32 results on '"Amato Mp"'
Search Results
2. Correction to: Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression.
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Portaccio E, Betti M, De Meo E, Addazio I, Pastò L, Razzolini L, Totaro R, Spitaleri D, Lugaresi A, Cocco E, Onofrj M, Di Palma F, Patti F, Maimone D, Valentino P, Clerici VT, Protti A, Ferraro D, Lus G, Maniscalco GT, Morra VB, Salemi G, Granella F, Pesci I, Bergamaschi R, Aguglia U, Vianello M, Simone M, Lepore V, Iaffaldano P, Comi G, Filippi M, Trojano M, and Amato MP
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- 2024
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3. Active and non-active secondary progressive multiple sclerosis patients exhibit similar disability progression: results of an Italian MS registry study (ASPERA).
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Chisari CG, Amato MP, Di Sapio A, Foschi M, Iaffaldano P, Inglese M, Fermo SL, Lugaresi A, Lus G, Mascoli N, Montepietra S, Pesci I, Quatrale R, Salemi G, Torri Clerici V, Totaro R, Valentino P, Filippi M, and Patti F
- Abstract
'Active' and 'non-active' secondary progressive MS (SPMS) have distinct pathophysiological mechanisms and clinical characteristics, but there is still no consensus regarding the frequency of these MS forms in the real-world setting. We aimed to evaluate the frequency of 'active' and 'non-active' SPMS in a large cohort of Italian MS patients and the differences in terms of clinical and MRI characteristics and disease progression. This multicenter study collected data about MS patients who have transitioned to the SP form in the period between 1st January 2014 and 31st December 2019 and followed by the MS centers contributing to the Italian MS Registry. Patients were divided into 'active SPMS' and 'non-active SPMS', based on both reported MRI data and relapse activity in the year before conversion to SPMS. Out of 68,621, 8,316 (12.1%) patients were diagnosed with SPMS. Out of them, 872 (10.5%) were classified into patients with either 'active' or 'non-active' SPMS. A total of 237 were classified into patients with 'active SPMS' (27.2%) and 635 as 'non-active SPMS' (72.8%). 'Non-active SPMS' patients were older, with a longer disease duration compared to those with 'active SPMS'. The percentages of patients showing progression independent of relapse activity (PIRA) at 24 months were similar between 'active' and 'non-active' SPMS patients (67 [27.4%] vs 188 [29.6%]; p = 0.60). In the 'active' group, 36 (15.2%) patients showed relapse-associated worsening (RAW). Comparison of the survival curves to EDSS 6 and 7 according to disease activity did not show significant differences (p = 0.68 and p = 0.71). 'Active' and 'non-active' SPMS patients had a similar risk of achieving disability milestones, suggesting that progression is primarily attributed to PIRA and only to a small extent to disease activity., (© 2024. The Author(s).)
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- 2024
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4. Disability trajectories by progression independent of relapse activity status differ in pediatric, adult and late-onset multiple sclerosis.
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Simone M, Lucisano G, Guerra T, Paolicelli D, Rocca MA, Brescia Morra V, Patti F, Annovazzi P, Gasperini C, De Luca G, Ferraro D, Margari L, Granella F, Pozzilli C, Romano S, Perini P, Bergamaschi R, Coniglio MG, Lus G, Vianello M, Lugaresi A, Portaccio E, Filippi M, Amato MP, and Iaffaldano P
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Background: To compare Expanded Disability Status Scale (EDSS) trajectories over time between Multiple Sclerosis (MS) groups with pediatric (POMS), adult (AOMS) and late (LOMS) onset, and between patients with and without progression independent of relapse activity (PIRA)., Methods: Patients with a first visit within 1 year from onset, ≥ 5-year follow-up and ≥ 1 visit every 6 months were selected from the Italian MS Register. Adjusted disability trajectories were assessed by longitudinal models for repeated measures. Comparisons between groups and between patients with and without PIRA in subgroups were performed by evaluating the yearly differences of mean EDSS score changes versus baseline (delta-EDSS). A first CDA event was defined as a 6-months confirmed disability increase from study baseline, measured by EDSS (increase ≥ 1.5 points with baseline EDSS = 0; ≥ 1.0 with baseline EDSS score ≤ 5.0 and ≥ 0.5 point with baseline EDSS > 5.5). PIRA was defined as a CDA event occurring more than 90 days after and more than 30 days before the onset of a relapse., Results: 3777 MS patients (268 POMS, 3282 AOMS, 227 LOMS) were included. The slope of disability trajectories significantly diverged in AOMS vs POMS starting from the second year of follow-up (Year 2: delta2-EDSS 0.18 (0.05; 0.31), p = 0.0054) and then mean delta2-EDSS gradually increased up to 0.23 (0.07; 0.39, p = 0.004) at year 5. Patients with PIRA had significant (p < 0.0001) steeper increase in EDSS scores than those without PIRA in all groups, although in POMS, the disability trajectories began to diverge later and at a lesser extent with delta-EDSS score of 0.48 vs 0.83 in AOMS and 1.57 in LOMS, at 3 years after the first PIRA., Conclusions: Age is relevant in determining disability progression in MS. POMS shows a less steep increase in EDSS scores over time than older patients. The effect of PIRA in accelerating EDSS progression is less pronounced in POMS than in AOMS and LOMS., (© 2024. The Author(s).)
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- 2024
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5. Pediatric-onset Multiple Sclerosis treatment: a multicentre observational study comparing natalizumab with fingolimod.
