DAGOBERTO CALLEGARO

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina

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  • article 7 Citação(ões) na Scopus
    Clinical and MRI measures to identify non-acute MOG-antibody disease in adults
    (2023) CORTESE, Rosa; BATTAGLINI, Marco; PRADOS, Ferran; BIANCHI, Alessia; HAIDER, Lukas; JACOB, Anu; PALACE, Jacqueline; MESSINA, Silvia; PAUL, Friedemann; WUERFEL, Jens; MARIGNIER, Romain; DURAND-DUBIEF, Francoise; RIMKUS, Carolina de Medeiros; CALLEGARO, Dagoberto; SATO, Douglas Kazutoshi; FILIPPI, Massimo; ROCCA, Maria Assunta; CACCIAGUERRA, Laura; ROVIRA, Alex; SASTRE-GARRIGA, Jaume; ARRAMBIDE, Georgina; LIU, Yaou; DUAN, Yunyun; GASPERINI, Claudio; TORTORELLA, Carla; RUGGIERI, Serena; AMATO, Maria Pia; ULIVELLI, Monica; GROPPA, Sergiu; GROTHE, Matthias; LLUFRIU, Sara; SEPULVEDA, Maria; LUKAS, Carsten; BELLENBERG, Barbara; SCHNEIDER, Ruth; SOWA, Piotr; CELIUS, Elisabeth G.; PROEBSTEL, Anne-Katrin; YALDIZLI, Ozgur; MUELLER, Jannis; STANKOFF, Bruno; BODINI, Benedetta; CARMISCIANO, Luca; SORMANI, Maria Pia; BARKHOF, Frederik; STEFANO, Nicola De; CICCARELLI, Olga
    MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T-2 lesions, T-1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (+/- 14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (+/- 14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (+/- 10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice. In a multicentre MAGNIMS study, Cortese et al. show that brain and cord lesion characteristics on conventional MRI, together with clinical features, can help differentiate non-acute MOG-antibody disease from AQP4-NMOSD and multiple sclerosis, aiding identification of non-acute patients for MOG antibody testing.
  • conferenceObject
    MRI and clinical features differentiate non-acute MOGAD from AQP4-NMOSD and RRMS: a MAGNIMS multicenter study
    (2021) CORTESE, R.; BATTAGLINI, M.; PRADOS, F.; BIANCHI, A.; HAIDER, L.; JACOB, A.; PALACE, J.; MESSINA, S.; PAUL, F.; WUERFEL, J.; MARIGNIER, R.; DURAND-DUBIEF, F.; RIMKUS, C. de Medeiros; CALLEGARO, D.; SATO, D. K.; FILIPPI, M.; ROCCA, M. A.; ROVIRA, A.; SASTRE-GARRIGA, J.; ARRAMBIDE, G.; LIU, Y.; DUAN, Y.; GASPERINI, C.; TORTORELLA, C.; AMATO, M. P.; ULIVELLI, M.; GROPPA, S.; GROTHE, M.; LLUFRIU, S.; SEPULVEDA, M.; LUKAS, C.; BELLENBERG, B.; SCHNEIDER, R.; SOWA, P.; CELIUS, E. G.; PROEBSTEL, A. -K.; YALDIZLI, O.; MUELLER, J.; STANKOFF, B.; BODINI, B.; CARMISCIANO, L.; SORMANI, M. P.; BARKHOF, F.; STEFANO, N. De; CICCARELLI, O.
  • conferenceObject
    MOG-IgA characterizes a subgroup of patients with central nervous system demyelination
    (2023) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; KULSVEHAGEN, Laila; LIPPS, Patrick; CAGOL, Alessandro; FUERTES, Nuria Cerda; NEZIRAJ, Tradite; FLAMMER, Julia; LERNER, Jasmine; LECOURT, Anne-Catherine; SIEBENBORN, Nina de Oliveira S.; CORTESE, Rosa; SCHADELIN, Sabine; SCHOEPS, Vinicius; MATOS, Aline; MENDES, Natalia; PEREIRA, Clarissa dos Reis; MONTEIRO, Mario Luiz; PEREIRA, Samira Luisa Dos Apostolos; SCHINDLER, Patrick; CHIEN, Claudia; SCHWAKE, Carolin; SCHNEIDER, Ruth; PAKEERATHAN, Thivya; KIM, Ki Hoon; AKTAS, Orhan; FISCHER, Urs; MEHLING, Matthias; DERFUSS, Tobias; KAPPOS, Ludwig; AYZENBERG, Ilya; RINGELSTEIN, Marius; PAUL, Friedemann; CALLEGARO, Dagoberto; KIM, Ho Jin; KUHLE, Jens; PAPADOPOULOU, Athina; GRANZIERA, Cristina; PROBSTEL, Anne-Katrin
  • article 103 Citação(ões) na Scopus
    Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients
    (2020) WHITTAM, Daniel H.; COBO-CALVO, Alvaro; LOPEZ-CHIRIBOGA, A. Sebastian; PARDO, Santiago; GORNALL, Matthew; CICCONI, Silvia; BRANDT, Alexander; BEREK, Klaus; BERGER, Thomas; JELCIC, Ilijas; GOMBOLAY, Grace; OLIVEIRA, Luana Micheli; CALLEGARO, Dagoberto; KANEKO, Kimihiko; MISU, Tatsuro; CAPOBIANCO, Marco; GIBBONS, Emily; KARTHIKEAYAN, Venkatraman; BROCHET, Bruno; AUDOIN, Bertrand; MATHEY, Guillaume; LAPLAUD, David; THOUVENOT, Eric; COHEN, Mikael; TOURBAH, Ayman; MAILLART, Elisabeth; CIRON, Jonathan; DESCHAMPS, Romain; BIOTTI, Damien; ROSTASY, Kevin; NEUTEBOOM, Rinze; HEMINGWAY, Cheryl; FORSYTH, Rob; MATIELLO, Marcelo; WEBB, Stewart; HUNT, David; MURRAY, Katy; HACOHEN, Yael; LIM, Ming; LEITE, M. Isabel; PALACE, Jacqueline; SOLOMON, Tom; LUTTEROTTI, Andreas; FUJIHARA, Kazuo; NAKASHIMA, Ichiro; BENNETT, Jeffrey L.; PANDIT, Lekha; CHITNIS, Tanuja; WEINSHENKER, Brian G.; WILDEMANN, Brigitte; SATO, Douglas Kazutoshi; KIM, Su-Hyun; HUDA, Saif; KIM, Ho Jin; REINDL, Markus; LEVY, Michael; JARIUS, Sven; TENEMBAUM, Silvia; PAUL, Friedemann; PITTOCK, Sean; MARIGNIER, Romain; JACOB, Anu
    Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19(+)B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.
