Showing posts with label Prognosis. Show all posts
Showing posts with label Prognosis. Show all posts

Thursday 11 April 2019

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:

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.

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

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


"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.

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.

Thursday 4 April 2019

A 15 year Longitudinal Study of French Autism and a look at Early Diagnoses of US Autism that Resolved

Today’s post is all about what to expect in the future; it covers a detailed look at 2 different studies that I think are best considered in a single post.

Forewarned is forearmed.

How high to set the bar?

In a recent post I highlighted the need for long term (longitudinal) studies showing what happened to people diagnosed with autism back in the 1990s in California and New York, when an autism diagnosis was much more meaningful and yet early intervention was already available. We could then see what the outcome was 20 years after diagnosis and this might help parents decide their own autism strategies for today.

I was encouraged to subsequently come across today’s study from France that traces the progress made over 15 years by a group diagnosed with autism.  I also include my take on a popular recent study that showed what “Optimal Outcome” looks like in American autism, but that looks just over a 4 year period.

Don’t raise your hopes.

All this leads to the practical question of how far to raise the bar? What should parents expect at diagnosis? What should clinicians be telling parents? and what kind of value is being delivered by hundreds of millions of dollars spent on early intervention and special schooling by each of many municipal authorities all over world. Is their spending delivering its potential return? Today's post suggests not.

Today we come across 2 autism rating scales. The Childhood Autism Rating Scale (CARS) is my long-time favourite; in this scale above 30 means autistic and if you get above 36.5 it is severe autism. If you come at 29 you have some features of autism but not enough to be diagnosed with even mild autism.

The Vineland Scale is a very scientific way to measure adaptive behaviour (life skills). These are really the most important skills you need to live semi-independently and have some kind of job.

The Vineland results really reflect what you are taught at school/home, rather than how “autistic” you are.  Vineland is not a measurement of IQ. You can be a functional adult who is still well and truly autistic and have had a CARS score of above 30 from diagnosis at 3 years old all the way to 18 years old.

If you are a genuine Aspie reading this, I very much doubt your CARS score was above 30 when you left high school. This is why Asperger’s has to be considered as a separate category.

The French Study

The way autism was treated in the 1990s and early 2000s in big cities in California was very different to how it was, and is, treated in France. In France hospitals and psychotherapy played a major role, whereas in the US it was and remains all about ABA early intervention.

The outcomes in France for the top 20% are not stellar, but they are actually quite OK, they end up at 20 years old with the adaptive life skills of a 13 year old. The results for the remaining 80% in the lower group show adaptive behaviour / living skills of a 2-3 years old at the age of 20.  The percentage with severe ID/MR (IQ less than 70) increased from 49% to 78.2% at the age of 20.  In effect virtually the entire lower group, that makes up 80% of the study participants, leave school with mental retardation / intellectual disability.  That is a lot.  I did highlight in earlier posts that people with severe autism usually see their IQ fall as they get older, because IQ tests gets harder as you get older and people with severe autism acquire skills more slowly than their typical peers, so they inevitably fall further behind.  

The good news was that 5.4% of the cohort lost their autism diagnosis by age 20 and all without any ABA. Time and time again we see that some people age out of their autism.

Not surprisingly, the higher your IQ and verbal skills at diagnosis the better your outcome will be.  The most dramatic progress occurs before the age of 8.  This we already knew and it is attributed to the brain being more plastic in early childhood, allowing a greater degree of self-repair.

The average CARS total score of the entire group was 35.7 on diagnosis. On CARS autism scale 30 is the threshold for an autism diagnosis. Mild to moderate autism is 30 to 36.5.

You cannot make the case that this group performed poorly because they were all profoundly autistic, some were, but that was balanced by some with mild autism. As a group they were likely more severe than a group diagnosed with autism aged 3 in California in 2019.

By diagnosing at 2 years old and sometimes even younger, there will be a sub-group included whose very plastic brains were on track to self-repair, so that they would never have been diagnosed with autism in most countries, which wait till 3, 4 or even 5 years old to make a diagnosis.

