Inflammatory mechanisms underlying cortical injury in progressive multiple sclerosis

Area of Science:

• Neuroimmunology
• Central Nervous System (CNS) Diseases
• Inflammatory Demyelinating Diseases

Background:

• Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS.
• Therapeutic advances primarily target relapsing MS, with less progress in managing progressive forms (SPMS, PPMS).
• Distinct mechanisms underlie relapsing and progressive MS, with progressive disease driven by chronic CNS-localized inflammation.

Purpose of the Study:

• To review the role of CNS-compartmentalized inflammation in cortical injury in MS.
• To emphasize the importance of immune-CNS crosstalk in driving MS progression.
• To highlight novel therapeutic targets for progressive MS based on disease biology.

Main Methods:

• Review of current literature on MS pathogenesis.
• Focus on immune cell interactions within the CNS, particularly meningeal inflammation.
• Analysis of the link between meningeal immune infiltrates and subpial cortical demyelination.

Main Results:

• Progressive MS is characterized by chronic, low-grade inflammation within the CNS.
• Peripheral immune cells (B cells, T cells, myeloid cells) reside in CNS niches like the meninges.
• Meningeal immune infiltrates are associated with subpial cortical demyelination, a key driver of MS progression.

Conclusions:

• CNS-compartmentalized inflammation, especially in the meninges, is crucial for cortical injury and MS progression.
• Immune cell interactions within the CNS represent a promising therapeutic target for progressive MS.
• Understanding immune-CNS crosstalk is vital for developing targeted interventions for progressive disease stages.