Oxidative Glial Biomarkers Predict Disability and Cognitive Decline in PPMS-NA

Overview

Primary progressive multiple sclerosis without inflammatory activity (PPMS-NA) is characterized by low systemic inflammation but elevated central oxidative stress. Elevated IL-8 and cerebrospinal fluid reactive oxygen species (CSF ROS) predict disability progression and cognitive decline over 10 years, highlighting their potential as early biomarkers.

Background

Multiple sclerosis (MS) is a chronic neurodegenerative disease with relapsing and progressive forms. Primary progressive MS (PPMS) progresses continuously from onset and can be subclassified into active (PPMS-A) and non-active (PPMS-NA) forms. PPMS-NA lacks inflammatory activity but involves neurodegenerative mechanisms driven by microglial activation and oxidative stress. Pro-inflammatory cytokines such as IL-6, IL-8, and IFNα2, along with reactive oxygen species (ROS), contribute to axonal damage and cognitive impairment in MS.

Data Highlights

Key Findings

• PPMS-NA patients exhibit reduced plasma IL-6 and IFNα2 levels, indicating low systemic inflammation.
• CSF reactive oxygen species (ROS) are elevated in PPMS-NA, reflecting central oxidative stress.
• Increased IL-8 levels predict disability progression and decline in processing speed over 10 years.
• IL-6 shows complex associations with cognition: initially linked to attention, later inversely related to visuospatial and working memory domains.
• CSF ROS levels correlate with brain atrophy, supporting oxidative stress as a driver of neurodegeneration in PPMS-NA.

Clinical Implications

Measurement of IL-8 and CSF ROS can aid early stratification of PPMS-NA patients at risk for disability and cognitive decline. Therapeutic strategies targeting oxidative stress and glial activation may be beneficial in managing neurodegeneration in this MS subtype. Monitoring IL-6 dynamics could provide insights into domain-specific cognitive changes over time.

Conclusion

PPMS-NA is characterized by a distinct immune-oxidative profile with low systemic inflammation but elevated central oxidative stress. IL-8 and CSF ROS serve as promising biomarkers for predicting disability and cognitive decline, supporting the development of targeted therapies addressing oxidative and glial mechanisms.

References

1. Author/Source/2024 -- An Oxidative Glial Profile as a Predictor of Disability and Cognitive Decline in Primary Progressive Multiple Sclerosis