Takeaways from Thinking Autism 2023

I did present at the Thinking Autism 2023 conference in London recently.  I was last there in 2019 and there were many familiar faces.

Emotions were very much on show - joy, desperation, bewilderment, hope, fear, frustration and more.

The United Kingdom is amongst the worst countries in the world if you want to treat autism.  Even the idea of treating autism can get you into trouble. For severe autism it is much better to say treating ID (intellectual disability) – what sane person could object to that?

My takeaways are very specific to me, but here they are anyway.

 

So many doctors!

This year I was approached by many doctors who have children with ASD.  Among them were GPs, pediatricians, a neurologist, and a psychiatrist.

When you understand the basis of autism it is not surprising that so many doctors have kids with autism, particularly doctors married to a doctor.

 

Fertility treatment increasing the risk of autism

I did mention in my book the link between difficulty conceiving and having children with autism. Mothers who have had miscarriages are at risk of having a child with autism and children produced via IVF therapy have an elevated chance of autism.

One of the speakers at the conference, who uses diet as a therapy, told us that 30-40% of her patients where conceived by IVF therapy.  Wow – I thought. They are mainly children with milder autism, only 10% of her patients have severe autism.

 

From struggling to get on IVIG to how to come off it

Many parents struggle to get onto IVIG therapy for their child.  It is very expensive and, being an intravenous therapy, it is not so easy to administer to a child with severe autism.

Having finally got on IVIG therapy and responded well to it, how do ever wean the child off it, without losing all those gains?

This was a side issue arising from the conference and is an issue to some other readers of this blog.

What is very interesting is the potential to give IVIG therapy just once to very young children who developed normally but then suffer a regression into “autism.”  It seems to work for some. You might get it in Russia, but don’t bother asking in the UK.

 

My son is 14, I have tried everything else now I am ready for pills

Some people do respond well enough to dietary modification and OTC supplements, but more severe autism likely needs pharmaceuticals. For one mother at the conference she had come to this conclusion.  It is never too late to start to treat severe autism. Good luck to her!

 

Never give up

Never give up was the last point on my talk.

One mother at the conference was a very good example. She had finally had her twins examined at the UK’s top children’s hospital, Great Ormond Street Hospital (GOSH).  They have had MRIs, lumbar punctures to get spinal fluid samples and they have had genetic testing.  That is a triumph in the UK health system.

As she told us, she had to play the cancer card. She told her doctors “why do you go to such great lengths to save my life from cancer and yet do nothing for my twin boys with severe autism?”

Now one has a diagnosis of cerebral folate deficiency and one has a mutation is DISC1, a schizophrenia gene already covered, with therapy ideas, in my blog.  High dopamine in spinal fluid was only to be expected - it is a feature of schizophrenia. Light is at the end of the tunnel.  This mother was also very helpful to other mothers present.

 

School reporting on parent treating autism

I was disappointed to hear that a school had reported one mother for treating her child’s autism.

 

Ketones really do benefit some!

I did write a lot about the multiple possible benefits of ketones/BHB in autism.

The week before the conference one mother wrote to tell me that both she and her child with autism respond well to HVMN Ketone-IQ.

I knew our doctor reader Agnieska was a big fan of the BHB ester product Ketoforce, which seems to have disappeared during Covid.

At the conference a Spanish psychiatrist was listing the therapies in my blog that have helped his son and they included NAC, Bumetanide and BHB.

There are several new ketone products based on diol ketone esters, like HVMN Ketone-IQ.

Our reader Daniel mentioned very recently that he is using a product called DeltaG, a proprietary blend of diol ketone esters. HVMN Ketone-IQ is a pure diol ketone ester, while DeltaG is a proprietary blend of diol ketone esters.

The active ingredient in Ketone-IQ is R-1,3 Butanediol, also referred to as R-1,3-Butylene glycol, which maintains FDA GRAS status as a flavor molecule.

 

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=173.220

 

1,3-Butylene glycol (1,3-butanediol) may be safely used in food in accordance with the following prescribed conditions:

(a) The substance meets the following specifications:

(1) 1,3-Butylene glycol content: Not less than 99 percent.

(2) Specific gravity at 20/20 deg.C: 1.004 to 1.006.

