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Advanced Neurologyurology
Advanced Ne Multiple sclerosis: Immunopathogenesis

prevalence rates in different regions, for example, up to relevant animal-based meta-analyses, systematic reviews,
140/100,000 population in North America, 108/100,000 observational studies, and randomized control trials
in Europe, and around 2.2/100,000 in East Asia and sub- published from 2014 to 2023. The majority of these
Saharan Africa . Worldwide, women are twice as likely as papers described researches conducted in the populations
[3]
men to develop MS . An increase in the incidence rate of of Europe, North America, and Asian countries. After
[2]
MS was also observed in Lithuania. According to the 2001 thoroughly examining the published articles focusing
– 2015 data derived from the Statutory Health Insurance on etiopathogenesis, epidemiology, genetics, current
Information System, there had been an annual increase of diagnostic and screening methods, and identifying
MS diagnoses in the period 2001 – 2015. In 2001, 162 new applicable studies from the articles’ reference lists, we
MS cases were recorded, while in 2015, there were 343 new collected a total of 100 articles for our review.
cases. The incidence rate of MS during the period 2001 –
2015 was 6.5 cases/100,000 persons. The gender-specific 3. Etiology
prevalence of MS is also consistent with some other The pathogenesis of MS relies on both genetic
European countries. Women were 1.5 – 2 times more likely predisposition and environmental exposure. Nevertheless,
than men to have MS in the period 2001 – 2015. In 2015, genetic predisposition to MS is considered a rare
the incidence rate of MS was 8.1 and 4.9/100,000 people for phenomenon in the population (<7.3%), and specific
[4]
women and men, respectively . combinations of non-additive genetic risk factors are
[13]
Relapsing-remitting MS (RRMS) is the most common required for MS pathogenesis . Moreover, genetic
phenotype of MS and accounts for approximately 85% of changes contributed to a higher percentage of T cell
all cases of MS, regardless of disease types. The remaining variation (30%) than B cell variation. This is thought to be
patients usually have a primary progressive MS (PPMS) caused by human leukocyte antigen (HLA) variations and
[14]
course since disease onset. The majority (50 – 80%) of T cell receptors . A consensus holds that MS is polygenic:
patients with RRMS tend to develop a progressive disease Multiple independent or interactive genes and risk
course (secondary progressive MS [SSMS]) 15 – 20 years alleles in the population are at play in MS pathogenesis,
after the initial onset of the disease, with about 5% of patients exerting a differential effect, from low to moderate, on
[13]
progressing from RRMS to SPMS per year [5-7] . It is quite the development of MS . A variety of environmental
[3]
clear that both degenerative and immunogenetic processes risk factors are also suspected . However, Epstein–Barr
are involved in the pathophysiology of MS. Unfortunately, virus (EBV) seroconversion precedes almost 99% of
the close interconnection between these two processes, the new cases of MS and likely predates the first clinical
[15]
which run through all phases of the disease, makes it symptoms . A recent study by Bjornevik et al. examined
extremely difficult for researchers to definitively resolve a cohort of 10 million participants and strongly implicated
the “outside-in” versus “inside-out” controversy. Similarly, EBV and its association with MS. The study has shown a
to other neurodegenerative diseases, the initial trigger is 32-fold risk increase (95% confidence interval [CI]: 4.3
unknown. The mechanism of chronic MS progression –245.3, P < 0.001) of MS development after EBV infection,
[16]
remains the most significant mystery, when solved it could but no increase after other virus infections . A prevailing
shed light on the prevention of irreversible disability . theory postulates that EBV increases the risk for MS and
[8]
Delays in early diagnosis of progressive MS are quite plays a part of MS pathogenesis because of molecular
common [6,9,10] . It has been observed that SPMS remained mimicry. It is thought that EBV being a cross-reactive
undiagnosed for 2 – 3 years before a definitive diagnosis . antigen (molecular mimic) and being a B-cell trophic virus
[11]
With the help of the revised McDonald criteria of 2017, the providing various cytokines, as well as costimulation, are
diagnosis of PPMS has become much more systemic and the requisite for the stimulation of T cell differentiation,
easier for neurologists. These new guidelines emphasize which leads to the activation of pathogenic autoreactive T
[17]
the importance of cerebrospinal fluid (CSF)-specific cell leading up to the development of MS . Other studies
oligoclonal bands and spatial spread of lesions on magnetic suggested that low levels of 25-hydroxyvitamin D (25[OH]
resonance imaging (MRI) . It is crucial to rule out other D) may be associated with increased disease activity in
[12]
causes of disease that present as chronic myelopathy with people with MS. Large-scale genome-wide association
temporal progression. This article therefore discusses the studies suggested that 25(OH)D levels are partly genetically
[18]
etiopathogenesis and clinical aspects of MS. determined .
HLAs are part of the major histocompatibility
2. Methods complex (MHC) and their association with MS was first
For this review, we searched through PubMed, mentioned several decades ago. The focus remains that MS
ScienceDirect, and SpringerLink databases. We included is primarily an antigen-associated autoimmune disease.

Volume 2 Issue 3 (2023) 2 https://doi.org/10.36922/an.1319