Autism, a Dynamic Encephalopathy, Indeed

 

With a title like that, not many people will stumble upon this post with Google.

So, for the hard-core of readers, today I am going to develop an idea of Martha Herbert, the pediatric neuroscientist from Harvard, who writes a lot about autism.

Incidentally, most researchers do not like publicity, and particularly those looking at autism.  Martha, herself makes some side remarks as to why this is; as I suggested in earlier posts it dates back 10+ years to a certain Dr Wakefield.

“A further barrier to considering the body’s impact on the brain was the reaction to the work of Wakefield, who argued not only that there was a link  between  autism  and  vaccines  but  also  that  this  link was mediated through the gastrointestinal system. For the better part of a decade any attempt to discuss gastrointestinal or immune issues with autism was construed as a support of Wakefield’s vaccine hypothesis, and it was difficult to discuss, let alone get funding for, clinical or research observations about these problems.  One way around the essentially taboo character of somatic problems in autism was to treat them as coincidental symptoms. For example, one could  talk about gut problems provided one made  it clear that they did not cause the autism in the brain. Improvement after treatment of gut problems, which is often observed, would then be explained as a consequence of reduction of pain and discomfort, but not of any direct impact on core brain mechanisms generating autistic behaviors.”

Another fearless autism researcher, not shy to voice his opinions by blog and tweet, is Paul Whiteley, in Sunderland.   Paul is very much a believer in the role the gut/diet in autism, he and Paul Shattock are the driving force behind the gluten and casein free diet as a therapy for autism.  Given what Martha writes above, and the association between Shattock and Wakefield, is it surprising that the GCF diet remains on the fringes?  I know some parents who wholly endorse it.

Here is a link to one of Martha’s recent works, for Herbert fans:-

From Static Genetic Brain Defect to Dynamic Gene- Environment- Modulated Pathophysiology

Dynamic Encephalopathy

It was Martha who called autism a dynamic Encephalopathy.  Encephalopathy just means a brain disease.

What she means is that over time autism changes, day to day and year to year.  Just as during fever, autism symptoms may wane, other environmental provocations may cause flare ups.  With age come hormonal changes that will inevitably change the central hormonal homeostasis, I hope for the better, as generally is the case.

Other than being a fancy word, Encephalopathy, is probably a much better word than autism.  There are many types of Encephalopathy and there are multiple causes, it refers to a syndrome of global brain dysfunction; this syndrome can have many different organic and inorganic causes.  As with autism the hallmark of encephalopathy is an altered mental state.

 
Forget Autism think Encephalopathy

If you have not already opened up Wikipedia, I suggest you do.

http://en.wikipedia.org/wiki/Encephalopathy

From my desk research and primary research, I know that one factor behind this encephalophy is chronic inflammation, otherwise known as neuroinflammation.

At this point, we should look at what neuroscience can tell us about neuroinflammation

The Dana Foundation is a private philanthropic organization committed to advancing brain research.  Founded in 1950 and with $230+ million in assets I think they should be a good source.  Here  is an excellent paper, that is written for non-scientists. 

 Consequences of the Inflamed Brain

Among the many interesting insights are these:- 

 “Until recently the CNS and peripheral immune sys­tem were thought to operate independently.”

“However, new research has led to important advances in our understanding of how immune-related events in the periphery can influence CNS processes, thereby altering cognition, mood, and behavior, and these advances are suggesting that inflammation may have important long term implica­tions for the brain.”

 “Inflammation in the body can lead to inflammation in the brain”

“The same cytokines that participate in produc­ing the inflammatory response in the body also initiate the communication process to the CNS. They accumu­late in the bloodstream and thereby travel to the brain”

“They cross into the brain in regions where the barrier is weak, and they bind to receptors on the insides of the cerebral vascular blood vessels, thereby inducing the production of soluble mediators within the epithelial cells that can cross into the brain.”

“In addition, there are neural as well as blood-borne communication routes. For example, there are cytokine receptors on nerves, such as the vagus, that innervate peripheral immune organs, and these nerves communicate to the brain and are activated during infection.”

“During a normal infection, neuroinflammation and the resulting adaptive sickness behaviors persist only for several days. However, if these responses become exaggerated or prolonged, the outcomes may well become estab­lished, leading to cognitive impairment instead of brief memory disruption,”

 “… physiology can become pathology when a set of processes designed to be rela­tively brief becomes prolonged.”

“However, peripheral inflammation is highly complex and involves many immune cells and their products. Existing anti-inflammatory drugs often target only one of these. For example, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, inhibit only a hor­mone, prostaglandins, leaving other actors in inflam­mation (cytokines, chemokines, etc.) untouched.”

“A second way that central neuroinflammation could be prolonged is less obvious. The CNS may come to over-respond to the same signal from the peripheral immune system. As noted above, microglia and the cytokines they produce when activated are at the core of the neuroinflammatory response that pro­duces sickness behaviors. If microglia were to become “sensitized,” which means they respond in exagger­ated or prolonged fashion, then sickness behaviors would become intensified and prolonged—pathology instead of physiology.”

“Most encouragingly, studies in numerous animal models show that the development and expression of chronic pain can be blocked with drugs that inhibit either microglial activation within the spinal cord, or the inflammatory cytokines that microglia produce.”

“In addition, microglia also can become sensi­tized without a prolonged peripheral inflammation. For example, aging appears to sensitize microglia so that microglia, particularly in the hippocampus, respond in exaggerated fashion to input. Thus, neuroinflammation produced by surgery, peripheral infection, and the like, is greatly exaggerated in aged subjects. Correspond­ingly, aging also augments the chances of depressive behaviors, cognitive impairments, and pain produced by peripheral inflammatory events. Encouragingly, however, some human studies show that inhibition of microglia and cytokines in the brain blunts such patho­logical outcomes.”

“Blockade of inflammation in the periphery and microglial activation/cytokine action in the CNS, may well become important therapies for a range of disorders not often thought of as mediated by these factors.”

Conclusion

There is nothing new to me in the Dana paper; this in itself is rather a shock.  If you have followed my blog from the start, you should also not be surprised; but I have never seen quite so much scientific good sense written in just four pages.  It tells me a lot and reassures me that I am on the right track with my cytokine blocking therapies, mast cell stabilization and somewhat far fetched, vagus nerve stimmulation ideas.

There are other science-based "inflammation control" therapies and I will be writing about them later.

P.S.  Why no Dean’s List for Martha?

Regular readers of my blog may have noticed that a small number of the several hundred researchers, whose papers are discussed here, are given a pat on the back and moved to the Dean’s List.  Why not Martha?

There is a good reason.  For many years Martha keeps going on about the “Fever Effect” in autism.  This is the strange phenomenon where autistic behaviours abate during fever, i.e. sickness associated with high temperature.  I myself witness this every time Monty, aged 10 with ASD, has a high temperature.  I think that conclusively solving this, might indeed tell us something profound about this wide phenotype of autism.

I think with the resources of Harvard, she should be able to figure this out.  Her TRANSCEND Program gives her a pool of research subjects.

Peter has just one mouse model of autism and, at the age of 10, he is getting a big to be called a mouse.

So Martha, put aside the MRIs and the calcium channelopathies, if you figure it out before me, you get on the Dean’s List.

If I can prove the underlying reason, I will put myself on the Dean’s List.