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3. Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience

Author

Ruggieri, Serena, Ianniello, Antonio, Copetti, Massimiliano, Altieri, Marta, Buscarinu, Maria Chiara, Centonze, Diego, Cortese, Antonio, De Giglio, Laura, Fantozzi, Roberta, Gasperini, Claudio, Grimaldi, Luigi M.E., Landi, Doriana, Marfia, Girolama A., Mirabella, Massimiliano, Nistri, Riccardo, Nociti, Viviana, Oddo, Oscar, Romano, Silvia, Salemi, Giuseppe, Tortorella, Carla, Pozzilli, Carlo, and Petracca, Maria

Published
2024
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4. Combining early lower eyelid surgery with neuromuscular retraining for synkinesis prevention after facial palsy: the role of the eye in aberrant facial nerve regeneration.

Author

Di Stadio, Arianna, Ralli, Massimo, De Luca, Pietro, Sossamon, Jake, Frohman, Teresa C., Altieri, Marta, La Mantia, Ignazio, Ferlito, Salvatore, Frohman, Elliot M., and Brenner, Michael J.

Subjects
MAGNETIC resonance imaging, OPHTHALMIC plastic surgery, FACIAL expression, FACIAL paralysis, FACIAL nerve
Abstract

Background: Facial synkinesis (FS) is a distressing sequela of facial palsy (FP) characterized by involuntary, simultaneous movements of facial muscles occurring during voluntary facial expressions. Treatment of synkinesis is challenging, and preventive methods are needed. Aim: This study evaluated the efficacy of physical facial nerve rehabilitation (PFNR) therapy alone vs. PNFR with eyelid surgery to correct lagophthalmos and prevent the onset of synkinesis. Methods: Twenty five outpatients were randomized to receive either PFNR alone (neuromuscular retraining and Kabat proprioceptive neuromuscular facilitation) or PNFR and early (90 days after FP onset) eyelid surgery (involving a conservative oculoplastic correction for lagophthalmos with epiphora or ectropion). Comprehensive otolaryngological assessments and Magnetic Resonance Imaging (MRI) were conducted. Synkinesis progression was measured using Another Disease Scale (ADS) at baseline, 3-, 6-, 12-, and 24-months post-treatment. The data were analyzed with ANOVA, τ-test, Chi-Square analyses. Results: Patients undergoing eyelid surgery with PFNR showed faster (p < 0.001) and better recovery of facial movements (p < 0.05) than patients receiving PFNR alone comparing T0 and T12 (p < 0.0001). No synkinesis were observed in the PFNR plus surgery group while 37% of patients in PFNR alone had synkinesis (p = 0.03). At 24months, none of the patients in the surgery group presented synkinesis. Conclusion: Combining early surgical treatment of paralytic lagophthalmos or epiphora with PFNR accelerated functional recovery and reduced synkinesis in patients with FP compared to facial rehabilitation alone. Further investigations in larger populations with long-term follow-up are needed. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Author

Bucello, Sebastiano, Annovazzi, Pietro, Ragonese, Paolo, Altieri, Marta, Barcella, Valeria, Bergamaschi, Roberto, Bianchi, Alessia, Borriello, Giovanna, Buscarinu, Maria Chiara, Callari, Graziella, Capobianco, Marco, Capone, Fioravante, Cavalla, Paola, Cavarretta, Rosella, Cortese, Antonio, De Luca, Giovanna, Di Filippo, Massimiliano, Dattola, Vincenzo, Fantozzi, Roberta, Ferraro, Elisabetta, Filippi, Maria Maddalena, Gasperini, Claudio, Grimaldi, Luigi Maria Edoardo, Landi, Doriana, Re, Marianna Lo, Mallucci, Giulia, Manganotti, Paolo, Marfia, Girolama Alessandra, Mirabella, Massimiliano, Perini, Paola, Pisa, Marco, Realmuto, Sabrina, Russo, Margherita, Tomassini, Valentina, Torri-Clerici, Valentina Liliana Adriana, Zaffaroni, Mauro, Zuliani, Cristina, Zywicki, Sofia, Filippi, Massimo, and Prosperini, Luca

Published
2021
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9. Proteomic profile of extracellular vesicles from plasma and CSF of multiple sclerosis patients reveals disease activity-associated EAAT2.

