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Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

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    Area of Science:

    • Neuroimmunology
    • Neurology
    • Pathophysiology

    Background:

    • Relapsing-remitting multiple sclerosis (MS) has effective therapies, but progressive MS (PMS) treatments are limited.
    • Understanding PMS pathogenesis is vital due to diagnostic challenges and lack of established biomarkers.
    • Current imaging shows reduced blood-brain barrier permeability and leptomeningeal inflammation in PMS.

    Purpose of the Study:

    • To review pathogenic mechanisms in progressive multiple sclerosis.
    • To correlate histopathology with MRI findings in PMS.
    • To discuss novel therapeutic strategies for progressive MS.

    Main Methods:

    • Review of current literature on progressive multiple sclerosis mechanisms.
    • Analysis of magnetic resonance imaging (MRI) studies in PMS.
    • Discussion of potential therapeutic targets and clinical trial outcomes.

    Main Results:

    • Progressive MS involves inflammation, potentially shielded by an intact blood-brain barrier.
    • Leptomeningeal inflammation and subpial demyelination are observed in PMS.
    • Immune responses, energy failure, and channel dysfunction are implicated in CNS damage.

    Conclusions:

    • Targeting specific mechanisms like immune activity behind the blood-brain barrier may offer neuroprotection.
    • Myelin repair and restoring axonal function are potential therapeutic goals.
    • Lessons from past trials are improving future progressive MS treatment strategies.