(3) Distillation range: 200deg.-215 deg.C.

(b) It is used in the minimum amount required to perform its intended effect.

(c) It is used as a solvent for natural and synthetic flavoring substances except where standards of identity issued under section 401 of the act preclude such use.

 

This raw ingredient is very cheap.

Once it is packaged up as a supplement, it becomes very expensive.

As Agnieszka mentioned on the conference sidelines, you do have to look at the ingredients. In HVMN Ketone-IQ there is potassium benzoate as the preservative.  Potassium benzoate is a DAO inhibitor. DAO, or diamine oxidase, is an enzyme that breaks down histamine, a compound that can cause a variety of symptoms in histamine-sensitive people, such as headache, flushing, hives, and diarrhea.

 

“If my son can take the bus aged 20, I’d be happy”

One doctor mother showed me a video of her untreated young son with severe autism.  I told her how I have treated my son since 2012 and what the result has been. He passed his high school exams (GCSEs) in maths, science, geography, and English.  Now he has learnt how to travel independently from home by bus.  Time for those pills.

High dose Betaine/TMG, Low Dose Ponstan, Galavit, Humira, HMB (β-hydroxy-β-methylbutyrate) and Cetirizine for Palilalia/Scripting

 

Our reader in Canada, AJ, did highlight a case series from Norway that showed that high dose Betaine/TMG was effective in improving functioning in people with autism due to creatine transporter deficiency.  The use of Betaine/TMG was really just stumbled upon and the authors considered what the beneficial possible mode of action could be. 

Betaine (TMG) and Gene Therapy as potential alternatives to Bumetanide Treatment in Autism? 

The effect was only present at high dose (7-10 g a day) not the much lower dose used by some DAN/MAPS doctors, who do prescribe TMG and the closely related DMG.

The paper suggested that one possible effect might have been lowering chloride levels within neurons.  This is also the effect of Bumetanide.

AJ suggested that Betaine/TMG might be an alternative to Bumetanide and one that does not need a prescription.

Our reader Nancy reported a benefit in her adult son.

The question is not whether or not high dose TMG is a useful therapy, we already know that it is, in some cases. The question is whether it is a bumetanide alternative.

My conclusion is that high dose TMG does not seem to be a bumetanide alternative.  If it was an effective alternative then I would be suggesting everyone using bumetanide should go and buy some.

I did try TMG for s couple of weeks and did not see any additional effect over the continued therapy of 2mg of bumetanide.  In our case there is a benefit from additional bumetanide/Azosemide. If TMG shared the same mode of action as Bumetanide then 7g TMG + 2mg Bumetanide should show some improvement over 2mg Bumetanide.  It did not.

There is a long list of other modes of action to explain why Nancy’s son and the two Norwegians improved.

 

Low dose Ponstan for sound sensitivity

Low dose Ponstan (Mefenamic Acid) was proposed as a treatment for sound sensitivity.  Within Europe it seems that Greece is the place to buy Ponstan; it is sold OTC and cheap.  One pack (15 x 500mg) costs less than 2 USD/EUR.

In some people the effect of 250mg lasts all day, while for others it lasts for a few hours.

Ponstan is also widely used as a syrup to reduce fever in young children (antipyretic).

In the US the common brand name is Ponstel, but the price is dramatically higher.

Galavit + Cromolyn Sodium

The combination of the common mast cell stabilizer Cromolyn Sodium, used by many readers, with a Russian drug called Galavit is used by at least two readers. Dragos recently told us that the combination has put an end to his adult son’s aggressive behaviors.

Galavit has multiple anti-inflammatory modes of action.  It is not a mast cell stabilizer like Cromolyn Sodium.

Galavit is not expensive, but may hard to get hold of.

It does look like there is an overlap between responders to Verapamil and responders to Galavit.  So, if you respond well to Verapamil but get one of the rare side effects, like Maja’s daughter, it might be worth investigating further. 

Humira 

Humira is a TNF alpha inhibitor normally used to treat auto-immune conditions like rheumatoid arthritis, Cohn's disease, ulcerative colitis, psoriasis and juvenile arthritis.

I was recently contacted by an Aspie lady with auto-immune conditions, who found Humira not only controlled those conditions but moderated her autism symptoms, notably sound sensitivity.  One injection produced a benefit that lasted 7 weeks.