Another key point here is that very likely a large proportion of 2019 autism diagnoses in the United States would correspond to a CARS score less than 30, but nobody bothered to measure it. As Dr Siegel suggests, their parents are now incentivized to want a diagnosis.  It is like a quirky badge of honour, with benefits.

There is limited data on long-term outcome of ASD with co-occurring intellectual disabilities (ID) and challenging behaviours in France. The EpiTED period cohort is a 15 years longitudinal study of the developmental trajectories of 281 children initially recruited at mean age of 5 years. Two contrasted developmental trajectories were identified. Low cognitive level, absence of language, and higher ASD scores at baseline were predictive of low growth at follow-up. As adults the participants were predisposed to persistent co-occurring challenging behaviours as well as underlying ID impacting their ability to function independently. The results underscore the need for development of services and supports for adults with ASD in France who may also have already lacked access to adequate interventions and support services.

The inclusion criteria in the EpiTED cohort were: (a) index child age below 7 years; (b) parental informed consent; (c) diagnosis of childhood autism, atypical autism, or Asperger Syndrome according to ICD-10 criteria (atypical autism corresponded to at least two domains of impairment according to ICD-10 criteria) (World Health Organization 1993) (autism will be subsequently referred to as ASD unless specifically signifying subtype). All diagnoses were validated by two independent, experienced child and adolescent psychiatrists among the research staff (including AB), on the basis of medical records, as well as videotaped observations during enrolment. Subjects for whom a consensual diagnosis could not be obtained or those for whom the date of appearance of ICD-10 autism symptoms emerged after 3 years were not enrolled. Between 1997 and 1999, among 362 eligible children, 281 with ASD (77%) aged between 3 and 7  years fulfilled the research inclusion criteria (T1); 62 children were excluded as they did not meet research inclusion criteria; 19 children (families) had moved away prior to enrolment and were also excluded.
The index children were followed prospectively over 15 years with four assessment points: ages 5 (T1), 8 (T2), 15 (T3), and 20 (T4) years (see flow chart, Fig. 1). At T2, from 2000 to 2002, 219 of children were reassessed; at T3, from 2007 to 2009, 152 adolescents were reassessed; and at T4, from 2012 to 2015, 106 young adult subjects were reassessed.

The primary outcome measures of the study were the standard scores in the three domains of the vineland adaptive behavior scale (VAB-S) (Sparrow et al. 1984). This scale is widely used to assess adaptive skills in different areas (daily living, communication, socialization and motor skills) in individuals from birth to adulthood including those affected by intellectual disabilities or ASD. VABS scores recorded at each of the follow-up times were used to identify developmental trajectories in communication, socialization, and daily living skills

ASD symptom severity was assessed using the total score of the childhood autism rating scale (CARS) (Eric Schopler et al. 2002), with scoring based on a 20 min and standardized video clip of the child interacting with an adult.

The diagnosis of ASD was stable (see Table 3): 94 (88.7%) subjects received a diagnosis of childhood autism and 12 subjects a diagnosis of atypical autism at T1; at 15 years follow up (T4), 82.6% of the cohort remained above the ADOS ASD threshold; 5.4% of the cohort lowered their ADOS scores under the ASD threshold; 12% of the cohort became “atypical autism”. Whereas the ASD diagnosis was remarkably stable between T1 and T2 follow up stages, most diagnostic changes occurred between T2 and T3. The ratio of participants without ID ranged between 7.5 and 22.5 according to measurement steps. Among the subjects with childhood autism, 59.6% were non-verbal at T1, with 39% remaining non-verbal at T4. With respect to comorbid ID, most changes occurred between 4 and 8 years of age. The proportion of children with either word/sentence language at T4 was 61%. The ratio of combined moderate and severe ID (IQ 20–25 to 50–55) measured by “best estimate” assessment of intellectual functioning was stable across time (around 80%), but the ratio of moderate ID (IQ 35–55 to 50–55) decreased from 27 to 5%, while that of severe ID (20–25 to 35–40) increased from 49 to 78.2% between T1 and T4.