  • article 6 Citação(ões) na Scopus
    Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination
    (2023) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; KULSVEHAGEN, Laila; LIPPS, Patrick; CAGOL, Alessandro; CERDA-FUERTES, Nuria; NEZIRAJ, Tradite; FLAMMER, Julia; LERNER, Jasmine; LECOURT, Anne-Catherine; SIEBENBORN, Nina De Oliveira S.; CORTESE, Rosa; SCHAEDELIN, Sabine; SCHOEPS, Vinicius Andreoli; MATOS, Aline de Moura Brasil; MENDES, Natalia Trombini; PEREIRA, Clarissa dos Reis; MONTEIRO, Mario Luiz Ribeiro; APOSTOLOS-PEREIRA, Samira Luisa dos; SCHINDLER, Patrick; CHIEN, Claudia; SCHWAKE, Carolin; SCHNEIDER, Ruth; PAKEERATHAN, Thivya; AKTAS, Orhan; FISCHER, Urs; MEHLING, Matthias; DERFUSS, Tobias; KAPPOS, Ludwig; AYZENBERG, Ilya; RINGELSTEIN, Marius; PAUL, Friedemann; CALLEGARO, Dagoberto; KUHLE, Jens; PAPADOPOULOU, Athina; GRANZIERA, Cristina; PROBSTEL, Anne-Katrin
    IMPORTANCE Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. OBJECTIVE To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. DESIGN, SETTING, AND PARTICIPANTS This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. MAIN OUTCOMES AND MEASURES Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. RESULTS After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P =.048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P =.02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P <.001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). CONCLUSION AND RELEVANCE In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.
  • conferenceObject
    Discriminating MS from MOGAD using deep learning attention maps
    (2023) CORTESE, Rosa; BATTAGLINI, Marco; SFORAZZINI, Francesco; FRANCH, Natalia Cantavella; PRADOS, Ferran; BIANCHI, Alessia; HAIDER, Lukas; JACOB, Anu; PALACE, Jacqueline; MESSINA, Silvia; PAUL, Friedemann; MARIGNIER, Romain; DURAND-DUBIEF, Francoise; RIMKUS, Carolina de Medeiros; CALLEGARO, Dagoberto; SATO, Douglas; FILIPPI, Massimo; ROCCA, Maria Assunta; CACCIAGUERRA, Laura; CANELLAS, Alex Rovira; SASTRE-GARRIGA, Jaume; ARRAMBIDE, Georgina; LIU, Yaou; YUN, Duan; GASPERINI, Claudio; TORTORELLA, Carla; RUGGIERI, Serena; AMATO, Maria Pia; ULIVELLI, Monica; GROPPA, Sergiu; GROTHE, Matthias; LLUFRIU, Sara; SEPULVEDA, Maria; LUKAS, Carsten; BELLENBERG, Barbara; SCHNEIDER, Ruth; SOWA, Piotr; CELIUS, Elisabeth; PROBSTEL, Anne-Katrin; GRANZIERA, Cristina; YALDIZLI, Ozgur; MULLER, Jannis; STANKOFF, Bruno; BODINI, Benedetta; BARKHOF, Frederik; CICCARELLI, Olga; STEFANO, Nicola De
  • conferenceObject
    Investigating grey matter atrophy and its relationship with white matter lesions in MS, MOGAD and AQP4-NMOSD
    (2022) CORTESE, R.; BATTAGLINI, M.; PRADOS, F.; GENTILE, G.; LUCHETTI, L.; BIANCHI, A.; HAIDER, L.; JACOB, A.; PALACE, J.; MESSINA, S.; PAUL, F.; WUERFEL, J.; MARIGNIER, R.; DURAND-DUBIEF, F.; RIMKUS, C. De Medeiros; CALLEGARO, D.; SATO, D. Kazutoshi; FILIPPI, M.; ROCCA, M. A.; CACCIAGUERRA, L.; ROVIRA, A.; SASTRE-GARRIGA, J.; ARRAMBIDE, G.; LIU, Y.; DUAN, Y.; GASPERINI, C.; TORTORELLA, C.; RUGGIERI, S.; AMATO, M. P.; ULIVELLI, M.; GROPPA, S.; GROTHE, M.; LLUFRIU, S.; SEPULVEDA, M.; LUKAS, C.; BELLENBERG, B.; SCHNEIDER, R.; SOWA, P.; CELIUS, E. G.; PROEBSTEL, A. -K.; YALDIZLI, O.; MULLER, J.; STANKOFF, B.; BODINI, B.; CARMISCIANO, L.; SORMANI, M. P.; BARKHOF, F.; STEFANO, N. De; CICCARELLI, O.