Kanner’s subject #1 went on to develop juvenile arthritis and this made his autism much worse.  There was no Humira back in his day, but his arthritis did respond to treatment.

Apparently, many children with autism and GI problems are taking Humira. 

IVIG seems to be the “go-to” therapy for immunomodulation in autism.  It is now quite commonly used in the US, but much less so elsewhere due to the cost.

I wonder if Humira might be an alternative for some?

 

HMB (β-hydroxy-β-methylbutyrate)

Our reader Natasa did mention the sports supplement HMB to me.

It has many interesting modes of action and it is a precursor to the ketone BHB, which has been covered in great depth in this blog.

Ketone Therapy in Autism (Summary of Parts 1-6)

In Europe ketone supplements like BHB fell foul of the rules on supplements and have been banned. In the US they are widely sold.

If you want to try BHB, by cannot buy it in Europe, you might want to look into HMB (β-hydroxy-β-methylbutyrate).

 

Cetirizine for Palilalia/Scripting 

I am a big fan of the OTC antihistamine Cetirizine/Zyrtec and I was interested to read the recent comment below about its effect on one 12-year-old boy.

“I realize this is 5 years old, but as a result of this blog, I tested cetirizine on my 12 yo yesterday. He has a nonstop palilalia (obsessive speaking that is nonsense or only makes sense to him). It's his "chief feature" and inhibits social development. For 4 glorious hours, it went away. Today, I gave him 5 mg of Zyrtec again. Yet again, the palilalia went away, AND he had strong focus on school (he has serious attention issues).”

 

Many people’s autism gets worse when auto-immune conditions flare up.  In some cases, the auto-immune condition is very mild, but the consequences are not.  For one person the result is aggressive behavior, while in another it is talking nonsense.

The Ketone D-BHB as a Medical Food for Heart, Kidney and Brain Disease (Alzheimer’s, some Autism …)

 Nestle’s research centre in Lausanne, Switzerland

I did write extensively about the potential to treat some autism using the ketone BHB (beta hydroxybutyrate). This can be achieved either by following a strict ketogenic diet or just by eating medical foods that contain/produce BHB.

Some readers are now big consumers of BHB supplements and anyone taking BHB should be interested in today’s paper, that I assume was paid for by Nestlé.

Nestlé make everything from baby milk formula to George Clooney’s Nespresso.  You may not be aware that they also have a business selling medical food; they have been looking at ketones to treat Alzheimer’s for some time.  This is quite similar to Mars developing Cocoa flavanols to improve heart and brain health.

Most ketone supplements are sold to help you lose weight or boost athletic performance.  The military also uses ketones in survival rations. 

We saw that you can increase the level of ketones in your body by supplementing: -

·        MCT oil (medium chain triglyceride oil, which usually contains about 60% caprylic C8 acid and 40% capric C10 acid).  This is a product already sold by Nestlé

·        Neat caprylic acid, C8

·        BHB salts (potassium, sodium, calcium etc)

·        BHB esters (also called ketone esters KE)

These products range from expensive to very expensive.

People requiring ketones as an alternative fuel to glucose, like those with Alzheimer’s need quite large amounts of the supplements.  In Alzheimer’s a glucose transporter at the blood brain barrier is restricting the flow of glucose in blood and so the brain is starved of “fuel”.  Mitochondria in the brain can be powered by both ketones and glucose, so if not enough glucose cannot get through, you have the option to increase the amount of ketones.

Babies fed with mother’s milk are on a high ketone diet.  You can safely combine both glucose and ketones as a fuel for your body.

The news from today’s paper has already been translated to a usable therapy. 

Metabolism of Exogenous D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart and Kidney

There is growing interest in the metabolism of ketones owing to their reported benefits in neurological and more recently in cardiovascular and renal diseases. As an alternative to a very high fat ketogenic diet, ketones precursors for oral intake are being developed to achieve ketosis without the need for dietary carbohydrate restriction. Here we report that an oral D-beta-hydroxybutyrate (D-BHB) supplement is rapidly absorbed and metabolized in humans and increases blood ketones to millimolar levels. At the same dose, D-BHB is significantly more ketogenic and provides fewer calories than a racemic mixture of BHB or medium chain triglyceride. In a whole body ketone positron emission tomography pilot study, we observed that after D-BHB consumption, the ketone tracer ¹¹C-acetoacetate is rapidly metabolized, mostly by the heart and the kidneys. Beyond brain energy rescue, this opens additional opportunities for therapeutic exploration of D-BHB supplements as a “super fuel” in cardiac and chronic kidney diseases.

