Why is the evidence for Early Intensive Behavioral Intervention for Autism so weak?

One to one autism therapy is pricey – is it worth it?

Only a handful of countries widely apply behavioral interventions to treat toddlers diagnosed with autism.  Behavioral interventions include Applied Behavioral Analysis (ABA), Verbal Behavior (VB), Pivotal Response Treatment (PRT) and the Denver model.

Even after several decades, the published evidence that these interventions actually work is quite weak.  This explains why most countries do not readily provide public funds for ABA.

In the US, efforts are being made to diagnose autism at younger and younger ages, because the child can then benefit from these “proven” interventions, that other countries do not believe work.  Who is right?  

You can read Manuel Casanova’s perspective at the end of this post.  He is not such a fan of expensive US developed therapies and concludes:-

"spending time with your children and group socialization, in my experience, have provided the most favorable outcomes"

Does ABA work?  If so, why can’t you prove it?

From my personal experience, behavioral intervention was very beneficial as a teaching method, but it does not make autism go away.

In today’s study the aim was to determine if behavioral intervention is cost effective.  The conclusion based on all the studies considered is that there is no conclusive evidence that behavioral intervention is cost effective.  So logically the countries that do not widely fund it, like the UK, can be reassured that they are on the “right side” of the argument.

My view is that is that autism is so heterogeneous you can prove almost nothing, with any degree of certainly.  It is always going to be a case of ifs, buts and maybes.  This also very much applies to clinical trials of drugs to treat autism.

Why did ABA ever catch on in the first place?  People want hope and the more expensive something is, the more people want it.  Forty hours a week of ABA is very expensive and nice to have, if someone else is paying.  

We saw in an earlier post that Lovaas (the founding father of ABA) later admitted to selectively retiring non-responders from his clinical trials, to improve the apparent success of his methods.  This pretty much means you have to ignore all his data and his papers should be retracted. 

Many parents want curative treatments for autism.

Lovaas claimed that ABA is curative and that the treated kids end up like typical kids.  Sadly, this is an exaggeration.

Is two years of ABA cost effective for severe autism?  I guess it depends whose money is paying for it.  Is two years of ABA going to be life changing for a person with severe autism?  Unfortunately, even after 20 years of ABA, that person will likely still have severe autism, if you have not treated their underlying biological problems.

Some parents rave about ABA and make comments like “after two years of ABA my son now makes eye contact”.  Great, but would you pay $120,000 of your own money for that?  I think not.  Should your local government regard that as money well spent?  I think they should be more demanding; the results of just $1,000 spent on the right personalized medicine will be much more impressive.

Today most people currently being diagnosed with autism have mild cases.  If they can talk and do not have intellectual disability (ID) / mental retardation (MR), they will likely see little benefit from 40 hours a week of discrete trial training.  It would be a huge waste of money and probably just annoy the child.  

Many children with mild autism need a different kind of therapy, they need to learn social and emotional skills they may not naturally possess - how to make friends, how to avoid making enemies and so how not to get bullied at school.  This will only be effective started very young, before being a victim becomes a badge of honour.

Interventions based on early intensive applied behaviour analysis for autistic children: a systematic review and cost-effectiveness analysis

Autism is a lifelong condition that affects how people understand the world and interact with others. Early intensive applied behaviour analysis-based interventions are an approach designed to help young (preschool) autistic children. This approach is often delivered on a one-to-one basis, for 20–50 hours per week, over a period of several years.

This project obtained and analysed the original data from studies of early intensive applied behaviour analysis-based interventions, to determine whether or not these interventions are beneficial. It also investigated whether or not the interventions represent good value for money.

The results suggest that early intensive applied behaviour analysis-based interventions may improve children’s intelligence, communication, social and life skills more than standard approaches. However, some results could be inaccurate or incorrect, and there was no evidence about other important outcomes, such as the severity of autism and where children went to school. Most studies lasted for around 2 years, which means that it is not known if early intensive applied behaviour analysis-based interventions have meaningful long-term benefits.

It was not possible to fully assess whether or not these interventions provided value for money, as the benefits of early intensive applied behaviour analysis-based interventions were unclear, although the available evidence suggested that they did not. Early intensive applied behaviour analysis-based interventions may, however, provide value for money if their effects were to last into adulthood, or if receiving early intensive applied behaviour analysis had a large impact on the type of school children attended.

Future studies of early interventions may be helpful, but should consider looking at which components of early applied behaviour analysis-based interventions are the most important, rather than at whether or not they work better than other interventions. Future studies should also follow best current research practice and evaluate outcomes that matter to autistic people and their families. 