Vineland Scale

Here below is an example tracking the adaptive development of a child with a disability.

If the child progressed 100% as a typical child in all three domains (communication, daily living skills and socialization) he/she would follow the sold black line at 45 degrees. If the child falls below expected level, then the line will track below the straight line at 45 degrees.

In the French data, the top 20% group reached the level of about 150 months of age by 20 years old. The Low growth group, which comprised almost 80% of the sample, reached the functional age of 24 months by the age of 20.

Fig. 2 Trajectories of adaptive level through adulthood among 94 participants of the EpiTED Cohort diagnosed as children. The figure shows the mean adaptive scores (CI 95%) over time for participants assigned to the two trajectory groups: _______Low growth group; ……………… lower CI 95%; - - - - - - - - upper CI 95%

The EpiTED is a unique prospective cohort of children with well-characterized ASD referred to five Departments in France. At the time of the cohort’s inception, the participating centers were the only public sites diagnosing and treating preschool children with ASD in the country. Although the cohort exhibited considerable rate of co-occurring ID, it must be noted that 20 years ago early diagnosis of high functioning children with ASD and interventions for them were not the norm in France. Therefore, children with ASD with more severe co-occurring levels of ID, communication, and adaptive impairments, so identified, were more likely to be referred to the study collaborating sites.
 Among the 106 study participants at the four collection time points, diagnostic stability was dominant, but not constant, and associated with a general improvement of ASD characteristics. However, the emerging trend in intellectual abilities, as measured by the best estimate procedure, was more unstable, with an increase of severe ID from 49 to 78.2%. This could result either from an actual decline of intellectual abilities, potentially and consequentially due to minimal exposure to educational interventions and learning opportunities (many children with ASD were historically excluded from mainstream education lacking access to support services), or alternatively as a result of lower performance scores on identical measures with advancing age, or both. While an improvement in adaptive skills measured by the VABS was the rule for the entire group, two contrasted developmental trajectories in adaptive functioning were identified. The majority of participants (around 80%) followed a low-growth developmental trajectory, with the remainder following a high-growth trajectory. Again, for majority of participants, a lower cognitive level, absence of functional speech, and increased CARS scores at T1 predicted a low-growth trajectory in communication, socialization, and daily living skills. Other studies have reported a similar relationship with IQ, non-verbal mental age, ASD severity and speech (Bal et al. 2015; Smith et al. 2012; Szatmari et al. 2015). Nonetheless, in the absence of studies on long-term effect of intervention, one cannot decide if this poor outcome is intrinsic to a fraction of the ASD population, or an effect of absence of interventions or limited exposure to learning opportunities. As regards co-occurring challenging behaviors, our results suggest that behavioral problems in children with ASD persist in early adulthood and are related to core symptom severity, levels of cognitive and language impairments, as well as medical comorbidities. The results also affirm that ASD symptom severity among adult subjects was a significant predictor of co-occurrence of challenging behaviors (Baghdadli et al. 2003, 2008). Another significant predictor was the presence of GI disorders. This is consistent with reports of a high correlation between the presence of pain and the frequency and severity of stereotypies (Courtemanche et al. 2016), as well as challenging behaviors in general (Chaidez et al. 2014). Nonetheless, these combined variables only explained at most 30% of the developmental variance observed in the study sample. Invariably, this means that other factors, not identified here, might explain the presence of challenging behaviors in adults with ASD. Additional research is needed to examine other influences, with particular relevance for the services and interventions