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Carotenuto A, Di Monaco C, Papetti L, Borriello G, Signoriello E, Masciulli C, Tomassini V, De Luca G, Ianniello A, Lus G, Novarella F, Spiezia AL, Di Somma D, Moccia M, Petracca M, Iacovazzo C, Servillo G, Portaccio E, Triassi M, Amato MP, Pozzilli C, Valeriani M, Brescia Morra V, and Lanzillo R
- Abstract
Background: Pediatric-onset Multiple Sclerosis (POMS) patients show more inflammatory disease compared with adult-onset MS. However, highly effective treatments are limited with only fingolimod being approved in Italy and natalizumab prescribed as off-label treatment., Objectives: to compare the efficacy of natalizumab versus fingolimod in POMS., Methods: This is an observational longitudinal multicentre study including natalizumab- and fingolimod-treated POMS patients (N-POMS and F-POMS, respectively). We collected Annual Relapse Rate (ARR), Expanded Disability Status Scale (EDSS), Symbol Digit Modality Test (SDMT), and MRI activity at baseline (T0), 12-18 months (T1), and last available observation (T2)., Results: We enrolled 57 N-POMS and 27 F-POMS patients from six Italian MS Centres. At T0, N-POMS patients showed higher ARR (p = 0.03), higher EDSS (p = 0.003) and lower SDMT (p = 0.04) at baseline compared with F-POMS. Between T
0 and T1 ARR improved for both N-POMS and F-POMS (p < 0.001), while EDSS (p < 0.001) and SDMT (p = 0.03) improved only for N-POMS. At T2 (66.1 ± 55.4 months) we collected data from 42 out of 57 N-POMS patients showing no further ARR decrease., Conclusion: Both natalizumab and fingolimod showed high and sustained efficacy in controlling relapses and natalizumab also associated to a disability decrease in POMS. This latter effect might be partly mediated by the high inflammatory activity at baseline in N-POMS., (© 2024. The Author(s).)- Published
- 2024
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6. Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression.
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Portaccio E, Betti M, De Meo E, Addazio I, Pastò L, Razzolini L, Totaro R, Spitaleri D, Lugaresi A, Cocco E, Onofrj M, Di Palma F, Patti F, Maimone D, Valentino P, Torri Clerici V, Protti A, Ferraro D, Lus G, Maniscalco GT, Brescia Morra V, Salemi G, Granella F, Pesci I, Bergamaschi R, Aguglia U, Vianello M, Simone M, Lepore V, Iaffaldano P, Comi G, Filippi M, Trojano M, and Amato MP
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- Humans, Male, Female, Adult, Middle Aged, Registries, Recurrence, Italy epidemiology, Follow-Up Studies, Disease Progression, Multiple Sclerosis, Relapsing-Remitting physiopathology, Multiple Sclerosis, Relapsing-Remitting epidemiology, Disability Evaluation
- Abstract
Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS)., Methods: Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively., Results: Over 11.8 ± 5.4 years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003)., Discussion: In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase., (© 2024. The Author(s).)
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- 2024
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7. Moving towards a new era for the treatment of neuromyelitis optica spectrum disorders.
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Preziosa P, Amato MP, Battistini L, Capobianco M, Centonze D, Cocco E, Conte A, Gasperini C, Gastaldi M, Tortorella C, and Filippi M
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- Humans, Neuromyelitis Optica therapy, Neuromyelitis Optica immunology, Neuromyelitis Optica drug therapy
- Abstract
Neuromyelitis optica spectrum disorders (NMOSD) include a rare group of autoimmune conditions that primarily affect the central nervous system. They are characterized by inflammation and damage to the optic nerves, brain and spinal cord, leading to severe vision impairment, locomotor disability and sphynteric disturbances. In the majority of cases, NMOSD arises due to specific serum immunoglobulin G (IgG) autoantibodies targeting aquaporin 4 (AQP4-IgG), which is the most prevalent water-channel protein of the central nervous system. Early diagnosis and treatment are crucial to manage symptoms and prevent long-term disability in NMOSD patients. NMOSD were previously associated with a poor prognosis. However, recently, a number of randomized controlled trials have demonstrated that biological therapies acting on key elements of NMOSD pathogenesis, such as B cells, interleukin-6 (IL-6) pathway, and complement, have impressive efficacy in preventing the occurrence of clinical relapses. The approval of the initial drugs marks a revolutionary advancement in the treatment of NMOSD patients, significantly transforming therapeutic options and positively impacting their prognosis. In this review, we will provide an updated overview of the key immunopathological, clinical, laboratory, and neuroimaging aspects of NMOSD. Additionally, we will critically examine the latest advancements in NMOSD treatment approaches. Lastly, we will discuss key aspects regarding optimization of treatment strategies and their monitoring., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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8. Early prediction of unfavorable evolution after a first clinical episode suggestive of multiple sclerosis: the EUMUS score.
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Mallucci G, Ferraro OE, Trojano M, Amato MP, Scalfari A, Zaffaroni M, Colombo E, Rigoni E, Iaffaldano P, Portaccio E, Saraceno L, Paolicelli D, Razzolini L, Montomoli C, and Bergamaschi R
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- Humans, Male, Female, Adult, Retrospective Studies, Prognosis, Middle Aged, Young Adult, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis diagnosis, Multiple Sclerosis physiopathology, Disease Progression, Magnetic Resonance Imaging
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Background: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA)., Methods: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort., Results: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort., Conclusions: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2024
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9. Late-onset multiple sclerosis: disability trajectories in relapsing-remitting patients of the Italian MS Registry.
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Lorefice L, Ferraro OE, Fenu G, Amato MP, Bresciamorra V, Conte A, De Luca G, Ferraro D, Filippi M, Gazzola P, Iaffaldano P, Inglese M, Lus G, Marfia GA, Patti F, Pesci I, Salemi G, Trojano M, Zaffaroni M, Monti MC, and Cocco E
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- Humans, Male, Disease Progression, Age Factors, Aging, Italy, Disability Evaluation, Multiple Sclerosis complications, Multiple Sclerosis, Relapsing-Remitting complications
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Background: Generally infrequent, multiple sclerosis (MS) with late onset (LOMS) is characterized by an onset over the age of 50 and a mainly progressive course, while relapsing-remitting (RR) forms are less frequently observed and explored. This study aimed to characterize a large cohort of MS patients with RRMS at onset to assess the baseline factors related to the worst disability trajectories and explore the role of LOMS., Methods: The data were extracted from the Italian MS Register (IMSR). Disability trajectories, defined using at least two and up to twenty expanded disability status scale (EDSS) assessments annually performed, were implemented using group-based trajectory models (GBTMs) to identify different groups with the same trajectories over time. MS profiles were explored using multinomial logistic regression., Results: A total of 16,159 RR patients [1012 (6.26%) presented with LOMS] were analyzed. The GBTM identified four disability trajectories. The group with the most severe EDSS trend included 12.3% of the patients with a mean EDSS score > 4, which increased over time and exceeded 6 score. The group with medium severity EDSS trend comprised 21.9% of the patients and showed a change in EDSS > 3 scores over time. The largest group with 50.8% of patients reported a constant EDSS of 2 score. Finally, the benign group comprised 14.9% of the patients with a low and constant EDSS of 1 score over time. The probability of being in the worst groups increased if the patient was male; had LOMS or experienced brainstem, spinal, or supratentorial symptoms., Conclusions: Four MS severity profiles among RRMS patients in the IMSR have been reported, with LOMS being associated with a rapid worsening of EDSS scores. These findings have important implications for recognizing and managing how older age, aging, and age-related factors interact with MS and its evolution., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2024
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10. Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry.