Economic evaluation

Using National Institute for Health and Care Excellence decision rules to benchmark the results of the cost-effectiveness analysis and adopting a £30,000 (USD 40,000) per quality-adjusted life-year threshold, these results indicate that early intensive applied behaviour analysis-based interventions would need to generate either further benefits or cost savings to be considered cost-effective.

Implications for service provision

Although individual participant data meta-analyses have shown small to moderate improvements in child cognitive ability and adaptive behaviour for early intensive applied behaviour analysis-based interventions relative to treatment as usual or eclectic approaches, all of the identified studies were at risk of bias, limiting the strength of conclusions that can be drawn from these results. Furthermore, results from individual studies varied considerably, with some showing no relative benefit of early intensive applied behaviour analysis-based interventions. 

Conclusion

For cases of severe autism, if you can afford intensive (and expensive) 1:1 intervention of any credible kind (Floortime, ABA, Denver etc - whatever works best in your case) it makes sense to use it.  It should improve skill acquisition and will make the parents feel better.

None of these interventions are curative, the child will still have autism.  When you no longer pay for the 1:1 intervention, the effects most definitely will start to fade away.  Don’t mortgage your house to pay for ABA.

Nothing stops you making your own 1:1 intervention program using family, friends and volunteers.  This does not cost much and is sustainable over many years; it is likely to be much for effective that 2 years of "professional" therapy.

I do find it odd that in the US there is free early intervention for toddlers and then provision just stops, as if it suddenly is no longer needed.

If you use ABA to teach a child to tie shoe laces, he/she will retain the skill as long as you keep buying shoes with laces.  If you do not practice/apply the skill for 6 months, do not be surprised if it has to be re-taught.

Our final ABA consultant was very experienced, she worked for 10+ years in the US before moving home to Athens, Greece.  She told me that in her experience all children with autism benefit from ABA, but the level of progress they make varies widely.  If a child does not respond to ABA, it very likely is not being done correctly.  ABA should be seen as fun, not like a punishment. If your child hates ABA sessions, they have no chance of working.

I come back to my earlier recommended strategy. Find your most effective novel medical treatment, which will inevitably be a polytherapy and combine this with a method of learning that works best for your particular child.

Then just keep going and let time do its work.

In countries like the UK, with free health and education provision, the government does not generally pay for early intervention because their medical advisors do believe it to be cost effective, which really means they think it does not work and so do not want to pay for it.  The cynic might just say they do not want to fund it. 

The idea was supposed to be that by investing upfront in ABA during the early years, you save money later on, by having a more functional child and then adult who requires less expensive provision.  Unfortunately, there is absolutely no proof this is true.  

If you go from early intervention, to an ABA special school and then ABA college, things clearly did not work out.

In the US early intervention is assumed to be very effective and the current idea is that doctors should hurry to diagnose autism before 24 months so as to get into the intervention program as soon as possible.  Where is the evidence to support the US view?  Are US outcomes any better?

We saw in recent research from UC Davis that looked at outcomes over time in autism that the best outcomes are not associated with any particular therapy.  The best outcomes happen because of the biological characteristics of that child, rather than any amount of behavioral intervention.

I expected the UC Davis study to show a relative benefit for those who received ABA therapy, but it did not.  We do have to take note.  I am actually pro-ABA and have spent a vast amount of money on this kind of therapy and 1:1 instruction.   

Ignoring treating the biological dysfunctions in autism while spending hundreds of thousands of dollars on 1:1 therapy and special education does not make a lot of sense.

Here is a relevant excerpt from a recent post by the neurologist, autism researcher and autism Grandfather, Manuel Casanova, from his Cortical Chauvinism blog: -

AUTISM: HOW CULTURE INFLUENCES OUTCOMES

Despite marked differences in geography, non-Westernized countries see autism as a social responsibility rather than a medical condition.  These countries offer a collectivist perspective that downplays individuality and prioritizes maintaining relationships within a given group of people.  In this regard, I have often marveled as to how vastly different countries, like Colombia and the more desolate regions of Eastern Russia (Siberia), share similar perspectives regarding autism. Indeed, due to a lack of resources, interventions in these countries are usually parent-mediated and heavily influenced by cultural norms.  Lack of personnel trained in behavioral analysis has been supplanted by art and music instruction.  Classes are provided in group settings where outperforming other members is not seen as conductive to the overall benefit of the group. Members are encouraged to adopt the norms of the group while teachers emphasize cooperation and nurturing. Students arrive early to school to participate in team building exercises.

