Charcot's pupil, Pierre Marie, focused on infection as being the cause of MS. One problem, many causes of infection weren't known then, so this theory fell by the wayside and the auto-immune theory took hold. The first antibiotic didn't become available until World War 2 and it is no use against the prime bacterial infection thought to cause MS: chlamydia pneumoniae, (see the antibiotics forum.)
Chronic infection can cause endothelial dysfunction:
C pneumoniae is known to patchily parasitize the cells which line small blood-vessels, causing episodes of vasculitis. This is a local inflammatory process characterised by tiny punctures in the vessel walls and leakage of blood-components into the surrounding tissue space. It can be visualized directly in the retinal veins, where the vessels appear to be coated with a thin greyish sheath. This sheath is comprised of T lymphocytes. A very similar pathology takes place in the brain in early MS. The association between sheathing of retinal veins and MS was first made in 1944. The anatomical distribution of lesions within the brain in MS is often centred on small veins; elongated plaques may follow the sinuous curves of the vessels they surround. [Esiri MM, ed. Oppenheimer's Diagnostic Neuropathology, 2nd edition, 1996 Blackwell: 256-9.] Vasculitic phemomena were recognised surprisingly early: in 1873 Rindfleisch commented: "If one looks carefully at freshly altered parts of the white matter in the brain, one sees with the naked eye a red point or line in the middle of each individual focus, the transversely or obliquely cut lumen of a small vessel engorged with blood. . . All vessels running inside the foci, but also that traverse the immediately surrounding but still intact parenchyma are in a state of chronic inflammation." Rindfleisch had recognized, over 130 years ago, that inflammation of small vessels — vasculitis — precedes neural damage.
Examination of the eye reveals retinal vasculitis in about a third of persons with early MS, but it is probably present in far more. It is especially common following optic neuritis (a common precursor of MS), and is characterised by leakage of dye in a fluorescein dye test, blood cells, and cuffing of the vessel walls by inflammatory cells. Where it is seen, there is a raised likelihood that MS will follow. I have noted that episcleritis (an inflammatory condition of the connective tissue between the conjunctiva and sclera involving vasculitic features) is also a frequent finding in those with MS. (Unpublished data.)
There seem to be a number of factors which need to be in place before MS develops, including chronic C. pneumoniae infection and a genetic inheritance which determines a certain kind of response to this infection. Some people have a disease-form which is primarily driven by the infection; it is characterised by rapid progression and intoxication with bacterial metabolites. Untreated it results in a swift decline; it is rapidly fatal. This is the form that Sarah had. Paradoxically, it seems very responsive to treatment. Other people seem to have a disease-form where the host reaction predominates; the infection is slow, bacterial numbers are probably few. This seems to be less amenable to antibacterial treatment, and the disease may remain active until the remains of the dead bacteria (endotoxins) are removed. This may be problematic in an enclosed area like the brain. One might speculate that there are even some disease forms where autoimmunity persists autonomously. I think that most people with MS fall somewhere within these extremes. My own experience from advising many people with MS is that those with relapsing-remitting disease and early progressive disease can do well. Patients with later progressive disease respond less well, though this is not always the case. Generally speaking, the earlier that treatment is begun the better the result is likely to be and the more complete the resolution.
People with dense neurological deficits which have been in place for many years and which are situated in confined anatomical bottlenecks such as the cord or cerebellum may recover little function, but treatment may halt disease progression.
A historic study was published by workers at the Vanderbilt School of Medicine in 1999. CSF samples from 17 patients with relapsing-remitting MS, 20 patients with progressive MS, and 27 patients with other neurological diseases (OND) were examined by culture, by PCR and by antibody detection. C pneumoniae was isolated from CSF in 64% of MS patients against 11% of OND controls. Polymerase chain reaction assays demonstrated the presence of C pneumoniae MOMP gene in the CSF of 97% of MS patients versus 18% of OND controls. Finally, 86% of MS patients had increased CSF antibodies to C pneumoniae elementary body antigens as shown by enzyme-linked immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls. The specificity of this antibody response was confirmed by western blot assays of the CSF, using elementary body antigens. Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic antibodies against C pneumoniae. [Sriram S, Stratton CW, Yao S, Tharp A, Ding L, Bannan JD, Mitchell WM. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann Neurol. 1999 Jul;46(1):6-14.] It should be noted that the methodology used by the Vanderbilt workers is fastidious. In tissue-culture isolation, for instance, repeated centrifugation and prolonged incubation was carried out; this is very important as in chronic infection the organism may produce few of the spore-like elementary bodies, and those that are produced may be damaged. (It is interesting to note that the discovery of Helicobacter pylori was made possible by extending traditional incubation times.)