One of the main benefits of ketones is their ability to act as an alternative energy source to glucose or fatty acids for production of ATP by mitochondria. Caloric restriction and intermittent fasting also produce transient mild-moderate ketosis (6, 7).

While a high dose of MCT can provide a moderate increase in blood ketones (+0.5–1.0 mM), gastrointestinal intolerance and high caloric load limit their use. Second, ketone esters (KE) made of a BHB ester linked to butanediol provide one molecule of D-BHB after digestion, with the butanediol being further metabolized by the liver to D-BHB (9). KE increase blood ketones above 1 mM but are also limited at high dose by their gastric tolerability and severe bitterness (10).

Third, perhaps the most physiologic way to raise blood ketones is via the oral intake of D-BHB itself. Exogenous D-BHB is directly absorbed into the circulation, with some of it being converted to AcAc by the liver, and both ketones being distributed throughout the body. Until recently, only racemic mixtures of dextro (D) and levo (L) BHB (D+L-BHB) were available and oral human studies with them have been reported (9, 11–14). As L-BHB is not metabolized significantly into energy intermediates and is slowly excreted in the urine (9, 15), D+L-BHB would be anticipated to be less ketogenic than pure D-BHB. 

Levo, Dextro and Racemic

When certain chemicals are manufactured, they usually contain an equal mixture of the left-handed and right-handed version, this is called a racemic mixture. These versions are called enantiomers.

One enantiomer is an optical stereoisomer of another enantiomer. The two molecules are mirror images of each other, which are not superimposable - much like your left and right hand.

In the case of the chemical BHB, only the right-handed version has an effect on your body.  If you take the salt potassium BHB, half of the product has no effect other than raise your level of potassium.

Zyrtec is an antihistamine made of Cetirizine, but it is a racemic mixture.  If you want pure L-Cetirizine, you would buy Xyzal not Zyrtec.

Arbaclofen/ R-baclofen is the right-handed version of baclofen

Rezular/R-verapamil is the right-handed version of verapamil.

Back to the study:

The study compared three therapies: -

D-BHB

14.1 g of pure salts of the D enantiomer of D-BHB were used. The D-BHB supplement tested was formulated as a mixture of three salts: sodium D-beta-hydroxybutyrate, magnesium (D-beta-hydroxybutyrate and calcium (D-beta-hydroxybutyrate). Each oral serving provided 12 g D-beta-hydroxybutyric acid, 0.78 g sodium, 0.42 g magnesium, and 0.88 g calcium, citrus flavouring and sweetener (Stevia), dissolved in 150 mL of drinking water.

D+L-BHB

14.5 g of an equimolar mixture of commercial D and L beta-hydroxybutyrate salt was used (KetoCaNa, KetoSports, USA). Each serving provided a mixture of 12 g D+L-Beta-hydroxybutyric acid, 1.3 g sodium, 1.2 g calcium, orange flavoring and stevia, dissolved in 150 mL of drinking water.

MCT oil

Fifteen grams of medium chain triglyceride (MCT) (60% caprylic C8 acid and 40% capric C10 acid) emulsified in 70 mL of a 5% aqueous milk protein solution.

This chart shows the concentration of ketones in your blood plasma after taking either of the three therapies.

This chart shows the concentration of just the ketone D-BHB in your blood plasma after taking either of the three therapies.

 This chart shows the concentration of the ketone ACAc in your blood plasma after taking either of the three therapies.

  

This chart shows where the ketones are going; the chart shows the distribution of the ketone “tracer” acetoacetate (AcAc) by organ after D-BHB oral intake.  The effect is greatest on the heart and kidney, but some does reach the brain.

