Ron, as far as I know this hasn't been posted here before.  Many similar things are posted from time to time on ThisisMS, usually indicating the worthlessness of MRI scans, either because the degree of disability doesn't correlate to the number of lesions or the fact that some lesions can be found in normal brains.  In my scan there is a very old area of damage which must have been there before I started showing visible symptoms.  From scan to scan it doesn't change one iota.  As far as disease processes outside visible lesions, I'm sure they occur because many people report only one or two lesions yet great levels of disability.  This was probably happening with me as well, although there didn't look like there was much room left when I saw my first scan.  I'm glad I didn't see it until it was compared to my second one and could see the improvements.  Then, six months later again, some peripheral lesions had actually disappeared, but a year later things were not much different.  Throughout all this and the following year, I carried on getting slow improvements, so I think all that can be said is that an MRI is a useful tool as an aid to diagnosis and means that many people don't need a lumbar puncture any more.  I never had one because it was so obvious.  I don't think I am going to look at them again, though, so I'll just leave them all in a folder on a shelf in David's study: too much of a reminder of bad times.......Sarah

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Thanks for posting this, Ron. Very interesting; it has been known for some time that there are functional changes in grey matter in MSi [1] which proceed independently of relapses; these can't be accounted for by demyelinationi [10]. A recently published study showed that changes in the 'normal appearing white matter' were related to distance from established plaques [Vrenken H, Geurts JJ, Knol DL, et al., Normal-appearing white matter changes vary with distance to lesions in multiple sclerosis. Am J Neuroradiol. 2006 Oct;27(9):2005-11.] (Abstract only read) These authors state: 'NAWM disease farther from the lesions may be mainly characterised by subtle blood-brain barrieri [11] damage, with leakage of fibrinogen into the parenchyma and microplaque formation.' This supports the idea of spreading infective vasculitisi [12] as a precursor of the neuropathology; this idea was first advanced by Rindfleisch in the 1860s. Here's another interesting study (again, abstract only read) which discusses the molecular nature of this disruption of the blood-brain barrier. [Hochmeister S, Grundtner R, Bauer J, Engelhardt B, et al., Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis. J Neuropathol Exp Neurol. 2006 Sep;65(9):855-65.] These authors comment: 'Dysferlin is a muscle protein involved in cell membrane repair. . . In the inflamed CNSi [13] of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosisi [14] factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.' Once the neuropathology starts, though, a lot goes on quietly. A person with MS said to me recently that she thought a lot of serious damage accrued silently between the obvious episodes. A very prescient remark.

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D W - [Myalgia and hypertensioni [15] (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazolei [7]. No medication now; just supplementsi [16] and IR sauna. Morning BP typically 105/75]

Hi Ron & DW,

Interesting.   I don't think I understood this about MSi [1] before.   The leaky blood vessels in the brain in MS sound very similar to the leaky blood vessels in rosaceai [17] facial skin.  Under the inflammatory theory of rosaceai [18], from what I understand, much of the edema is caused by an excess of this leaking infiltrate, etc, and much of the tissue destruction is caused by things such as the MMP's (including collagenase), nitric oxide and ROSi [19], that are released by leaked neutrophils into the surrounding tissues.   It's explained fairly clearly in the first part of this short video:

http://rosaceatoday.com/MOA.asp?Display=1&Player=mov [20]

Is this kind of like what's going on with MS too? 

In rosacea we also seem to have some sort of nerve involvement, relating specifically with what has been described a neuropathic pain (or continual burning), that seems to be stimulated via the inflammatory response.   I haven't read much on how this occurs, but could it somehow be related to the nerve damage in MS?

 

 

 

On Combined Antibiotic Protocol for Cpni [21] in Rosacea since 01/06

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Treatment for Rosaceai [17]

• CAPi [3]:  01/06 - 07/07
• High-Dose Vit D3, NACi [22] & FIRi [23] Sauna Only:  07/07 - 11/08
• Intermittent CAP, High-Dose Vit D3:  11/08 - Present

