Clinical Scorecard: An Oxidative Glial Profile as a Predictor of Disability and Cognitive Decline in Primary Progressive Multiple Sclerosis
At a Glance
Category
Detail
Condition
Primary Progressive Multiple Sclerosis without inflammatory activity (PPMS-NA)
Key Mechanisms
Low systemic inflammation with elevated central oxidative stress driven by reactive oxygen species (ROS) and glial activation
Target Population
Adults diagnosed with PPMS-NA per 2017 McDonald criteria, without relapses or MRI inflammatory activity
Care Setting
Neurology and neuroimmunology clinics with access to CSF and plasma biomarker analysis
Key Highlights
PPMS-NA exhibits reduced plasma IL-6 and IFNα2 but increased CSF ROS compared to RRMS and other neurological disorders.
Elevated IL-8 predicts disability progression and 10-year decline in processing speed in PPMS-NA.
CSF ROS correlates with brain atrophy, supporting oxidative stress as a driver of neurodegeneration in PPMS-NA.
Guideline-Based Recommendations
Diagnosis
Classify PPMS patients into active (PPMS-A) or non-active (PPMS-NA) based on absence of relapses, gadolinium-enhancing lesions, and new/enlarging T2 lesions over 3 years.
Use plasma cytokine profiling (IL-6, IL-8, IFNα2) and CSF ROS measurement to support diagnosis and subtype stratification.
Management
Consider therapies targeting oxidative stress and glial activation in PPMS-NA to potentially slow neurodegeneration.
Monitor IL-8 levels as a biomarker for disability progression and cognitive decline risk.
Monitoring & Follow-up
Regular assessment of disability using Expanded Disability Status Scale (EDSS).
Longitudinal cognitive evaluations focusing on processing speed, attention, visuospatial, and working memory domains.
MRI monitoring for brain atrophy as a surrogate marker of neurodegeneration.
Risks
Progressive neurodegeneration driven by oxidative stress may lead to irreversible disability and cognitive decline.
Subclinical inflammation may be missed without comprehensive biomarker profiling.
Patient & Prescribing Data
Adults with PPMS-NA without active inflammatory lesions or relapses
Disease-modifying therapies classified as no treatment, moderately effective, or highly effective were used; oxidative stress and glial-targeted therapies are supported by biomarker findings but require further clinical validation.
Clinical Best Practices
Perform comprehensive biomarker profiling including plasma IL-6, IL-8, IFNα2, and CSF ROS to inform prognosis and guide therapy in PPMS-NA.
Use longitudinal cognitive testing to detect early decline and tailor interventions accordingly.
Incorporate MRI assessment of brain atrophy to monitor neurodegeneration progression.
Exclude other neurodegenerative or psychiatric conditions and corticosteroid use to avoid confounding biomarker interpretation.
by Albert Miguela, Joana Maria Huertas-Pons, Clàudia Coll-Martinez, Ariadna Gifreu-Fraixinó, Judit Salavedra-Pont, Manuel Comabella, Luisa María Villar, Jordi Gich, Gary Álvarez-Bravo, Lluís Ramió-Torrentà, Ana Quiroga-Varela