I have often marveled at the achievements of troupes of autistic children performing autochthonous musicals and their accompanying choreography.  Adopting the norms of the group have served them far better than any Westernized behavioral intervention.  Participants in these groups seem genuinely happy; in part, given the sense of achievement at contributing to a piece of artistic expression.  In addition, the structured activities in such groups offer norms that minimize uncertainty.  Participants feel a sense of security in a group that fast becomes their extended family.

Autism is a medical condition but, without a cause that we can target, treatment options have remained symptomatic.  This is one of the reasons for looking at other countries and learning what has worked for them.  Indeed,  I believe that we can gain from adopting the cultural perspective of other countries to benefit our own children. Whether it is an improvisation on an autism chair, electroacupuncture, or using a zen bowl, spending time with your children and group socialization, in my experience, have provided the most favorable outcomes.

Manuel is one of a very small group of thoughtful researcher-clinicians, who have been working in the field of autism for decades, like Dr Kelley from Johns Hopkins and that psychologist Dr Siegel who wrote the Politics of Autism and revealed how Lovaas really did his "research". 

Manuel's researcher son-in-law is interested in precision medicine and drug re-purposing, I guess driven by his own young son's rare genetic "autism", NGLY1 deficiency. This very severe condition leads to the body not being able to breakdown and remove damaged and misfolded proteins.  You would think that reducing Endoplasmic Reticulum (ER) stress, that produces misfolded proteins, might be useful. This was covered here, along with a long list of possible therapeutics:-

https://epiphanyasd.blogspot.com/2019/12/er-stress-and-protein-misfolding-in.html

Some readers are following the details of the Covid-19 situation.

The Indian Experiment rather than the Swedish Experiment

A recent study suggests that more than half of the 6 million slum dwellers in Mumbai have had Covid-19; another 6 million do not live in slums. Government research showed that in the capital Delhi 23% have Covid-19 antibodies.

Mumbai slums have an extremely high population density, extreme poverty and so not much social distancing. So they show what Covid-19 does with no serious intervention, better than Sweden does.  Mumbai has reported 6,200 deaths in total.

You can extrapolate from the data (57% of slum dwellers and 16% of non slum dwellers with Covid antibodies) for the total 12 million population of Mumbai.  4.4 million had the virus and 0.14% died.  In the worst case scenario, when everyone finally gets infected in the next few years, there would be another 7.4 million with the virus and another 10,800 deaths.  The death/mortality rate for the city would be 0.14%.  (In reality it will probably be less than 0.14%, because some people will not get the virus)

The 0.14% Covid-19 mortality rate compares to the 2.5% mortality rate of the 1918/9 global flu pandemic; worse still that flu pandemic affected fit young people the most, making the demographic impact huge. 

The crude death rate from all causes in the US is around 0.8% each year (just 0.7% in India).  That puts the 0.14% from Covid-19 into some perspective. If Americans are as healthy as Indians and India did not under-report the number of Covid deaths in Mumbai (both are big ifs), you could apply the 0.14% mortality from Covid-19  to 330 million Americans and get 460,000 people. I think the realistic number would be higher, given deaths to date in the US.  

I think the world has been very lucky to have been affected by a pandemic that has such a low mortality rate.  It could easily have been 20 times worse, perhaps next time?  In the Middle Ages, the Black Death killed hundreds of millions of people - a truly apocalyptic pandemic.

There is no certainty that a vaccine is going solve the Covid-19 problem, indeed the UK government is buying 12 different vaccines, in the hope that one is effective.  Vaccines are often least effective in older people, who are main risk group for Covid-19.

If no vaccine turns out to be 90% effective, the Mumbai slum dwellers and the Swedes will have been the smart ones.


Controlled Infection vs Vaccination

If I was a dentist I would be seriously worried about Covid-19. I would favor a small infection today, caught from my party-going offspring, rather than in two year's time catch it while peering into a stranger's mouth during an hour long procedure, and get a huge initial exposure, leading to a more severe infection.  The fact that Mumbai policemen, London bus drivers and of course doctors and nurses without good PPE have had so many fatalities does suggest the amount of virus you are initially exposed to is a critical factor to the outcome.  This would be logical anyway.

I am really glad at least my older son and myself have had Covid-19.  If I was a dentist, I would be hugely relieved. A few months ago we assumed Covid-19 was both highly infectious and often deadly, now we know the reality.  If you are youngish, slim and healthy the risk is very low.  Many in rich societies are old, overweight and in poor health.

I did take my younger son Monty, aged 17 with autism, for a visit to the dentist two months ago and I really felt sorry for her.  She was wearing a mask, but that is no guarantee of her safety.  

    

Treatable Chiari 1 “brain hernia” present in 7% of Autism

Today’s post is again prompted by a reader’s comment.

Regular readers will be accustomed to learning here about “rare”, often treatable, disorders that may cause, or just aggravate autism; add Chiari 1 to that list.

