions were detectable in the presymptomatic phase in 32/41 (78%) patients; (ii) the lesion volume increased by 62.8 % for each month spent in the prediagnostic phase; (3) the prediagnostic phase length was 150.8±74.9 days; (4) PML MRI features were detectable before the 24th month of therapy in 31.7 % of patients in our cohort.ConclusionsConsidering the latency of PML clinical manifestation, the presymptomatic phase length supports the usefulness of MRI surveillance every 3–4 months. Early diagnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.

Published
2019

30. To do or not to do? plasma exchange and timing of steroid administration in progressive multifocal leukoencephalopathy

Author

Scarpazza, Cristina, Prosperini, Luca, De Rossi, Nicola, Moiola, Lucia, Sormani, Maria Pia, Gerevini, Simonetta, Capra, Ruggero, Altieri, Marta, Amato, Maria Pia, Artusi, Carlo Alberto, Bandini, Fabio, Barcella, Valeria, Bertolotto, Antonio, Morra, Vincenzo Brescia, Capobianco, Marco, Cavaletti, Guido, Cavalla, Paola, Centonze, Diego, Clerico, Marinella, Cocco, Eleonora, Cordioli, Cinzia, Cosottini, Mirco, D'Aleo, Giangaetano, de Luca, Giovanna, de Riz, Marilena, Deotto, Luciano, Durelli, Luca, Falcini, Mario, Ferrari, Ernesta, Ferrante, Claudio, Fusco, Maria Luisa, Gasperini, Claudio, Ghezzi, Angelo, Grimaldi, Luigi, Guidotti, Mario, Laroni, Alice, Lugaresi, Alessandra, Naldi, Paola, Pane, Chiara, Perrone, Patrizia, Pizzorno, Matteo, Pozzilli, Carlo, Rezzonico, Monica, Rovaris, Marco, Salemi, Giuseppe, Salvetti, Marco, Santuccio, Giuseppe, Scarpini, Elio, Sessa, Edoardo, Solaro, Claudio, Tabiadon, Giulia, Tortorella, Carla, Trojano, Maria, Valentino, Paola, Scarpazza, Cristina, Prosperini, Luca, De Rossi, Nicola, Moiola, Lucia, Sormani, Maria Pia, Gerevini, Simonetta, and Capra, Ruggero, Amato MP, Artusi CA, Bandini F, Barcella V, Bertolotto A, Bresciamorra V, Capobianco M, Cavaletti G, Cavalla P, Centonze D, Clerico M, Cordioli C, D’Aleo G, de Riz M, Deotto L, Durelli L, Falcini M, Ferrari E, Fusco ML, Gasperini C, Ghezzi A, Grimaldi L, Guidotti M, Laroni A, Lugaresi A, Naldi P, Pane C, Perrone P, Pizzorno M, Pozzilli C, Prosperini L, Rezzonico M, Rovaris M, Salemi G, Salvetti M, Santuccio G, Scarpini E, Sessa E, Solaro C, Tabiadon G, Tortorella C, Trojano M, Valentino P

Subjects
Adult, Male, Databases, Factual, Disability Evaluation, Female, Humans, Immune Reconstitution Inflammatory Syndrome, Leukoencephalopathy, Progressive Multifocal, Plasma Exchange, Retrospective Studies, Steroids, Young Adult, Neurology, Neurology (clinical), Progressive Multifocal, Databases, Leukoencephalopathy, Retrospective Studie, Settore MED/26 - Neurologia, Steroid, Factual, Human
Abstract

OBJECTIVE: To retrospectively analyze the effect of plasma exchange (PLEX; yes = PLEX+ , no = PLEX- ) and steroids administration timing (prophylactically [proST] or therapeutically [therST]) on the longitudinal clinical course of patients with natalizumab-related progressive multifocal leukoencephalopathy (PML) and full-blown immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: Clinical and radiological data of 42 Italian patients with PML were analyzed. Patient's data are available until 12 months after PML diagnosis. PLEX and steroids treatment as time-dependent covariates were entered in: (1) a Cox model to investigate their impact on full-blown PML-IRIS latency; (2) an analysis of variance ANOVA to investigate their impact on IRIS duration; and (3) a linear mixed model to assess their impact on the longitudinal clinical course (measured by means of Expanded Disability Status Scale [EDSS]). RESULTS: Treatment with PLEX was not associated to PML-IRIS latency (hazard ratio [HR] = 1.05; p = 0.92), but once IRIS emerged, its duration was significantly longer in patients who underwent PLEX (101 vs 54 days in PLEX+ and PLEX- patients; p = 0.028). Receiving proST versus therST was not associated to IRIS latency (HR = 0.67; p = 0.39) or duration (p = 0.95). Patients who underwent proST had a significantly higher EDSS increase during PML (0.09 EDSS points per month; p = 0.04) as compared to those who had therST. INTERPRETATION: This study highlights that: (1) caution on the use of PLEX should be considered as the current data do not support a beneficial effect of PLEX and (2) caution on the early use of steroids is suggested because their prophylactic use to prevent full-blown PML-IRIS seems to negatively impact on the longitudinal disability course.