in the community provided. It is of interest that for children with ASD, the main risk factors for self-injurious behaviour (SIB) were ASD symptom severity and cognitive level (Baghdadli et al. 2003, 2008). In the present study, the symptom severity remained a significant risk factor, but language skills instead of cognitive level predicted the presence of SIB. One possible explanation for this might be that SIB at adulthood may reflect a relationship with communicative deficits. This finding emphasizes the crucial role of communicative abilities and the need for targeted behavioural interventions for children with ASD aiming at developing better communication in order to prevent as well as manage subsequent challenging behaviours. The impact of having a child with ASD on parental QoL was strong with several implications not only on daily life but also on parental emotional well-being, lasting through adolescence through young adulthood. The results did not affirm that raising a child with ASD often leads to the breaking up of the parental relationship, as has been commonly believed. Overall, parental QoL at early adulthood appears to be mainly predicted by the presence of co-occurring challenging behaviours, whereas at adolescence parental QoL was also predicted by the children’s adaptive level, namely in communication and daily living skills. Again, the impact of co-occurrence of challenging behaviours on family life argues for the importance of implementing specific interventions targeting them at a younger age. In a functional behavioural assessment perspective (O’neill and Jones 1997), challenging behaviours are described as a way to obtain reinforcement or escape a negative experience, which is most of the time related to poor communication. From our perspective, the best way to prevent subsequent development of adverse behaviours is to propose specific treatment aiming at the development of communicative abilities in the very early years. It is also crucial to provide parental training and disability support guidance as parental involvement and knowledge is key predictive factor of parental satisfaction and performance (Renty and Roeyers 2006). We can hypothesize that the participants of the EpiTED cohort had limited access to this type of interventions, as the educational approaches have considerably changed since the children were included in this follow-up study 20 years ago (Happé and Charlton 2012). Finally, the EpiTED as a “period” cohort reflects the ASD diagnostic practices in France in the mid-1990s and in the ensuing two decades. High-functioning verbal individuals were frequently not given ASD diagnoses, due to the dominant use of alternative diagnoses in the French classification of mental health disorders (Classification Française des Troubles Mentaux de l’Enfant et de l’Adolescent, CFTMEA), particularly for verbal subjects, and the dominant influence of psychoanalysis. An important limitation of the EpiTED cohort therefore is that the prevalence of co-occurring challenging behaviours, ID, as well as associate medical comorbidity, including epilepsy cannot be representative of a contemporary profile of children with ASD that will be currently recruited from child and adolescent psychiatry services and ASD evaluation clinics in public centers. Nonetheless, the EpiTED cohort provides a distinctive portrait of French children with official diagnosis of ASD enrolled in public centers and how they fared over a 20-years follow-up as they became young adults. While there was improvement in their adaptive skills, the substantial social and communication difficulties among the children in the cohort tended to persist in adulthood reflecting the salient effects of non-specific, delayed or Journal of Autism and Developmental Disorders 1 3 absent interventions. As adults the subjects in the EpiTED cohort were noted to be predisposed to persistent challenging behaviours impacting their ability to be independent and have acceptable QoL. As the Government of France is increasingly recognizing the widespread shortcomings in services and supports for children with ASD and their families, the current EpiTED analyses underscore the need for service provision for adults with ASD as an urgent policy priority. This is a unique and relevant finding not only for researchers and clinicians but for policy makers in planning for the next National Autism Plan.