Red, it does seem likely that there's a similar underlying inflammatory pathology in many of these chronic disorders. Elevated MMPs are the rule. The activity of MSi [1] is linked to MMP levels [Fainardi E, Castellazzi M, Bellini T, et al., Cerebrospinal fluid and serum levels and intrathecali [24] production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler. 2006 Jun;12(3):294-301.] The route the disease takes, and its appearance within that disease-form is likely to depend on multilayered host factors. Small-vessel disease and nerve injury at a local level seem to be a common pattern, though; it is found in Crohn's diseasei [25] (mesenteric vasculitisi [12]) and in interstitial cystitisi [26], where damage to vessels and nerves in the muscularis and sub-urothelial layers. Giant-cell arteritis is another disease-form in which chronic infection with Chlamydia pneumoniae may be implicated. Many of these conditions can give rise to severe intractible pain, presumably due to nerve involvement. Many associations between different disease forms are not seen because medicine is compartmentalized. There is, for instance, a raised incidence of white-matter MRI abnormalities in people with Crohn's disease. Retinal vasculitis has been known to be associated with MS for about 60 years.

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D W - [Myalgia and hypertensioni [15] (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazolei [7]. No medication now; just supplementsi [16] and IR sauna. Morning BP typically 105/75]

Interesting.  I've seen terms small vessel disease and vasculitisi [12], etc mentioned on the site before, but not having a medical background myself, I don't think I understood the implications, and didn't realize how closely linked some of these disease pathogenesis are or potentially could be (since I don't know much about these other diseasesi [27]).

Thanks as always for the added info... 

 

On Combined Antibiotic Protocol for Cpni [21] in Rosaceai [17] since 01/06

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Treatment for Rosaceai [17]

• CAPi [3]:  01/06 - 07/07
• High-Dose Vit D3, NACi [22] & FIRi [23] Sauna Only:  07/07 - 11/08
• Intermittent CAP, High-Dose Vit D3:  11/08 - Present

 Exactly, Red. The reason we have kept mentioning small vessel disease and vasculitisi [12] is that both David and Chuck (Stratton) have repeatedly drawn the links between these factors and Cpni [21], as the basis really for a number of the diseasesi [27] in which Cpn is implicated. It is this inflammatory infiltration which also allows entry into tissues and organs from the circulatory system, for example across the Brain Blood Barrier, or the spreading into microcirculation in the epidermis in rosaceai [17], or the cardiac epithelium in heart diseasei [28].

Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndromei [29] & Fibromyalgiai [30]- Currently: 150mg INHi [31], Doxycycline/Zithromycin, Tinidazole pulses. Northern Ohio, USA

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CAPi [3] for Cpni [21] 11/04. Dx: 25yrs CFSi [4] & FMSi [30]. Currently: 150mg BID Roxithromycin, Doxycycline 100mg BID, Tinii [32] 1000mg/day pulses; Vit D2000 units, T4 & T3

 Linking more on MMPs 7 and 9 in MSi [1].

Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions .

Here [33] is link.

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

Linking more on MMPs 9, Chlamydia Pneumonia and Atherosclerosis.

Matrix metalloproteinase-9 expression is associated with the presence of Chlamydia pneumoniae in human coronary atherosclerotic plaques

^{Here [34] is link.}

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

 Linking more on MMP, Chlamydia (non pneumonia)

A role for matrix metalloproteinase-9 in pathogenesis of urogenital Chlamydia muridarum infection in mice. (Microbes Infection 2007)

Here [35] is the link.

Chlamydia trachomatis enhances the expression of matrix metalloproteinases in an in vitro model of the human fallopian tube infection.

Here [36] is link. 

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

 Linking more on Cpni [21] and MMP

Exposure of human monocytes to Chlamydia pneumoniae resulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production. 

Here [37] is link.

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

Linking more on MMP and numerous autoimmune diseasesi [27]. 

This [38] 2006 Bayer patent has a very comprehensive explanation of MMP and it's association with nearly every disease

" The invention provides a human MMP9 which is associated with the infectionsi [39], cardiovacular diseases, dermatological diseases, endocrinological diseases, metabolic diseases, cancer, inflammationi [40], gastroenterological diseases, hematological diseases, respiratory diseases, muscle skeleton diseases, neurological diseases, urological diseases, reproduction diseases."

So let's see - CPNi [21] causes significant enhancement of MMP 9 - hmmmm.     