  

The Chiari 1 brain hernia occurs when part of the brain is forced downwards into the spinal column.  It is supposedly very rare, occurring in only one person per thousand.  It is generally not life-threatening and can be surgically repaired.  The symptoms of Chiari 1 do rather overlap with those of autism.

You can diagnose Chiari 1 using an MRI scan.  Very few people with autism ever receive any diagnostic follow up, be it genetic testing, metabolic testing or a scan of their brain.

There have been anecdotal reports associating Chiari with autism, and indeed of the corrective surgery greatly improving autism symptoms.  This goes back to the day of Bernie Rimland (Autism Research Institute and DAN).

Finally we have some genuine data:-

Chiari malformation I and autism spectrum disorder: an under recognized coexistence.

Abstract

OBJECT:

Patients with symptomatic Chiari malformation Type I (CM-I) frequently present with headaches, neck pain, difficulty swallowing, and balance disturbances. In children with autism spectrum disorder (ASD), diagnosing CM-I can be a challenging task. Moreover, even if symptomatic, some patients do not undergo further evaluation or management, as their presentations are attributed to autism and its myriad symptoms. Therefore, cranial MRI findings were reviewed after evaluating and treating patients with coexisting ASD and CM-I. In this paper, the authors report on 5 children with ASD and symptomatic CM-I, including their clinical presentation, imaging studies, management, and outcomes, and discuss the likely under recognized coexistence of these conditions.

METHODS:

All pediatric patients with ASD and cranial MRI conducted for any reason in the period from 1999 to 2013 were considered for analysis. All cases with concomitant symptomatic CM-I were eligible for this retrospective analysis.

RESULTS:

One hundred twenty-five pediatric patients diagnosed with ASD had undergone MRI, and 9 of them had evidence of cerebellar tonsillar herniation. Five patients were symptomatic and underwent suboccipital craniectomy, a C-1 or a C-1 and C-2 laminectomy, and duraplasty with bovine pericardium or Type I collagen allograft. There were no intraoperative complications. All patients showed symptom improvement and/or resolution of presenting symptoms, which included headache, dysphasia, speech, and irritability.

CONCLUSIONS:

There is no identified cause of autism. Children with ASD can be difficult to assess specifically in a neurological examination. Thus, cranial MRI considered when completing a comprehensive diagnostic evaluation. While cranial MRI is not a routine part of ASD evaluation, this study demonstrates that CM-I and ASD may coexist and be underrecognized. The study reinforces the importance of a comprehensive medical evaluation designed to elucidate neurological findings in children with impaired communication abilities and suggests the judicious use of neuroimaging.

KEYWORDS:

ASD = autism spectrum disorder; CM-I = Chiari malformation Type I; Chiari malformation I; autism; autism spectrum disorder; suboccipital craniectomy

Conjecture

We know that in many cases of classic autism there is accelerated brain growth until the age of five (Courchesne, UC San Diego) and frequently this is associated with large heads (Macrocephaly).

As usual in autism, both extremes exist and so Microcephaly (small brains/heads) is also present.  The result is that in studies the average head size is meaningless.  Just as with many other possible markers, like cholesterol levels.  The same is true with signaling pathways like mTOR, Wnt, ERK and BDNF; both hypo function and hyper function exist and both can lead to “autism”.

   

Microcephaly and macrocephaly in autism.

Data from a series of 126 autistic children ages 2-16 years and referred to an Autism Diagnosis Unit in South-West France were examined. Macrocephaly (head circumference > 97th centile) was observed in 16.7% of the sample, a significantly higher proportion than that expected. Macrocephaly was more frequent among older subjects but was otherwise not associated with gender, developmental level, the presence of epilepsy or of medical disorders, or severity of autistic symptomatology. Microcephaly (head circumference < 3rd centile) was also significantly raised and found in 15.1% of the sample. Microcephaly was significantly associated with the presence of medical disorders. Results support those from recent studies suggesting a raised rate of macrocephaly in autism which, pooling published data, can be estimated to be 20%. It is argued that the raised incidence of microcephaly among low-functioning autistic subjects with medical disorders might have contributed to delay the recognition of an increased head circumference among a minority of subjects with idiopathic autism.

It is not hard to imagine what might happen if the brain is expanding faster than the skull is growing.  It would be reasonable to think that, in some cases, autism might cause Chiari malformation I.

Most people consider Chiari malformation I to be genetic.  In people with no underlying cause(s) of autism, the hernia itself may be the sole cause of the associated symptoms.

