Cross-sectional side view of a human brain against a background of colorful stained glass

The Importance of Grey and White Matter in MS

Think Grey and White
to Complete the Picture

DIVING DEEPER—To Complete the Picture in MS, Think Grey and White


  • In MS, permanent damage can begin early in the course of disease—driven by both inflammatory and neurodegenerative mechanisms3-6
  • Researchers have documented brain volume loss (MS atrophy) as early as the time of the first clinical attack1
    • Studies have shown that brain volume loss can occur early and is correlated with both physical and cognitive impairment3,7,8
  • In addition to physical disability, cognitive impairment has been observed in patients with early MS1
    • Up to 30% of patients with early MS have experienced cognitive changes by the time of their first clinical event1,9
    • Even in patients with little or no physical disability, researchers have observed early cognitive deficits1
    • Cognitive deficits identified in patients with early MS include problems with working memory, visual-spatial memory, and information processing speed10
    • Among the tools used to test for multiple sclerosis cognitive deficits is the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), which includes several neuropsychological examinations (eg, the Symbol Digit Modalities Test [SDMT] and the California Verbal Learning Test®–Second Edition)11



  • Researchers have found that Grey Matter pathology starts early, is widespread, and is a major driver of disability12-14
    • Imaging studies confirmed the presence of Grey Matter pathology in the earliest phases of disease, even in patients with minimal White Matter pathology (early pathology can include both Grey Matter lesions and Grey Matter atrophy [loss of Grey Matter volume])14,15
    • Data from several cross-sectional studies indicate that Grey Matter damage and Grey Matter loss are significantly correlated with both cognitive and physical disability2,7,8,16-20
    • Clinical research has also found that Grey Matter atrophy (loss of Grey Matter in the brain) is a major driver of whole brain atrophy18
  • Both Grey Matter volume loss (atrophy) and Grey Matter lesions occur in patients with active disease, and both correlate with neurological and cognitive deficits in MS2
    • In a 5-year study (n=312), patients with MS with high cortical lesion load had the worst physical and cognitive prognosis compared with all other patient groups—92% of patients experienced significant MS cognitive impairment and 86% of patients experienced worsening of physical disability16
  • Thalamic volume loss is associated with impaired ambulation and cognition, and may be a better predictor of future disability than any other region of the brain8
    • In a longitudinal study, researchers found that the thalamus was consistently one of the first areas of the brain to become atrophic, regardless of the type of MS diagnosed in these patients21
    • This same study indicated that thalamic atrophy begins early in most patients with MS, regardless of phenotype, and proceeds at a high rate throughout the disease course21
    • Thalamic atrophy is also an independent and additional contributor to SDMT deficits in patients with MS22


  • Fatigue is a common and debilitating symptom of MS, affecting nearly 80% of patients—with more than half describing it as one of the worst symptoms of the disease23
    • Studies have shown that fatigue has a major impact on quality of life, adversely affecting a patient’s ability to work and socialize23
    • Increased cognitive and physical impairment has been associated with fatigue, along with higher rates of healthcare utilization23
  • MS has a high socioeconomic impact on patients with negative effects reported early in the course of disease24
    • In a recent global survey of 11,515 patients with MS, almost 40% were unemployed—with the vast majority (82%) citing their disease as the primary reason25
    • Of patients with MS who reported being unemployed, nearly half had an Expanded Disability Status Scale score of 3.0 to 3.5—a level that is not overtly associated with physical disability26
    • Among various MS-related factors (eg, disability, disease duration, MS course, other cognitive tests, and personality characteristics), the SDMT is the most reliable predictor of employment status, showing a clear correlation between unemployment in patients with MS and cognitive function26
  • Caregivers of patients with MS were found to experience high levels of distress and reduced quality of life related to their caregiving27
    • In this study, cognitive deficits in patients with MS contributed significantly to the overall burden of caregivers27
    • More than half (54%) of those who provide direct care for a partner with MS said they stopped working because of their partner’s condition, according to an international survey of >1400 people25
    • Partners of patients with MS also reported substantial physical and psychological burdens to their own health, affecting their employment status—in a large-scale survey (N=1288), more than 40% reported missing work due to their partner’s condition28

By targeting both Grey Matter and White Matter pathologies earlier in the course of MS, we may be able to preserve patients’ physical and cognitive functioning for longer.