Aspirations vs Expectations

A couple of years ago, I came across a very useful paper that helps deal with that nagging question all parents of autistic children probably have;  that question is of course what will the future bring?  The paper is called Counseling Parents Regarding Prognosis in Autistic Spectrum Disorder.  It is only three pages long and it is free to download.

It is written by a very experienced Neurodevelopmental Paediatrician called Dr James Coplan, naturally he is an American.  He has an excellent website and he has his own channel on YouTube.  There are 4 short videos about the history of treating autism and one quite heavy one about challenging behaviors in autism.  In one he comments that autism is 130 years behind most areas of medical science.  He certainly knows his stuff, but he is not a researcher like us. 

 

Coplan applies four premises:-

1.    Atypicality (how autistic you are) occurs along a spectrum from mild to severe.

2.    The observed severity of autism in the same individual varies with age.  Many children with ASD do experience significant improvement over time.

3.    ASD of any degree of severity can occur with any degree of general intelligence.

4.    The long term prognosis represents the joint impact of ASD and their cognitive ability; higher IQ leads to better outcome.

The ideal outcome is for child B, whose atypical symptoms were always mild and whose intelligence is average or better.  The core features of ASD break up into fragments, which diminish in severity with the passage of time.

A less favourable outcome is child A, who has severe autism, plus mental retardation (MR).  As time goes by, he continues to exhibit the same level of autism, plus MR.

Clearly most children will be somewhere in between child A and child B.

 

Aspirations

I learnt from using ABA (Applied Behavioural Analysis) that it is always important to aim high, but not so high that your child is going consistently to fail.  If you aim low, you are certain not to achieve much; it is common sense really.  Every day raise the bar slightly and as the months go by, you will surely see progress.  If you are too ambitious, the child will get too used to failure and your efforts will be counter productive.

Expectations

I think it is best to leave the expectations to Dr Coplan and his framework.  Dr Coplan seems a bit fatalistic, he says that there is little evidence that the prognosis today is different to that in the 1970s or 80s. 

In my opinion, the tools available to parents today are far beyond the wildest dreams of parents in the 1970s; you just have to reach out, take them and apply them.  Rather than accepting a mediocre prognosis, do something about it.

 

 

Glutathione (GSH) Part III - Say Goodbye to Obsessive Behaviours

Stereotypy is a word you may never have used, but it is there in the dictionary.  In the world of autism, they made up their own word for it; “stimming”.  Stimming does not appear in the Oxford English dictionary, but here is a nice definition from Urban-dictionary.

Stim, stims or stimming is short for "self-stimulation". Almost everyone does it (tapping feet, cracking knuckles, twiddling thumbs), but in autistic people these behaviours are more pronounced and may seem downright strange.

Stimming is an obsessive behaviour that can get in the way of doing anything else.  If you are wiggling your fingers 10 cm in front of your eyes, not surprisingly, you are lost to the outside world.

But there are plenty of other obsessions; here is an eclectic mix:-

·         Tearing up papers into tiny pieces

·         Jumping, rocking, trampolining

·         Roller coasters

·         Thomas the Tank Engine

·         Watching the same part of a cartoon over and over again

·         Going to the theatre

·         Eating a Big Mac every day for lunch

·         Always following the same route, walking to the park

Using behavioural techniques from ABA, you can go a long way to managing, and then dramatically reducing, these obsessive behaviours.

Now, thanks to some science, it seems that these obsessions can finally be got fully under control.

By implementing a program to increase GSH using NAC, the science of which was outlined in Glutathione (GSH) Part II -N-Acetylcysteine (NAC), we have witnessed a near immediate cessation of uncontrollable obsessive behaviours.  The obsessions remain, but they are now firmly under self-control.

 

"Curtains close"

Glutathione(GSH) Part I

Glutathione (GSH) Part II

 

 

 

 

Nela and the Magic Flute

Nela is Monty’s excellent assistant at school, but today, because he is a bit sick, she came to Monty’s house instead.  Nela also has her own theatre school, which she runs in the afternoons.  Monty loves the theatre, and the curtains in particular.

Shortly after Nela arrived at our house, she said “Monty is going to see the Magic Flute”.