Since we know that autism is often caused by multiple “hits”, in some people the Chiari malformation might just be one of those handful of hits/triggers.  Oxidative stress and inflammation are both key drivers and consequences of autism; clearly hernia(s) growing in the spinal column are going to aggravate this.

To Treat or Not?

Surprisingly, some neurologists/neurosurgeons are unwilling to repair Chiari malformation I in children with autism.

If you recall my recent post on the history of autism, the reason becomes clearer.

Those neurologists/neurosurgeon hold the historical view that autism is untreatable and so how could surgery possible help?  It seems that in as many as 7% of autism cases, surgery might indeed help.  That is a surprise to me.

Fortunately, enough people with autism and Chiari 1 have been treated for it to be known that it does improve autism.

Since treatment involved a brain operation, it is not without risks.  Not treating the brain hernia likely also has risks.

Dr. Manuel Casanova on Chiari and Autism

Dr Casanova is a neurologist with a blog and an interest in autism. He is of the opinion that Chiari does not cause autism, but just makes it worse.

I am not a neurologist, but if you accept that autism, like cancer, is often caused by multiple hits, Chiari would seem like quite a dangerous hit, and perhaps more so than an immune over-reaction to childhood vaccines. In my recent autism history post we saw that for Hannah Poling the vaccine was enough to cause profound autism; she had two hits the first being a genetic mitochondrial dysfunction and the second an inflammatory reaction to the vaccines.

Over to Dr Casanova:-

Headaches, neck pain, disequilibrium and autism

"If you ever do a search through the internet you will find a lot of interest among multiple health boards on the possible correlation between the Chiari malformation and autism. Dr. Neil Felstein, Director of the Pediatric Neurosurgery Division of the Morgan Stanley Children’s Hospital, has seen many children with both conditions (http://abclocal.go.com/wabc/story?section=news/health&id=5251975 ). He believes that there is an association but can’t provide an explanation. Although a Chiari malformation is certainly not the cause of autism, it can aggravate the same. It may be worth noting that the Chiari malformation is seen as a comorbidity to both the Ehlers-Danlos and Marfan syndromes (Milhorat et al., 2007).  Both of these conditions manifest autistic symptomatology in a high percentage of cases (http://bit.ly/167eZuR )."

Head Circumference

Since data on head circumference is routinely collected during childhood, it would not be difficult to go back to the 125 cases studied by MRI in the research study, quoted at the start of this post.  You could then look for a correlations between head size, brain size and the Chiari hernia.

This might show that in autism the head was just not big enough at some critical point in time.

More links

The CSF Project to Analyze the Prevalence of Chiari Malformation Within the ASD Population

MRI at Boston Children’s Hospital

Conclusion

It looks like you might want to add an MRI to those metabolic and genetic tests that most children with autism never receive, but perhaps should.

Or, as put in today’s study:-

“The study reinforces the importance of a comprehensive medical evaluation designed to elucidate neurological findings in children with impaired communication abilities and suggests the judicious use of neuroimaging.”

ASD variants - (mis and missed) diagnoses. Calcium ion channel dysfunctions Cav1.1, 1.2, 1.3 and 1.4

This post serves to introduce some ideas relevant to a post that is will shortly arrive on calcium ion channel dysfunctions (Cav1.1, 1.2, 1.3 and 1.4).

As we have seen, nearly all behavioral and psychiatric disorders are just diagnosed based on observation.  Only in very rare cases is the underlying biological problem diagnosed.  So it is fair to say that these are not accurate medical diagnoses.

Under the wide umbrella term of ASD are likely hundreds of thousands of  discrete variants, since ASD generally results from the combination of multiple hits/dysfunctions.  A single one of these dysfunctions is usually not enough to trigger autism, but some may indeed trigger something else noticeable.  A small number of individual hits, like Fragile-X and Retts can trigger autism, but these are the exception.

Mis and Missed diagnoses

One reader of this blog received a diagnosis for his child as “late onset regressive autism or possible childhood disintegrative disorder”.  Neither of these options is very good, since you are talking about an entirely typical child who, after the age of four, begins to regress and lose his acquired skills.

After a long struggle, he found the biological diagnosis, which is mitochondrial disease.  After a few months of the Richard Kelley (from Johns Hopkins), therapy the regression was halted and now new skills are again being acquired.

This is another example of how unacceptable simple observational diagnoses are.  What would have happened if the reader had not stumbled upon this blog and then later sought out help from the leading experts (just look on my Dean’s list)?

Attention Deficit Disorder (ADHD)

ADHD is very commonly diagnosed in the US, much more so than in other countries.  More severe cases of ADHD look much like ASD, which is why I call them autism-lite.