Published
2017

31. Measuring evoked responses in multiple sclerosis

Author

Paolo Rossi, T. Locatelli, Letizia Leocani, Giancarlo Comi, Vittorio Martinelli, Stefania Medaglini, Giuseppe Santuccio, Comi, Giancarlo, Leocani, ANNUNZIATA MARIA LETIZIA, Medaglini, S, Locatelli, T, Martinelli, V, Santuccio, G, and Rossi, P.

Subjects
Multiple Sclerosis, Central nervous system, Disease, Lesion, Central nervous system disease, 03 medical and health sciences, 0302 clinical medicine, Reaction Time, medicine, Humans, Longitudinal Studies, 030212 general & internal medicine, Evoked potential, Evoked Potentials, Clinical Trials as Topic, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Hyperthermia, Induced, medicine.disease, Magnetic Resonance Imaging, Electrophysiology, medicine.anatomical_structure, Neurology, Somatosensory evoked potential, Disease Progression, Neurology (clinical), medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.

Published
1999

32. Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis

Author

G Santuccio, Giancarlo Comi, Maria Pia Sormani, Bruno Colombo, G. Iannucci, Marco Bozzali, Massimo Filippi, Marco Rovaris, Rovaris, M, Bozzali, M, Santuccio, G, Iannucci, G, Sormani, Mp, Colombo, B, Comi, G, and Filippi, M

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Cord, Central nervous system disease, Lesion, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Histogram, Humans, Medicine, Magnetization transfer, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Middle Aged, medicine.disease, Spinal cord, Magnetic Resonance Imaging, Editorial Commentary, Psychiatry and Mental health, medicine.anatomical_structure, Spinal Cord, Papers, Female, Surgery, Neurology (clinical), medicine.symptom, business
Abstract

OBJECTIVE To assess ( a ) the correlations between magnetisation transfer ratio (MTR) histogram derived measures of the brain and the cervical cord from patients with different multiple sclerosis phenotypes and ( b ) the correlation between these metrics and clinical disability. Magnetisation transfer imaging is sensitive to the most destructive aspects of multiple sclerosis pathology. Magnetisation transfer ratio histogram analysis encompasses the macroscopic and the microscopic lesion burdens. METHODS Seventy seven patients with multiple sclerosis were studied (40 relapsing-remitting (RR), 28 secondary progressive (SP), and nine primary progressive (PP)). For the brain, we obtained dual echo, T1 weighted, and gradient echo (GE) scans (with and without an MT saturation pulse). For the cervical cord, fast short tau inversion recovery (STIR) and GE scans (with and without an MT saturation pulse) were obtained. Brain T2 and T1 weighted lesion volumes (LVs) were measured. The number and length of cord lesions on fast STIR scans were assessed. Magnetisation transfer ratio maps were created from GE images and MTR histograms of the entire brain and cervical cord were obtained. RESULTS Brain T1 LV, and number and size of cord lesions were significantly higher and brain MTR histogram peak location was significantly lower in patients with SPMS than those with RRMS or PPMS. Cord MTR histogram peak location was also significantly lower in patients with SPMS than in those with RRMS. The univariate correlations between MTR histogram derived metrics obtained from the brain and the cervical cord were all non-significant, with the exception of that between average brain MTR and cord MTR histogram peak location. On a multivariable analysis, both increasing brain T2 LV and decreasing cord MTR histogram peak location values were significantly associated with a higher probability for patients to have SPMS or to have locomotor disability. CONCLUSIONS This study shows that the extent and severity of tissue damage in the brain and cervical cord are both relevant to determine disability in multiple sclerosis and that the assessment of brain and cord pathology provides complementary information.