From the dynamic brain scan, CMR_AcAc and K_AcAc could be determined for all main regions of the brain and compared to baseline values previously determined in healthy young adults. Overall and compared to baseline, each region demonstrated an increase in CMR_AcAc and K_AcAc of ~4.7 and 2.3-fold, respectively, about 1 h after taking D-BHB. This indicated that AcAc is effectively taken by the brain and by other organs particularly the heart and the kidney.

Ketone production from an exogenous dietary source has been traditionally achieved by MCT. This requires a bolus intake to saturate the liver with MCFA, producing excess acetyl-CoA which is then transformed to AcAc and BHB, which are released into systemic circulation. The C_max achieved with MCT is usually between 300 and 600 μM, with higher values being difficult to reach due to GI side effects and liver saturation. Here we show that D-BHB, a natural and biologically active ketone isomer, raises blood ketone C_max above 1 mM without noticeable side effects. In comparison, an equivalent dose of D+L-BHB or MCT only achieved half this ketone level, with similar T_max at 1 h. Thus, compared to D+L-BHB, D-BHB significantly reduces the salt intake needed to achieve the same plasma ketone response.

Results from a previous study (9) comparing KE to D+L-BHB showed that at the same dose of D-BHB equivalent, the increase blood ketone iAUC had the same magnitude, suggesting that exogenous D-BHB and KE produce similar ketosis.

Note that KE means Ketone Ester and the study (9) is this one: -

On the Metabolism of Exogenous Ketones in Humans

Ketone esters are available, but horribly expensive and taste really bad.

Conclusion

In previous posts the numerous possible beneficial modes of action of BHB were outlined. The summary post is here: -

Ketone Therapy in Autism (Summary of Parts 1-6)

In practise some people with autism seem to benefit a lot, some moderately and some not at all.

Monty, aged 16 with ASD, fits in the “moderately benefits” category.  The combination of about 20ml of caprylic acid (C8) plus a scoop of Potassium BHB powder does produce more speech.

It is not a cheap or very convenient therapy, compared the others I use.

I would agree with Nestlé that the limiting factor with BHB salts is the “salt”.  As they comment in their paper 

“compared to D+L-BHB, D-BHB significantly reduces the salt intake needed to achieve the same plasma ketone response”

Giving someone with heart disease "sodium anything" is not a good idea. A potassium salt would be safer, but even then, your heart is the limiting factor on potassium use.  Calcium salts are unwise in people with autism, because it appears to be able to upset calcium ion signalling, which would also be a potential risk in heart disease.

As I mentioned to one parent who is a big time user of BHB salts, if you switch to D-BHB you can either produce twice the ketones of regular potassium BHB, with the existing potassium load, or reduce your dosage by half and keep the same effect and save some money.

I think potassium D-BHB is good choice.  If you are taking bumetanide you may no longer need a potassium supplement (K-BHB becomes your potassium supplement).

I think people with autism and genuine mitochondrial disease are highly likely to benefit from D-BHB.  These are people who show symptoms in their entire body, i.e. lack of exercise endurance. For these people, eating (or producing via diet) large amounts of ketones will increase the production of ATP in their brains and so improve cognitive function.  D-BHB undergoes a different process to glucose, as it “converted” to ATP by the process called OXPHOS
(Oxidative phosphorylation). Some people with autism lack the enzyme complexes needed to complete OXPHOS, these people who should try D-BHB.

BHB has other beneficial effects, some relating to inflammation that seem to explain its benefit in other types of autism.  The effects were investigated here.

In the brains of people with Alzheimer’s there is decreased expression of glucose transporter 1 (GLUT 1) at the blood brain barrier. This starves the brain of glucose, which is fuel for the brain. D-BHB is an alternative fuel for mitochondria that is not dependent on GLUT 1.  People with early onset Alzheimer's would seem the best ones for this therapy, that would include many people with Down Syndrome. 

Autism Polypill Version 5

Agnieszka's KetoForce and C8 are new additions, last time it was Tyler's Agmatine as additions to the Full Polypill

I recently updated my autism Polypill. It is now the fifth version, so it is becoming ever more personalized to one specific case of autism.  I added caprylic acid C8 and KetoForce Beta Hydroxybutyrate.

The full Polypill version 5 is here:

   https://epiphanyasd.blogspot.com/p/polypill-for-autism.html

I do feel that I am getting near the final version. I already am pretty sure what is going to be added in the sixth version. There are one or two potentially clever ideas in this blog that I have not yet developed.