So how did Nela know that Monty is going to the opera (albeit the children’s version)?  Well, Monty told her, of course.  Now this might not sound much to you, but for me that is worthy of a big WOW.  Autistic kids are not big conversationalists at the best of times.   Even stranger, said Nela, was that he was really talkative all morning.

Now when his brother Ted is sick, it is about the only time he ever stops talking.

Then I said to Nela, actually it’s not strange at all; it is a proven fact that when autistic kids have a temperature they behave more “normal”.  I said that I would write about in my blog, so now I have to. I was actually saving this for a later post, when I set out the “Peter hypothesis of TRH induced homeostasis in autism”.

 

The post I originally intended to write

But, first a quick detour.  For those serious scientists among you, there is an excellent blog that you should take a look at.  It is written by a professional autism researcher, Paul Whitely.  The blog is called Questioning-Answers.

Now, late last night I was looking at Paul’s blog and reading all about something called tetrahydrobiopterin (also known as BH_{4 ,}THB, trade name Kuvan, or even sapropterin) and how it might be a useful drug to treat autism.  Then I looked at his links to the research papers and then I looked at the citations listed in those papers; it looked like another long session on Google might lie ahead.  Then, I concluded that since people have been talking about BH₄ and autism for 24 years; somebody should have done a serious controlled study by now.  So I will wait until they do, before getting out my textbooks.  Actually, by reading the label (the citations at the bottom of the study) I saw the following at number 53:-

 

53.  Klaiman C, Huffman L, Elliott GR. Sapropterin as a treatment for Autism Spectrum Disorders: a double-blind, placebo-controlled trial. J Child Adol Psychop 2013 (in press).

So after 24 years, it looks like someone has finally done a serious study.  I expect in a month or so it will appear on Paul’s blog, then I will take a good look.

Back to the Opera

So as not to disappoint Nela, let’s get back to business.  When I started this blog I was going to match my observations of Monty’s quirky behaviours to some solid science.  One observation was that whenever he stayed home sick, he was always great at his piano lesson, and with me on Whizz.com, the maths program, or doing literacy/numeracy with his assistant.

So applying some ANA, I found that the American Academy of Pediatrics (Americans spell it like that) had published a study called:-

“BehaviorsAssociated with Fever in Children with Autism Spectrum Disorders”

They concluded that it is indeed true; a fever makes you less autistic; but why ?

They put forward five possible reasons:- 

(1)  neurobiological effects of selected pro-inflammatory and/or anti-inflammatory cytokines, which have been found to be increased in cerebrospinal fluid (in the absence of fever) and postmortem brain tissue of individuals with autism and may be generated during different phases of responses to fever,  

(2)  modification of neuronal and synaptic function secondary to variations in body temperature that influence neural conduction velocities or synaptic transmission,  

(3)  modification of dynamic neural networks as a result of changes in cellular signal transduction and gene transcription that regulate synapse formation and function, 

(4)  increased production of other stress-related proteins, such as heat-shock proteins, during fever that might modify energy consumption and mitochondrial activity  

(5)  stimulation of the hypothalamic-pituitary-adrenal axis leading to modifications of neurotransmitter production and interaction.

 

And noted:- 

Should any of these mechanisms be proved to effect behavior changes in individuals with ASDs, this would stimulate research on potential treatments focused on these pathways.

Well this was another of my Eureka moments, since reason (5) fits very neatly with my TRH hypothesis, which was again based on other observations of Monty’s behavior.

For now, at least Paul and Nela will be intrigued; the rest of you may be bemused.  All will be revealed shortly, when my I finish my TRH project.

Now, as Monty would say,  “curtains close”.

 

 

 

Great Minds Don't Always Think Alike

Today’s post may appear to be just ramblings, but rest assured it is another necessary piece of our jigsaw puzzle.

What do you think I have in common with the President of the United States?

A.    Peter and Barack are fans of the Discovery Channel show, Myth Busters

or

B.    Peter and Barack had a drink with both  Michael Bloomberg and Vladimir Putin

It was a trick question.  The answer is (A) and (B).

For those of you who do not have Discovery Channel at home, Myth Busters is a hit TV show filmed in San Francisco, where Adam Savage and Jamie Hyneman set out to test popular myths, to see if they are plausible, confirmed or busted.  Adam and Jamie worked in the Hollywood special effects industry, but they have very unusual backgrounds.  They have a great approach to testing myths/hypotheses and always start with an open mind.