Conclusion on the French Study

This is French data that I think can be best considered as tracking outcome from DSM3-like autism. So it is Strictly Defined Autism (SDA), not the much broader 2019 type of American autism.

Based on my earlier review of the epidemiology of autism I found it roughly splits into 0.3% of all kids have Strictly Defined Autism (SDA), 0.3% have true Asperger’s (genuine little professors) and 0.4% have something in between. That takes us to 1% prevalence. In my opinion today’s figures of even greater than 2% prevalence include many people will very mild symptoms of ASD, so a likely CARS score of 25 to 29.  Beyond 1% is likely over-diagnosis, diagnosing for dollars, self-diagnosis, educational autism (school diagnosed), private psychologist diagnosis or whatever you choose to call it.

The Big Question

Would a 15 year longitudinal study in California (the home of ABA) look any better? In the next study at age 7 even the optimal outcome group did not look in any way “recovered”.  Perhaps by 20 years old things would look much better.

I would love to know and I keep an open mind.

Is French Autism therapy so much worse than in most developed countries? Different, yes; but is the result at age 20 any better in Germany, Italy, the United Kingdom or the United States?  How about some facts?

Now to the study on Optimal Outcome in US Autism

The sad news is that the US study only looks at outcomes of those with early diagnosis up to the age of about 7. The French study looked at all the way up to 20 years old.

Given those limitations of the US study, it does at least show us what the star performers look like at age 7. These are the ones that technically lost their autism diagnosis, but as you will read are still far from typical kids at the age of 7.

The study concerns the outcome for children diagnosed with DSMIV autism when then were 2.6 years old and then entered an early intervention program. Four years later about 9% no longer met the criteria for an autism diagnosis.

This loss of diagnosis is what we now seem to call “optimal outcome”. Today we get to see what optimal outcome means for those 9%, which accounts for the 38 children in the study.  So did 9% essentially “recover”?  Not really.

In research papers I usually skip to the data and what I saw was that of the 38 kids with “optimal outcome” only 10 were in mainstream school, without needing an assistant; that is what I would see as “recovery”. Those 10 kids are about 2% of all the 569 kids with an initial autism diagnosis.

Only 1% were free of any psychiatric diagnosis (ADHD, anxiety, OCD, MR/ID etc).  So, even optimal outcome does not look such a great place to be.

I wonder how many will be in mainstream school, without an assistant, when they are 16?  I think it will be more than 2%, I certainly hope so. I was expecting at least 10% would be mainstreamed without an assistant before they turned 7 years old.

Inner city New York is doing well diagnosing children so young and putting them into their early intervention program, but their results four years later look nothing like Lovaas suggested.

I am really surprised that more people did not lose their diagnosis. This sample is from New York where you might expect autism to be over-diagnosed and to have the best early intervention offerings.

Recall in the old post on autism with tics (Tourette’s type autism) that 6% of kids lost their diagnosis without any intervention.

If at 2 years old CARS is above 30 you have autism, if at 6 years old it has fallen below 30, you have lost your diagnosis and achieved “optimal outcome”.

A chart review was performed of 38 children diagnosed with autism spectrum disorder (ASD) by 3 years of age at an inner-city developmental program who subsequently experienced resolution of ASD symptomatology and no longer met diagnostic criteria for ASD at follow-up an average of 4 years later. 

Demographic, developmental/cognitive data, Childhood Autism Rating Scale, and Autism Diagnostic Observation Schedule data as available were reviewed from the initial diagnostic evaluation and at the time of follow-up. Services received by the children between the time of diagnosis and follow-up, educational setting at the time of follow-up, and emotional/behavioral and learning diagnoses made by the multidisciplinary team at follow-up were reviewed. The findings indicate that residual emotional/behavioral and learning problems were present at follow-up in the vast majority of children in this group and that the majority continued to require educational support.

Although autism spectrum disorder (ASD) has generally been considered a lifelong condition, it has been acknowledged for more than 40 years that some individuals with an early diagnosis of ASD do not meet criteria for the diagnosis at a later age. Lovaas used the term recovery to characterize the outcome of this group of children who received intensive behavioral intervention and later could be educationally mainstreamed and had average Intelligence Quotient (IQ). The term optimal outcome was coined by Fein to characterize a group of 34 individuals with early ASD whose later social functioning could not be distinguished from typical controls and who appeared to be cured of ASD. Follow-up studies have spoken of varying degrees of learning or emotional vulnerability that continue in the “positive outcome” populations, including attention problems and language problems. More recently, a long-term follow-up study of 198 children diagnosed with ASD at ages 2 to 4.5 years found that 17 children no longer met the criteria for ASD at the 2-year follow-up. Later, when the children were about 10 years of age, parents were interviewed by phone regarding the children’s school age needs. Based on parent report, all 17 children continued to have some type of ongoing developmental and/or neuropsychiatric challenge.

The goals of the current study were to further characterize the residual learning, cognitive, and emotional/behavioral diagnoses as well as the range of educational supports required at school age in a group of children with a history of an early diagnosis of ASD that resolved.

