The Importance of Grey and White Matter in MS

OVERVIEW—The Importance of Grey and White Matter in MS

This site covers key areas of thought regarding the management of multiple sclerosis (MS):

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

PERMANENT DAMAGE CAN BEGIN EARLY

• In MS, permanent damage can begin early in the course of disease—driven by both inflammatory and neurodegenerative mechanisms^3-6
• 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 impairment^3,7,8
• 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 event^1,9
  • 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

EMERGING SCIENCE FOCUSES ON GREY MATTER

• Researchers have found that Grey Matter pathology starts early, is widespread, and is a major driver of disability^12-14
  • 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 disability^2,7,8,16-20
  • 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

COMPREHENSIVE IMPACT OF MS

• 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