After my first year of autism research my doctor mother thought the result was good enough to stop, but I persevered and some further improvement did come. She was supportive of the concept but rather surprised it was possible. I think I have now achieved most of what is possible, which took an additional five years.

Having recently been reviewing the expected prognosis in longitudinal autism studies, including the one up to 22 years of age by Catherine Lord in the US, I think the result speaks for itself. In long term studies the remarkable improvement that rarely does occur, takes place by the age of eight. Verbal skills at the age of two is the best predictor of outcome at 19 years old.  I only started with my Polypill at the age of nine, when we were five years into trying to teach prepositions and maths was at the level of struggling with single digit addition and subtraction. Today at 15 years old, maths is at the same level as neurotypical 13-year-old classmates; so, we can say his maths age is 13.

I did suggest years ago to the French Bumetanide researchers that they measure IQ to show the impact of their therapy.

I think that in severe autism, and also Down Syndrome, huge strides forward are possible just by raising IQ.  We saw from the 15-year French study that the entire lower group, representing 80% of the total, had an IQ far less than 70 when they age out of school. An IQ of 70 is the threshold for MR/ID and affects 2.3% of the population.  Many of those French had IQs less than 40. 

Many parents do not like the term Mental Retardation (MR), so they made a nicer term Intellectual Disability (ID), which to me sounds like you might struggle playing chess, rather than dressing yourself and tying shoelaces.

Much MR/ID clearly is treatable.  That makes what is left of autism much easier to deal with. It makes the impact of any expensive 1:1 therapy much more substantial and therefore cost effective.

Recall we also have 81 other types of MR/ID that have been identified and are treatable.

        http://www.treatable-id.org/

As part of another project, I recently updated an old chart from this blog that shows the change in my autism index over time, including 6 years of the Polypill. I started treatment with Bumetanide on 17 December 2012. That was the sharp drop in the black line, followed rapidly by NAC and Atorvastatin. 

The big spike in the black line is the effect of the summertime allergy “stopping” the cognitive effect of bumetanide and producing the self-injurious behaviour of the same kind as the first big spike in the orange line.

The orange line after December 2012 is my forecast of what would happen, including a spike in bad behaviors likely to be triggered by puberty.

The spike in the black line at 13.5 years was a PANS-like episode that only lasted a couple of weeks, and was immediately treated using prednisone.

Heading towards 16 years old, Monty is still above the blue area, which we could call the “nerd cloud”. This is where you will find all those very mildly autistic, fully verbal people that now receive a medical or educational diagnosis of autism. Back in 1970s, 80s and 90s these were the nerdy kids at your school, who generally got by without any medical diagnosis/label. A small percentage will subsequently have attempted suicide.

On my chart typical development is not zero on the autism scale.

What is “normal” changes, typical kids develop their sense of “cool” group behavior before puberty and this continue until they become parents or just busy and fully employed. Then cool gradually fades and by 30 years old a socially awkward Aspie type really is not so different from a Dad who is juggling his job, commuting and his family obligations. There is no time to be cool.

I think around 18 is the peak difference between an NT young person and an Aspie.  Once the Aspie gets to College/University and meets more fellow Aspies life should get much better.  Find a job in a University or NASA and you will do just fine.

My therapy goal is just to keep heading towards zero on my scale. Entering the nerd cloud would be a great success; all that effort to reach the point many people with today's "autism" start from!

The IQ difference is already overcome. If you can do algebra, your IQ is way above 70.

Optimizing adaptive behaviour is the remaining goal. As the French longitudinal study and Catherine Lord from Cornell University highlighted in their studies, being fully verbal is a big part of enhancing adaptive behavior.  If you can be chatty, many aspects of life and functioning automatically get much easier.

So, in Monty’s case the emphasis has to be on expressive verbal communication, which is his weak point.

Fortunately, the additions in version 5 of the Polypill (Caprylic acid C8 and KetoForce BHB) and the expected additions in Version 6 will target this area. 

I did also write about critical periods and sensitive periods in the treatment of autism. It is clear that while it is never too late to start therapy, the sooner you start the bigger the effect will be. This is another reason why I doubt I will ever get to Version 10 - the clock is ticking.

