Peter Polygon of Impairments in Autism - Pizza Time

Most kids love pizza; Monty is no exception and today he gets his own, by special delivery.

The first slice is that rather dull triad of impairments, which is taught to therapists learning about autism.  Autism is supposed to be the place where these three impairments overlap.  I was always rather underwhelmed by this; definitely a slice needing extra ketchup. 

So based on what I have learned myself, and read in the literature I propose a more colourful pizza, which of course gets a fancy name.

In the literature, whether or not there was a regression after birth, seems to be relevant in understanding the cause of autism, in that particular case.  It would also therefore be a factor indicating the appropriate therapy.

You may be surprised to see "depression", but it is there because there are many biological markers in autism that are also present in people with depression (and other mental health disorders).  These will be discussed in a subsequent science-heavy post.  I also note that while some autistic people look happy, at least some of the time, others look pretty miserable.  Perhaps they have depression, but nobody stopped to think about it.

Aggression is pretty self-explanatory.  Some people with autism never seem to get aggressive, but for others it can become a real issue.

Serious comorbidities, in plain English, means other serious symptoms that co-exist in that particular person's type of autism.  This again is extremely relevant in both understanding the cause of that person's autism and also the the most effective ways of treating it.  Not only do many people with autism also have epilepsy, but there is a clear overlap between what causes some types of convulsion and what provokes some autistic behaviours.  This is not fully understood in the literature.  There is already an overlap between novel therapies for epilepsy and novel therapies for autism.

MR is mental retardation; it is quite commonly associated with autism.  I suspect some unfortunate children with un-managed autism end up in such a condition where they are falsely labeled with MR.

GI disorders are gastrointestinal stomach problems such as diarrhea, constipation and reflux.  In some studies as many as 50% of autistic children have GI disorders, many being chronic.  In the literature, there is much about the connection between these disorders and autism; although to talk about it outside the literature is verging on heresy.

You will likely know that ADHD is attention deficit hyperactive disorder.  This is another diagnosis that has become extremely fashionable, particularly in the US.  I found a paper entitled "The worldwide prevalence of ADHD: is it an American condition?", the full version is free, just click it.  Anyway, lack of attention and hyperactivity are definitely symptoms of certain types of autism.  Therapy that works for ADHD should be interesting for us too. Incidentally, in my earlier posts about Autistic Sensory Overload (ASO) and the similarity with Hypokalemic Sensory Overload (hypoSO), if you read the links you would have seen that hypoSO is now being linked with ADHD, although I seem to be the only person to claim a link to ASO.

Fog and present, or not present is a phenomenon that you may know but call something else.  One reader of this blog referred to his child's zombie-like state.  Some older autistic people, who now have much reduced symptoms, refer to knowing what was going on in their youth, but as if being surrounded by fog.  People who speak better French than English, say things along the lines of "today in school, Monty was not present".  It does not quite work in English.  They mean Monty was physically in school, but his mind was somewhere else.  Fortunately, Bumetanide seems to make kids "present"; and this is a good thing.

Since all autistic kids seem to be unique, I have left the 12th triangle as a spare; for you to customize as you see fit.

Monty's own pizza is looking a bit thin and so it is time to order a Margherita for him and a Margarita for me.

Neurology – I think I like it

In the real world coincidences are quite rare;  in this blog they seem to happen alarmingly often.  Here is another one.

You will surely have noticed by now that an old diuretic called Bumetanide has found a new application in the treatment of autism.

Similarly less known, is a strange phenomenon called Hypokalemic Sensory Overstimulation (HypoSO). This is when the sufferer gets overwhelmed by their senses of sound, light etc, but reverts to normal, as if by magic, after drinking oral potassium.  The extreme case of this is Hypokalemic Periodic Paralysis (HypoPP), when you don’t just get sensory overload, you actually become paralyzed.

My ANA hypotheses number 2 was that maybe sensory overload in autism was a form of Hypokalemic Sensory Overstimulation (HypoSo).  It seemed a wild idea, but when we tested it, we found the hypothesis entirely plausible.  We made an experiment with Monty, Ted and Dule. (click the link).  In other words, we found that autistic children seem to suffer from HypoSO and maybe some also suffer from its scarier cousin HypoPP.

Well, having decided to give my blog a rest for a couple of days, I did a mere 5 minutes work on Saturday and look what I found.

