Role of the innate and adaptive immune responses in the course of multiple sclerosis

Emerging role of neuregulin-1beta1 in pathogenesis and progression of multiple sclerosis

The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance?

Background. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) traditionally known as a disease of young adults. However, in recent years MS has «aged», which is associated with significant advances in treatment and improvements in the diagnosis of late­onset MS (diagnosed after the age of 50). An analysis of data from 2019 to 2022 on the age distribution of MS in the United States showed that the median age was 45–54 years, comprising 229,216 individuals (31%), of whom 186,758 were aged 55–64 years (25%). A study on the increasing prevalence and changing age structure in Manitoba (Canada) demonstrated that the peak age­specific prevalence shifted from 35–39 years in 1984 to 55–59 years in 2004. A study of the age distribution among patients with MS in Denmark showed that the mean age of patients with MS increased to 54.2 years in 2023. Thus, in real­world practice, people older than 50 years constitute the largest proportion of patients with MS; however, most clinical trials evaluating the efficacy and adverse effects of disease­modifying therapies (DMTs) did not include this age group. For the same reason, there are currently no clear clinical guidelines for the treatment of these patients. Age-related characteristics of the immune system, comorbidities, polypharmacy, and differences in disease course do not allow DMTs to be used with the same level of confidence as in younger patients, whose treatment safety has been established in clinical trials. Understanding immunosenescence and its impact on the course of MS, the level of drug efficacy in older patients, and the potential risks of DMT­related adverse effects, which are compounded by comorbidities and a reduced immune response in this population, are key to the successful management of older patients with MS. Treatment success depends on an individualized approach to each specific case, taking into account age, comorbidities, the course and activity of MS, and a careful weighing of the potential benefits against the likely risks of DMTs. Therefore, improving knowledge through the accumulation of information on this topic will be useful in selecting safe therapeutic strategies for people with MS older than 50 years. Purpose – to determine the impact of aging on the course and activity of MS, the clinical and radiological features of late­onset MS, the effectiveness of disease­modifying therapy (DMT), and the adverse effects characteristic of older individuals (over 50 years). To learn how to properly assess risks in this patient group when prescribing DMT. Materials and methods. Scientific publications were selected from publicly available medical sources (PubMed, Medscape, MDPI) on the topic of our study and related areas, and their analysis was performed using meta­analyses, case series descriptions, and randomized studies. Results. Today, multiple sclerosis is no longer exclusively a «disease of the young», and patients older than 50 years constitute a substantial proportion of the clinical population. At the same time, this group remains the least studied in terms of the safety of disease-modifying therapy. The combination of age-related changes in the immune system, comorbid conditions, and long disease duration creates a unique risk profile that requires separate analysis and specific clinical attention. Moreover, most randomized clinical trials did not include patients in this age category, which limits the applicability of the obtained data to real­world clinical practice. In this context, studying the adverse effects of disease­modifying therapy in patients with MS older than 50 years is an important step toward developing a safe and effective individualized treatment strategy. Conclusions. Patients over 50 years old represent the largest group of individuals with multiple sclerosis (MS), yet clinical guidelines for their treatment are lacking. Immunosenescence alters disease course, with a shift from relapsing to progressive MS, fewer relapses, and low radiological activity, but faster accumulation of disability. Disease­modifying therapies (DMTs) carry increased risks in this population, including severe infections (PML, varicella), malignancies, hypertension, macular edema, and cardiovascular events, especially in the presence of comorbidities and polypharmacy. Although DMT efficacy decreases with age, treatment should be continued with careful consideration of individual patient characteristics and close monitoring of blood pressure, renal and liver function, lipid profile, coagulation, and immune status. Contemporary clinical studies indicate significant progress in the treatment of progressive multiple sclerosis and increased inclusion of older patients, which expands the possibilities for safe and effective disease­modifying therapy in patients over 50 years of age.