Published
2000

33. A multiparametric MRI study of frontal lobe dementia in multiple sclerosis

Author

Giuseppe Santuccio, Vittorio Martinelli, Francesca Possa, Eraldo Paulesu, Massimo Filippi, Monica Falautano, Maria A. Rocca, Marco Rovaris, Letizia Leocani, Giancarlo Comi, Comi, Giancarlo, Rovaris, M, Falautano, M, Santuccio, G, Martinelli, V, Rocca, Ma, Possa, F, Leocani, ANNUNZIATA MARIA LETIZIA, Paulesu, E, Filippi, Massimo, Comi, G, Rocca, M, Leocani, L, and Filippi, M

Subjects
medicine.medical_specialty, Multiple Sclerosis, MRI, Neuropsychological Tests, Nerve Fibers, Myelinated, White matter, Central nervous system disease, medicine, Dementia, Humans, Multiple sclerosi, Cognitive decline, medicine.diagnostic_test, business.industry, Multiple sclerosis, Cognitive disorder, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Surgery, Frontal Lobe, medicine.anatomical_structure, Neurology, Frontal lobe, Neurology (clinical), Nuclear medicine, business, Psychology, Follow-Up Studies
Abstract

Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.

Published
1999

34. EEG correlates of cognitive impairment in MS

Author

Letizia Leocani, Vittorio Martinelli, G. Comi, Massimo Filippi, Giuseppe Santuccio, Francesca Possa, Monica Falautano, Marco Rovaris, Giuseppe Magnani, T. Locatelli, Leocani, ANNUNZIATA MARIA LETIZIA, Magnani, G, Locatelli, T, Martinelli, V, Rovaris, M, Filippi, Massimo, Falautano, M, Santuccio, G, Possa, F, and Comi, Giancarlo

Subjects
medicine.medical_specialty, Neurology, Subcortical dementia, Dermatology, Electroencephalography, Audiology, Multiple sclerosis, medicine, EEG, Reaction time, medicine.diagnostic_test, General Neuroscience, Neuropsychology, Magnetic resonance imaging, General Medicine, medicine.disease, Psychiatry and Mental health, Cognitive impairment, Frontal lobe, Movement-related potentials, Neurology (clinical), Psychology, Neuroscience, Coherence, Stroop effect
Abstract

Cognitive impairment is a frequent complication of multiple sclerosis (MS), generally reflecting subcortical dementia. In order to explore functional cortico-cortical connections in MS, we studied electroencephalogram (EEG) coherence in a group of 21 clinically defined MS patients. Patients also underwent magnetic resonance imaging (MRI) and neuropsychological examinations. Compared to unimpaired MS patients, cognitively involved patients had reduced short-distance and long-distance theta and alpha band coherencies. Anteroposterior and interhemispheric coherencies were significantly correlated with MRI lesion load immediately underlying cortex but not were exclusively associated with periventricular lesions. These data support the hypothesis that cognitive impairment in MS is mostly related to demyelination or axonal loss of cortico-cortical connections. In a second study, we evaluated the neurophysiological correlates of frontal lobe dysfunction. Frontal lobes are also involved in motor planning and execution. We evaluated the EEG movement-related potential (MRP) in MS patients with and without frontal neuropsychological deficits. Reaction times to the Stroop test, which evaluates frontal functions, and MRP components were delayed in both MS groups compared to normal subjects and in frontal compared to nonfrontal MS patients. These data suggest that frontal cognitive involvement in MS corresponds to abnormal bioelectrical activity also during simple motor tasks. © Springer-Verlag 1998.

Published
1998

35. In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis

Author

Giuseppe Santuccio, Marco Bozzali, Gianluigi Mancardi, Antonio Bertolotto, Massimo Filippi, Vittorio Martinelli, Roberto Bergamaschi, Giancarlo Comi, Enrico Montanari, Ruggero Capra, Marco Rovaris, Domenico Caputo, Angelo Ghezzi, Rovaris, M, Bozzali, M, Santuccio, G, Ghezzi, A, Caputo, D, Montanari, E, Bertolotto, A, Bergamaschi, R, Capra, R, Mancardi, G, Martinelli, V, Comi, Giancarlo, and Filippi, Massimo

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Cord, Multiple Sclerosis, Central nervous system disease, Lesion, Atrophy, medicine, Humans, Aged, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Multiple Sclerosis, Chronic Progressive, Middle Aged, medicine.disease, Spinal cord, Magnetic Resonance Imaging, medicine.anatomical_structure, Chronic Progressive, Spinal Cord, Cervical Vertebrae, pathology, Female, Neurology (clinical), medicine.symptom, business, Adult, Aged, Brain, pathology, Cervical Vertebrae, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, pathology, Spinal Cord, Cervical vertebrae
Abstract

In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivo indirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T(1)-weighted sequences. For the brain, T(2) hyperintense and T(1) hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.