If Adam and Jamie were to join us on our quest – they would probably call it a crusade – we would have valuable support indeed.

Cold calling and networking in Business, but not in Medical Science

Now I could write a book about cold calling and networking in the business world.  If you have a bright idea, you can use it to open doors in most parts of the world.  Like most things, it works best in America, but it even worked well in some former communist countries, just a few years after the Berlin Wall came tumbling down. Romania is a good example, still in my 20s, I managed to get one to one meetings with important people, including with two of the five richest people in the country.  From my flat in Kensington, I got summoned to meet Lord Rothermere, the last of the great English press barons, to discuss an idea.  The list goes on.

But either I have lost my magic, or it just does not work on doctors and medical researchers.  They are not interested to talk to me, I find this quite perplexing.   Maybe I need a white coat?

They seem to be very closed-minded, or just not interested in autism.  Even American researchers are not interested!  Even when they are working in the field of neuroscience.

I think the medical world needs some kind of shock from the real world.  It seems, at least in case of polio and malaria, they are getting just that.

 

Bill Gates, Paul Allen and Peter (me)

Next cryptic puzzle; what do Bill, Paul and Peter have in common?

Well, you surely know that Bill Gates is the man behind Microsoft.  You may not know that Paul Allen is the co-founder of Microsoft.   Paul also set up the Allen Institute for Brain Science, which he and his sister endowed with $100 million.

Now Bill Gates is applying his business acumen (and not inconsiderable fortune) to eradicating polio.  If you want some inspiration just listen to Bill talk about how he is going about eradicating polio.  He is applying business common sense, rather than any medical knowledge.  He is making great progress.  If you live in the UK you can watch the full 60 minute lecture on the BBC iplayer just search:-   Bill Gates: The Impatient Optimist - The Richard Dimbleby Lecture. If you do not live in the UK you can only watch access the short preview on YouTube.

There is so far only a very weak link between Peter and Paul.  Before starting this blog, but after watching Bill talk about polio, I wrote to Paul.  In essence, I said go talk to those French research guys about Bumetanide and put your millions to good use.  Well at least I got a polite reply from the Institute.

I have not met Bill;  maybe one day I will.  It turns out that Mike (Bloomberg) and Bill are now joining forces to eradicate Polio.

By the way, in case you did not know, Mike is Mayor of New York and founder of Bloomberg LP a leading global provider of financial data, analysis and news.  He is also a great guy (and my former client).

Conclusion

Well, does all this really fit together?  I think it does.  We need a little something from the Myth Busters (Adam and Jamie) and some more from the philanthropists (Bill, Paul and Mike).  I think it’s called inspiration !

As for Vladimir, well Barack might not agree, but I think he is doing a pretty good job over there in the Kremlin.

до свидания

 

The Holy Grail - and where to find it

If you were are a 12 year old boy, like Ted, who loves watching the History Channel, you would know all about the Holy Grail.  Depending on your religion, you may know it as a sacred cup linked to certain important Christian events; but there are also Celtic myths about a cauldron with magical powers.  Throughout history, people have been searching for the Grail, from King Arthur to Indiana Jones.

This blog is itself a search for the Holy Grail.

Monty is a big fan of a well-known picture book series called Meg & Mog.  It is about a nice witch called Meg and her black cat called Mog.  Featured prominently is a magic cauldron, which Meg uses to cast her magic spells.  Just click on the above link and all will become clear.

So, we are looking for the Grail

Well, if you have struggled through all of this blog from the begining, you already know where to start looking.  California looks pretty hot, but then again there are some rumours about somewhere in France.  All will be explained, as we proceed further.

Homeostasis

First we need to learn a new word, Homeostasis, if you already know what it means, you are much brighter than me.

Do not confuse it with Homeopathy.  There may be another coincidence here as well.  Those generous people at Wikipedia give us this definition:-

Homeopathy  /ˌhoʊmiˈɒpəθi/ (also spelled homoeopathy or homœopathy; from the Greek hómoios- ὅμοιος- "like-" + páthos πάθος "suffering") is a system of alternative medicine originated in 1796 by Samuel Hahnemann, based on his doctrine of similia similibus curentur ("like cures like"), according to which a substance that causes the symptoms of a disease in healthy people will cure similar symptoms in sick people.  Scientific research has found homeopathic remedies ineffective and their postulated mechanisms of action implausible. The scientific community regards homeopathy as a sham;  the American Medical Association considers homeopathy to be quackery,^]and homeopathic remedies have been criticized as unethical.