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

Hi Daisy,

Add MMP-1, -3 and -9 in Rosaceai [17]:

http://rosaceatoday.com/TheoriesofRosacea.asp [42]

On Combined Antibiotic Protocol for Cpni [21] in Rosacea 01/06 - 07/07, On Vit D3 + NACi [22] since 07/07 and daily FIRi [23] Sauna since 08/07

___________________________________________________________

Treatment for Rosaceai [17]

• CAPi [3]:  01/06 - 07/07
• High-Dose Vit D3, NACi [22] & FIRi [23] Sauna Only:  07/07 - 11/08
• Intermittent CAP, High-Dose Vit D3:  11/08 - Present

 January 2008, Respiratory Research Article on persistencei [43] of other forms of chlamydia (and association with COPD).  Here [44] is article.

^"The release of matrix metalloproteinases (MMP-9) is shown to be stimulated by chlamydial heat shock proteini [45] 60. Release of MMPs is also crucial for tissue destruction by macrophages in human emphysema"

Yes the article is on horses but it's pretty cool they are proving persistence of infection in other strains of Chlamydia.

"For the first time persistence of CPP and CPA in the lungs of clinically healthy horses and acute (possibly reactivated) chlamydial infectionsi [39] in those with obvious disease is demonstrated. Respiratory chlamydial infection probably becomes clinically relevant only in animals affected by additional pathogenic factors. In this context, inflammationi [40] seems to be associated with the activation of chlamydiae. Furthermore, the high prevalence of these chlamydial agents in horse lungs deserves further attention as a reservoir, especially in the light of recent studies,...."

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

And just to keep it all in one thread for inquiring minds that may want to know in the future, MMP9 is suppressed by tetracyclines see it HERE [46] This protocol is really a multi factorial benefit for the person with these diseasesi [27]. Yet another reason for people to consider it...even if they feel the connection between MSi [1] and CPni [21] is not as solid as they'd like. marie On CAPi [3] since Sept '05 for MS, RA, Asthmai [47], sciatica. EDSSi [9] at start 5.5.(early cane) Now 6 (cane full time) Currently on: Doxyi [5] 200, Azith 3x week, Tinii [32] cont. over summer '07, back to pulses of flagyli [7] winter '08 all supplementsi [16]. "Color out side the lines

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On CAPi [3] since Sept '05 for MSi [1], RAi [48], Asthmai [47], sciatica. EDSSi [9] at start 5.5.(early cane) Now 6 (cane full time) Originally on: Doxyi [5] 200, Azith 3x week, Tinii [32] cont. over summer '07, Revamp of protocol in Summer '08 by Stratton due to functional loss; clarithromy

I had lost this thread completely, because I really couldn't follow some of the discussion easily. So, I am getting better; today I read it like a newpaper.

The connections to MMP-9 are very interesting, Daisy. I wonder what other bacteria can cause elevated MMP's?  I did a (very) little checking, just for curiosity's sake. Borrelia burgdorferi looked interesting; Toxoplasma gondii less so. HIV is another henchman in the destruction of the BBB by MMP-9. [49]

At any rate, thanks for digging out this old thread. I'd forgotten all about it, partly because I couldn't really follow the discussion very well. 

I wonder when the MRI for T1 changes will be available outside the lab? It could perhaps flag individuals whose MSi [1] is worsening despite the lack of change in the lesions.

It seems that traditional MRIs (like Sarah's old ones) are like trying to judge the health of a plant by looking at holes in the leaves. I mean: a leaf can have a fairly chewed-up appearance (lesions) but still be functioning pretty well (nice and green); another leaf may have only a couple of small holes, but be all yellow and wilty.

Counting the holes just wouldn't tell the story. It seems the T1 MRI looks more at  "yellow wilty"  generalized damage. or is that a bad analogy?

 Ron

On CAPi [3] for CFSi [4] starting 01/06 (NE Ohio, USA)

Currently: doxyi [5] & zithi [6] -- continuous; metronidazolei [7] -- 5 days on, 9 days off.

Get the research results you paid for: support Open Access

___________________________________________________________

Ron

On CAPi [3] for CFSi [4] starting 01/06 (NE Ohio, USA)

Currently: doxyi [5] & zithi [6] -- continuous; metronidazolei [7] -- 5 days on, 9 days off.

Get the research results you paid for: support Open Access

 Marie - I agree !  The protocol is really a multi factorial benefit for the person with these diseasesi [27]. 

There are loads of studies on the use of doxycycline and minocycline suppressing MMP9 in stroke, MSi [1], diabetes, asthmai [47], COPD, uterine fibroidsi [50], etc....  with the spam catcher it would take hours to post them all. 

