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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 -
Brain : a Journal of Neurology Nov 2023Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation...
Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients was 39 (95% confidence interval: 37 to 43) years. Higher latitude [median hazard ratio = 1.21, 95% credible interval (1.16, 1.26)], higher national multiple sclerosis prevalence [1.07 (1.03, 1.11)], male sex [1.30 (1.22, 1.39)], older age at onset [1.35 (1.30, 1.39)], higher disability [2.40 (2.34, 2.47)] and frequent relapses [1.18 (1.15, 1.21)] at inclusion were associated with increased hazard of secondary progressive multiple sclerosis. Higher proportion of time on high-to-moderate efficacy therapy substantially reduced the hazard of secondary progressive multiple sclerosis [0.76 (0.73, 0.79)] and reduced the effect of latitude [interaction: 0.95 (0.92, 0.99)]. At the country-level, patients in Oman, Tunisia, Iran and Canada had higher risks of secondary progressive multiple sclerosis relative to the other studied regions. Higher latitude of residence is associated with a higher probability of developing secondary progressive multiple sclerosis. High-to-moderate efficacy immunotherapy can mitigate some of this geographically co-determined risk.
Topics: Humans; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Ultraviolet Rays; Disease Progression; Neoplasm Recurrence, Local
PubMed: 37369086
DOI: 10.1093/brain/awad218 -
Cells Mar 2020Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of the disease are available to study MS pathogenesis and to develop new therapeutic options. During the last decade, the model of toxic demyelination induced by cuprizone has become more and more popular, and it has contributed substantially to our understanding of distinct yet important aspects of the MS pathology. Here, we aim to provide a practical guide on how to use the cuprizone model and which pitfalls should be avoided.
Topics: Animals; Body Weight; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Gene Expression Regulation; Multiple Sclerosis
PubMed: 32244377
DOI: 10.3390/cells9040843 -
Current Neurology and Neuroscience... Aug 2022COVID-19 has posed a continuously evolving challenge for providers caring for patients with multiple sclerosis (MS). While guidelines from national and international... (Review)
Review
PURPOSE OF REVIEW
COVID-19 has posed a continuously evolving challenge for providers caring for patients with multiple sclerosis (MS). While guidelines from national and international organizations came quickly, these have required constant reassessment and modification as the pandemic has progressed. This review aims to assess the first 2 years of literature on COVID-19 relevant to the clinical management of patients with MS. In particular, we will review how MS impacts the risk of COVID-19 infection, how disease-modifying therapies may alter this risk, and explore considerations regarding disease-modifying therapy (DMT) and vaccination for COVID-19. We will also explore potential ways in which a COVID-19 infection may impact multiple sclerosis. Our goal is to provide an overarching review of the major findings at this stage of the pandemic relevant to those that care for patients with MS.
RECENT FINDINGS
Over the course of the COVID-19 pandemic, providers have had to re-evaluate the priorities in the management of MS. A growing number of studies have evaluated the relevant risk factors and considerations regarding MS and particular disease-modifying therapies. The long-term impacts of the pandemic on the health of those with MS will continue to be revealed. In general, most patients with MS do not need major revisions to their treatment plan due to COVID-19 risk. However, individuals who are older, more disabled, and on more potent therapies may need to consider strategies for decreasing their overall risk. Regardless, continued improvement in our understanding of interactions between infections, disease-modifying therapy, and MS are paramount to optimizing the care of those with MS going forward.
Topics: COVID-19; Humans; Multiple Sclerosis; Pandemics; Risk Factors; SARS-CoV-2
PubMed: 35687314
DOI: 10.1007/s11910-022-01211-9 -
Current Neurology and Neuroscience... Sep 2023Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly considered a treatment option for patients with multiple sclerosis (MS), an autoimmune... (Review)
Review
PURPOSE OF REVIEW
Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly considered a treatment option for patients with multiple sclerosis (MS), an autoimmune demyelinating and degenerative disease of the central nervous system (CNS). AHSCT persistently suppresses inflammation and improves the disease course in large proportions of patients with relapsing-remitting (RR) MS. Aim of this article is to review the relevant new knowledge published during the last 3 years.
RECENT FINDINGS
Laboratory studies reported confirmatory and new insights into the immunological and biomarker effects of AHSCT. Retrospective clinical studies confirmed excellent outcomes in RRMS, showing possible superior effectiveness over standard therapies and suggesting a possible benefit in early secondary progressive (SP) MS with inflammatory features. New data on risks of infertility and secondary autoimmunity were also reported. Further evidence on the high effectiveness and acceptable safety of AHSCT strengthens its position as a clinical option for aggressive RRMS. Further research is needed to better define its role in treatment-naïve and progressive forms of MS, ideally within randomised clinical trials (RCTs).
