Pathoetiology of multiple sclerosis: are we barking up the wrong tree?

Abstract

Despite a century of intensive investigation, the underlying cause of multiple sclerosis has eluded us. It is clear that there exists a prominent progressive degenerative phenotype together with an important autoimmune inflammatory component, and careful histopathological examination always shows, to a greater or lesser degree, concomitant degeneration/demyelination and adaptive T cell-dependent immune responses. Given this picture, it is difficult, if not impossible, to definitively say whether degeneration or autoimmunity is the initiator of the disease. In this review, I put forward the evidence for and against both models and speculate that, in contrast to the accepted view, it is equally likely that multiple sclerosis may be a degenerative disease that secondarily elicits an autoimmune response, and suggest how this might influence therapeutic approaches.

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination

“…The loss of myelin and the death of oligodendrocytes lead to the impaired neurotransmission of axons because the myelin sheath permits that the conduction of a nervous impulse occurs quickly and efficiently by nervous cells [3][4][5]. Furthermore, demyelination increases the axon's susceptibility to oxidative stress and inflammatory damage because myelin also plays an important role in axonal protection [6,7].…”

Time to Revisit Non-Pharmacological Research Approaches to Ameliorate Multiple Sclerosis Symptoms

“…What is encouraging is that there is beginning to be some recognition that the immune response seen in MS might be secondary to damage to oligodendrocytes and myelin [13][14][15]. A novel idea recently proposed by Dr Paoli Zamboni and colleagues is that obstructed venous return may play some role in the etiology of MS. Dr Zamboni upon observing altered venous drainage in many MS patients [16,17] that was associated with altered CSF dynamics [18] proposed that "hampered cerebral venous return may contribute to the clinical course of MS" [19].…”

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

“…5 The epileptic seizures that have been observed in the course of chronic levamisole treatments have all been reported in children but not in adults. This offers another interesting parallel with vitamin B6 metabolism alteration: experimental studies showed that vitamin B6 deficiency results in epileptic crisis in young animals but not in the adults (Daniel et al 1942;Guilarte 1989). It is generally admitted that the etiology of multiple sclerosis involves an autoimmune component (for review : Goverman 2009;Cieślak et al 2011;Stys 2013). In particular, T cells are suspected to play a prominent role in multiple sclerosis.…”