Now let’s get back to Homeostatis and to help us really understand it, I decided to give a detailed example using the medical condition diabetes.

Homeostatis is a process through which the body's internal environment is kept stable.  For example, when the level of sugar in your blood is too high, your body detects this, an alarm goes off and the body acts to reduce it; conversely when blood sugar is too low, again the body detects this and sends a signal to raise it.  All this happens 24/7 and you do not even need to think about it.  That is, unless you are diabetic.

So we have:-

·         A  receptor, like a tiny sensor that is constantly measuring blood sugar.

·         Positive feedback, when the receptor detects a low level and then tells the body to raise the level of sugar 

·        Negative feedback is when another receptor alarm goes off, and the body needs to lower the level of sugar in the blood. 

·        Homeostatic imbalance occurs when the body is overwhelmed and can no longer regulate itself and regain stability.  Many diseases are indeed the result of such an imbalance; diabetes is but one.

Insulin is the principal hormone that regulates uptake of glucose (sugar) from your blood.  Insulin is released into the blood after eating.  Insulin is also the principal control signal for conversion of glucose to glycogen, for storage in your liver (and muscle cells).

Lowered glucose levels result both in the reduced release of insulin and in the conversion of glycogen to glucose. This is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin. Glucose is forcibly produced from the liver (where it had been stored as glycogen) and enters the bloodstream.

Both insulin and, its opposite, glucagon are produced in the pancreas.

Summary

So we have a receptor constantly measuring your blood sugar.  You eat a chocolate bar, blood sugar rises fast, an alarm goes off.  Release the insulin !  Insulin is released from the pancreas.  Remove excess glucose and store it (as glycogen) in the liver !  Blood sugar level is falling. Homeostatis restored; panic over.

Then you go for jog in the park.  Receptor detects falling blood sugar.  Release glucagon !  Glucagon is released from the pancreas.  Go to the liver and tell it to start converting glycogen back to glucose !  Blood sugar level is now rising.  Homeostatis restored, panic over.

Back to Ted and the quest for the grail

Ted sometimes finds it hard to explain what Dad’s job really is;   he is not the first to ponder this.  Now, Ted has decided that his Dad can officially be described as a wizard.  This helps me a great deal with this blog. 

We will now opt for the pagan Celtic myth about a cauldron with magical powers, this will be our Holy Grail.  We just need a cauldron, a wizard, some ingredients and a magic spell.  We are nearly there.

We even know part of the spell:- “ homeostatis and channelopathy  .........”

A final few words

In our first two weeks of this blog, we have been busy travelling.  We started in France, went all the way to the Punjab to meet a clever chap called Baldeep in  Chandigarh.  Then we headed over to Palo Alto in California.

The good news is that back at Monty's house, the cauldron is bubbling and the magic already seems to be working.  We just lack a few more ingredients and that elusive spell.

Eat Fish! - all about Omega-3

I did put one very well-known therapy on my list to investigate; that of omega-3 fish oil supplementation.  This is the territory of Complementary and Alternative Medicine (CAM) and maybe not surprisingly there is a lack of high quality research.  This is a pity, because there are some very good scientific reasons why it just might work.

There is only one study that was carried out like a serious clinical drug trial and seemed to show a serious positive result.  It was carried out at the Medical University of Vienna and involved 1.5 g per day of EPA/DHA (0.84g EPA and 0.7g DHA).

It seems nobody else has been able to repeat this result with a similar randomized controlled trial.  What does that tell you?  Maybe those Austrians have a special kind of fish oil ?  Or maybe there is a chemical reaction going on with all that Apple Strudel they were eating?

Even this study did not convince the serious scientists at the University of California, San Francisco.  They did a review of all omega 3 trials from 1966 to September 2008, mentioning autism and omega-3.  It is very readable and their full report  Omega-3 Fatty Acids for Autistic Spectrum Disorder: A Systematic Review  is available free (just click it). A summary, in table form, is on page 1148.  But if you are in a hurry, their conclusion was:-

“there is currently insufficient scientific evidence to determine if omega-3 fatty acids are safe or effective for ASD”

I still have not finished my research, but I can already say with 90% certainly, I know what my final conclusion is likely to be;  Eat Fish ! and I have already implemented it.
 