Demographics The 38 subjects of this study represented 7% of the 569 children receiving an early diagnosis at the center in a 10-year period. (In order to provide a real denominator for calculating the percentage of children no longer meeting criteria for ASD at follow-up, we need to know the number of children of the 569 who actually came for follow-up. Unfortunately, a change in our program’s clinical affiliation since the original cohort was studied with resultant changes in the charting system does not allow us to establish the exact number of the 569 children who came for follow-up. Our best estimate of the follow-up rate is on the basis of a prior study involving a subset of 108 children from this group of 569 who were diagnosed by 24 months. The follow-up rate for that group was 71%. Utilizing the 71% follow-up rate, the 38 children no longer meeting criteria for ASD would represent 9.4% of the sample.) The mean age of the sample was 2.6 + 0.9 years of age at initial diagnosis and 6.4 + 2.8 years at follow-up. The sample was 80% male with a diverse demographic representative of the community served: 36% self-identifying as Caucasian, 44% Hispanic, and 10% African American. Forty-six percent of the sample had Medicaid, and 42% were bilingual (Spanish and English). Eighty percent of the children received Early Intervention services (most commonly weekly special instruction for 1 hour per week and twice-weekly speech and occupational therapies) and 39% had received Applied Behavioral Analysis.

The above chart shows that the CARS evaluation of autism severity fell below the cut-off point of 30 and generally there was an increase in IQ of about 10.  So the kids became less autistic and a bit smarter. Severe autism starts at a CARS score of 36.5, you can see that these kids were only mild to moderate autistic at the time of their initial diagnosis.

One child went from CARS of 38 to CARS of 27. His parents should be very happy. He went from very serious autism to trivial autism.

Follow-up Evaluation Results

At follow-up, it was the clinical impression of the multidisciplinary team using DSM IV that none of the participants continued to meet criteria for an ASD diagnosis. Mean Childhood Autism Rating Scale score at follow-up for the group was 25+ 4, with 30 being the cutoff for ASD (Table 1). On the Autism Diagnostic Observation Schedule (available in 23 of the 38), all available scores were in the non-autistic range. However, other diagnoses were present (Table 2). Only 8% (n ¼ 3) of the children warranted no diagnosis other than having had a history ofASD. Sixty-eightpercent (n¼26) had language/ learning disabilities, 49% (n ¼ 19) of the children were diagnosed with externalizing behavior problems (attention-deficit hyperactivity disorder [ADHD], oppositional defiant disorder, disruptive behavior disorder), 24% (n¼9) were diagnosed with internalizing problems (mood disorder, anxiety disorder, obsessive compulsive disorder [OCD], selective mutism), and 5% (n ¼2) were given a significant mental health diagnosis (psychotic disorder not otherwise specified). Sixty percent (n ¼ 23) of the children received 2 diagnoses, with the most common combination being language/learning disability and ADHD. Follow-up cognitive testing, available in 33 of the 38 participants (Table 1), revealed that none of the children functioned in the range of intellectual disability, including those who previously tested as delayed on the Bayley. The average Full Scale IQ of the sample at follow-up was 93+14; 6% (n ¼ 2) scored in the borderline category; 27% (n ¼ 9) in the low average range; and 67% (n ¼ 22) in the average range (Table 1). The mean Verbal IQ of the sample at follow-up was 92+14 and mean Nonverbal IQ was 95+12 (Figure 1).

Follow-Up Educational/Academic Setting
Information regarding academic setting at follow-up was available for 34 of the 38 children: 26% of the children (n ¼ 10) were in a mainstream class, 13% (n¼5) were in a mainstream class with assistant teacher support, 29% (n ¼ 11) were in an integrated co-teaching (ICT) or collaborative team teaching (CTT) class/or received resource room, and 21% (n ¼ 8) were in a self-contained classroom (Table 2).


