Multiple Sclerosis is Not a Disease of the Immune System

Abstract

Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system. The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations. Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease. I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses during acute-phase inflammatory response triggered by a pathogen, trauma, or stress, starting a feedback loop of increased oxidative stress, inflammatory response, and proliferation of cytoxic foam cells that cross the blood brain barrier and both catabolize myelin and prevent remyelination. Understanding MS as a chronic metabolic disorder illuminates four aspects of disease onset and progression: 1) its pathophysiology; 2) genetic susceptibility; 3) environmental and pathogen triggers; and 4) the skewed sex ratio of patients. It also suggests new avenues for treatment.

Epidural blood patch in a patient with multiple sclerosis: is it safe?

“…This causes action potentials to travel at reduced velocity, and conduction may become partially or completely blocked. [1][2][3] It is well established that conduction of action potentials in healthy axons can be blocked by pressure, and the threshold for this effect is inversely related to the duration of applied pressure. In in vivo and in vitro animal studies, propagation of evoked compound action potentials may be blocked by pressures as low as 30 mmHg when applied for hours, and much more rapid block is observed with pressures exceeding 200 mmHg.…”

“…[1][2][3] Cerebral spinal fluid samples obtained by lumbar puncture may be performed to help support the diagnosis of MS. 4 A well-described complication of lumbar puncture is the postdural puncture headache (PDPH), but the classic treatment of this complication -epidural blood patch (EBP) -may be of theoretical concern in this unique type of patient. There is extensive literature showing that pressure can interfere with axonal conduction of nervous impulses, [5][6][7][8] and it is unknown whether affected axons of the MS patient are particularly vulnerable to the increase in epidural pressure that can occur as a consequence of the blood patch.…”

Vi-2 : Apport De l'ÉLECTROPHYSIOLOGIE Chez l'ADULTE : Exemples

“…L'hypothèse de son origine auto-immune jusqu'ici probable [Korn, 2008] est actuellement battue en brèche par celle évoquant le dysfonctionnement possible du métabolisme des lipides induit par un stress oxydatif à l'origine d'une réponse inflammatoire [Corthals, 2011].…”

Antibodies to Heterogenous Nuclear Ribonucleoprotein A1 Penetrate Neurons Leading to Multiple Downstream Effects Resulting in Neurodegeneration

“…Neurodegeneration in MS involves multiple mechanisms including autoimmunity to CNS targets, axonal hypoxia and oxidative stress, mitochondrial dysfunction, and disturbances in lipid metabolism and nuclear receptors. [3][4][5][6] MS has historically been viewed primarily as a white matter disease. However, recent data indicates that both white matter and gray matter destruction contribute to its pathogenesis.…”

“…3,4,30,31 However, none successfully identified a single pathological mechanism, likely because MS is a heterogeneous disease with a multifaceted etiology. 32,33 Although it has not been proven, the data presented could lead to the hypothesis that various disease causing entities likely lead to the form of MS present within each individual.…”