Here are some undisputed facts:-

1.    Autistic children have lower levels of omega 3 relative to omega 6 and lower levels of the good cholesterol HDL, than typical children.  This implies a lipid metabolism disorder.  If you read my Glutathione (GSH) Part II you will know that such a  lipid disorder should be expected in people with a GSH Redox problem.  NADP/NADPH which is required for lipid and cholesterol synthesis is also required for the GSH Redox chemical reaction.  So if there is a GSH Redox problem (proved already by serious scientists),  NADP/NADPH are highly likely to be involved and if they are, then it is no surprise if omega 3 and cholesterol levels are way off where they should be.  We are already getting side-tracked into the details, just to tell you that NADP is Nicotinamide Adenine Dinucleotide Phosphate and NADPH is the reduced form of the same chemical.  For more info click here.

2.    Omega-3 is proven to be good for the heart, in just about everyone.  The main benefits are related to cholesterol (Hypertriglyceridemia to be precise), cardiovascular disease prevention and high blood pressure.  For a full list of conditions for which Omega-3 has a benefit, to those where it is proved to have no benefit, we have a ready-made solution from the US National Institutes of Health. (Just click and read on), if you are curious to know more.

3.    Always read the label.  There are only two omega-3 oils that seem to have any potential medical benefit; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).  Nobody seems to know which is better than the other or what the optimal ratio is.  To do much good to your heart, the research shows you need something like 2g of EPA/DHA daily, note that 2g = 2000 mg. 

Now go look on the label of those expensive fish oil tablets you have in the bathroom cabinet.  For a start you can forget about Omega-6 oil, your diet already has way too much and also ALA, you do not need any more of that either.  It also looks like any Omega-9 is not going to do much either, your body can make that itself. Omega-3 and Omega-6 oils are considered “essential” fatty acids, since your body cannot make them, and it does need them.  Western diets have far too much Omega-6 and too little Omega-3. It seems that the ration is often 10:1, when it should be much closer to 1:1.  Processed junk food is full of omega-6.

 

 

one capsule contains  180 mg of EPA /DHA ( no data given is it mainly EPA or DHA)

one capsule contains 192 mg of EPA / DHA (24g EPA and 168g DHA)

 

Eye q liquid.  5ml contains 244mg of EPA / DHA (186g EPA and 58g DHA)

• Entire 200ml bottle has 9.8g EPA/DHA.
• 500g of farmed atlantic salmon contains 10.7g EPA/DHA

 

If you do want to give EPA/DHA to your child why not give them fish to eat?  It may be true that tuna and swordfish have high levels of mercury, this is because they are large fish.  Large fish eat small fish and then accumulate mercury.  Large sea fish tend to be very expensive and beyond your budget anyway.  There are smaller cheaper fish that are full of EPA/DHA.  The U.S. Department of Health and Human Services (go on, click it) produces a great list of hoe much EPA/DHA is in 80+ types of fish.  Note that tinned tuna has almost no EPA/DHA because it is cooked before it is canned.

 

• A cheap fish like farmed trout has 1.15g EPA/DHA per 100g
•  Herring has even more oil; it has 2g EPA/DHA per 100g

•  Farmed salmon has 1.2g EPA/DHA per 100g

•  Don’t forget sardines, anchovies, mackerel, whitebait etc.

 

Depending on where on the planet you live, the price of both supplements and fish varies greatly; but by my calculations it is much cheaper to eat the fish.  Fortunately for me, Monty just loves to eat all kinds of fish, not just fish fingers.

 

Conclusion

 

There is currently no proven scientific case to give expensive omega 3 supplements as a treatment in autism.  It would be pretty straightforward to conduct such research; the fact that it has not been done, must tell you something.
 

There is a single interesting study that has not been replicated.  Even that study used dosage  levels of EPA/DHA that are 6 times higher than the supplement makers are recommending.  So a EUR 20 bottle of Eye Q would last you just 6 days.

 

There is plenty of evidence that fish is good for you and your son.  So just eat fish, and plenty of it. Maybe it will help with his autism, maybe not; it is certainly much healthier than red meat, processed meat and even his favourite chicken nuggets.