A given for this study is that there is a subset of children with an early ASD diagnosis who show a categorical improvement in their original social communicative impairment, such that they no longer manifest a social communicative impairment impacting on their functioning at some later point. Such a phenomenon has been repeatedly documented for a small group of children with ASD. Less clear has been whether children with this history continue to experience residual learning and emotional/behavioral problems. The findings of this small sample suggest that at least in the early elementary years, such residual problems are very common for this group. In this sample, although the loss of the ASD diagnosis was associated with gains in cognition, the vast majority of these children who experienced resolution of ASD continued to manifest symptoms of other emotional/behavioral and/or learning diagnoses (92%) and continued to require educational supports (74%).

Though it has been reported in multiple studies that a small subset of children with early ASD improve in terms of their social functioning and no longer warrant a diagnosis of autism,11 this persistent finding continues to beg severalquestions: Was autism overcalled in these children to begin with? Are some children better able to respond to intervention? Does the specific intervention the child receives contribute to outcome? All are possible. Based on our experience, our sense is that the symptoms evolve—in some children in response to intervention, in others due to their individual developmental trajectories. And who is most likely to evolve in this positive direction? Those with the mildest symptoms to begin with. This study as well as previous studies all support that it is the children with milder autistic symptoms who are most likely to follow this pattern of resolution of autistic symptoms. The milder forms of autism likely serve as a holding area. There, children await the emergence of the signs and symptoms of a more specific developmental or emotional-behavioral condition—whether that is language/learning disability or emotional-behavioral disorders that require more language, cognition, and increased behavioral expectations in order to be specifically identified and diagnosed. A 2-year-old simply does not have sufficient language or cognition to manifest the signs of schizophrenia, or to give voice to anxiety

Conclusions on the US and French Studies

I think that clinicians and therapists can too easily take cover behind the accepted mantra that each case of autism is unique, to justify why little Charlie did not make the hoped for miraculous “recovery” or achieve what Lovaas claimed as the outcome for 50% of such kids.  

In the wider world there is a concept of benchmarking performance, so you can see how your product or service compares.

Whoever is paying all these hundreds of millions of dollars in early intervention should demand proof of their effect. I myself do not see any proof.  The results overall look pretty terrible. Time to start treating severe autism medically?

By studying the trajectories of just a thousand kids from diagnosis to adulthood, you could reliably say what is typical and what you might expect in the upper and lower quartiles. Then you could look at the effect of different types of therapy and schooling. Nobody has done this, clearly too much bother and it would take many years.

My conclusion is that the bar has been set very low, too low. To be a star performer you do not have to be as dramatically improved as you might think.

I would love to know what percentage of these 569 kids from New York will go on to get a driver’s license.

Apparently, in the US we can expect about a third of those with an autism diagnosis, but no learning disability, to go on to pass their driving test.  I fail to see how you can safely drive a car in a busy city if you could not attend mainstream school without an assistant.

People diagnosed with autism at 3 years old versus 11, 21 or even 51 years of age have a completely different scale of disorder. I do not believe many of those diagnosed in later years would have ever had a CARS score of more than 30. 

I think if CARS needs to be 30 or greater to warrant an autism diagnosis, people with a lower score should not be given an autism diagnosis. I think this would immediately reduce the incidence of autism in the US by half, back down to the 1 in 100.

Why are not all children given a CARS assessment as part of their diagnosis? An ancestor of mine created a scale (the Baron score) used today to assess the severity of ulcerative colitis when carrying out an endoscopy. If a gastroenterologist can be bothered to give your ulcers a score, why cannot the developmental pediatrician or child psychiatrist?

Perhaps we should add a new label for CARS between 25 and 29; perhaps a “teeny tiny bit autistic”. Yes, you too can be on the spectrum, but don’t confuse your case with that of people with CARS above 36.

Sunday 7 April 2013

Conceptual Map of Behavioural Homeostasis in Autism

In the research there are various scales to measure how autistic a child is, for example the Childhood Autism Rating Scale (CARS).  They are very subjective, but clearly better than nothing at all. I read a study on older children with ASD that was highlighting that as the children get older, they become less autistic.  In the CARS scale there are 14 behavioural areas to grade and then there is number 15, which is the general impression of the clinician.  In effect, number 15 is how autistic the clinicians feel the subject to be;  you would expect that number 15 would be consistant with the findings in the first 14 areas.  In the test the older children all showed a big improvement in areas 1 to 14, but not in number 15, which is the one that really matters.  This really means that either the use of CARS was inappropriate or CARS is flawed.

