Using combined endpoints to define no evident disease activity (NEDA) is becoming increasingly common when setting targets for treatment outcomes in multiple sclerosis (MS). Historically, NEDA has taken account of the occurrence of relapses, brain magnetic resonance imaging (MRI) lesions and disability worsening, but this approach places emphasis on inflammatory activity in the brain and mostly overlooks ongoing neurodegenerative damage. Combined assessments of NEDA which take account of changes in brain volume or neuropsychological outcomes such as cognitive function may begin to address this imbalance, and such assessments may also consider blood or spinal-fluid neurofilament levels or patient-reported outcomes and quality of life measures. If a combined NEDA assessment can be validated in prospective studies as indicative of long-term disease remission at the individual patient level, treating to achieve NEDA could become the goal of clinical practice and achieving NEDA may become the "new normal" state of disease control for patients with MS.

• Keywords
• Brain volume loss, NEDA-4, cognition, combined assessments, no evident disease activity, treatment algorithms,
• MeSH
• Outcome Assessment, Health Care methods   standards   MeSH
• Humans MeSH
• Multiple Sclerosis diagnosis   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.

• MeSH
• Atrophy MeSH
• Cognition Disorders * pathology   physiopathology   MeSH
• Humans MeSH
• Brain * pathology   physiopathology   MeSH
• Cerebral Cortex pathology   physiopathology   MeSH
• Disease Progression MeSH
• Multiple Sclerosis * pathology   physiopathology   MeSH
• Inflammation * pathology   physiopathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH