Early prognosticators of later TSPO-PET-measurable microglial activation in multiple sclerosis

Area of Science:

• Neuroimmunology
• Neuroinflammation
• Radiology

Background:

• Innate immune cell activation, particularly microglia/macrophages, is implicated in multiple sclerosis (MS) progression.
• Understanding the drivers of this activation is critical for predicting clinical disability accumulation.
• Early inflammatory processes may influence long-term MS pathology.

Purpose of the Study:

• To investigate demographic, clinical, and paraclinical factors associated with innate immune cell activation in MS.
• To identify predictors of positron emission tomography (PET)-measurable microglial activation.

Main Methods:

• Positron emission tomography (PET) imaging with a TSPO-binding tracer ([11C]PK11195) was used to assess microglial activation.
• The study included 37 patients with relapsing-remitting MS, aged 40-55, with at least five years of disease duration.
• Medical records and diagnostic MRI scans were analyzed for early disease parameters.

Main Results:

• Increased microglial activation correlated with a higher number of T2 lesions on diagnostic MRI.
• A higher immunoglobulin G (IgG) index in cerebrospinal fluid (CSF) at diagnosis was associated with greater microglial activation.
• Expanded Disability Status Scale (EDSS) scores of ≥ 2.0 at five years post-diagnosis also correlated with enhanced activation.

Conclusions:

• The number of T2 lesions on MRI and CSF IgG index at MS diagnosis are linked to later TSPO-PET-measurable innate immune cell activation.
• These early inflammatory markers suggest that both focal and diffuse inflammatory events contribute to the development of progressive MS pathology.
• Identifying these early predictors can aid in understanding and potentially managing MS progression.