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Iaffaldano P, Lucisano G, Guerra T, Patti F, Cocco E, De Luca G, Brescia Morra V, Pozzilli C, Zaffaroni M, Ferraro D, Gasperini C, Salemi G, Bergamaschi R, Lus G, Inglese M, Romano S, Bellantonio P, Di Monte E, Maniscalco GT, Conte A, Lugaresi A, Vianello M, Torri Clerici VLA, Di Sapio A, Pesci I, Granella F, Totaro R, Marfia GA, Danni MC, Cavalla P, Valentino P, Aguglia U, Montepietra S, Ferraro E, Protti A, Spitaleri D, Avolio C, De Riz M, Maimone D, Cavaletti G, Gazzola P, Tedeschi G, Sessa M, Rovaris M, Di Palma F, Gatto M, Cargnelutti D, De Robertis F, Logullo FO, Rini A, Meucci G, Ardito B, Banfi P, Nasuelli D, Paolicelli D, Rocca MA, Portaccio E, Chisari CG, Fenu G, Onofrj M, Carotenuto A, Ruggieri S, Tortorella C, Ragonese P, Nica M, Amato MP, Filippi M, and Trojano M
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- Humans, Immunologic Factors therapeutic use, Cross-Sectional Studies, Recurrence, Italy epidemiology, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Multiple Sclerosis, Relapsing-Remitting chemically induced, Multiple Sclerosis, Chronic Progressive drug therapy
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Background: Active relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as "relapsing MS" (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD)., Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT's class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]., Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02-0.37), Natalizumab (0.48, 0.30-0.76), Ocrelizumab (0.1, 0.02-0.45) and Rituximab (0.23, 0.06-0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31-0.59), especially anti-CD20 drugs (0.14, 0.05-0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs., Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2024
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11. Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.
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Li Y, Saul A, Taylor B, Ponsonby AL, Simpson-Yap S, Blizzard L, Broadley S, Lechner-Scott J, Karabudak R, Patti F, Eichau S, Onofrj M, Ozakbas S, Horakova D, Kubala Havrdova E, Grand'Maison F, Alroughani R, Gerlach O, Amato MP, Altintas A, Girard M, Duquette P, Blanco Y, Ramo-Tello C, Laureys G, Kalincik T, Khoury SJ, Shaygannejad V, Etemadifar M, Singhal B, Mrabet S, Foschi M, Habek M, John N, Hughes S, McCombe P, Ampapa R, van der Walt A, Butzkueven H, de Gans K, McGuigan C, Oreja-Guevara C, Sa MJ, Petersen T, Al-Harbi T, Sempere AP, Van Wijmeersch B, Grigoriadis N, Prevost J, Gray O, Castillo-Triviño T, Macdonell R, Lugaresi A, Sajedi SA, and van der Mei I
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- Adult, Female, Humans, Male, Middle Aged, Age of Onset, Australia epidemiology, Case-Control Studies, Recurrence, Risk Factors, Multicenter Studies as Topic, Multiple Sclerosis epidemiology, Multiple Sclerosis etiology, Multiple Sclerosis, Chronic Progressive epidemiology, Multiple Sclerosis, Chronic Progressive etiology
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It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications., (© 2023. The Author(s).)
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- 2024
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12. Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study.
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Amato MP, Bergamaschi R, Centonze D, Mirabella M, Marfia GA, Totaro R, Lus G, Brescia Morra V, Aguglia U, Comi C, Cavalla P, Zaffaroni M, Rovaris M, Grimaldi LM, Leoni S, Malucchi S, Baldi E, Romano M, Falcini M, Perini P, Assetta M, Portaccio E, Sommacal S, Olivieri N, Parodi F, Todaro DS, Grassivaro N, Farina A, Mondino MM, Filippi M, and Trojano M
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- Humans, Cognition, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Disabled Persons, Motor Disorders
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Background: Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed., Methods: This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test., Results: The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96)., Conclusion: Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition., (© 2023. The Author(s).)
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- 2023
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13. Abnormal thalamic functional connectivity correlates with cardiorespiratory fitness and physical activity in progressive multiple sclerosis.
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Romanò F, Motl RW, Valsasina P, Amato MP, Brichetto G, Bruschi N, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Freeman J, Inglese M, Meza C, Salter A, Sandroff BM, Feinstein A, Rocca MA, and Filippi M
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- Humans, Thalamus, Magnetic Resonance Imaging, Atrophy pathology, Multiple Sclerosis complications, Cardiorespiratory Fitness, Multiple Sclerosis, Chronic Progressive diagnostic imaging, Multiple Sclerosis, Chronic Progressive pathology
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Background: Altered thalamic volumes and resting state (RS) functional connectivity (FC) might be associated with physical activity (PA) and cardiorespiratory fitness (CRF) in people with progressive multiple sclerosis (PMS)., Objectives: To assess thalamic structural and functional alterations and investigate their correlations with PA/CRF levels in people with PMS., Methods: Seven-day accelerometry and cardiopulmonary exercise testing were used to assess PA/CRF levels in 91 persons with PMS. They underwent 3.0 T structural and RS fMRI acquisition with 37 age/sex-matched healthy controls (HC). Between-group comparisons of MRI measures and their correlations with PA/CRF variables were assessed., Results: PMS people had lower volumes compared to HC (all p < 0.001). At corrected threshold, PMS showed decreased intra- and inter-thalamic RS FC, and increased RS FC between the thalamus and the hippocampus, bilaterally. At uncorrected threshold, decreased thalamic RS FC with caudate nucleus, cerebellum and anterior cingulate cortex (ACC), as well as increased thalamic RS FC with occipital regions, were also detected. Lower CRF, measured as peak oxygen consumption (VO
2peak ), correlated with lower white matter volume (r = 0.31, p = 0.03). Moreover, lower levels of light PA correlated with increased thalamic RS FC with the right hippocampus (r = - 0.3, p = 0.05)., Discussion: People with PMS showed widespread brain atrophy, as well as pronounced intra-thalamic and thalamo-hippocampal RS FC abnormalities. White matter atrophy correlated with CRF, while increased thalamo-hippocampal RS FC was associated to worse PA levels. Thalamic RS FC might be used to monitor physical impairment and efficacy of rehabilitative and disease-modifying treatments in future studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)- Published
- 2023
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14. Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study.