 

Bumetanide prevents transient decreases in muscle force in murine Hypokalemic Periodic Paralysis

That link takes you to a very recent paper (last month, in fact), and look how the abstract ends:- 

Conclusions: The Na-K-2Cl inhibitor bumetanide was highly effective in preventing attacks of weakness in the NaV1.4-R669H mouse model of HypoPP and should be considered for management of patients with HypoPP due to sodium channel mutations.

What does this really mean?  Well I have my opinions, but I am not yet ready to share them.  I did write to the authors of the study, but my experience to date is that Neurologists are far too busy to reply to a poor speller like myself.
 
Anyway, it looks like another reason to favour Bumetanide. I like coincidences, so it seems that I have got to like Neurology.

 

Nom de guerre, Mon frère - Manchopathy

Today’s post had better be a quick one.  The desk research in the background is getting complicated and I have just ordered a 900 page book on Human Physiology, so as not to spout complete nonsense.  Worse still, a couple of days ago, I received in the mail, a big brown envelope from Tokyo with a juicy report on the use of Ceredist, a TRH analog.  It is 20 pages long, and the bad news is that 18 pages are in Japanese.  The good news is that I had expected all 20 pages to be in Japanese.

To business.   You are slowly being introduced to the cast members of this blog.

The star of course is “Monty”, aged 9.

His supposedly “typical” big brother, aged 12, is going to be called “Ted”.

Head of Applied Research, part-time biker and Speech Therapist will be called Dule (“Doolay”)

Last week I decided that it was time for some good old fashioned primary research, to test a hypothesis that I had formulated.  This is what we presented to the in-house ethics committee, for approval:-

1.    Many children with autism exhibit what appears as sensory overload.  On hearing a moderately loud sound, they will cover their ears, almost as if in pain.  Bright lights, darkness, certain smells, even touch can trigger similarly strong reactions.  Entire books have been written documenting these odd behaviours, but I never read an explanation for them.

2.    In my trawl through the literature, I noted that a disorder with surprisingly similar symptoms has been documented -   Hypokalemic sensory overstimulation

This disorder manifests itself as an overwhelming feeling of sensory stimulation.  But then disappears 20 minutes after a dose of oral potassium.  A related, but much more severe, disorder that causes temporary paralysis also exists -  Hypokalemic periodic paralysis

3.    The recommended daily amount of potassium for adults is 3,500mg.  A typical banana contains 400 mg of potassium. A dissolvable tablet of Potassium Citrate contains 500mg of potassium.  So 500mg is a safe dose to experiment with.

4.    A laboratory experiment is proposed using an MP3 file of a baby crying. Dule will first establish a baseline volume (VB) at which Monty will cover his ears. Monty will be sitting in a fixed position in the lab. This test will be repeated over a few days to see if VB varies.

 

5.    Then the subject will receive 500mg of oral potassium and wait for 20 minutes. The MP3 file will be played again while he is sitting in the identical test position. Dule will crank up the volume and note the new threshold volume (VT).

 

6.    The same test will be repeated with Ted and Dule as subjects.

 

Prior to providing Dule with the oral potassium solution, Peter suggested to Dule that he would perhaps prefer if the test did not show up anything worthy of further investigation.  Since that would again drive Peter crazy, that no serious scientist had noticed this, done something about it and published their work.

Here is the raw data from the test:-

 

Volume * at which sound becomes disturbing
	7-Mar-13	8-Mar-13		11-Mar-13		11-Mar-13
						after K+
Monty	9	9		9		16
Ted				23		26
Dule				21		23
* sound level on digital display of Philips mini HiFi
room is about 20 m2, subjects were 2.5 m from HiFi unit

 

Discussion

As you see, Monty is far more sensitive to sound than both Ted and Dule.  Monty experiences a sharp increase in his capacity to cope with sound stimulation after drinking the potassium.  Ted and Dule show a small increase in capacity, that may be just down to measurement tolerance/error. (Dule was testing himself, after all)

Mon Dieu!  It looks like we have to do a serious follow on study with more subjects and some flashy equipment.  Worse still, now I have to be able to explain scientifically why this is happening !

 

The cause is related to something called VDCC (voltage dependent calcium channels) these are like little valves that open to let  Ca²⁺ ions in or out; they are misbehaving.   Recall that Bumetanide works in a similar way by triggering NKCC1 and NKCC2 (Sodium, Potassium, Chloride Cotransporters) to let in/out  Cl^- ions.  The subject of misbehaving ion channels has already been given a fancy name by scientists, its Channelopathy.  Now I was wondering how I was going to explain my use of French in this post.  It's all about the English Channel or should I say la Manche, and so we'll call it Manchopathy.