Image of stained glass showing brain affected by multiple sclerosis

A Comprehensive Look at Multiple Sclerosis

3 Key Factors to Consider

Worldwide, multiple sclerosis (MS) is the most prevalent chronic inflammatory disease of the central nervous system (CNS).1,2 MS causes early, permanent neurological damage that can lead to the development of scars, called lesions, on nerve tissues throughout the CNS.1 When lesions form, a sudden attack of symptoms can follow, known as a relapse.1 In relapsing-remitting MS—the most common course of the disease—patients experience acute attacks (relapses) that develop over a few days, then plateau and fade away (remit) over time, as damage is addressed by CNS repair mechanisms.1 To fully understand disease activity in MS, it is important to consider a number of factors that can contribute to CNS damage and impair neurological function. This site explores 3 key factors:

Examining the Whole Picture in MS

Multiple Sclerosis–An Autoimmune Disease of the CNS

This site provides an overview of how MS affects brain and spinal cord tissue, causing permanent damage that starts early in the course of the disease.3,6-8,13,14,17-20,24-28 In people with MS, the body’s own immune system attacks nerve fibers in the brain and spinal cord causing inflammation, demyelination, nerve damage, and the destruction of axons and neurons.1,20 This neurological damage can lead to the development of scars, known as lesions, on nerve tissues throughout the central nervous system (CNS).1 Although lesions can occur in both White Matter and Grey Matter, they are most easily seen in the White Matter of the brain, using magnetic resonance imaging (MRI) technology.2,7,20 Since the year 2000, MRI scans have been the primary means of definitively diagnosing the disease in people with MS.2

A Range of Symptoms and Phenotypes

Depending on where the MS lesions form, they can disrupt nerve function and lead to a sudden attack of symptoms, known as a relapse.1 Early symptoms commonly include numbness, tingling, burning pain, muscle weakness, stiffness, clumsiness, difficulty walking, visual disturbances, and fatigue.1 In relapsing-remitting forms of MS, patients experience acute attacks (relapses) that develop over a few days, then plateau and fade away (remit) over time, as damage is addressed by CNS repair mechanisms.1 Relapsing-remitting MS is the most common course of multiple sclerosis, with 80% to 90% of MS patients initially starting with this disease phenotype.1 Other multiple sclerosis phenotypes include primary progressive MS, secondary progressive MS, and clinically isolated syndrome.1,20 All together, there are 2.3 million people with MS worldwide, making it the most prevalent chronic inflammatory disease of the central nervous system.1,2

Multiple Sclerosis Damage Begins Early

Another important finding is that the damage caused by multiple sclerosis can begin early in the course of disease—driven by both inflammatory and neurodegenerative mechanisms.1,3-5 While the brain is naturally able to compensate for tissue damage for a period of time, some nerve tissue is irreversibly destroyed, causing permanent injury and a loss of brain volume.1 Although White Matter damage has long been associated with early damage, recent studies have found that Grey Matter damage also occurs early in the disease.6-12 Evidence of early atrophy has been found in both cortical Grey Matter and Deep Grey Matter.9-12 In addition, researchers have found evidence of early lesions in Grey Matter, too.20 In one study (n=107), 64% of patients with early RMS were found to have Grey Matter damage caused by cortical lesions.18 Together, this information gives us a much more robust understanding of the complex pathology of MS. Only by developing a comprehensive understanding of this disease can we promote CNS health, work to protect neurological function, and help maintain cognitive ability in patients with MS.

A Disease of Both White and Grey Matter

While MS has historically been considered a White Matter disease, a growing body of evidence has shown that Grey Matter pathology plays a major role in both disease pathology and progression.13-16 Research from numerous longitudinal and imaging studies has shown that Grey Matter damage is widespread, starts early in disease progression, and is strongly correlated with disability.8,13,14,16-20 Among the negative outcomes associated with Grey Matter pathology are cognitive impairment, physical disability, painful syndromes, fatigue, and ocular motility disturbances.16 Grey Matter pathology generally takes the form of cortical lesions, cortical atrophy, deep Grey Matter lesions, and deep Grey Matter atrophy.17,18,20,25,26 In particular, recent research has found that thalamic atrophy is an especially potent driver of long-term patient disability.26 Thalamic atrophy has been associated with physical disability, cognitive impairment, and fatigue.26,29 In a post hoc analysis of 1214 patients with MS, thalamic atrophy was a better predictor of future disability than other regions.26 Another key area of importance in MS is Grey Matter in the spinal cord, which can be highly predictive of disease progression.19 One clinical study of 113 MS patients and 20 healthy controls demonstrated that Grey Matter atrophy in the spinal cord was more strongly correlated with physical disability than any other variable examined.19

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