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New Ways of "Seeing" the Mechanistic Heterogeneity of Multiple Sclerosis Plaque Pathogenesis
Ethan I Meltzer1, Fiona E Costello, Elliot M Frohman
1Department of Neurology (EM), Partner's Neurology Residency Training Program, Massachusetts General and Brigham and Women's Hospitals, Harvard Medical School, Massachusetts; The Department of Neurology (TCF, EMF), The Dell Medical School, The University of Texas, Austin, Texas; and Department of Neurology (FC), University of Calgary, Calgary, Canada.
Background:
Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments.
Evidence Acquisition:
A constellation of inflammation, ion channel derangements, bioenergetic supply: demand mismatches within the intra-axonal compartment, and alterations in the dynamics and oximetry of blood flow in CNS tissue compartments are observed in MS. These findings have raised questions regarding how histopathologic heterogeneity may influence the diverse clinical spectrum of MS; and, accordingly, how individual treatment needs vary from 1 patient to the next.
Results:
We are now on new scaffolding in MS; one that promises to translate key clinical and laboratory observations to the application of emerging patient-centered therapies.
Conclusions:
This review highlights our current knowledge of the underlying disease mechanisms in MS, explores the inflammatory and neurodegenerative consequences of tissue damage, and examines physiologic factors that contribute to bioenergetic homeostasis within the CNS of affected patients.
Insights
Multiple sclerosis (MS) is now understood to involve more than inflammation and demyelination, affecting both white and grey matter. New research explores diverse mechanisms and patient-centered therapies for this complex neurological disorder.
Area of Science:
- Neuroscience
- Immunology
- Pathobiology
Background:
- Multiple sclerosis (MS) understanding has evolved from an inflammatory demyelinating disorder of central nervous system (CNS) white matter.
- Contemporary views recognize MS as affecting both white and grey matter, involving diverse injury mechanisms.
Purpose of the Study:
- To review current knowledge of MS disease mechanisms.
- To explore inflammatory and neurodegenerative consequences of tissue damage in MS.
- To examine physiological factors in CNS bioenergetic homeostasis in MS patients.
Main Methods:
- Literature review of MS pathobiology.
- Analysis of inflammation, ion channel function, and bioenergetics in MS.
- Examination of CNS blood flow dynamics and oximetry in MS.
Main Results:
- MS involves a complex interplay of inflammation, ion channel dysfunction, and bioenergetic imbalances.
- Histopathological heterogeneity in MS correlates with diverse clinical presentations.
- Altered CNS blood flow dynamics and oximetry are observed in MS.
Conclusions:
- Current understanding of MS pathophysiology is expanding beyond traditional concepts.
- Research is paving the way for patient-centered therapies based on a broader understanding of MS mechanisms.
- Addressing bioenergetic homeostasis and neuroinflammation is crucial for managing MS.
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