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Veldkamp R, D'hooge M, Sandroff BM, DeLuca J, Kos D, Salter A, Feinstein A, Amato MP, Brichetto G, Chataway J, Farrell R, Chiaravalloti ND, Dalgas U, Filippi M, Freeman J, Motl RW, Meza C, Inglese M, Rocca MA, Cutter G, and Feys P
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- Humans, Processing Speed, Cognition, Walking, Retinoids, Gait, Multiple Sclerosis, Cognitive Dysfunction etiology, Multiple Sclerosis, Chronic Progressive complications
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Background: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown., Objective: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level., Methods: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTC
motor with clinical measures. Adjusted significance level was 0.01., Results: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039)., Conclusion: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)- Published
- 2023
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15. Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis.
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Preziosa P, Rocca MA, Pagani E, Valsasina P, Amato MP, Brichetto G, Bruschi N, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Freeman J, Inglese M, Meani A, Meza C, Motl RW, Salter A, Sandroff BM, Feinstein A, and Filippi M
- Subjects
- Humans, Task Performance and Analysis, Brain pathology, Brain Mapping, Magnetic Resonance Imaging, Multiple Sclerosis complications, Multiple Sclerosis, Chronic Progressive diagnostic imaging, Multiple Sclerosis, Chronic Progressive pathology
- Abstract
Background: Frontal cortico-subcortical dysfunction may contribute to fatigue and dual-task impairment of walking and cognition in progressive multiple sclerosis (PMS)., Purpose: To explore the associations among fatigue, dual-task performance and structural and functional abnormalities of frontal cortico-subcortical network in PMS., Methods: Brain 3 T structural and functional MRI sequences, Modified Fatigue Impact Scale (MFIS), dual-task motor and cognitive performances were obtained from 57 PMS patients and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connections and their resting state effective connectivity (RS-EC) with fatigue and dual-task performance were investigated using random forest., Results: Thirty-seven PMS patients were fatigued (F) (MFIS ≥ 38). Compared to HC, non-fatigued (nF) and F-PMS patients had significantly worse dual-task performance (p ≤ 0.002). Predictors of fatigue (out-of-bag [OOB]-accuracy = 0.754) and its severity (OOB-R
2 = 0.247) were higher Expanded Disability Status scale (EDSS) score, lower RS-EC from left-caudate nucleus to left-DLPFC, lower fractional anisotropy between left-caudate nucleus and left-thalamus, higher mean diffusivity between right-caudate nucleus and right-thalamus, and longer disease duration. Microstructural abnormalities in connections among thalami, caudate nuclei and DLPFC, mainly left-lateralized in nF-PMS and more bilateral in F-PMS, higher RS-EC from left-DLPFC to right-DLPFC in nF-PMS and lower RS-EC from left-caudate nucleus to left-DLPFC in F-PMS, higher EDSS score, higher WM lesion volume, and lower cortical volume predicted worse dual-task performances (OOB-R2 from 0.426 to 0.530)., Conclusions: In PMS, structural and functional frontal cortico-subcortical abnormalities contribute to fatigue and worse dual-task performance, with different patterns according to the presence of fatigue., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)- Published
- 2023
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16. The late onset of emotional distress in people with progressive multiple sclerosis during the Covid-19 pandemic: longitudinal findings from the CogEx study.
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Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Filippi M, Freeman J, Inglese M, Meza C, Motl RW, Rocca MA, Sandroff BM, and Salter A
- Subjects
- Humans, Female, Middle Aged, Male, Pandemics, Follow-Up Studies, Communicable Disease Control, Anxiety epidemiology, Anxiety etiology, Depression epidemiology, Depression etiology, Depression diagnosis, COVID-19, Multiple Sclerosis complications, Multiple Sclerosis, Chronic Progressive, Psychological Distress
- Abstract
Objective: An earlier follow-up study from the CogEx rehabilitation trial showed little change in symptoms of depression, anxiety and psychological distress during the first COVID-19 lockdown compared to pre-pandemic measurements. Here, we provide a second follow-up set of behavioral data on the CogEx sample., Methods: This was an ancillary, longitudinal follow-up study in CogEx, a randomized controlled trial of exercise and cognitive rehabilitation in people with progressive MS involving 11 centres in North America and Europe. Only individuals impaired on the Symbol Digit Modalities Test (SDMT) were included. Participants repeated the COVID Impact survey administered approximately a year later and completed self-report measures of depression, anxiety and MS symptoms that had been obtained at the trial baseline and during the first COVID Impact survey. Participants who completed the second COVID Impact follow-up were included. To identify predictors of the participants' ratings of their mental and physical well-being, step-wise linear regression was conducted., Results: Of the 131 participants who completed the first COVID impact survey, 74 participants completed the second follow-up survey (mean age 52 (SD = 6.4) years, 62.2% female, mean disease duration 16.4 (SD = 9.0) years, median EDSS 6.0). Pandemic restrictions prevented data collection from sites in Denmark and England (n = 57). The average time between measurements was 11.4 (SD = 5.56) months. There were no significant differences in age, sex, EDSS, disease course and duration between those who participated in the current follow-up study (n = 74) and the group that could not (n = 57). One participant had COVID in the time between assessments. Participants now took a more negative view of their mental/psychological well-being (p = 0.0001), physical well-being (p = 0.0009) and disease course (p = 0.005) compared to their last assessment. Depression scores increased on the HADS-depression scale (p = 0.01) and now exceeded the clinically significant threshold of ≥ 8.0 for the first time. Anxiety scores on the HADS remained unchanged. Poorer mental well-being was predicted by HADS depression scores (p = 0.012) and a secondary-progressive disease course (p = 0.0004)., Conclusions: A longer follow-up period revealed the later onset of clinically significant depressive symptoms on the HADS and a decline in self-perceptions of mental and physical well-being associated with the COVID-19 pandemic relative to the first follow-up data point., Trial Registration: The trial was registered on September 20th 2018 at www., Clinicaltrials: gov having identifier NCT03679468. Registration was performed before recruitment was initiated., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
- Published
- 2022
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17. Correction to: Early use of high-efficacy disease-modifying therapies makes the difference in people with multiple sclerosis: an expert opinion.