Another group of ADHD may indeed be purely behavioral – too much time with smart phones, iPads and video games.  This is supported by the fact that the data on incidence of ADHD shows that a large group of children with ADHD, “grow out of it”, or were misdiagnosed in the first place.

However, it does look like there is another group of ADHD which is biological, but may be different to autism.  On this subject I will bring you the comments of Dr. Manuel Casanova, a neurologist and along with that, thoughtful and knowledgeable about autism. 

Then we have the recurring clinical trials on high EPA/DHA fish oil, which really do show an effect in most trials in ADHD, but fail in most trials in autism.  This will be developed further in the later post on calcium channels.  The suggested view is that either the vitamin A, or the omega 3 oil, is somehow helping and even perhaps some people have a problem absorbing some types of vitamin A.  I was always unconvinced by this. 

However, it has now been shown that the EPA in fish oil has an effect on certain L-type calcium channels.  If you had a mild dysfunction (channelopathy) of one of the L-type calcium channels, then a big enough dose of EPA might have an effect on them.  This becomes more interesting when you learn that some doctors in the US think that dyslexia is another autism-lite.

One suggested cause of dyslexia is visual deficit that makes reading difficult, but it also accompanied by a difficulty seeing in the dark.  This night blindness is known to be caused by vitamin A deficiency (or an inability to absorb it properly) and also by an ion channel dysfunction in Cav1.4.

It appears that the high EPA fish oil would increase vitamin A and also affect the function of Cav1.4.  The calcium ion channel Ca1.4 is widely expressed in your eyes.

Another interesting point is that it is thought that a dysfunction in one type of Calcium channel will often affect the function of others.  This is important because when you look at the effect of dysfunctions in these channels you will a listing including:-

·        Autism (Timothy Sydrome)

·        Mood disorder

·        Depression

·        Bipolar

As well as things like

·        Night blindness

·        Heart defects (Timothy Sydrome)

We also should note that many people (without autism) with sight problems claim improvement from taking high EPA fish oil.

Dyslexia

Dyslexia is the most common learning disability. It affects about 3 to 7 percent of people. While it is diagnosed more often in males, some believed it affects males and females equally. Up to 20 percent of the population may have some degree of symptoms

Dyslexia and attention deficit hyperactivity disorder (ADHD) commonly occur together; about 15 percent of people with dyslexia also have ADHD and 35 percent of those with ADHD have dyslexia.

The causes appear to be genetic and epigenetic. For example the gene KIAA0319

People usually think of dyslexia only in children, but that may be because many adults do not read very much.  Or do they "grow out of it".

ADHD

“It affects about 6–7% of children when diagnosed via the DSM-IV criteria and 1–2% when diagnosed via the ICD-10 criteria.  Rates are similar between countries and depend mostly on how it is diagnosed. ADHD is diagnosed approximately three times more in boys than in girls. About 30–50% of people diagnosed in childhood continue to have symptoms into adulthood.”

So it would seem that most people “grow out” of ADHD 

Dr. Manuel Casanova

Dr. Manuel Casanova is a neurologist and along with that is clever, thoughtful and knowledagable about autism.  He looks at measurable anatomical differences and how these may be related to behaviour.  So he is more into the consequences of unchangeable differences in brains.

If you start looking at ion channels and transporters as being key drivers in behaviour then you have the chance to make alterations.  We saw that the same applies to fine tuning the function and indeed structure of key neurotransmitter receptors.

In lay terms, Manuel is showing how brains are indeed “hardwired” differently in many cases of autism, ADHD and even dyslexia.  This might reinforce the old view that really it is “case closed” and nothing more can be done.

However the really clever scientists looking in greater depth show us that notwithstanding some structural variation, much of the problem lies in the aspects of the brain that can be modified and indeed some are constantly in a state of change, for example the shape of dendritric spines and indeed the very substructure of those  GABA_A receptors.

He groups dyslexia with ADHD and sees them as fundamentally different to autsim.  Having said that, Manuel tells us that attention disorders may be found in close to 30% of autistic individuals

 He has his own blog.

Dyslexia, Attention Deficit Hyperactivity Disorder and Autism

I suggest you read his full article, but here are some excerpts:-

“Claiming that there is comorbidity across neurodevelopmental disorders based on a single behavioral symptom negates many aspects of the individuality of each condition. In this regard, there are marked differences in the cognitive styles of dyslexic or ADHD individuals and those within the autism spectrum. Dyslexics enjoy a top-down cognitive style, tend to be holistically-oriented and have a gestalt processing bias (e.g., they see the forest but lose track of the individual trees). They are considered to have strong central coherence and excel in synthesizing sensory or cognitive experiences. Individuals within the autism spectrum enjoy a bottom-up cognitive style which makes them detail-oriented. Thus, contrary to dyslexic/ADHD subjects, ASD individuals see the tree but tend to lose sight of the forrest. In addition, they have a local processing bias with weak central coherence and appear to be good analyzers.”