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxy, Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

 Ron - Definitely other bacteria  (and virii) induce elevations in MMP9. 

Strep, borrelia, h.pylori, mycoplasma, HPV, hepatitis, HSVi [51], etc... 

To me it's a bit of a chicken or the egg situation.  MMP's are involved in "good" normal biological processes and "bad" pathological processes. 

It's theorized that MMP9's (matrix degrading) are induced by neutrophils responding to the site of infection.  Once there it is believed MMP9 induce inflammatory angiogenesis.

Some days I am dazzled by the good quality clinical science that has been reproduced indicating various pathogens as "present" in various "auto-immunei [52]" diseasesi [27] and the associated mechanisms of fall out like MMP9.

It further makes me queazy when I think of how much research in MS is focused on EAE model.  I want to stand up to the herd and say - whoa - Wrong Way.  Stop and look at the ICAAC and Antimicrobial journals - it's all there.  Free your minds and the rest will follow...

Re the MRI's.  Good point.  I imagine that a high enough TESLA machine will show the lesions that don't show on the MRI equipment used by most. 

Also, think that even though MRI's can show no new enhancing or current lesion changes in the face of clear disease progression you must also consider brain size (lack of shrinkage), midline shift, sulcus patterns etc... 

It's always been interesting to me that many "healthy" people will show some sort of brain lesions on MRI later in life.  Of couse cognitive decline also shows in many too. Correlation?   Slow growing infectionsi [39] gaining ground as the immune system ages or is overwhelmed?  Maybe?

It's ALL - already in the literature.  The benchwork and proof of concepts are there.  The left and right hands just aren't talking. 

Well - at Vanderbilt they are. 

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

More good stuff: 

Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? [53]

 

On Combined Antibiotic Protocol for Cpni [21] in Rosaceai [17] 01/06 - 07/07, On Vit D3 + NACi [22] since 07/07 and daily FIRi [23] Sauna since 08/07

___________________________________________________________

Treatment for Rosaceai [17]

• CAPi [3]:  01/06 - 07/07
• High-Dose Vit D3, NACi [22] & FIRi [23] Sauna Only:  07/07 - 11/08
• Intermittent CAP, High-Dose Vit D3:  11/08 - Present

Red -

Genius article on Vita D and MMP !  Thanks!

Here's [55] one on pycogenol and MMP9. 

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

___________________________________________________________

Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

Alpha Lipoic reduce MMP9's. 

"also inhibited high-glucose- and TNF-alpha-induced increases in MMP-9 expression."  Here's [56] link.

And from another article.  "ALA and DHLA reduced matrix metalloproteinase-9 (MMP-9) activity by 18-90% in Jurkat cell supernatants"  Here's [57] link.

Alpha Lipoic in MSi [1].  Reducing MMP9.  Here's [58] link.

^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

 NACi [22] reduces MMP9's.   FC below equals macrophage induced foam cell. 

"We further examined whether FC gelatinolytic activity is dependent on the presence of reactive oxygen species (ROSi [19]). We found that treatment (1 to 5 days) with 1 to 10 mmol/L N-acetyl-L-cysteine (NAC), an ROS scavenger, decreased not only gelatinolytic activity but also gelatinase expression by FCs. Similarly, NAC treatment of explanted lesions abolished in situ gelatinolytic activity and MMP-9 expression."   Here [59] is link.

Curiously, my husband's pathology report from his Sept 2006 crainotomy showed a preponderance of "foamy macrophages".

 ^{Daisy - Husband on CAPi [3] 5/07.   Roxithromycin, Minocycline, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi [5], Azithromycin, Flagyli [7], Diflucan}

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Daisy - Husband on CAPi [3] 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

Good stuff, Daisy.   Thanks! 

On Combined Antibiotic Protocol for Cpni [21] in Rosaceai [17] 01/06 - 07/07, On Vit D3 + NACi [22] since 07/07 and daily FIRi [23] Sauna since 08/07

___________________________________________________________

Treatment for Rosaceai [17]

• CAPi [3]:  01/06 - 07/07
• High-Dose Vit D3, NACi [22] & FIRi [23] Sauna Only:  07/07 - 11/08
• Intermittent CAP, High-Dose Vit D3:  11/08 - Present