Author

D'Ambrosio, Antonella, Zamboni, Silvia, Camerini, Serena, Casella, Marialuisa, Sanchez, Massimo, Pietraforte, Donatella, Vanacore, Nicola, Diociauti, Marco, Altieri, Marta, Di Piero, Vittorio, Francia, Ada, Pontecorvo, Simona, Puthenparampil, Marco, Gallo, Paolo, and Margutti, Paola

Subjects
GLUTAMATE transporters, EXTRACELLULAR vesicles, NEURAL transmission, DISEASE relapse, COMPLEX fluids
Abstract

Background and objectives: There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. Methods: EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. Results: The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). Conclusion: Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Proteomic Profile of Extracellular Vesicles from Plasma and CFS of Multiple Sclerosis Patients Reveals Disease Activity- Associated EAAT2

Author

D’Ambrosio, Antonella, primary, Zamboni, Silvia, additional, Camerini, Serena, additional, Casella, Marialuisa, additional, Sanchez, Massimo, additional, Pietraforte, Donatella, additional, Vanacore, Nicola, additional, Diociauti, Marco, additional, Altieri, Marta, additional, Piero, Vittorio Di, additional, Francia, Ada, additional, Pontecorvo, Simona, additional, Puthenparampil, Marco, additional, Gallo, Paolo, additional, and Margutti, Paola, additional

Published
2024
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14. Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative ‘window of discovery’

Author

Di Stadio, Arianna, primary, De Luca, Pietro, additional, Koohi, Nehzat, additional, Kaski, Diego, additional, Ralli, Massimo, additional, Giesemann, Anja, additional, Hartung, Hans-Peter, additional, Altieri, Marta, additional, Messineo, Daniela, additional, Warnecke, Athanasia, additional, Frohman, Teresa, additional, and Frohman, Elliot M., additional

Published
2023
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15. Focal Muscle Vibration (fMV) for Post-Stroke Motor Recovery: Multisite Neuroplasticity Induction, Timing of Intervention, Clinical Approaches, and Prospects from a Narrative Review

Author

Viganò, Alessandro, primary, Celletti, Claudia, additional, Giuliani, Giada, additional, Jannini, Tommaso B., additional, Marenco, Francesco, additional, Maestrini, Ilaria, additional, Zumpano, Rosaceleste, additional, Vicenzini, Edoardo, additional, Altieri, Marta, additional, Camerota, Filippo, additional, Di Piero, Vittorio, additional, and Toscano, Massimiliano, additional

Published
2023
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20. Habituation deficit of visual evoked potentials in migraine patients with hypermobile Ehlers-Danlos syndrome

Author

Maestrini, Ilaria, primary, Rocchi, Lorenzo, additional, Puledda, Francesca, additional, Viganò, Alessandro, additional, Giuliani, Giada, additional, Jannini, Tommaso Benedetto, additional, Celletti, Claudia, additional, Altieri, Marta, additional, Camerota, Filippo, additional, Toscano, Massimiliano, additional, and Di Piero, Vittorio, additional

Published
2023
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21. Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Author

Di Stadio, Arianna, primary, Bernitsas, Evanthia, additional, La Mantia, Ignazio, additional, Brenner, Michael J., additional, Ralli, Massimo, additional, Vaira, Luigi Angelo, additional, Colizza, Andrea, additional, Cavaliere, Carlo, additional, Laudani, Matteo, additional, Frohman, Teresa C., additional, De Vincentiis, Marco, additional, Frohman, Elliot M., additional, and Altieri, Marta, additional

Published
2023
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22. Efficacy of interoceptive and embodied rehabilitative training protocol in patients with mild multiple sclerosis: A randomized controlled trial

Author

Paolucci, Teresa, primary, de Sire, Alessandro, additional, Agostini, Francesco, additional, Bernetti, Andrea, additional, Salomè, Angela, additional, Altieri, Marta, additional, Di Piero, Vittorio, additional, Ammendolia, Antonio, additional, Mangone, Massimiliano, additional, and Paoloni, Marco, additional

Published
2022
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27. Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment

Author

Prezioso, Carla, primary, Ciotti, Marco, additional, Brazzini, Gabriele, additional, Piacentini, Francesca, additional, Passerini, Sara, additional, Grimaldi, Alfonso, additional, Landi, Doriana, additional, Nicoletti, Carolina Gabri, additional, Zingaropoli, Maria Antonella, additional, Iannetta, Marco, additional, Altieri, Marta, additional, Conte, Antonella, additional, Limongi, Dolores, additional, Marfia, Girolama Alessandra, additional, Ciardi, Maria Rosa, additional, Mastroianni, Claudio Maria, additional, Palamara, Anna Teresa, additional, Moens, Ugo, additional, and Pietropaolo, Valeria, additional

Published
2022
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28. Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study