Topics: Humans; Multiple Sclerosis; Retrospective Studies; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Hematopoietic Stem Cell Transplantation
PubMed: 37589918
DOI: 10.1007/s11910-023-01290-2 -
Seminars in Neurology Apr 2020Multiple sclerosis is being increasingly recognized and diagnosed in children. In the past several years, advances have been made in diagnosing multiple sclerosis in... (Review)
Review
Multiple sclerosis is being increasingly recognized and diagnosed in children. In the past several years, advances have been made in diagnosing multiple sclerosis in children, identifying new genetic and environmental risk factors, delineating underlying immunobiology, characterizing imaging findings, and implementing new treatment strategies. In this review, we discuss these advances. Future research into the determinants of multiple sclerosis in children and into new treatment options will be aided by continued international collaboration.
Topics: Child; Humans; Multiple Sclerosis
PubMed: 32294785
DOI: 10.1055/s-0040-1703000 -
International Journal of Molecular... May 2023Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around the age of 20-30 years.... (Review)
Review
Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around the age of 20-30 years. Still, in recent years, MS has been increasingly recognized among the pediatric population, being characterized by several peculiar features compared to adult-onset disease. Unfortunately, the etiology and disease mechanisms are poorly understood, rendering the already limited MS treatment options with uncertain efficacy and safety in pediatric patients. Thus, this review aims to shed some light on the progress in MS therapeutic strategies specifically addressed to children and adolescents. In this regard, the present paper briefly discusses the etiology, risk factors, comorbidities, and diagnosis possibilities for pediatric-onset MS (POMS), further moving to a detailed presentation of current treatment strategies, recent clinical trials, and emerging alternatives. Particularly, promising care solutions are indicated, including new treatment formulations, stem cell therapies, and cognitive training methods.
Topics: Adolescent; Adult; Humans; Child; Young Adult; Multiple Sclerosis; Neurodegenerative Diseases; Central Nervous System; Risk Factors; Diagnosis, Differential
PubMed: 37175954
DOI: 10.3390/ijms24098251 -
Neurologic Clinics Feb 2024The unprecedented scope of the coronavirus disease 2019 (COVID-19) pandemic resulted in numerous disruptions to daily life, including for people with multiple sclerosis... (Review)
Review
The unprecedented scope of the coronavirus disease 2019 (COVID-19) pandemic resulted in numerous disruptions to daily life, including for people with multiple sclerosis (PwMS). This article reviews how disruptions in multiple sclerosis (MS) care prompted innovations in delivery of care (eg, via telemedicine) and mobilized the global MS community to rapidly adopt safe and effective practices. We discuss how our understanding of the risks of COVID-19 in PwMS has evolved along with recommendations pertaining to disease-modifying therapies and vaccines. With lessons learned during the COVID-19 pandemic, we examine potential questions for future research in this new era of MS care.
Topics: Humans; COVID-19; Multiple Sclerosis; Pandemics; Telemedicine
PubMed: 37980121
DOI: 10.1016/j.ncl.2023.06.006 -
Neurotherapeutics : the Journal of the... Jul 2021Many autoimmune diseases confer a higher risk of cancer on patients compared to the general population. A controversial factor tying autoimmune diseases to malignancy is... (Review)
Review
Many autoimmune diseases confer a higher risk of cancer on patients compared to the general population. A controversial factor tying autoimmune diseases to malignancy is harm from immunosuppressive treatment. Nonetheless, multiple sclerosis is different from other autoimmune diseases, and findings from other disease populations may not apply. In this issue of Neurotherapeutics, Dolladile and colleagues from France present new evidence about the risks of cancers in patients with multiple sclerosis treated with disease-modifying therapies based on analyses of spontaneous reporting data. This commentary discusses the context, limitations, and implications of these findings.
Topics: Humans; Immunosuppressive Agents; Multiple Sclerosis; Neoplasms; Risk Factors
PubMed: 34409568
DOI: 10.1007/s13311-021-01107-5 -
Developmental Medicine and Child... Sep 2019Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults,... (Review)
Review
Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-A antibodies (AQP4-Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long-term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow-up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long-term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short- and long-term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon-β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. WHAT THIS PAPER ADDS: Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody-mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.
Topics: Child; Humans; Immunosuppressive Agents; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Prognosis
PubMed: 30932181
DOI: 10.1111/dmcn.14212