36. Monocyte-to-platelets ratio (MPR) at diagnosis is associated with inferior progression-free survival in patients with mantle cell lymphoma: a multi-center real-life survey.

Author

Duminuco A, Romano A, Ferrarini I, Santuccio G, Chiarenza A, Figuera A, Caruso LA, Motta G, Palumbo GA, Mogno C, Moioli A, Di Raimondo F, and Visco C

Subjects
Humans, Male, Female, Aged, Middle Aged, Blood Platelets pathology, Aged, 80 and over, Adult, Progression-Free Survival, Retrospective Studies, Platelet Count, Prognosis, Italy epidemiology, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell diagnosis, Lymphoma, Mantle-Cell blood, Lymphoma, Mantle-Cell therapy, Monocytes pathology
Abstract

Mantle cell lymphoma (MCL) pathogenesis is strongly related to the role of the tumor immune microenvironment (TIME) in which MCL cells proliferate. TIME cells can produce growth signals influencing MCL cells' survival and exert an antitumoral immune response suppression. The activity of TIME cells might be mirrored by some ratios of peripheral blood cell subpopulations, such as the monocyte-to-platelet ratio (MPR). We reviewed the clinical features of 165 consecutive MCL patients newly diagnosed and not eligible for autologous stem cell transplantation (both for age or comorbidities) who accessed two Italian Centers between 2006 and 2020. MPR was calculated using data obtained from the complete blood cell count at diagnosis before any cytotoxic treatment and correlated with PFS. Univariate analysis showed that MPR ≥ 3 was associated with inferior PFS (p = 0.02). Multivariate analysis confirmed that MPR ≥ 3, LDH > 2.5 ULN, and bone marrow involvement were significant independent variables in predicting PFS. For these reasons, MPR ≥ 3 seems the most promising prognostic factor in patients with MCL, and it could be considered a variable in new predictive models., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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37. Baseline IgM Amounts Can Identify Patients with Poor Outcomes: Results from a Real-Life Single-Center Study on Classical Hodgkin Lymphoma.

Author

Duminuco A, Santuccio G, Chiarenza A, Figuera A, Motta G, Caruso AL, Petronaci A, Ippolito M, Cerchione C, Di Raimondo F, and Romano A

Abstract

Hodgkin Lymphoma (HL) is characterized by an inflammatory background in which the reactive myeloid cells may exert an immune-suppressive effect related to the progression of the disease. Immunoglobulin M is the first antibody isotype produced during an immune response, which also plays an immunoregulatory role. Therefore, we investigated if, as a surrogate of defective B cell function, it could have any clinical impact on prognosis. In this retrospective, observational, single-center study, we evaluated 212 newly diagnosed HL patients, including 132 advanced-stage. A 50 mg/dL level of IgM at baseline resulted in 84.1% sensitivity and 45.5% specificity for predicting a complete response in the whole cohort (area under curve (AUC) = 0.62, p = 0.013). In multivariate analysis, baseline IgM ≤ 50 mg/dL and the presence of a large nodal mass (<7 cm) were independent variables able to predict the clinical outcome, while, after two cycles of treatment, IgM ≤ 50 mg/dL at baseline and PET-2 status were independent predictors of PFS. The amount of IgM at diagnosis is a valuable prognostic factor much earlier than PET-2, and it can also provide information for PET-2-negative patients. This can help to identify different HL classes at risk of treatment failure at baseline.

Published
2024
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38. Two Years Follow up of Domain Specific Cognitive Training in Relapsing Remitting Multiple Sclerosis: A Randomized Clinical Trial.

Author

Mattioli F, Bellomi F, Stampatori C, Provinciali L, Compagnucci L, Uccelli A, Pardini M, Santuccio G, Fregonese G, Pattini M, Allegri B, Clerici R, Lattuada A, Montomoli C, Corso B, Gallo P, Riccardi A, Ghezzi A, Roscio M, Tola MR, Calanca C, Baldini D, Trafficante D, and Capra R

