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EBioMedicine Jul 2023Neurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, is associated with multiple sclerosis (MS) relapsing activity... (Randomized Controlled Trial)
Randomized Controlled Trial
Blood neurofilament light levels predict non-relapsing progression following anti-CD20 therapy in relapsing and primary progressive multiple sclerosis: findings from the ocrelizumab randomised, double-blind phase 3 clinical trials.
BACKGROUND
Neurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, is associated with multiple sclerosis (MS) relapsing activity and has demonstrated some prognostic ability for future relapse-related disease progression, yet its value in assessing non-relapsing disease progression remains unclear.
METHODS
We examined baseline and longitudinal blood NfL levels in 1421 persons with relapsing MS (RMS) and 596 persons with primary progressive MS (PPMS) from the pivotal ocrelizumab MS trials. NfL treatment-response and risk for disease worsening (including disability progression into the open-label extension period and slowly expanding lesions [SELs] on brain MRI) at baseline and following treatment with ocrelizumab were evaluated using time-to-event analysis and linear regression models.
FINDINGS
In persons from the RMS control arms without acute disease activity and in the entire PPMS control arm, higher baseline NfL was prognostic for greater whole brain and thalamic atrophy, greater volume expansion of SELs, and clinical progression. Ocrelizumab reduced NfL levels vs. controls in persons with RMS and those with PPMS, and abrogated the prognostic value of baseline NfL on disability progression. Following effective suppression of relapse activity by ocrelizumab, NfL levels at weeks 24 and 48 were significantly associated with long-term risk for disability progression, including up to 9 years of observation in RMS and PPMS.
INTERPRETATION
Highly elevated NfL from acute MS disease activity may mask a more subtle NfL abnormality that reflects underlying non-relapsing progressive biology. Ocrelizumab significantly reduced NfL levels, consistent with its effects on acute disease activity and disability progression. Persistently elevated NfL levels, observed in a subgroup of persons under ocrelizumab treatment, demonstrate potential clinical utility as a predictive biomarker of increased risk for clinical progression. Suppression of relapsing biology with high-efficacy immunotherapy provides a window into the relationship between NfL levels and future non-relapsing progression.
FUNDING
F. Hoffmann-La Roche Ltd.
Topics: Humans; Acute Disease; Disease Progression; Intermediate Filaments; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 37354600
DOI: 10.1016/j.ebiom.2023.104662 -
Multiple Sclerosis and Related Disorders May 2024
Topics: Humans; Multiple Sclerosis
PubMed: 38574723
DOI: 10.1016/j.msard.2024.105575 -
Disease-a-month : DM Sep 2023Multiple sclerosis is an autoimmune chronic inflammatory disease characterized by selective destruction of myelin in the CNS neurons (including optic nerve). It was... (Review)
Review
BACKGROUND
Multiple sclerosis is an autoimmune chronic inflammatory disease characterized by selective destruction of myelin in the CNS neurons (including optic nerve). It was first described in the 19 century and remained elusive owing to the disease's unique relapsing and remitting course. The widespread and debilitating prevalence of multiple sclerosis (MS) has prompted the development of various treatment modalities for its effective management.
METHODS AND OBJECTIVES
A literature review was conducted using the electronic databases PubMed and Google Scholar. The main objective of the review was to compile the advances in pathogenesis, classifications, and evolving treatment modalities for MS.
RESULTS
The understanding of the pathogenesis of MS and the potential drug targets for its precise treatment has evolved significantly over the past decade. The experimental developments are also motivating and present a big change coming up in the next 5 years. Numerous disease-modifying therapies (DMTs) have revolutionized the management of MS: interferon (IFN) preparations, monoclonal antibodies-natalizumab and ocrelizumab, immunomodulatory agents-glatiramer acetate, sphingosine 1-phosphate receptor 1 (S1PR1) modulators (Siponimod) and teriflunomide. The traditional parenteral drugs are now available as oral formulations improving patient acceptability. Repurposing various agents used for related diseases may reinforce the drug reserve to manage MS and are under trials. Although at a nascent phase, strategies to enhance re-myelination by stimulating oligodendrocytes are fascinating and hold promise for better outcomes in patients with MS.
CONCLUSIONS
The recent past has seen staggering inclusions to the management of multiple sclerosis catalyzing a significant turnabout in our approach to diagnosis, treatment, and prognosis. Since the advent of DMTs various other oral and injectable agents have been approved. The advances in MS therapeutics and diagnostics have laid the ground for further research and development to enhance the quality of life of afflicted patients.
