It is therefore important to diagnose MS as early as possible, before Neurological Reserve is exhausted and the progressive stage of the disease begins.
—Giovannoni et al2
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
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.
Grey Matter Fact:
Independent
In Multiple Sclerosis, Grey Matter demyelination is largely independent of White Matter demyelination9,10
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.
…THE MOST VISIBLE ELEMENT OF PATHOLOGY, WHITE MATTER (WM) LESIONS, REPRESENTS ONLY A FRACTION OF THE DISEASE BURDEN BORNE BY THE BRAIN…
CHARD ET AL18 GM atrophy is present early in the disease across different clinical subtypes and is associated with physical disability and cognitive decline.
—Steenwijk et al22
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.