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Filippi M, Amato MP, Centonze D, Gallo P, Gasperini C, Inglese M, Patti F, Pozzilli C, Preziosa P, and Trojano M
- Published
- 2022
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18. Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion.
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Filippi M, Amato MP, Centonze D, Gallo P, Gasperini C, Inglese M, Patti F, Pozzilli C, Preziosa P, and Trojano M
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- Expert Testimony, Humans, Recurrence, Severity of Illness Index, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis drug therapy
- Abstract
Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients' preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients' preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
- Published
- 2022
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19. The impact of the COVID-19 pandemic on an international rehabilitation study in MS: the CogEx experience.
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Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Filippi M, Freeman J, Inglese M, Meza C, Motl R, Rocca MA, Sandroff BM, and Salter A
- Subjects
- Communicable Disease Control, Exercise, Humans, Pandemics, COVID-19, Multiple Sclerosis therapy
- Abstract
Pandemic restrictions have led to changes in therapy plans and disrupted rehabilitation services for people with multiple sclerosis. CogEx is an international, multicentre MS dual-intervention (cognitive rehabilitation, aerobic exercise) randomized, controlled rehabilitation trial confined to people with progressive disease. The primary outcome is cognition (processing speed).There are 11 treatment sites in six countries with participants required to make 27 site visits over 12 weeks. Collectively, the large, in-person demands of the trial, and the varying international policies for the containment of COVID-19, might disproportionately impact the administration of CogEx. During the first lockdown, all centres closed on average for 82.9 (SD = 24.3) days. One site was required to lockdown on two further occasions. One site remained closed for 16 months. Ten staff (19.2%) were required to quarantine and eight staff (15.4%) tested positive for COVID. 10 of 264 (3.8%) participants acquired COVID-19. All survived. The mean duration of enrollment delay has been [236.7 (SD = 214.5) days]. Restarting participants whose interventions were interrupted by the pandemic meant recalculating the intervention prescriptions for these individuals. While the impact of the pandemic on CogEx has been considerable, all study sites are again open. Participants and staff have shown considerable flexibility and resilience in keeping a complex, international endeavour running. The future in general remains uncertain in the midst of a pandemic, but there is cautious optimism the study will be completed with sufficient sample size to robustly evaluate our hypothesis and provide meaningful results to the MS community on the impact of these interventions on people with progressive MS.Trial registration: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
- Published
- 2022
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20. PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study.
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Chisari CG, Comi G, Filippi M, Paolicelli D, Iaffaldano P, Zaffaroni M, Brescia Morra V, Cocco E, Marfia GA, Grimaldi LM, Inglese M, Bonavita S, Lugaresi A, Salemi G, De Luca G, Cottone S, Conte A, Sola P, Aguglia U, Maniscalco GT, Gasperini C, Ferrò MT, Pesci I, Amato MP, Rovaris M, Solaro C, Lus G, Maimone D, Bergamaschi R, Granella F, Di Sapio A, Bertolotto A, Totaro R, Vianello M, Cavalla P, Bellantonio P, Lepore V, and Patti F
- Subjects
- Adult, Female, Humans, Immunologic Factors adverse effects, Middle Aged, Natalizumab adverse effects, Retrospective Studies, Leukoencephalopathy, Progressive Multifocal epidemiology, Multiple Sclerosis drug therapy, Multiple Sclerosis epidemiology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology
- Abstract
Background: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients., Materials and Methods: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other"., Results: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p < 0.001]; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22-4.75; p = 0.02; HR 1.36, 95% CI 1.18-5.41; p = 0.04)., Conclusions: Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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21. The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis.
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Chiaravalloti ND, Amato MP, Brichetto G, Chataway J, Dalgas U, DeLuca J, Meza C, Moore NB, Feys P, Filippi M, Freeman J, Inglese M, Motl R, Rocca MA, Sandroff BM, Salter A, Cutter G, and Feinstein A
- Subjects
- Anxiety epidemiology, Depression epidemiology, Europe epidemiology, Female, Humans, Male, Middle Aged, North America epidemiology, Quality of Life, Surveys and Questionnaires, COVID-19 epidemiology, Emotions, Mental Health statistics & numerical data, Multiple Sclerosis epidemiology, Multiple Sclerosis psychology, Pandemics
- Abstract
Objective: Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional symptomatology and quality of life in individuals with Progressive Multiple Sclerosis (PMS)., Methods: Data were obtained during a randomized clinical trial on rehabilitation taking place at 11 centers in North America and Europe. Participants included 131 individuals with PMS. Study procedures were interrupted in accordance with governmental restrictions as COVID-19 spread. During study closure, a COVID Impact Survey was administered via telephone or email to all participants, along with measures of depressive symptoms, anxiety symptoms, quality of life, and MS symptomatology that were previously administered pre-pandemic., Results: 4% of respondents reported COVID-19 infection. No significant changes were noted in anxiety, quality of life, or the impact of MS symptomatology on daily life from baseline to lockdown. While total HADS-depression scores increased significantly at follow-up, this did not translate into more participants scoring above the HADS threshold for clinically significant depression. No significant relationships were noted between disease duration, processing speed ability or EDSS, and changes in symptoms of depression or anxiety. Most participants reported the impact of the virus on their psychological well-being, with a little impact on financial well-being. The perceived impact of the pandemic on physical and psychological well-being was correlated with the impact of MS symptomatology on daily life, as well as changes in depression., Conclusions: Overall, little change was noted in symptoms of depression or anxiety or overall quality of life.
- Published
- 2021
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22. Treatment of MOG antibody associated disorders: results of an international survey.
