Image of stained glass showing brain affected by multiple sclerosis

What Role Does White Matter Pathology Play in Multiple Sclerosis?

A Disease Framed in White: The Traditional Focus in MS


Multiple sclerosis (MS) historically has been considered a disease of White Matter (WM), with early research focused on the demyelinating activity of MS in the cerebral WM of the central nervous system (CNS). The term White Matter is derived from the lipid-rich myelin content found in these areas of the CNS, which causes the tissue to appear white.1-4

The classic hallmark of relapsing-remitting MS (RRMS) is the presence of widespread focal demyelinating lesions in WM tissue.5,6 These lesions interfere with axonal conduction, compromising the ability of the CNS to transmit signals. This can cause a wide range of symptoms in patients including physical disability, visual impairment, cognitive deficits, and fatigue.7


In damaged WM, axonal loss can be as high as

MS lesions can appear anywhere in the CNS; however, they are found most commonly in the periventricular areas of the brain, the brain stem, the optic nerve, and the spinal cord.8 In addition to WM lesions, WM atrophy also has been observed in patients with relapsing forms of MS.5,9 Yet, in many patients with MS, atrophy of GM tissue appears to be more clinically relevant as a major predictor of declining disability.10

Though MS is historically considered a WM disease, GM also plays an important role

Learn more about Grey Matter atrophy

White Matter and Neurological Function: Preserving the Reserve

After diagnosis has been confirmed, early intervention is now considered to be essential for patients with MS due to the irreversible damage that can be caused—even to patients who may appear to be clinically stable.11

Evidence shows that early damage can impact Neurological Reserve—the finite capacity of the brain to retain function by remodeling itself after an MS-related injury. 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.7

For patients with MS, disease activity (even in the early stages) can negatively impact7:

  • Cognition
  • Emotional well-being
  • Quality of life
  • Day-to-day activities
  • Ability to work

With RRMS, disease management goals typically focus on7:

  • Preventing new lesions
  • Reducing the number of relapses
  • Slowing disability progression
  • Minimizing brain atrophy

Even after decades of research, these goals remain the primary focus for patients with RRMS.

Learn more about White and Grey Matter

A Deeper Look Into White Matter

Advances in neuroimaging have significantly improved our understanding of MS disease activity. Imaging technologies continue to make a notable impact by helping with both the diagnosis and management of the disease.12

During the past 20 years, magnetic resonance imaging (MRI) has become the gold standard for patients with MS, resulting in a more rapid diagnosis than previously possible.7,13

MRI enables us to see WM lesions in many different regions of the CNS. Lesions that form around subependymal veins are periventricular lesions, a form of WM lesions that are easier to spot due to their ovoid appearance.12

MRI image of periventricular White Matter lesions

Figure A: Katdare A, Ursekar M. Systematic imaging review: multiple sclerosis. Ann Indian Acad Neurol. 2015;18(suppl 1):S24-S29.

Figure B: Reproduced from Trip SA, Miller DH. Imaging in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2005;76(suppl III):iii11-iii18, with permission from BMJ Publishing Group Ltd.

In contrast to WM lesions, GM lesions are more difficult to see with current neuroimaging technologies. In fact, only 30% to 50% of histologically confirmed GM lesions can be detected, even with the most advanced imaging processes.14

Learn more about GM lesions

MS Progression: More Than White Matter

WM is an important part of preserving neurological function, but it is just 1 component of a comprehensive approach to understanding MS.

WM pathology alone does not fully explain disease activity in MS, as it is moderately correlated with outcomes (such as disability).15,16

However, GM pathology in the CNS (brain and spinal cord) has been identified to play an important role and has been shown to be significantly correlated with both cognitive impairment and physical disability in MS patients.4,6,17,18

Persistent Quality-of-Life Concerns

Despite dramatic improvements in the management of MS, patients continue to struggle with a range of issues, including employment.19


of patients with MS are unemployed19

According to the 2016 Global MS Employment Report, in a survey of 11,515 patients with MS, 39% of patients with MS worldwide were unemployed—with 82% citing their disease as the primary reason.19

  • 43% of the unemployed patients stopped working within 3 years of diagnosis
  • More than 70% of patients stopped working within 10 years of diagnosis

Uncover the important role GM pathology plays in MS

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