“The above related differences in cognitive style appear to have anatomical correlates. As compared to neurotypicals, dyslexics tend to have smaller brain volumes with a concomitant striking increase in the size of their corpus callosum (the white matter projections that join homologous areas in both cerebral hemispheres). In addition, they have a simplification of their convolutional pattern and their cortical modules for information processing (minicolumns) are wider than expected. We find completely the opposite in patients within the autism spectrum.”

Yet more labels

Since we will be looking at calcium channels and one thing that does affect them is EPA, we should look at another label, dyspraxia, which also is reportedy  affected by fatty acids.

  

Fatty Acids in Dyslexia, Dyspraxia, ADHD and the Autistic Spectrum

Here is the link     Dyslexia, dyspraxia, ADHD and the autistic spectrum

What is Dyspraxia, also known as Developmental Coordination Disorder (DCD) ?

Dyspraxia, also known as Developmental coordination disorder (DCD), is is a chronic neurological disorder beginning in childhood that can affect planning of movements and co-ordination as a result of brain messages not being accurately transmitted to the body.

People with developmental coordination disorder sometimes have difficulty moderating the amount of sensory information that their body is constantly sending them, so as a result dyspraxics are prone to sensory overload and panic attacks.
Many dyspraxics struggle to distinguish left from right, even as adults, and have extremely poor sense of direction generally.

Moderate to extreme difficulty doing physical tasks is experienced by some dyspraxics, and fatigue is common because so much extra energy is expended while trying to execute physical movements correctly. Some (but not all) dyspraxics suffer from hypotonia, low muscle tone, which like DCD can detrimentally affect balance.

Gross motor control

Whole body movement, motor coordination, and body image issues mean that major developmental targets including walking, running, climbing and jumping can be affected. The difficulties vary from person to person and can include the following:

• Poor timing
• Poor balance (sometimes even falling over in mid-step). Tripping over one's own feet is also common.
• Difficulty combining movements into a controlled sequence.
• Difficulty remembering the next movement in a sequence.
• Problems with spatial awareness, or proprioception.
• Some people with developmental coordination disorder have trouble picking up and holding onto simple objects such as pencils, owing to poor muscle tone and/or proprioception.
• This disorder can cause an individual to be clumsy to the point of knocking things over and bumping into people accidentally.
• Some people with developmental coordination disorder have difficulty in determining left from right.
• Cross-laterality, ambidexterity, and a shift in the preferred hand are also common in people with developmental coordination disorder.
• Problems with chewing foods.

Fine motor control

Fine-motor problems can cause difficulty with a wide variety of other tasks such as using a knife and fork, fastening buttons and shoelaces, cooking, brushing one's teeth, styling one's hair, shaving, applying cosmetics, opening jars and packets, locking and unlocking doors, and doing housework.

Difficulties with fine motor co-ordination lead to problems with handwriting, which may be due to either ideational or ideo-motor difficulties. Problems associated with this area may include:

• Learning basic movement patterns.
• Developing a desired writing speed.
• Establishing the correct pencil grip
• The acquisition of graphemes – e.g. the letters of the Latin alphabet, as well as numbers.
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Associated disorders

People who have developmental coordination disorder may also have one or more of these co-morbid problems:

• Attention deficit hyperactivity disorder (ADHD) (inattention, hyperactivity, impulsive behaviour).
• Dyscalculia (difficulty with mathematics),
• Dysgraphia (an inability to write neatly and/or draw),
• Dyslexia (difficulty with reading and spelling),
• Hypotonia (low muscle tone)
• Sensory processing disorder
• Specific language impairment (SLI)
• Visual perception deficits

Dysjustabouteverything (DJE)

If you consider the early years of classic autism, you will see that, in many cases, it includes all of the above disorders, even hypertonia.

But some people are otherwise pretty much typical/normal, are diagnosed with a single disorder like dyscalculia.

The problem is that these are all just observational diagnoses.  Does something biological underlie and connect them?  I think it does.

An autistic person’s struggles with mathematics may be more to do with a problem of understanding the language used to explain it.  This is why, in many cases, they struggle to move beyond counting.  Special methods of teaching maths have been created for such people, but they only take you to an elementary level.

If you have Asperger’s, you have no problem with the language used to explain the concepts or to frame the questions.  Some people with Asperger’s excel at mathematics.

The same is true for dysgraphia, autistic people tend to have very scruffy handwriting, but does this mean that they have dysgraphia? 

