The sequence of events that eventually produces sclerosis multiple or single areas is a consequence of initial damage to the blood-brain barrier of venules in the nervous system and MRI has shown that this precedes symptoms1.
These events can be observed in the venules of the retina where it is termed ‘retinal periphlebitis’. This condition affects at least 25% of patients labelled as MS2.
The damage must be caused by an agent present in blood as there is no evidence that barrier failure can occur from events within the tissues of the nervous system.
Nine pathologists have observed that micro embolism due to body fat can reproduce the typical acute lesion of multiple sclerosis and this has been confirmed by CT and MRI3.
Micro embolism can account for both the clinical and pathological features of the disease4.
Broman showed in 19475 that when multiple veins are present in a typical plaque in a patient only one has blood-brain barrier damage; this indicates that a local mechanism is responsible.
When the blood-brain barrier of venules is damaged the resultant leakage induces hypoxia and leads to neutrophils recruitment and inflammation.6
There is no need to postulate immune abnormalities notably all the immune changes researched in multiple sclerosis occur in patients with cerebrovascular disease or even after head injury.7
Once the blood brain barrier is damaged attacks may follow from nothing more sinister than a hot bath8 because it results in dilatation of blood vessels.
References
1. Kermode AG, Thompson AJ, Tofts P, et al. Breakdown of the blood brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Brain 1990;115:1477-89.
2. McDonald WI, The pathogenesis of optic neuritis. In: Hess RF, Plant GT, eds. Optic neuritis, Cambridge University Press, 1986.
3. Chrysikopoulos H, Maniatis V, Pappas J, et al. Case report: post-traumatic cerebral fat embolism: CT and MR findings:report of two cases and review of the literature. Clin Radiol 1996;51:728-32.
4. James PB. Evidence for subacute fat embolism as the cause of multiple sclerosis. Lancet 1982; i :380-86.
5. Broman T. Supravital analysis of disorders in the cerebral vascular permeability II: two cases of MS. Acta Psychiat Neurol 1947; suppl46: 58-71.
6. Nathan, C. Oxygen and the inflammatory cell. Nature 2003;422:675-6.
7. Wang WZ, Olsson T, Kostulas B, et al. Myelin antigen reactive T cells in cerebrovascular diseases. Clin Exp Immunol 1992;88:157-62.
8. Berger JR, Sheremata WA. Persistent neurological deficit precipitated by hot bath test in multiple sclerosis. JAMA 1983;249:1751-53.