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Whittam DH, Karthikeayan V, Gibbons E, Kneen R, Chandratre S, Ciccarelli O, Hacohen Y, de Seze J, Deiva K, Hintzen RQ, Wildemann B, Jarius S, Kleiter I, Rostasy K, Huppke P, Hemmer B, Paul F, Aktas O, Pröbstel AK, Arrambide G, Tintore M, Amato MP, Nosadini M, Mancardi MM, Capobianco M, Illes Z, Siva A, Altintas A, Akman-Demir G, Pandit L, Apiwattankul M, Hor JY, Viswanathan S, Qiu W, Kim HJ, Nakashima I, Fujihara K, Ramanathan S, Dale RC, Boggild M, Broadley S, Lana-Peixoto MA, Sato DK, Tenembaum S, Cabre P, Wingerchuk DM, Weinshenker BG, Greenberg B, Matiello M, Klawiter EC, Bennett JL, Wallach AI, Kister I, Banwell BL, Traboulsee A, Pohl D, Palace J, Leite MI, Levy M, Marignier R, Solomon T, Lim M, Huda S, and Jacob A
- Subjects
- Adult, Child, Humans, Myelin-Oligodendrocyte Glycoprotein, Plasmapheresis, Surveys and Questionnaires, Autoantibodies, Immunoglobulins, Intravenous therapeutic use
- Abstract
Introduction: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed., Objective: To survey the current global clinical practice of clinicians treating MOGAD., Method: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019)., Results: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT., Conclusion: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
- Published
- 2020
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23. Retrospectively acquired cohort study to evaluate the long-term impact of two different treatment strategies on disability outcomes in patients with relapsing multiple sclerosis (RE.LO.DI.MS): data from the Italian MS Register.
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Paolicelli D, Lucisano G, Manni A, Avolio C, Bonavita S, Brescia Morra V, Capobianco M, Cocco E, Conte A, De Luca G, De Robertis F, Gasperini C, Gatto M, Gazzola P, Lus G, Iaffaldano A, Iaffaldano P, Maimone D, Mallucci G, Maniscalco GT, Marfia GA, Patti F, Pesci I, Pozzilli C, Rovaris M, Salemi G, Salvetti M, Spitaleri D, Totaro R, Zaffaroni M, Comi G, Amato MP, and Trojano M
- Subjects
- Adult, Drug Administration Schedule, Female, Fingolimod Hydrochloride administration & dosage, Humans, Immunologic Factors administration & dosage, Interferon beta-1a administration & dosage, Italy, Male, Middle Aged, Retrospective Studies, Disease Progression, Fingolimod Hydrochloride pharmacology, Immunologic Factors pharmacology, Interferon beta-1a pharmacology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting physiopathology, Outcome Assessment, Health Care, Registries, Severity of Illness Index
- Abstract
Background: The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies., Objective: To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS 'real-world' settings., Methods: Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register., Results: We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-β1a) 44 µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-β1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48-2.04), p = 0.98 and 0.81 (0.42-1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00-2.12), p = 0.05]., Conclusion: The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-β1a to FTY.
- Published
- 2019
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24. Efficacy of fingolimod and interferon beta-1b on cognitive, MRI, and clinical outcomes in relapsing-remitting multiple sclerosis: an 18-month, open-label, rater-blinded, randomised, multicentre study (the GOLDEN study).
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Comi G, Patti F, Rocca MA, Mattioli FC, Amato MP, Gallo P, Centonze D, Pozzilli C, Saccà F, Bergh FT, Bartezaghi M, Turrini R, and Filippi M
- Subjects
- Adolescent, Adult, Depression drug therapy, Depression etiology, Disability Evaluation, Electrocardiography, Executive Function drug effects, Female, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Pilot Projects, Statistics, Nonparametric, Treatment Outcome, Young Adult, Cognition Disorders diagnostic imaging, Cognition Disorders drug therapy, Cognition Disorders etiology, Fingolimod Hydrochloride therapeutic use, Immunologic Factors therapeutic use, Interferon beta-1b therapeutic use, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting drug therapy
- Abstract
Cognitive impairment (CI) affects 40-65% of multiple sclerosis (MS) patients. This study attempted evaluating the effects of fingolimod and interferon beta-1b (IFN β-1b) on CI progression, magnetic resonance imaging (MRI) and clinical outcomes in relapsing-remitting MS (RRMS) patients over 18 months. The GOLDEN study was a pilot study including RRMS patients with CI randomised (2:1) to fingolimod (0.5 mg daily)/IFN β-1b (250 µg every other day). CI was assessed via Rao's Brief Repeatable Battery and Delis-Kaplan Executive Function System test. MRI parameters, Expanded Disability Status Scale scores and relapses were measured. Overall, 157 patients were randomised, of whom 30 discontinued the study (fingolimod, 8.49%; IFN β-1b, 41.18%; p ≤ 0.0001). Patients randomised to fingolimod had more severe clinical and MRI disease characteristics at baseline compared with IFN β-1b. At Month (M) 18, both treatment groups showed improvements in all cognitive parameters. At M18, relapse rate, total number and volume of T2/T1 gadolinium-enhancing lesions were higher with IFN β-1b, as well as the percentage brain volume change during the study. Safety and tolerability of both treatments were similar to previous studies. Both treatments showed improvements in cognitive parameters. Fingolimod demonstrated significantly better effects on MRI parameters and relapse rate. Imbalance in baseline characteristics and the drop-out pattern may have favoured IFN β-1b. A longer duration trial may be needed to observe the complete expression of differential effects on CI scales reflecting the between-groups differences on MRI. Although limited in size, the GOLDEN study confirms the favourable benefit-risk profile of fingolimod reported in previous studies.
- Published
- 2017
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25. Rebound after Fingolimod suspension in a pediatric-onset multiple sclerosis patient.
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Piscolla E, Hakiki B, Pastò L, Razzolini L, Portaccio E, and Amato MP
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- Age of Onset, Brain pathology, Child, Cyclophosphamide therapeutic use, Female, Fingolimod Hydrochloride, Humans, Magnetic Resonance Imaging, Plasma Exchange, Sphingosine adverse effects, Young Adult, Immunosuppressive Agents adverse effects, Multiple Sclerosis, Relapsing-Remitting drug therapy, Propylene Glycols adverse effects, Sphingosine analogs & derivatives
- Published
- 2013
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26. Treatment of cognitive impairment in multiple sclerosis: position paper.