Abstract

Cognitive rehabilitation in multiple sclerosis (MS) has been reported to induce neuropsychological improvements, but the persistence of these effects has been scarcely investigated over long follow ups. Here, the results of a multicenter randomized clinical trial are reported, in which the efficacy of 15 week domain specific cognitive training was evaluated at 2 years follow up in 41 patients. Included patients were randomly assigned either to domain specific cognitive rehabilitation, or to aspecific psychological intervention. Patients who still resulted to be cognitively impaired at 1 year follow up were resubmitted to the same treatment, whereas the recovered ones were not. Neuropsychological tests and functional scales were administered at 2 years follow up to all the patients. Results revealed that both at 1 and at 2 years follow up more patients in the aspecific group (18/19, 94% and 13/17, 76% respectively) than in the specific group (11/22, 50% and 5/15, 33% respectively) resulted to be cognitively impaired. Furthermore patients belonging to the specific group showed significantly less impaired tests compared with the aspecific group ones (p = 0.02) and a significant amelioration in the majority of the tests. On the contrary patients in the aspecific group did not change. The specific group subjects also perceived a subjective improvement in their cognitive performance, while the aspecific group patients did not. These results showed that short time domain specific cognitive rehabilitation is a useful treatment for patients with MS, shows very long lasting effects, compared to aspecific psychological interventions. Also subjective cognitive amelioration was found in patients submitted to domain specific treatment after 2 years.

Published
2016
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39. A RCT Comparing Specific Intensive Cognitive Training to Aspecific Psychological Intervention in RRMS: The SMICT Study.

Author

Mattioli F, Stampatori C, Bellomi F, Danni M, Compagnucci L, Uccelli A, Pardini M, Santuccio G, Fregonese G, Pattini M, Allegri B, Clerici R, Lattuada A, Montomoli C, Corso B, and Capra R

Abstract

Background: Specific cognitive rehabilitation in multiple sclerosis (MS) resulted to be effective compared to no treatment. So far the possible role of an aspecific psychological intervention on cognition has not been investigated., Objective: The aim of the SMICT RCT was to compare the efficacy of a specific cognitive training with an aspecific psychological intervention in relapsing-remitting MS patients., Methods: From a sample of 150 patients, with the same disability and immunomodulatory therapy, submitted to neuropsychological examination, 45 impaired in at least one test were included and 41 randomized to have either a specific cognitive training for the impaired function (22) or to an aspecific psychological intervention (19) for 4 months, starting after baseline examination. Neuropsychological tests and functional scales were administered at baseline and 1 year later., Results: After 1 year, the mean number of pathological tests was significantly lower in the specific treatment group, compared to the aspecific group. Memory and attention/speeded information processing functions were mostly improved. Depression and quality of life were not different between groups at follow up., Conclusion: Our study demonstrates that an intensive and domain specific cognitive approach results to be more effective than aspecific psychological intervention in patients with MS.

Published
2015
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41. In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis.

Author

Rovaris M, Bozzali M, Santuccio G, Ghezzi A, Caputo D, Montanari E, Bertolotto A, Bergamaschi R, Capra R, Mancardi G, Martinelli V, Comi G, and Filippi M

Subjects
Adult, Aged, Cervical Vertebrae, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Brain pathology, Multiple Sclerosis, Chronic Progressive pathology, Spinal Cord pathology
Abstract

In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivo indirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T(1)-weighted sequences. For the brain, T(2) hyperintense and T(1) hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.

Published
2001
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42. Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis.

Author

Rovaris M, Filippi M, Minicucci L, Iannucci G, Santuccio G, Possa F, and Comi G

Subjects
Adult, Brain pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuropsychological Tests, Cerebral Cortex pathology, Cognition Disorders diagnosis, Image Enhancement, Magnetic Resonance Imaging, Multiple Sclerosis diagnosis
Abstract

Background and Purpose: We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS)., Methods: Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis., Results: All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment., Conclusion: The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.

Published
2000

43. Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis.

Author

Rovaris M, Comi G, Rocca MA, Cercignani M, Colombo B, Santuccio G, and Filippi M

Subjects
Adult, Aged, Disease Progression, Female, Humans, Male, Middle Aged, Recurrence, Brain pathology, Magnetic Resonance Imaging methods, Multiple Sclerosis diagnosis
Abstract

Background and Purpose: Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures., Methods: Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS)., Results: Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1-22); their median load was 1.4 mL (range, 0.05-12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense lesions shown by fast FLAIR imaging were significantly higher in patients with secondary progressive MS. Significant correlations were found between Expanded Disability Status Scale scores and MR lesion load. A multivariate analysis showed that only the presence of hypointense lesions on fast FLAIR images significantly separated cases of relapsing-remitting MS from cases of secondary progressive MS (relative risk, 7.1; 95% confidence interval, 2.0-25.9)., Conclusion: The presence of hypointense lesions on fast FLAIR images was a strong predictor of disease severity in cases of MS, although the low sensitivity of this approach might limit its use for the assessment of MS evolution.

Published
1999

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