Thursday, July 8, 2010

2005 neuroinflammation article

As Laura pointed out, my link to the neuroinflammation article is only to an abstract. The full publication is protected by copyright, and I don't think it is (legally) available for free anywhere on the internet. However, thanks to the Eide's blog, I found a copy of a second publication by the same authors that discuss the same findings. You can get your copy here.

Laura wondered whether the patients in the study included Hannah Poling. I can't really tell that, but the paper does tell us the following:

1) the brain tissues came from several different Brain Banks: Harvard, the University of Miami and University of Maryland.

2) There were tissue samples from 15 autistic individuals and 12 controls. 6 of the autistic individuals also had epilepsy. 3 of them had experienced regression, and it was unknown whether an additional 4 had or not; this states that 8 of them had not experienced regression. Their ages are really spread out. there's one 5 year old and one 44 year old. there are 7 tissue samples from children aged 7 to 10, one 14 year old, and 5 samples from individuals in their 20s.

3) An overwhelming majority of the autistic individuals had some mental retardation. Only one of them is listed as not having it, plus 2 that they weren't sure about. So that is certainly an important factor.

4) There were differences in the preservation of the different samples, and this affected which samples they performed some of the tests on.

5) It says "All autistic cases fit the diagnostic
criteria established in the Diagnostic and Statistical Manual–
IV and confirmed by the Autism Diagnostic Interview–
Revised (ADI-R).23,24 The ADI-R was administered previously
by researchers at the Autism Tissue Program (ATP) as
a criterion for inclusion in the repository. Additional clinical
and neurological information also was obtained from the

So although I'm not sure about this, it seems that they perhaps all had classic autism. Most of them were mentally retarded, which tells us something, perhaps, but since they didn't all have regression, I don't think they were all Hannah Poling cases, since I thought that regression was a key piece of her case.

Most of this is very difficult for me to read, but one section was a little easier to slog through, so I'll provide my summary here for any who are interested. In this section they are looking for pro-inflammatory cytokines. They only had 7 frozen samples from autistic individuals, so this portion of the study only involved those 7 and were compared to 7 controls. 3 of the 7 autistic individuals had regression, 3 hadn't, and one it was unknown. all of them had retardation, except for one, as to whom it was unknown. 4 had epilepsy and the other 3 did not.

They do not really come out and say that the cytokines were really elevated in all 7 of the individuals, although in several places it sounds like they are saying that. For example, they say: "A statistical analysis of the relative expression of cytokines in autistic and control tissues showed a consistent and significantly higher level of subsets of cytokines in the brains of autistic patients." But this could just mean that the average level in the autistic group was higher than the average level in the control group. There is one other statement that makes it sound as though they found higher levels of inflammation in all of the autistic samples. It says: "We found that in the three regions studied, the antiinflammatory
cytokine TGF- 1 was consistently and significantly higher in the autistic group than in the controls."

At any rate, unless I am misreading something, I think they do make it clearer in the Johns Hopkins FAQs that they found inflammation in all of the samples: "However, the presence of microscopic and immunological findings showing neuroimmune reactions in all of our autistic patients and the cytokine findings in the cerebrospinal fluid (CSF) support a potential role for neuroglia and neuroinflammation in the CNS effects in a number of individuals with autism."

The FAQs point out that some of the samples had epilepsy and mental retardation, and that therefore neuroinflammation is not necessarily ALWAYS present in the brain of an autistic individual. However, I was really surprised to see that they failed to point out that by far MOST of their samples had mental retardation, rather than just "some." In fact, only one of the samples was definitely not mentally retarded.

The Eides blogged about this at the time and included pictures from the study that showed the cell destruction. You can see them here.

The study also reports that they found evidence of Purkinje cell loss in every sample but one 8-year-old. Previous studies had seen reduced Purkinje cell numbers, but this study is suggesting that the cell loss is due to the inflammation. I was able to figure out that the 8 year old without signs of Purkinje cell loss did not have epilepsy or regression, but he did have retardation. But it would appear that all of the other individuals without regression also had Purkinje cell degeneration, including the one individual who is listed as definitely not having retardation.

I have seen a lot of things suggesting that the reduction in Purkinje cells is congenital, but I think what this study is to strongly suggest that the damage is ongoing. I don't doubt that it started prenatally, but I think it's still going on. The study also found evidence of anti-inflammatory chemicals that are used to restore and repair, in the same area where the degeneration was going on, suggesting to me this sort of eternal battle going on, of cell destruction and rebuilding. This would explain a lot in terms of my personal experience. So often it seems like we have two steps forward, one step back. I have never thought of T as "regressive" exactly, but he does exhibit abilities one day that are just gone the next day. And it takes SO LONG for him to learn something, so many repetitions. Could this be because this horrible destruction and rebuilding is going on in there?

I don't want to believe it, but my instinct tells me it is. I really think it is.

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