Multiple sclerosis is a systemic venous vasculopathy: A single unifying mechanism

Area of Science:

• Neurology
• Immunology
• Pathology

Background:

• Multiple sclerosis (MS) is a leading cause of neurological disability, characterized by central nervous system (CNS) demyelination and autoimmune processes.
• Current understanding points to genetic and environmental factors, but the precise pathogenic mechanisms remain unclear.
• Diagnosis relies on clinical presentation, imaging, and biochemical markers, with characteristic lesion distribution observed historically.

Purpose of the Study:

• To propose a unifying theory for multiple sclerosis (MS) pathogenesis.
• To re-evaluate the role of vascular abnormalities in MS.
• To integrate diverse clinical, anatomical, immunological, and pathological findings into a cohesive framework.

Main Methods:

• Review and synthesis of existing clinical, pathological, and immunological data on MS.
• Analysis of lesion distribution and venous abnormalities in CNS pathology.
• Evaluation of blood-brain barrier integrity and inflammatory markers.

Main Results:

• MS lesions exhibit a characteristic perivenular distribution, consistent with venous involvement.
• Pathological findings reveal venous abnormalities and perivenous inflammatory infiltrates.
• Blood-brain barrier dysfunction is evident even in normal-appearing white matter, suggesting a systemic inflammatory component.

Conclusions:

• Multiple sclerosis (MS) is proposed as a primary autoimmune vasculopathy with a predilection for CNS venous structures.
• Characteristic CNS lesions are hypothesized to be secondary to an immune response triggered by the uncovering of CNS antigens.
• This vasculopathy theory offers a unifying explanation for the complex and seemingly disparate findings in MS.