Multiple Sclerosis (MS) Overview

MS is a chronic autoimmune disorder that damages myelin, axons, and cells in the central nervous system, leading to a wide variety of symptoms.¹ These can include fatigue, dizziness, muscle weakness, loss of balance or vision, incontinence, and cognitive or mood changes. People with MS may also experience numbness, tingling, or pain in the arms, legs, or face.^{1 , 2} The age of onset for this condition is usually between 20 to 40 years, although it can affect people of any age. A small percentage of cases occur before age 18.^{3 , 4}

The course of MS varies between individuals. The most common form of MS, known as relapsing-remitting MS (RRMS), is characterized by periods of disease attack followed by periods of stability. People with other forms of this condition have progressively worsening symptoms.^{3 , 5} However, it is now clear that even patients with RRMS may have worsening neurologic disability between relapses, a situation known as progression independent of relapse activity (PIRA).^{6 , 7} Finding new ways to prevent both disability progression and relapses through research are important goals for physicians and scientists.

In general, women are twice as likely to be affected by MS as men, although this discrepancy can vary among the different types of MS.⁸ Some of the symptoms of MS may worsen during the premenstrual phase of the menstrual cycle or during menopause. There is evidence that without appropriate treatments, people with RRMS may have relapses after pregnancy. Pregnancy itself appears to be protective against disease flare-ups in many women with MS.^{9 , 10} While some small studies have suggested that certain fertility treatments may increase the risk of experiencing relapses, these findings have not been corroborated by more recent research.^{11 , 12}

Currently, there is no cure for MS. However, certain medications, including interferon-beta, glatiramer acetate, ocrelizumab, natalizumab, diroximel fumarate, teriflunomide, fingolimod, siponimod, ozanimod, and cladribine, can reduce the frequency of attacks and prevent the formation of new demyelinating lesions.^{5 , 13}

Research into MS is ongoing. Some of the current areas of interest include determining the precise causes of MS, developing a better understanding of disability progression in women with this condition, and identifying novel neuroprotective and remyelinating treatments.

The National Institute of Neurological Disorders and Stroke (NINDS) supplies funding for research on the brain and nervous system, including research on MS. Recently, NINDS researchers used magnetic resonance image (MRI)-guided spatiotemporal RNA profiling to track the development of lesions in the brains of marmosets with a condition that is similar to MS. This technique allowed the researchers to identify gene activity that occurs in astrocytes before brain lesions become visible.¹⁴ These results may help characterize the early stages of lesion formation in people with MS. In addition, identifying potential MRI and molecular biomarkers could enable earlier detection and intervention in people with MS before irreversible demyelination occurs.¹⁵

NINDS also contributed funding to research that explored the mechanisms behind DNA damage and repair in neurons that are exposed to neuroinflammation. The researchers report that excitatory neurons in cortical layers 2 and 3 that express CUT-like homeobox 2 (CUX2) are uniquely vulnerable to the inflammation caused by conditions like MS. Activating transcription factor 4 (ATF4) can repair the damage done to the DNA of these neurons, but this mechanism does not appear to be adequate to prevent the loss of CUX2 neurons during long-term neuroinflammation. These findings provide a better understanding of the mechanisms of neurodegeneration in people with MS.^{16 , 17}