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In a pilot study, we identified Chlamydia pneumoniae in the cerebrospinal fluid by polymerase chain reaction in 5 of 10 patients with definite multiple sclerosis (MS). In a second series, 2 of 20 patients with definite MS and 3 of 17 patients with possible/probable MS or MS variants, but none of 56 patients with other neurological, diseases were polymerase chain reaction-positive. We confirm that C. pneumoniae can be found in the cerebrospinal fluid of MS patients, but our rate of positive results is lower than in a recent report.

Well, on Tuesday I had my follow up MRI scan, luckily at very short notice because I always get terribly worried, not about the machine itself but what it is going to show. Its all very well feeling that you are doing so much better, but what might be going on behind the scenes? Very silly really, but I can’t help it. On Monday I could have walked the couple of miles to the hospital, given time, but yesterday? I was wobbling all over the place by lunchtime, so had to call a taxi.

The scan actually showed improvements beyond all expectations: some lesions on the outside edge had completely vanished and all the others where greatly diminished. There were no new lesions at all. This just does not happen with either of the progressive forms of the disease. The radiologist, who went through the scans with us, had never seen anything like it and is going to take the sequential scans to the neuroradiologists at both Addenbrookes, our regional neurology centre, and Oxford, to show them.

Very shortly now I will be reducing the antibiotics, maybe to just 2 roxithromycin a day, cutting down then to one a day, or maybe intermediate treatment with doxycycline for three weeks every now and then, with five day bursts of metronidizole in the middle of the three weeks. Personally, I would prefer the first option because metronidizole makes me deathly tired and also weepy, but we will see.

David is now treating several MS patients and chronic fatigue patients, very successfully. He gives adequate amounts of time to each one, explaining everything to them and telling them to email him whenever they want reassuring about something. A paper is still very much in the offing, but he keeps finding new and relevant cases to add to it!

As for ‘my’ neurologist, who wrote me off a year ago, in an incredibly brief session on one of his afternoons over from Addenbrookes, where he is based, I don’t yet know what he will think when and if he sees the scans. I know he saw the second scans but I heard nothing. In a way, I don’t care, but in another way I do, because so many people could be benefiting from this, but as yet only a few GPs seem willing to refer someone with MS to a microbiologist. Actually quite a lot now do so locally.

The pity is that it has been found both by David and the team at Vanderbilt, where most of the research is going on, that the more deeply entrenched the progressive forms of the disease, the less likely one is to have much improvement, if at all. Therefore the earlier one starts the treatment the better. Luckily I had only been progressive for three years at most.

Sarah

A response to Byron's post.

Your points are acutely observed and well thought out. I've learnt a lot in the last year through treating a number of patients with MS. As a patient goes through RRMS, he or she tends to accrue progressive deficits; this is often unnoticed at first, but seems to equate with rising bacterial load. It's almost as though there were two parallel components to the disease, an idea which is supported by studies of sequential MRI data. I've recently seen two patients with early RRMS who have had no reactions on starting antibiotics. Both are improving, and have lost many of their accrued deficits. In the case of one patient, the deficits were so slight that the patient noticed them only when they started to go. In later RRMS and in early SP disease the reactions are often more severe; one assumes that this is because the bacterial load has grown. As the disease progresses ever deeper the immune system usually gains the upper hand and destroys the organism. It's a hard-won victory, and there may be immense collateral damage. At this stage there is little or no reaction to antibiotics, and little benefit from treatment. But a trial is worthwhile.

These acute reactions on starting doxycycline/minocycline are probably due to a freezing of bacterial protein synthesis. The organisms are intracellular; one of the host-cell defences against intracellular infections is host-cell suicide; this releases bacterial antigen so that antibodies can be raised against it. In an amazing evolutionary strategy, Chlamydia pneumoniae can prevent host-cell suicide. This, however, requires continuous synthesis of a specific protein. (It is now known that Chlamydia pneumoniae in the CSF of MS patients actively makes this protein; furthermore, persons with MS have antibodies to the same protein.) So the infected host cells are now free to die, releasing their bacteria; these cannot survive in their current state and die also. Their death releases endotoxins, which are a component of the bacterial cell wall. (In an interesting parallel, another chlamydia with a similar strategy is associated with a very rare periocular lymphoma which shrinks when treated with tetracycline.) Unfortunately, a lot of bacteria remain in other cell-lines, and need to be actively killed.

Roxithromycin is a powerful immunomodulator, and partially suppresses the immune system, allowing the toxins to be flushed away rather than evoking an inflammatory response. Both doxycycline and minocycline are immunomodulatory too.

The risk of the emergence of a resistant mutant is, as you say, an unpleasant thought. Workers have tried to do produce resistance in the laboratory with negative results. I suspect the risk of resistance emerging is actually minimal. Resistant mutants usually emerge in rapidly growing cultures treated with minimally inhibitory concentrations of antibiotic; this gives the right evolutionary drive to produce resistance. The organism is in 'tickover' mode in chronic infections like MS and some of the evolutionary pressure is removed. Using two antibiotics which act synergically certainly reduces any risk.

So I should be in no hurry to start metronidazole. Long-term minocycline is likely to be effective, with roxithromycin if this can be obtained, together with full supplementation - I'd allow three months before metronidazole is considered; and it should be started gently. Having witnessed a bad reaction to minocycline it would be beneficial to 'waste' as many organisms as possible before starting the killing phase.

One interesting rider. Serology is usually negative in MS, but this is not always the case. I've just seen a man with early PPMS (18 months), retinal vasculitis and follicular conjunctivitis. He has raised antibodies to Chlamydia pneumoniae, with an MIF of 1:1024 and high Chlamydia pneumoniae-specific IgA. (This is a fairly reliable indicator of persistent infection.) It's early days, but his carer reports good early improvement. His neurologist was very dismissive (rudely so), so I must write to him and tell him the serology results.

MS is multifactorial. A number of genes seems to play a part in the expression of the disease. I have recently seen a patient with a multisystem disorder including retinal vasculitis and Crohn's disease. She had grossly elevated Chlamydia pneumoniae serology. An MRI scan showed typical white-matter hyperintensities which transected the long motor tracts in several places. However, she had no focal neurological signs. Presumably she was fortunate in her genetic make-up.

Work has been done in many different disciplines, in microbiology, immunohistology, cellular biochemistry and neuroimmunology. The science is all there, but not many people have yet joined up the dots.

And you are right; treating someone close to you for a large-load Chlamydia pneumoniae infection of the brain is an emotional roller-coaster.