Bacterial toxins and Multiple Sclerosis

Abstract

The primary pathogenetic mechanism responsible for the distinctive demyelinating lesions in the Central Nervous System (CNS) in Multiple Sclerosis (MS), first described in remarkable detail by Charcot more than 170 years ago, remains one of the most baffling conundrums in medicine. A possible role for bacterial cell molecules and transportable proteins in the pathogenesis of MS is reviewed. The ability of bacterial toxins to distort immunity and to cause distinctive toxic damage in the nervous system is discussed in the light of largely forgotten data linking bacterial nasopharyngeal infections with optic neuritis, optochiasmatic arachnoiditis and MS. While the blood-brain barrier substantially protects the CNS from hematogenous toxins, there is a route by which the barrier may be by-passed. Data is reviewed which shows that the CSF and extra-cellular fluid circulation is bi-directionally linked to the lymphatic drainage channels of the nasopharyngeal mucosa. While this provides a facility by which the CNS may mount immunological responses to antigenic challenges from within, it is also a route by which products of nasopharyngeal infection may drain into the CNS and be processed by the immune cells of the meninges and Virchow-Robin perivascular spaces. If potentially toxic bacterial products are identified in early MS tissues at these sites, this would provide an entirely new insight into the pathogenetic mechanisms of this frustratingly enigmatic disease.

Back on the scent: the olfactory system in CNS demyelinating diseases

“…As anosmia can similarly occur early in MS, pathological involvement of the olfactory bulb/tract and its relationship to adjacent cortical demyelination may not only explain this symptom but also may spin a different light onto observations which link chronic sinusitis to MS susceptibility, relapse risk and its demography (figure 5). 64 65 In ADEM where olfactory bulb/tract demyelination is highly inflammatory and symptom onset occurs within days, disease is typically preceded by contraction of an upper respiratory tract infection (URTI) 68. Might the olfactory system play a role in permitting a nasopharyngeal agent into the CNS where it initiates a process of acute or chronic neuroinflammation?…”

Clinical and symptomatological reflections: the fascial system

“…Recent studies have demonstrated that the liquor is mostly drained by the lymphatic system, flowing from the perineural and perivascular sheaths to the lymphatic vessels; when it is in the lymphatic system, the liquor flows to the cribriform plate of the ethmoid bone, and then to the epithelium and the nasal mucosa (Figure 6). 103,104…”

“…An imbalance in the quantity of liquor can alter the immunological environment, whether cerebral or systemic, as it transports many substances (ie, electrolytes, catabolites, hormones and neuropeptides) 100,104,107. Altered homeostasis of the nasal mucosa and of the olfactory nerve can develop disorders in the superior respiratory tract, which can convey germs to the cerebral area, through the lymphatic pathways departing from the brain 104…”

Nose to brain: Is the trigeminal nerve a conduit for CNS disease?

“…Highly significant clinical, epidemiological and pathogenetic similarities between multiple sclerosis and nasopharyngeal sinusitis has led to the hypothesis that MS is caused by the leakage of bacterial toxins generated by the flora of the paranasal sinuses into the extracellular fluid compartments of the CNS (Gay, 2007). The inflammation observed in the trans-cisternal trigeminal nerve of MS patients may be the result of ascending lymphatic drainage Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/msard from the nasopharynx, as described by Orr and Rose (1914).…”