McAlpine's Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated disease of the centralnervous system (CNS) affecting the brain, spinal cord, andoptic nerves. In patients who have MS, the immune system attacks,damages, and strips the myelin sheath, the insulating cover of nervecells responsible for facilitating the conduction of impulses alongaxons. This injury leads to the interruption of nerve impulses travelingthrough the CNS, producing a multitude of symptoms. 1 The diseasecourse of MS may vary between patients, with some experiencing isolatedattacks and others a more progressive disease. 2

Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system (1–86), with substantial long-term neurologic consequences (1,4,9,25,34, 52,54,55,57,60,63,65). After 10 years with MS, 50% of patients are unable to perform household and occupational responsibilities; after 15 to 20 years, 50% are unable to walk without assistance; after 25 years, 50% are unable to ambulate. The average annual cost of MS in the United States is greater than 6.8 billion dollars (1). There are three main subtypes of the disease: relapsing remitting (RR), secondary progressive (SP), and primary progressive (PP). This update reviews the current status of MS therapy (1–86). We have chosen to focus on the new and emerging immunomodulatory therapies for disease relapses and the treatments to prevent disease progression. We do not review the treatments for common MS-related sensory and motor symptoms, fatigue, or depression (35).

Editorial: Challenges in developing new multiple sclerosis therapies

Comorbidity is one of the factors determining the course of multiple sclerosis. Cardiovascular pathology is one of the most common in the population as a whole, especially in age groups over 50. Several studies showed that arterial hypotension and dyslipidemia affected the course, progression rate, and neuroimaging characteristics of patients with multiple sclerosis. An important issue is the effect of disease modifying therapy on the course of concomitant diseases in patients with multiple sclerosis and the effect of concomitant diseases on the effectiveness and safety of disease modifying therapy. The question of the use of statins in multiple sclerosis remains controversial. This review presents data on vascular comorbidity in multiple sclerosis, including the prevalence of risk factors for cardiovascular pathology and concomitant vascular diseases in the population of patients with multiple sclerosis. Data on the effect of cardiovascular pathology on the course and treatment of multiple sclerosis were also analyzed.

Vitamin D as add-on therapy for multiple sclerosis

Multiple sclerosis is a chronic disease of the central nervous system, characterised by two pathophysiological processes taking place independently from the onset: inflammatory-demyelinating and neurodegenerative. During the course of the disease, disability accumulates over time as a result of relapses and progressive neurodegeneration associated with the so-called smouldering lesions. Treating patients with multiple sclerosis and other co-occurring autoimmune conditions is a major challenge for physicians. Therefore, it is rational to choose a disease-modifying therapy that has a positive therapeutic effect in both comorbidities. The use of combination therapies in the treatment of multiple sclerosis is not currently recommended. Studies conducted to assess the effectiveness of combining standard disease-modifying therapies with corticosteroids, methotrexate, azathioprine, or cyclophosphamide have yielded ambiguous or negative results. Selecting an appropriate disease-modifying therapy for patients with co-occurring multiple sclerosis and another autoimmune disease requires close cooperation of many specialists (neurologist, rheumatologist, gastroenterologist, dermatologist, immunologist). The decision should always be made on an individual basis and focus on achieving monotherapy that is effective in both diseases. The neurologist should know the impact of disease-modifying therapies used in other autoimmune diseases on the course of multiple sclerosis. The article reviews the literature and examines the impact of disease-modifying therapies used in the treatment of multiple sclerosis on the course of other common autoimmune diseases, as well as the effect of disease-modifying therapies used in other autoimmune diseases on the course of multiple sclerosis.

Progress in Multiple Sclerosis Research

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Blood transcriptome profiling captures dysregulated pathways and response to treatment in neuroimmunological disease.

Mitoxantrone trial in multiple sclerosis

The predominant clinical disease course of multiple sclerosis starts with reversible episodes of neurological disability, which transforms into progressive neurological decline. This review provides insight into the pathological differences during relapsing and progressive phases of multiple sclerosis. The clinical course of multiple sclerosis is variable, and the disease can be classified into relapsing and progressive phases. Pathological studies have been successful in distinguishing between these two forms of the disease and correlate with the clinical findings in terms of cellular responses, the inflammatory environment, and the location of lesions. Available therapies for multiple sclerosis patients, while effective during the relapsing phase, have little benefit for progressive multiple sclerosis patients. Development of therapies to benefit progressive multiple sclerosis patients will require a better understanding of the pathogenesis of progressive multiple sclerosis. This review discusses and compares the pathological findings in relapsing and progressive multiple sclerosis patients.