Author

Zingaropoli, Maria Antonella, primary, Pasculli, Patrizia, additional, Iannetta, Marco, additional, Perri, Valentina, additional, Tartaglia, Matteo, additional, Crisafulli, Sebastiano Giuseppe, additional, Merluzzo, Chiara, additional, Baione, Viola, additional, Mazzochi, Lorenzo, additional, Taglietti, Ambra, additional, Pauri, Flavia, additional, Frontoni, Marco, additional, Altieri, Marta, additional, Gaeta, Aurelia, additional, Antonelli, Guido, additional, Conte, Antonella, additional, Mastroianni, Claudio Maria, additional, and Ciardi, Maria Rosa, additional

Published
2022
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30. Assessment and management of infectious risk in multiple sclerosis patients treated with disease-modifying therapies

Author

Zingaropoli, Maria Antonella, Pasculli, Patrizia, Iannetta, Marco, Perri, Valentina, Tartaglia, Matteo, Crisafulli, Sebastiano Giuseppe, Merluzzo, Chiara, Baione, Viola, Mazzocchi, Lorenzo, Taglietti, Ambra, Pauri, Flavia, Frontoni, Marco, Altieri, Marta, Gaeta, Aurelia, Antonelli, Guido, Conte, Antonella, Mastroianni, Claudio, and Ciardi, Maria Rosa

Published
2021
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31. Chronic Migraine Preventive Treatment by Prefrontal–Occipital Transcranial Direct Current Stimulation (tDCS): A Proof-of-Concept Study on the Effect of Psychiatric Comorbidities

Author

Mastria, Giulio, primary, Viganò, Alessandro, additional, Corrado, Alessandra, additional, Mancini, Valentina, additional, Pirillo, Cristina, additional, Badini, Simone, additional, Petolicchio, Barbara, additional, Toscano, Massimiliano, additional, Altieri, Marta, additional, Delle Chiaie, Roberto, additional, and Di Piero, Vittorio, additional

Published
2021
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33. The role of stress and psychiatric comorbidities as targets of non-pharmacological therapeutic approaches for migraine

Author

Pancheri, Corinna, Maraone, Annalisa, Roselli, Valentina, Altieri, Marta, Di Piero, Vittorio, Biondi, Massimo, Pasquini, Massimo, and Tarsitani, Lorenzo

Subjects
Migraine Disorders, migraine, comorbidity, mental disorder, psychiatric disorders, psychotherapy, Quality of Life, Humans, Comorbidity, Anxiety, Psychotherapy, Psychodynamic
Abstract

This narrative review addresses the interconnections among stress, mental disorders and migraine with a specific focus on non-pharmacological interventions that may be effective in improving both migraine and the psychiatric comorbidity. Migraine is often comorbid with depression, anxiety, personality disorders, and sleep disorders. Subjective stress and stressors are common triggers for migraine attacks and are risk factors for chronification, whilst mental disorders and stress responses are closely linked in a bidirectional relation. Recent studies show that psychiatric comorbidity is associated with migraine severity, worse outcomes, increased disability and reduce quality of life. Numerous studies on non-pharmacological interventions for migraine were published and behavioural treatments included biofeedback, cognitive-behavioural therapy, relaxation training, stress management and brief psychodynamic psychotherapy. Taken together, psychological interventions proved to be effective in migraine treatment and a combination of pharmacological and psychological treatment appear to be more effective than either medication or psychotherapy alone. Non-pharmacological interventions effectiveness should be due to the improvement of migraine, stress-related vulnerability and mental disorders together and the combined treatment could prevent the chronification circuit of migraine. Well-designed long-term studies are needed to clarify comparative effectiveness of non-pharmacological techniques in the treatment and the prevention of migraine.

Published
2020

38. Straighten your back! Self-correction posture and postural balance in “non rehabilitative instructed” multiple sclerosis patients

Author

Paolucci, Teresa, primary, Bernetti, Andrea, additional, Sbardella, Silvia, additional, La Russa, Chiara, additional, Murgia, Massimiliano, additional, Salomè, Angela, additional, Villani, Ciro, additional, Altieri, Marta, additional, Santilli, Valter, additional, Paoloni, Marco, additional, Agostini, Francesco, additional, and Mangone, Massimiliano, additional

Published
2020
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41. CONTRIBUTORS

Author

Afinowi, Rasheed A., primary, Ahima, Rexford S., additional, Altieri, Marta, additional, Alvarez, Hortensia, additional, Amukotuwa, Shalini A., additional, Anziska, Yaacov, additional, Artz, Gregory J., additional, Ashina, Messoud, additional, Bamiou, Doris-Eva, additional, and Bass, Christopher, additional

Published
2007
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45. 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

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

Author

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, Valentino, P, 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, Valentino, P, 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, and Rottoli, Maira Rosa

Abstract

Objective early 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. Methods all 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. Conclusions considering 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

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