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Amato MP, Langdon D, Montalban X, Benedict RH, DeLuca J, Krupp LB, Thompson AJ, and Comi G
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- Humans, Cognition Disorders etiology, Cognition Disorders therapy, Multiple Sclerosis complications, Multiple Sclerosis therapy
- Abstract
Cognitive impairment in multiple sclerosis (MS) is common, debilitating and burdensome. Key evidence from trials was reviewed to enable recommendations to be made to guide clinical practice and research. Behavioural and pharmacological interventions on cognition reported in published studies were reviewed. Most studies evaluating behavioural treatment for impairment in learning and memory, deficits of attention and executive function have demonstrated some improvement. Controlled studies in relapsing remitting MS indicate interferon (IFN) β-1b and IFN β-1a were associated with modest cognitive improvement. The effects of symptomatic therapies such as modafinil and donepezil are inconsistent. Most studies yielding positive findings have significant methodological difficulties limiting the confidence in making any broad treatment recommendations. There are no published reports of glatiramer acetate, natalizumab and fingolimod being effective in improving cognition in controlled trials. The effects of disease modifying therapies in other forms of MS and clinically isolated syndrome have not yielded positive results. Data linking behavioural therapy, symptomatic treatment or disease modifying treatment, to either reducing cognitive decline or improving impaired cognition are limited and inconsistent. The treatment and prevention of cognitive impairment needs to remain a key research focus, identifying new interventions and improving clinical trial methodology.
- Published
- 2013
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27. Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution.
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Bizzoco E, Lolli F, Repice AM, Hakiki B, Falcini M, Barilaro A, Taiuti R, Siracusa G, Amato MP, Biagioli T, Lori S, Moretti M, Vinattieri A, Nencini P, Massacesi L, and Matà S
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Animals, Child, Child, Preschool, Cross-Sectional Studies, Demyelinating Autoimmune Diseases, CNS epidemiology, Demyelinating Autoimmune Diseases, CNS physiopathology, Female, Humans, Italy epidemiology, Longitudinal Studies, Male, Middle Aged, Oligoclonal Bands blood, Oligoclonal Bands cerebrospinal fluid, Prevalence, Rats, Retrospective Studies, Severity of Illness Index, Statistics, Nonparametric, Young Adult, Neuromyelitis Optica epidemiology, Neuromyelitis Optica physiopathology, Phenotype
- Abstract
Neuromyelitis optica spectrum disorder (NMOsd) is a group of demyelinating disorders recently redefined and associated with NMO-IgG/anti-aquaporin 4 antibodies. Because NMOsd is of unknown prevalence worldwide, we conducted a retrospective, cross-sectional study of 850 patients with demyelinating disorders hospitalized in North East Tuscany from 1998 to 2006 to examine the prevalence of NMO and related disorders among unselected consecutive neurological patients with inflammatory CNS diseases and to evaluate the clinical phenotype spectrum of identified cases. Clinical data were updated after at least 2 years of follow-up. An immunofluorescence technique was used to detect NMO-IgG on rat brain tissue. Sera from other 828 neurological patients, 65 non-neurological patients and 50 healthy donors served as controls. The prevalence of NMOsd was 1.5%, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up. The final EDSS score ranged from 1 to 10, mainly depending on brainstem involvement occurrence. Our findings confirm a low prevalence of NMO and related disorders among demyelinating inflammatory diseases in a Caucasian population. Moreover, this study demonstrates an unexpectedly high prevalence of limited and atypical variants of this disease, not previously documented.
- Published
- 2009
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28. Motor evoked potentials in multiple sclerosis patients without walking limitation: amplitude vs. conduction time abnormalities.
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Gagliardo A, Galli F, Grippo A, Amantini A, Martinelli C, Amato MP, and Borsini W
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- Adult, Case-Control Studies, Disability Evaluation, Female, Humans, Male, Middle Aged, Neural Conduction physiology, Neural Conduction radiation effects, Reaction Time radiation effects, Retrospective Studies, Severity of Illness Index, Transcranial Magnetic Stimulation methods, Evoked Potentials, Motor physiology, Multiple Sclerosis physiopathology, Reaction Time physiology, Walking
- Abstract
We used Motor Evoked Potentials (MEPs), elicited by transcranial magnetic stimulation, for assessing a motor pathways dysfunction in a selected group of Multiple Sclerosis (MS) patients, without limitation in walking. We selected 32 Relapsing Remitting MS patients, in remission phase, with EDSS < or = 3.5 and 20 healthy individuals with similar height and age distribution. We measured the following MEP parameters: motor thresholds; central motor conduction time (CMCT); amplitude and area, both expressed as MEP/CMAP ratio. Patients were divided into two groups according to the EDSS score: non-disabled group (ND; EDSS 0-1.5) and disabled group (D; EDSS 2-3.5). Mean average MEP values were significantly different in the patients compared with the controls. Even in MS patients with no or minor neurological signs (ND group), MEP parameters showed differences from controls and furthermore all MEP parameters were significantly different in the D group compared with the ND group. The 75% of the patients had an amplitude or area alteration; this percentage was significantly higher than the percentage of patients with a CMCT alteration (56.2%). In addition, CMCT increase was always associated with reduced amplitude and area, but amplitude and area alterations were present also in patients with normal CMCT. In early stages of MS, the higher percentage shown in alteration of MEP amplitudes and areas as opposed to CMCTs has not previously been highlighted in the literature. Independently of its pathogenesis (demyelination or axonal loss), the amplitude or area decrease should be considered in clinical trials and in follow-up studies, as a marker of the motor pathways dysfunction, at least as much as CMCT increase.
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- 2007
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29. Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort.