As children get older the concept of "normal" changes.  So there is not much point comparing a 15 year old with ASD to a normal/typical 3 year old.  So I decided that kids with ASD deserve a better framework, so that clinicians and parents have a better way to understand many important issues, ranging from prognosis, to just what is autism and where its boundaries really are.

In the Peter Autism Scale (PAS), typical kids start at birth with a score of zero. After 12 months, typical kids show rapid development; they acquire an increasingly negative PAS score. After puberty has ended, the PAS score stops declining and gradually heads back towards minus 20.  Much later in life, after starting their own family, the PAS drifts back up towards minus 10.

Autistic children are likely born with a positive PAS score; as they show either regression, or just the emergence of ASD-type behaviours, the score will increase. At a score of 60, self injurious behaviour is exhibited; at a score of 80 there is serious aggression and violence. The scale stops at 100, where the child needs physical restraint and is likely to be sent to an institution (depending on which country they live in).

There has been an explosion in the number of children diagnosed with ASD, most notably in the US.  Undoubtedly a great deal of this is explained by a bizarre, ever-widening of the definition of autism.  At one end of the scale, what were formerly nerds/geeks are now "on the spectrum" and at the other end of the scale, cases of mental retardation (MR) are now labeled as severe autism.  This ever changing, ever stretching, diagnosis is extremely harmful to the search for genuine therapies.

Mild social difficulties and obsession with computers or music is nothing new; it may indeed be worthy of a diagnostic term, but I do not think it is autism, or ASD.  On the PAS framework, you will note a blue cloud.

Asperger's syndrome already has a nice name; in the PAS conceptual map it follows in parallel the general path of typical development but has a score 12 higher.  It passes through the lower edge of the blue cloud.

Now to the serious case of what I shall term "disabling autism".  These are children with a PAS score of greater than 20.  These children need immediate therapy and their parents need external training and support.  If this help is received, there is good chance that the PAS score will never reach 60, let alone 80.  If help is not received and the PAS reaches 100, there will not be a happy ending.

In a perfect world, the prompt intervention (both behavioural and pharmacological) will give the child a fighting chance of gradually heading south to that big blue cloud.

Monty no BU no NAC
This is my estimation of Monty's development with no drugs
Monty + NAC
This is my estimated outcome using NAC alone
Monty + BU + NAC
This is my curreent prognosis using Bumetanide and NAC
Monty + BU + NAC + Agent X
This is my optimal prognosis achieved by adding the unkown Agent X

Monty himself is the first subject to have a PAS assessment.  Clearly this is just conceptual and so is purely illustrative;  nonetheless I think it has value.

Monty was not born a typical baby; he was always a bit different.  These differences grew and it was in his fourth year that he really began to acquire and demonstrate lots of new skills.  Then, with a great deal of behavioral support, it was plain sailing until he was about 8 and a half years old, when almost overnight, his world fell apart.  His longtime assistant had to leave him and his cosy world was overturned.  All the behaviours that he had avoided earlier, such as head banging and aggression to others, emerged with a vengeance.  Nine months later things had finally returned to "normal", but at a higher plateau of autism than 12 months before.

Three months later I trialed Bumetanide (BU in the chart) and three months after that plateau I trialed NAC.  In the PAS framework, Bumetanide appeared to provide a one-off 40% reduction.  Then with NAC, I took a wild guess at a 25% one-off reduction in PAS score.

Now we are in sight of the blue cloud, but a lot of work remains to be done.

Within 12 months, I would like to have found Agent X, which would give another 25% reduction in PAS score.  I think that will be as much help as can be reasonably expected from drugs.     

If it was not for puberty, it would be plain sailing into the future.  In the prediction, I have forecast another behavioral meltdown (loss of behavioural homeostatis), but since we now have experience of such a shock, I hope to manage it better.