Topics: Humans; Multiple Sclerosis; Quality of Life; Glatiramer Acetate; Antibodies, Monoclonal; Prognosis; Immunosuppressive Agents
PubMed: 36280474
DOI: 10.1016/j.disamonth.2022.101497 -
Multiple Sclerosis and Related Disorders May 2024
Topics: Humans; Multiple Sclerosis; Lymphocytes
PubMed: 38479047
DOI: 10.1016/j.msard.2024.105533 -
Neurologic Clinics Feb 2024
Topics: Humans; Multiple Sclerosis
PubMed: 37980125
DOI: 10.1016/j.ncl.2023.08.001 -
Practical Neurology Aug 2023
Topics: Humans; Sclerosis; Multiple Sclerosis
PubMed: 37100592
DOI: 10.1136/pn-2022-003677 -
Neurologic Clinics Feb 2024Multiple sclerosis has a 3:1 female-to-male predominance and commonly presents in young adult women. The hormonal changes in women throughout their lifetime do affect... (Review)
Review
Multiple sclerosis has a 3:1 female-to-male predominance and commonly presents in young adult women. The hormonal changes in women throughout their lifetime do affect the underlying pathology of multiple sclerosis, and the needs of women therefore change with age. Although multiple sclerosis does not adversely affect fertility or pregnancy, there are many factors to consider when caring for women throughout family planning, pregnancy, and the postpartum period. The care of these women and complex decisions regarding disease-modifying therapy use in family planning should be individualized and comprehensive.
Topics: Pregnancy; Young Adult; Female; Humans; Male; Multiple Sclerosis; Women's Health; Postpartum Period
PubMed: 37980119
DOI: 10.1016/j.ncl.2023.07.004 -
Multiple Sclerosis (Houndmills,... Oct 2023Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem.
BACKGROUND
Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem.
OBJECTIVE
Describe the prevalence, determinants and consequences of delayed diagnoses.
METHODS
This single-centre ambispective study analysed 146 adult relapsing-remitting MS patients (2016-2021) for frequency and determinants of diagnostic delays and their associations with clinical, cognitive, imaging and biochemical measures.
RESULTS
Diagnostic delays were identified in 77 patients (52.7%), including 42 (28.7%) physician-dependent cases and 35 (24.0%) patient-dependent cases. Diagnosis was delayed in 22 (15.1%) patients because of misdiagnosis by a neurologist. A longer diagnostic delay was associated with trends towards greater Expanded Disability Status Scale (EDSS) scores ( = 0.03; = 0.034) and greater -score of the blood neurofilament light chain ( = 0.35; = 0.031) at the time of diagnosis. Compared with patients diagnosed at their first clinical relapse, patients with a history of >1 relapse at diagnosis ( = 63; 43.2%) had a trend towards greater EDSS scores ( = 0.06; = 0.006) and number of total ( = 0.13; = 0.040) and periventricular ( = 0.06; = 0.039) brain lesions.
CONCLUSION
Diagnostic delays in MS are common, often determined by early misdiagnosis and associated with greater disease burden.
Topics: Adult; Humans; Multiple Sclerosis; Delayed Diagnosis; Prevalence; Multiple Sclerosis, Relapsing-Remitting; Recurrence; Magnetic Resonance Imaging; Brain
PubMed: 37840276
DOI: 10.1177/13524585231197076 -
Multiple Sclerosis and Related Disorders Nov 2023Multiple sclerosis (MS) is a chronic inflammatory and autoimmune neurodegenerative disease characterized by the destruction of myelin in the central nervous system,... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory and autoimmune neurodegenerative disease characterized by the destruction of myelin in the central nervous system, leading to significant health and quality of life burdens for patients. MS is most prevalent in younger individuals aged 20-40, a critical period when many patients hope to establish relationships and start families. While neurological disability, such as fatigue, sensory dysfunction, spasticity, and cognitive dysfunction, have been greatly improved with the advances in managing MS, physicians are frequently confronted with sexual and reproductive problems among younger male people with MS (PwMS). These issues mainly include erectile dysfunction, ejaculatory disorders, reduced libido, decreased sperm quality, and impaired male fertility. Despite recent studies indicating that MS negatively impacts the sexuality and fertility of male PwMS, these issues have not received sufficient attention. Genetic factors, autoimmunity, chronic inflammation, psychological factors, and the use of drugs may contribute to sexual/reproductive dysfunction in PwMS. However, like the overall understanding of MS pathophysiology, the complete mechanisms of its development remain unclear. In this study, we review the existing literature to summarize the range of sexual and reproductive issues unique to males with MS, explore potential underlying mechanisms, and aim to improve these issues in male PwMS. By shedding light on this overlooked aspect of MS, we hope to enhance the care and well-being of male PwMS facing these challenges.
Topics: Humans; Male; Multiple Sclerosis; Quality of Life; Neurodegenerative Diseases; Reproductive Health; Semen; Sexual Dysfunction, Physiological; Inflammation
PubMed: 37832256
DOI: 10.1016/j.msard.2023.105059 -
International Journal of Molecular... May 2024Neuroinflammatory conditions in the central nervous system (CNS) are implicated in the pathogenesis of several neuroimmune disorders such as acquired demyelinating...
Neuroinflammatory conditions in the central nervous system (CNS) are implicated in the pathogenesis of several neuroimmune disorders such as acquired demyelinating syndromes, autoimmune encephalopathies, acute or chronic bacterial and viral CNS infections as well as multiple sclerosis (MS) [...].
Topics: Humans; Neuroinflammatory Diseases; Animals; Multiple Sclerosis; Central Nervous System; Inflammation
PubMed: 38892158
DOI: 10.3390/ijms25115973