Time is indeed a great healer, so even just Version 5 for another five years should continue to help Monty close the gap with typical people.

At another visit to the dentist last week when Monty had anaesthetic in his rear lower jaw, which apparently is the most difficult for a dentist treating a person with autism, the dentist was visibly relieved “it was exactly as you said it would be … he was better than my typical patients”.  That is the result of Polypills version 1 to 4 from 2012 to 2119; it is not down to parenting as the dentist believes. We did practise with a syringe and a drill at home, but it really was not needed. Monty understands why the process is necessary and what the steps involved are and so he is happy to sit back and open wide. Ten years ago this was not the case.

According to Catherine Lord at Cornell, based on her longitudinal studies from diagnosis up to adulthood, verbal skills at the age of 2 are the best predictor of outcome at 19 years old. Monty's verbal skills at the age of 2 were zero.

Unfortunately over 60% of the children she followed from 2 years old end up with a very poor outcome in adulthood - severe MR/ID, the adaptive skills of a four year old  and drugged up on psychotropic meds.  As in the 15 year long French longitudinal study of autism we looked at, the measured IQ falls over time. Anyone still think severe autism should not be treated? Perhaps they need their heads examining?

The optimal group of 10% do well, with an IQ shooting up to 111 (average IQ for typical people is 100) and OK with an adaptive functional age of 101 months (8.5 years old). Of them, 63% had a job and the great majority were not on psychotropic meds.  

It appears that in Lovaas' flawed ABA research he selected the kids that completed his trial from this Optimal 10% group. So yes, 50% did great, but they were already on track to do pretty well.  We learned from Dr Siegel that he weeded out the less able kids who did not respond to his therapy during the trial itself. You might think that all his research should now be rescinded.

LA ASD = less able ASD  (62% of the group) have IQ less than 70<70 div="">

MA ASD = more able ASD (38% of the group) with a subset called Optimal = the top 10%

Source: Catherine Lord's Presentation at UC Davis

https://www.youtube.com/watch?v=C-XczxdYM4E&t=14m36s

I always wondered why American Psychiatrists decided to keep relaxing the boundaries of autism. There was no rational reason to do it, because it makes all the data incompatible and so comparisons meaningless. One good reason would be to hide the appalling outcomes of severe autism (DSM3 autism, Strictly Defined Autism etc), by adding more and more much milder autism the overall outcome looks quite acceptable.

Dr Lord is a psychologist and she comments in her presentation that today the prognosis results would look much better, as if that is a good thing. Being of logical engineer origin, I would counter that this is a nonsense. The results today would be exactly the same for those kind of kids; just that a sample in 2019 of 200 kids with newly diagnosed autism would include 100 who would not have been given a diagnosis 25 years ago when Dr Lord started her study. Nobody would have even sent those fully verbal quirky two year olds for evaluation.

For the final word on prognosis, we might recall from this earlier post

          Autism Biology, Comorbidity, Mortality and Better use of Existing Research 

that 

"Autistic adults with a learning disability were found to die more than 30 years before non-autistic people."

Time to customize your personalized medical therapy for autism?  If your child was fully verbal at two years old, then you might not need to bother.

Conclusion

My conclusion is that after 480 posts, this blog is now giving a fairly complete picture of autism. The features provided by Blogger/Google make it hard to navigate this blog and the very useful index by label is no longer available. Only a few people have read the entire blog.

It could be reorganized as follows.

• Prevalence of the many Autisms
• Prognosis
• Evidence from clinical trials and case studies that shows improvement is genuinely possible and so it is worth your while to commit serious time to the process
• Lots of science blah blah 
• Precision medicine leading to a personalized therapy 

Unfortunately the science blah blah does get very detailed and does lose many people.  Biology is not complicated like math, there is just an awful lot of it and it remains only partially understood, so it changes.  Most people can follow the science, if they are willing to spend enough time, but you need to know that genuine improvement is indeed possible.  Some people are lucky and find their type of autism is similar to someone else's who has already found an effective therapy.

At some point I will get someone to write the java script to make a better index to the blog, so at least I can find things. 

Hopefully Version 6 of the Polpill will include two steps forward.