BBB : Vasculitis and rheumatologic diseases may play a role

[PANDAS_Denmark]

Two things made me wonder the other day :

 

1. Buster wrote in a comment, that "My wife and I wonder if perhaps this is really a blood-brain barrier problem and all the variants are really just different manifestations of how the BBB gets inflammed -- or how antibodies cross the BBB."

 

2. In a poll Buster asked if "My child is a canary for strep in the household (i.e., behavior changes when someone has strep)"

 

To take the latest first : My son is for sure like a canary for strep in the household (and every where else!) - and a very good and reliable canary : Besides the raise/explosion of tics and/or OCD when exposed to strep (or other bacterias/vira) he gets petecchias as well. Allways in this order :

 

Exposed

Within few hours : Petecchias

Within a day or two : A raise/explosion of tics and/or OCD, separations anxiety etc.

 

As such I ALLWAYS know when he has been exposed to strep (to an extend, where he/his immune system reacts) BEFORE he gets the raise in tics and/or OCD.

 

The pettechia he gets is due to vasculitis, that showed up and that he was diagnosed with at the same time as the PANDAS : That is a chronic inflammatory destruction of the blood vessels (http://en.wikipedia.org/wiki/Vasculitis).

 

I have allways thought of my sons two diagnosis/medical conditions as two independent, "paralel" (autoimmune) conditions, but Busters comment on the BBB made me think : What if the the vasculitis (and the chronic inflammatory destruction of the blood vessels) is the condition that makes (my sons and other kids) PANDAS (not only in my opinion considered a variant of ADEM or MDEM) "possible" ? That is : What if vasculitis might play a role in making the antibodies due to a strep infection able to cross the BBB ?

 

In my search for an answer I found this article :

 

"Vasculitis and rheumatologic diseases may play role in the pathogenesis of acute disseminated encephalomyelitis (ADEM).

Sabayan B, Zolghadrasli A.

 

Research Center of Shiraz University of Medical Sciences, Shiraz, Fars, Iran. b.sabayan@gmail.com <b.sabayan@gmail.com>

 

ABSTRACT : Acute disseminated encephalomyelitis (ADEM) is defined as a multifocal, monophasic, demyelinating, and inflammatory disease involving the central nervous system. It typically begins within 6 weeks of an antigenic challenge such as infection or immunization. Perivenous inflammation, edema and demyelination are the pathological hallmarks of ADEM. Reactivity of T-cells against myelin components such as myelin basic protein has been found in children with ADEM. The triggers for immune responses in ADEM are not known, but the two most widely accepted hypotheses are molecular mimicry and self-sensitization secondary to CNS infection. Inflammatory cytokines including tumor necrosis factor alpha (TNFalpha), interleukin 2 (IL2) and interferon gamma (INFgamma) are thought to be important in lesion formation in ADEM. Due to the active role of inflammatory cytokines in the pathogenesis of ADEM, any disease contributing to systemic formation of inflammatory cytokines can potentially be an etiologic factor for the initiation of ADEM. In vasculitis and rheumatologic diseases the number of T-cells, T helper type 1 cytokines and other inflammatory cytokines such as TNFalpha increase substantially. We present this hypothesis that in such setting of inflammation, adhesion molecules are up-regulated on the brain capillary endothelium by cytokines and other inflammatory mediators, altering the permeability of the brain blood barrier and so allowing for inflammatory cell migration. The migratory cells attack the basic myelin protein and the final result is the demyelination seen in ADEM. So we propose that vasculitis and rheumatologic diseases may play role in the pathogenesis of ADEM"

 

I am aware, that the article doesn´t prove anything. However I find it very, very interesting - as I would find your comments on it too ! -

 

Best wishes to you all -

 

PANDAS_Denmark

[kim]

PandasD.

 

We present this hypothesis that in such setting of inflammation, adhesion molecules are up-regulated on the brain capillary endothelium by cytokines and other inflammatory mediators, altering the permeability of the brain blood barrier and so allowing for inflammatory cell migration.

 

I think you are basically looking at the same thing that was discussed in this thread. Buster refers to them as handholds (adhesion molecules).

 

http://www.latitudes.org/forums/index.php?...=6063&st=15

 

I was trying to spend a little time again this morning working on my theory about why these antibodies are so attracted to "self tissue," and it made me think of this post of yours.

 

 

You might want to read through these too, if you haven't seen them

 

http://www.ncbi.nlm.nih.gov/pubmed/1776774...ogdbfrom=pubmed

 

Arthritis Res Ther. 2007;9 Suppl 2:S9.

 

Vasculitis: mechanisms involved and clinical manifestations.

Guillevin L, Dörner T.

 

Service de Médecine Interne, Hôpital Cochin, rue du Faubourg Saint-Jacques, F-75014 Paris, France. loic.guillevin@cch.aphp.fr

 

Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/1712249...ogdbfrom=pubmed

 

Am J Dermatopathol. 2006 Dec;28(6):486-506.

 

Cutaneous vasculitis update: small vessel neutrophilic vasculitis syndromes.

Carlson JA, Chen KR.

 

PMID: 17122493 [PubMed - indexed for MEDLINE]

 

http://www.ncbi.nlm.nih.gov/pubmed/1828426...ogdbfrom=pubmed

 

Clinical approach to cutaneous vasculitis