Current Concepts in Multiple Sclerosis: Autoimmunity Versus Oligodendrogliopathy

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that affects millions of patients worldwide. The current disease-modifying therapies (DMTs) that are widely used to treat MS only show modest effects. Because MS is a chronic disease, it is important to develop treatments that have better long-term efficacy. Recently, several new-generation DMTs have been developed, most of which target specific immune molecules based on the assumption that MS is an autoimmune disease. These DMTs are designed to inhibit inflammation that is thought to directly cause demyelination. Preliminary studies suggest that these new therapies are likely to show a greater effect in reducing relapses in early MS patients, although their long-term efficacy is still unknown. In contrast, it was recently reported that the initial course of MS does not significantly influence long-term disability and that disability increases approximately at the same rate despite variable relapse frequencies. Furthermore, new neuropathological evidence now argues against the autoimmune hypothesis and suggests that MS is a primary oligodendrogliopathy disease in which the inflammatory response may be a mere epiphenomenon. So can we be optimistic about the unproven long-term outcomes of new DMTs or should we reconsider the pathogenesis of MS when developing more disease-specific treatments?

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

“…However, as recently discussed, this aetiology remains speculative [1][2][3][4]. As with other CNS diseases, there are multiple issues confounding direct research, and thus, understanding the mechanism(s) underlying this disease has been challenging.…”

“…Accumulating evidence suggests that MS may be initiated by an underlying degeneration of the myelinating cells, oligodendrocytes, within the CNS. The presence of T cells in the CNS may thus represent a secondary immune response [1,4,5]. The aetiology of oligodendrocyte degeneration is currently unknown.…”

Encephalomyelitis Due to Brucellosis

“…Encephalomyelitis is a general term for inflammation of the CNS, describing a number of disorders and acute disseminated encephalomyelitis. MS is a demyelinating disease of the CNS, which is possibly triggered by infection (mostly viral), stress, smoking, autoimmune disorders, and genetic factor (5)(6)(7)(8)(9). A patient with MS can have almost any neurological sign or symptom including motor, sensory, and visual problems, which are the most common presentation.…”

“…These symptoms may be loss of sensitivity or changes in sensation such as pins and needles or numbness, muscle spasms, muscle weakness, or difficulty in moving and coordination. Visual problems such as nystagmus, optic neuritis, or double vision can be seen (5,6). Many rare complications of neurobrucellosis have been reported (2)(3)(4)10 (4).…”

Effect of 8-Week Aquatic, Land- based and Combined (Aquatic-Land) Training Programs On Walking Capacity in Women with Multiple Sclerosis (MS): A Burdenko Approach

“…Multiple Sclerosis (MS), a chronic progressive disorder of the central nervous system, [1,2] is an autoimmune disease, whose pivotal mechanism is damage to the body by immune system or impairment of myelin-producing cells [3]. Although the cause of the disease is unclear, its occurrence is highly influenced by genetic and environmental factors, such as infection [4], and is usually diagnosed based on symptoms and medical examination results [5].…”