Image of stained glass showing brain affected by multiple sclerosis

The Long-Term Consequences of Early Damage to White and Grey

Early Multiple Sclerosis Damage Can Cause Irreversible Harm1-5

Early Damage, Permanent Results

In Multiple Sclerosis (MS), permanent damage to White Matter and Grey Matter (GM) begins early in the course of disease—driven by both inflammatory and neurodegenerative mechanisms.2-5 Both WM and GM pathologies are important drivers of disease activity in patients with MS.

This central nervous system (CNS) damage includes not only relapses, White Matter lesions, and a decline in physical function, but also whole brain volume loss, Grey Matter atrophy (including thalamic atrophy), cortical lesions, and cognitive impairment.1-8

Information about More Than White Matter

Depleting the Neurological Reserve

Exhausting the Brain’s Ability to Respond to Multiple Sclerosis Damage

Impact of Early Damage on Neurological Reserve

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.2

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.2

Ironically, the brain’s ability to compensate for early nerve damage may actually mask the ongoing neurodegeneration taking place, causing it to go unrecognized until Neurological Reserve has significantly deteriorated.2

View references on Neurological Reserve.

Beyond White Matter Damage

Together, White and Grey Complete the Picture

White Matter Damage Is Only 1 Component of Disease Activity in Multiple Sclerosis (MS)

Historically, early multiple sclerosis damage has been associated with White Matter,11,12 with an emphasis on focal demyelinating lesions in White Matter tissue.10,13 However, while early damage to White Matter is an important contributor to disease activity, it is just 1 component of a comprehensive approach to understanding multiple sclerosis and neurological function.

White Matter pathology alone does not fully explain disease activity in multiple sclerosis, as it is only moderately correlated with outcomes (such as disability).14,15 Grey Matter pathology in the central nervous system (brain and spinal cord) has been identified to play an important role.10,16,17

View references on White Matter pathology.



Grey Matter Atrophy in Multiple Sclerosis

Research Has Shown That Grey Matter Atrophy Begins Early

Evidence of Early Atrophy

  • In several studies, researchers found evidence that Grey Matter atrophy begins early in the course of disease, with atrophy documented in both cortical Grey Matter and Deep Grey Matter19‑23
    • Thalamic atrophy is one of the earliest and most prominent subcortical signs of MS pathology16
  • In a 2-year longitudinal study, researchers found significant Grey Matter atrophy in patients (n=21) with a mean disease duration of 2.1 years20
  • Thalamic atrophy was found to occur early and consistently throughout the course of MS in a 2018 longitudinal study that included 520 patients24

View references on Grey Matter atrophy.

Information about More Than White Matter

Grey Matter Lesions in Multiple Sclerosis

Grey Matter Lesions Appear Early in the Disease Progression

Evidence of Early Lesions

  • Imaging studies confirmed the presence of Grey Matter lesions in the earliest phases of disease—even in patients with minimal White Matter pathology13
  • In some cases, researchers have discovered Grey Matter lesions in patients with radiologically isolated syndrome—before any clinical symptoms are present13
  • In a prospective longitudinal MRI study of 107 MS patients, 64% of RMS patients were found to have Grey Matter damage caused by cortical lesions at baseline7

In a prospective longitudinal MRI study of 107 MS patients,


with early RMS
had cortical lesions7

Register for More Information

To learn more about the role of White and Grey Matter in multiple sclerosis, please provide your contact information below.


Are You a Healthcare Professional?