Multiple Sclerosis Progression and Relapse Activity in Children DOI
Pietro Iaffaldano, Emilio Portaccio,

Giuseppe Lucisano

et al.

JAMA Neurology, Journal Year: 2023, Volume and Issue: 81(1), P. 50 - 50

Published: Nov. 27, 2023

Importance Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years age, it has been suggested that people pediatric-onset MS (POMS) are protected against disability because greater capacity for repair. Objective To assess the incidence and factors associated progression independent relapse activity (PIRA) relapse-associated worsening (RAW) in POMS compared typical adult-onset (AOMS) late-onset (LOMS). Design, Setting, Participants This cohort study on prospectively acquired data from Italian Register was performed June 1, 2000, September 30, 2021. At time extraction, longitudinal 73 564 120 centers were available register. Main Outcomes Measures The main outcomes included age-related cumulative adjusted hazard ratios (HRs) PIRA RAW factors. Exposures Clinical magnetic resonance imaging features, receiving disease-modifying therapy (DMT), first DMT. Results After applying inclusion exclusion criteria, assessed 16 130 (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared AOMS LOMS, had less disability, exhibited more active disease, exposed DMT a longer period. A 48-week-confirmed occurred 7176 (44.5%): 558 (40.4%), 6258 (44.3%), 360 LOMS (56.8%) ( P < .001). Factors older (AOMS vs HR, 1.42; 95% CI, 1.30-1.55; 2.98; 2.60-3.41; .001), disease duration (HR, 1.04; 1.04-1.05; shorter exposure 0.69; 0.64-0.74; 1.3% 20 but rapidly increased approximately 7 times between 21 30 (9.0%) nearly doubled each decade 40 70 (21.6% years, 39.0% 50 61.0% 60 78.7% years). events followed similar trend (0.5% 3.5% 7.8% 14.4% 24.1% years); no further increase found (27.7%). Delayed initiation higher risk 1.16; 1.00-1.34; = .04) 1.75; 1.28-2.39; Conclusions Relevance can occur any although pediatric is not fully protective progression, this study’s findings suggest likely exhibit over follow-up. However, these also reinforce benefit POMS, as treatment reduced occurrence both regardless onset.

Language: Английский

Multiple sclerosis DOI
Dejan Jakimovski, Stefan Bittner, Robert Zivadinov

et al.

The Lancet, Journal Year: 2023, Volume and Issue: 403(10422), P. 183 - 202

Published: Nov. 7, 2023

Language: Английский

Citations

189
Advances in Neurodegenerative Diseases DOI Open Access
Jeroen Van Schependom, Miguel D’haeseleer

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(5), P. 1709 - 1709

Published: Feb. 21, 2023

Neurological disorders are the leading cause of physical and cognitive disability across globe, currently affecting approximately 15% worldwide population [...].

Language: Английский

Citations

89
Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis DOI
Jannis Müller, Alessandro Cagol, Johannes Lorscheider

et al.

JAMA Neurology, Journal Year: 2023, Volume and Issue: 80(11), P. 1232 - 1232

Published: Oct. 2, 2023

Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there no uniform agreed-upon definition PIRA, limiting the comparability published studies.

Language: Английский

Citations

89
Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis DOI
Ahmed Abdelhak, Pascal Benkert,

Sabine Schaedelin

et al.

JAMA Neurology, Journal Year: 2023, Volume and Issue: 80(12), P. 1317 - 1317

Published: Nov. 6, 2023

Importance Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity people MS (MS); however, data on the association between NfL level and have been conflicting. Objective To determine whether when levels elevated context confirmed worsening (CDW). Design, Setting, Participants This study included 2 observational cohorts: results from Expression, Proteomics, Imaging, Clinical (EPIC) at University California San Francisco (since 2004) were Swiss Multiple Sclerosis Cohort (SMSC), multicenter 8 centers since 2012. Data extracted EPIC April 2022 (sampling July 1, 2004, December 20, 2016) SMSC June 6, 2012, September 2, 2021). The cohorts tertiary centers. All participants both available study, no eligible excluded or declined participate. Exposure Association z scores CDW. Main Outcome Measures CDW was defined as Expanded Disability Status Scale (EDSS) that after 6 more months classified into associated clinical relapses (CDW-R) independent (CDW-NR). Visits relation events CDW(−2) for visits preceding event, CDW(−1) directly CDW(event) first diagnosis EDSS increase, confirmation visit. Mixed linear Cox regression models used evaluate dynamics assess future CDW, respectively. Results A total 3906 (609 participants; median [IQR] age, 42.0 [35.0-50.0] years; 424 female [69.6%]) 8901 (1290 41.2 [32.5-49.9] 850 [65.9%]) included. In CDW-R (EPIC, 36 events; SMSC, 93 events), 0.71 (95% CI, 0.35-1.07; P < .001) units higher CDW-R(−1) 0.32 0.14-0.49; compared stable samples. elevation could be detected CDW-NR 191 342 events) CDW-NR(−2) (EPIC: 0.23; 95% 0.01-0.45; = .04; SMSC: 0.28; 0.18-0.37; CDW-NR(−1) 0.27; 0.11-0.44; .001; 0.09; 0-0.18; .06). Those findings replicated subgroup relapsing-remitting MS. Time-to-event analysis within approximately 1 year (in 1-2 years). Conclusions Relevance cohort documents occurrence advance may hint potential window ongoing dynamic central nervous system pathology precedes