Hypotonia is an interesting one.  Many parents report low muscle tone and indeed DAN doctors actually treat it (apparently with Creatine).  I think hypotonia, if present in autism, is likely to be connected to the disruption in the various growth factors that has occurred and this itself may related to GABA_B dysfunctions. (I mentioned this connection in an earlier post).  In Monty, aged 11 with ASD, when he was a baby he had Hypertonia.  He was big and all muscle.  As he got older he slid down from the 80-90^Th percentile to the 20^th percentile.  This fits one very distinct pattern of classic autism.

In the case of Monty, almost all the earlier signs of Dysjustabouteverything have now vanished.  Is this always the case?  Why would that happen in some people and not others?  Did his Polypill interventions play a role?

To investigate

What we need to know is whether there is a common link between all these various “dys-disorders”.

Probably in some (mis/over-diagnosed) people there is no link; but in others there may well be.

In some people there really is a link.  I did not tell you that my old “favourite”, hypokalemic periodic paralysis (HPP), can be caused by a Cav1.1 dysfunction.  HPP-lite is something called hypokalemic sensory overload.  In a little experiment I demonstrated that autistic sensory overload can be just hypokalemic sensory overload.  You just need 250 mg of potassium and a disturbing noise or light to illustrate it.  This is also a symptom of what they call Dyspraxia.

So Cav1.1 associates with HPP (hypokalemic periodic paralysis) and by my inference, sensory overload and some hypotonia;  Cav1.2 associates directly with autism (Timothy Syndrome) and bipolar; Cav1.3 associates with mood disorders, depression, bipolar; Cav1.4 associates with night blindness and perhaps some dyslexia.

A dysfunction in one L-type channel (Cav1.1, Cav1.2, Cav1.3 and Cav1.4) can apparently cause dysfunction in the others.  This surprised me.

So if you have autism, is not surprising if you appear afraid of the dark, feel depressed, experience sensory overload and are not very muscular.

The good news is that much of this appears to be treatable.

For the scientists among you:-

CACNB2    

Voltage-dependent L-type calcium channel subunit beta-2 is a protein that in humans is encoded by the CACNB2 gene

http://www.ebi.ac.uk/interpro/entry/IPR005444

Mutation in the CACNB2 gene are associated with Brugada syndrome, autism, attention deficit-hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, and schizophrenia.

I did forget to remind readers that I see the label schizophrenia as just another name for adult onset autism.

So it is no surprise that adults with autism have a 22 times higher chance of also being diagnosed with schizophrenia compared to non-ASD people.  Note bipolar, OCD etc; and this does not include all those adults with autism who get forgotten.

Source:  Adults with autism are at risk for host of health problems

Conclusion

I am not suggesting “medicalizing” people with dyslexia, or indeed most with ADHD. 

However, it might be useful for somebody affected to know if Cav1.1 to 1.4 were dysfunctional, then at critical moments, like exam time at school, you could indeed give them some extra help.

People with dyslexia, and I presume other “dys-disorders” do often get given extra time at school for exams.  People with ADHD are often entitled to financial benefits in developed countries, and it has been suggested that these countries are the ones with high incidence of diagnosis.  In the US 11% of children and 4.4% of adults have a diagnosis.   ADHD has been medicalized in the U.S. since the 1960s.  In the UK, 3.62% of boys and 0.85% of girls have an ADHD diagnosis.  In France less than 0.5% of children are taking medication for ADHD.

Here is a nice quote:-

Why Are ADHD Rates 20 Times Higher in the U.S. Than in  France?

“it makes perfect sense to me that French children don't need medications to control their behavior because they learn self-control early in their lives. The children grow up in families in which the rules are well-understood, and a clear family hierarchy is firmly in place.

In French families, as Druckerman describes them, parents are firmly in charge of their kids—instead of the American family style, in which the situation is all too often vice versa.”

In the case of ADHD, it looks like the French have got it right; but not sadly for autism.

Knowing many different nationalities, I can certainly confirm that French parenting is much tougher than the UK or US variety.  The UK variety is very similar to the US, but without the liberal use of drugs for ADHD or indeed autism.

In tough cases of ADHD, that even French parenting cannot control, perhaps it really is a calcium channelopathy.  Perhaps in these cases a mild calcium channel blocker like fish oil, or indeed Olive Leaf Extract may be potent enough, so you could use these daily without the need for any prescription medication.

In any case, Verapamil, if shown effective, looks a much safer bet than the usual ADHD stimulants like Ritalin.  If your ADHD was caused by calcium channel dysfunction, it would likely later appear elsewhere in your body; all those years on stimulants would not have helped you.

Recall that Verapamil can also be effective in bipolar.