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Amato MP, Zipoli V, Goretti B, Portaccio E, De Caro MF, Ricchiuti L, Siracusa G, Masini M, Sorbi S, and Trojano M
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- Adult, Cognition, Cognition Disorders diagnosis, Female, Humans, Logistic Models, Male, Middle Aged, Multiple Sclerosis complications, Multiple Sclerosis physiopathology, Neuropsychological Tests, Cognition Disorders etiology, Depression etiology, Disabled Persons psychology, Fatigue etiology, Multiple Sclerosis psychology
- Abstract
Objectives: A study of cognitive, psychological and social aspects in benign multiple sclerosis (MS). Methods One hundred and sixty three patients with benign MS (defined as disease duration > or = 15 years and Expanded Disability Status Scale (EDSS) score < or = 3.0 ) underwent neuropsychological testing on the Rao's Brief Repeatable Battery (BRB) and the Stroop test, evaluation of depression on the Montgomery and Asberg Depression Rating Scale (MADRS), of fatigue on the Fatigue Severity Scale (FSS) and of handicap on the Environmental Status Scale (ESS). Patients' cognitive performance was compared with that of 111 demographically matched healthy controls. Cognitive impairment was defined as the failure in at least 3 tests, using the fifth percentile of controls' performance as the cut-off point. Clinical correlates of cognitive impairment were determined by multiple logistic regression analysis., Results: Cognitive assessment led to the identification of 74 subjects (45%) with cognitive impairment. Significant fatigue was found in 80 subjects (49%) and depression in 88 patients (54%). In comparison with cognitively preserved subjects, cognitively impaired patients exhibited higher handicap scores on the ESS (p = 0.005). In the regression analysis, only EDSS scores were significantly associated with cognitive impairment (OR 1.8, 95%CI 1.2-2.6)., Conclusion: Current definitions of benign MS may overestimate this entity, since they are mainly weighted for the patients' motor abilities and fail to capture relevant disease-related cognitive, psychological and social problems.
- Published
- 2006
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30. Clinical correlations of CSF single IgG bands.
- Author
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Franciotta D, Bergamaschi R, Amato MP, Zardini E, Persico A, Portaccio E, and Lolli F
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Child, Child, Preschool, Electrophoresis, Agar Gel, Female, Humans, Immunoglobulin G metabolism, Immunohistochemistry, Infant, Isoelectric Focusing, Male, Middle Aged, Multiple Sclerosis blood, Multiple Sclerosis classification, Multiple Sclerosis diagnosis, Peroxidase metabolism, Retrospective Studies, Immunoglobulin G analysis, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis immunology, Oligoclonal Bands immunology
- Published
- 2005
- Full Text
- View/download PDF
31. European validation of a standardized clinical description of multiple sclerosis.
- Author
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Amato MP, Grimaud J, Achiti I, Bartolozzi ML, Adeleine P, Hartung HP, Kappos L, Thompson A, Trojano M, Vukusic S, and Confavreux C
- Subjects
- Adult, Disability Evaluation, Female, Humans, Male, Medical Records, Multiple Sclerosis classification, Nervous System physiopathology, Observer Variation, Databases, Factual standards, European Union, Multiple Sclerosis physiopathology
- Abstract
Objectives: The EDMUS system is a clinical database specifically tailored to the description of multiple sclerosis (MS). The EVALUED (Evaluation of the EDMUS system) study is an European project with two objectives: 1) to assess the inter-examiner reliability of the whole EDMUS system; 2) to validate the EDMUS-Grading Scale (EGS),which is a simplified version of the Kurtzke Disability Status Scale (DSS)., Methods: The protocol included 12 neurologists working in pairs within six European centres (Bari, Basel, Florence, London, Lyon, Würzburg). They assessed independently 30 MS patients in their centre, filling in the EDMUS forms. The reliability of the system was assessed on selected key items in the history of the MS onset, the clinical course and the disease course classification. The clinical examination of the patients permitted an assessment of the Kurtzke Expanded Disability Status Scale (EDSS) and the EGS. Level of agreement was measured in terms of kappa and weighted kappa indexes whenever appropriate., Results: The study included 180 patients with definite or probable MS of whom 37% were males. Age was 35.8+/-9.6 years (mean +/- SD), disease duration 7.8+/-5.7 years, and mean EDSS score 4.1+/-2.2. The disease course was relapsing-remitting in 67%, secondary progressive in 22%, and progressive from disease onset in 11%. For key items of the history, the inter-examiner reliability level ranged from moderate to excellent. Concerning the disability scales, perfect agreement was reached in 59 % for EDSS and 78% for EGS. The close correlation and linear association (r=0.94, p<0.0001) between both scales demonstrated EGS's construct validity., Conclusion: The EDMUS system allows a consistent clinical description of MS using a common language. This standardized follow-up of MS patients is valuable especially in studies requiring a critical mass of informative patients.
- Published
- 2004
- Full Text
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32. The costs of multiple sclerosis: a cross-sectional, multicenter cost-of-illness study in Italy.
- Author
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Amato MP, Battaglia MA, Caputo D, Fattore G, Gerzeli S, Pitaro M, Reggio A, and Trojano M
- Subjects
- Adolescent, Adult, Caregivers economics, Caregivers statistics & numerical data, Cross-Sectional Studies, Disease Progression, Economics, Pharmaceutical statistics & numerical data, Female, Humans, Italy, Male, Middle Aged, Multiple Sclerosis epidemiology, Patient Acceptance of Health Care statistics & numerical data, Prospective Studies, Sex Factors, Sick Leave economics, Sick Leave statistics & numerical data, Socioeconomic Factors, Health Care Costs statistics & numerical data, Multiple Sclerosis economics
- Abstract
Objectives: To estimate the socio-economic impact of multiple sclerosis (MS) in Italy., Methods: Outpatients with MS were enrolled at 44 centres across Italy. Socio-demographic, clinical and resource utilization data were collected using a validated questionnaire. Each patient completed a weekly diary of expenses due to MS over a three-month period. Direct health care costs and indirect costs (lack of productivity for the patient and for caregivers) were assessed for the whole population and were compared among five groups, categorised by disease severity (EDSS score). An analysis of variance was carried out on socio-demographic variables., Results: For the total population of 566 patients, the mean direct cost over three months was ITL 2,134,000, the mean indirect cost was ITL 7,775,000. Costs were significantly higher for male patients (p < 0.05) and showed a significant increase with increasing age (p < 0.0005), disease duration (p < 0.0005) and disease severity (p < 0.0005). Costs for patients in a progressive phase were significantly higher (p < 0.0005). There were no significant geographical differences among the regions of Italy., Conclusions: This study confirms that MS represents a high economic burden, with indirect costs greatly exceeding direct costs. Unpaid caregivers remain the culturally accepted mode of care for MS patients in Italy and this study illustrates the impact of their loss of earnings. As costs increase with disease progression, these findings suggest that treatment efforts should focus on patients in the early stages of MS, in order to slow down disease progression.
- Published
- 2002
- Full Text
- View/download PDF
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