Language: Английский

Citations

44
The neuropathobiology of multiple sclerosis DOI
Marcel S. Woo, Jan Broder Engler, Manuel A. Friese

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(7), P. 493 - 513

Published: May 24, 2024

Language: Английский

Citations

33
Clinical trials for progressive multiple sclerosis: progress, new lessons learned, and remaining challenges DOI
Jeremy Chataway, Thomas Williams, Vivien Li

et al.

The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(3), P. 277 - 301

Published: Feb. 15, 2024

Language: Английский

Citations

28
Multiple sclerosis: emerging epidemiological trends and redefining the clinical course DOI Creative Commons
Emilio Portaccio, Melinda Magyari, Eva Havrdová

et al.

The Lancet Regional Health - Europe, Journal Year: 2024, Volume and Issue: 44, P. 100977 - 100977

Published: Aug. 23, 2024

SummaryMultiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system major cause neurological disability in young adults. Its prevalence incidence are increasing, it has been estimated at over 2.8 million cases worldwide, addition to recent trends towards shift MS older ages, with peak estimates sixth decade life. Although historically relapsing progressive phases have considered separate clinical entities, evidence progression independent relapse activity (PIRA) led reconsideration multiple as continuum, which features variably coexist from earliest stages disease, challenging traditional view course. In this Series article, we provide an overview how description course epidemiological Europe evolved. For purpose, focus on concept PIRA, discussing its potential main mechanism by patients acquire disability, definition varies between studies, ongoing research field. We emphasise importance incorporating assessment hidden manifestations into patient management help uncover quantify PIRA phenomenon possible implications for future changes classification disease. At same time, insights overcoming challenges identifying defining adopting new understanding MS.

Language: Английский

Citations

26
B cell-targeting chimeric antigen receptor T cells as an emerging therapy in neuroimmunological diseases DOI Creative Commons
Aiden Haghikia, Georg Schett,

Dimitrios Mougiakakos

et al.

The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(6), P. 615 - 624

Published: May 15, 2024

Language: Английский

Citations

23
Using the Progression Independent of Relapse Activity Framework to Unveil the Pathobiological Foundations of Multiple Sclerosis DOI
Olga Ciccarelli, Frederik Barkhof, Massimiliano Calabrese

et al.

Neurology, Journal Year: 2024, Volume and Issue: 103(1)

Published: June 18, 2024

Progression independent of relapse activity (PIRA), a recent concept to formalize disability accrual in multiple sclerosis (MS) relapses, has gained popularity as potential clinical trial outcome. We discuss its shortcomings and appraise the challenges implementing it settings, experimental trials, research. The current definition PIRA assumes that acute inflammation, which can manifest relapse, neurodegeneration, manifesting progressive accrual, be disentangled by introducing specific time windows between onset relapses observed increase disability. term PIRMA (progression MRI activity) was recently introduced indicate absence both new brain spinal cord lesions. Assessing practice is highly challenging because necessitates frequent assessments scans. commonly assessed using Expanded Disability Status Scale, scale heavily weighted toward motor disability, whereas more granular assessment deterioration, including cognitive decline, composite measures or other tools, such digital would possess greater utility. Similarly, an outcome measure randomized trials also requires methodological considerations. underpinning pathobiology accumulation, not associated with may encompass chronic active lesions (slowly expanding paramagnetic rim lesions), cortical lesions, atrophy, particularly gray matter, diffuse focal microglial activation, persistent leptomeningeal enhancement, white matter tract damage. propose use understand main determinant observational, cohort studies, where regular scans are included, introduce "advanced-PIRMA" investigate contributions abovementioned processes, conventional advanced imaging. This supported knowledge reflects MS pathogenic mechanisms better than purely descriptors. Any residual remains unexplained after considering all these imaging, will highlight future research priorities help complete our understanding pathogenesis.

Language: Английский

Citations

21
Smouldering‐Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions DOI Creative Commons
Antonio Scalfari, Anthony Traboulsee, Jiwon Oh

et al.

Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(5), P. 826 - 845

Published: July 25, 2024

Despite therapeutic suppression of relapses, multiple sclerosis (MS) patients often experience subtle deterioration, which extends beyond the definition "progression independent relapsing activity." We propose concept smouldering-associated-worsening (SAW), encompassing physical and cognitive symptoms, resulting from smouldering pathological processes, remain unmet targets. provide a consensus-based framework possible substrates manifestations MS, we discuss clinical, radiological, serum/cerebrospinal fluid biomarkers for potentially monitoring SAW. Finally, share considerations optimizing disease surveillance implications clinical trials to promote integration MS into routine practice future research efforts. ANN NEUROL 2024;96:826-845.

Language: Английский

Citations

18