Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients—A Comprehensive Review DOI Open Access
Sara Gómez-Melero, Javier Caballero‐Villarraso,

Begoña Ma Escribano

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(11), P. 3321 - 3321

Published: June 4, 2024

Multiple sclerosis (MS) is characterized by a variety of symptoms that have major impact on quality life (QoL) even in early stages. In addition to individual motor, sensory, visual disturbances, and brainstem sphincter disorders, which are expressed through the widely used Expanded Disability Status Scale (EDSS), other manifestations MS detrimental effect overall functioning life, such as cognitive impairment, depression, anxiety, fatigue, pain. However, when talking about QoL, categorical definitions cannot be because although concept generally understood, it highly nuanced. Suffering from can significantly reduce QoL. Numerous research studies focused trying identify assess elements most affect loss QoL people. fact measurement subjective, very difficult consider these isolation, they interrelated. One limiting factor has been investigated impairment (CI). This shown an lives people, different approaches taken CI evident limitations.

Language: Английский

Hallmarks of neurodegenerative diseases DOI Creative Commons

David M. Wilson,

Mark Cookson, Ludo Van Den Bosch

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 693 - 714

Published: Feb. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Language: Английский

Citations

801
Multiple sclerosis progression: time for a new mechanism-driven framework DOI
Tanja Kuhlmann, Marcello Moccia, Timothy Coetzee

et al.

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 22(1), P. 78 - 88

Published: Nov. 18, 2022

Language: Английский

Citations

336
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

181
Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis DOI Creative Commons
Christian Barro, Brian C. Healy, Yanqing Liu

et al.

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 14, 2022

Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) can be quantified by serum neurofilament light chain (sNfL) glial fibrillary acidic protein (sGFAP). We investigated sNfL sGFAP as tools for stratifying patients with MS based on progression disease activity status.We leveraged our Comprehensive Longitudinal Investigation at the Brigham Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data samples collected over more than 20 years. included a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds classifier high risk underlying pathology. analyzed within 6 months from EDSS corresponding baseline visit. Patients who further developed 6-month disability (6mCDP) were classified progressors. stratified into active/nonactive new brain/spinal cord lesions or relapses in 2 years before during follow-up. Statistical analysis log-transformed sGFAP/sNfL assessed association demographic, features associations future disability.We 257 had an average 4.0 median follow-up after 7.6 was higher (adjusted β = 1.21; 95% CI 1.04-1.42; p 0.016), first 1.17; 1.01-1.36; 0.042). not increased presence activity. Higher levels, but associated 6mCDP hazard ratio [HR] 1.71; 1.19-2.45; 0.004). The stronger low HR 2.44; 1.32-4.52; 0.005) nonactive prior sample.Higher levels correlated subsequent progression, particularly patients, whereas reflected acute Thus, may used to stratify clinical research studies trials inform care.

Language: Английский

Citations

107
Bruton tyrosine kinase inhibitors for multiple sclerosis DOI Open Access
Julia Krämer, Amit Bar‐Or, Timothy J. Turner

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(5), P. 289 - 304

Published: April 13, 2023

Language: Английский

Citations

99
Microglia in multiple sclerosis: Protectors turn destroyers DOI Creative Commons
V. Wee Yong

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3534 - 3548

Published: July 25, 2022

Language: Английский

Citations

90
CNS remyelination and inflammation: From basic mechanisms to therapeutic opportunities DOI Creative Commons
Robin J.M. Franklin, Mikael Simons

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3549 - 3565

Published: Oct. 12, 2022

Language: Английский

Citations

88
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

25
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

19
Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability DOI Creative Commons
Alise Carlson, Moein Amin, Jeffrey A. Cohen

et al.

Drugs, Journal Year: 2024, Volume and Issue: 84(3), P. 285 - 304

Published: March 1, 2024

Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed therapeutic landscape MS through robust efficacy on clinical manifestations MRI lesion activity, currently anti-CD20 mAb therapies for use in a cornerstone highly effective disease-modifying treatment. Ocrelizumab is only with regulatory approval primary progressive MS. There few data regarding relative these therapies, though several trials ongoing. Safety concerns applicable this class therapeutics relate primarily immunogenicity mechanism action, include infusion-related or injection-related reactions, development hypogammaglobulinemia (leading increased infection malignancy risk), decreased vaccine response. Exploration alternative dose/dosing schedules might be an strategy mitigating risks. Future biosimilar medications make more readily available. Although have led significant improvements disease outcomes, CNS-penetrant still needed effectively address compartmentalized inflammation thought play important role disability progression.

Language: Английский

Citations

18