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Tuesday, 19 May 2015

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  GABAA 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.



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





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.

Associated disorders


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




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 GABAB 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 80-90Th percentile to the 20th 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


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.









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.








23 comments:

  1. Very interesting. Dr Mary Megson has pioneered a protocol of Cod Liver Oil and Bethenacol that does wonders in a segment of ASD children. The theory is that these kids have a G Protein defect which among other things inhibits the retinoid receptors which happens to be the cause of night blindness. Cod Liver oil besides being a great fish oil, also is probably the best for of Vitamin A (cis form) in addition to be good source of vitamin D. I wonder is Dyslexia wouldn't fall into the same category

    ReplyDelete
  2. A very recent study relating to neurodegenerative disease and Parkinson's especially:

    http://www.sciencedaily.com/releases/2015/05/150512150022.htm

    discusses the use of a new drug as well as another blood pressure drug sometimes used in conjunction with Bumetanide called Candesartan. Their goal in this study was to explore how to attenuate chronic microglial activation (a hallmark of autism) by targeting toll-like receptors TLR1 and TLR2 via these two drugs.

    Candesartan also modulates NKCC2 activity:

    http://www.ncbi.nlm.nih.gov/pubmed/18305093

    which is interesting considering the original cited research above deals with attenuating microglial activation, rather than modulating the chloride levels within GABA inhibitory neurons as Bumetanide does.

    ReplyDelete
    Replies
    1. Thanks. That is very interesting, but so is this:-

      Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

      http://www.jneuroinflammation.com/content/9/1/38

      This paper suggests that the effect of Candesartan on microglia is :-


      "Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions."

      It looks to me that PPAR-γ is very important in some types of autism. I am very impressed with results so far of my mild PPAR-γ agonist, the Sytrinol/tangeretin flavonoid.

      Delete
    2. Hi same person as above.

      Kinda off topic and you can delete this post and email me if you want to discuss this offline (I have three kids with ASD, one severe, BTW and have been in the same boat as yours for the last 4 years) but some research I read today dealing with aging sparked my interest because it discusses how the gut changes with age, specifically with respect to Interleukin-6 which I am sure you are super duper familiar with.

      http://www.sciencedaily.com/releases/2015/05/150521095018.htm

      In particular it is suggested that a novel finding they had was that:

      "Further experiments showed that the increased levels of IL-6 directly lead to making the gut barrier 'leaky' to small, soluble molecules, although no physical differences in its structure were seen".

      It was shown earlier this year that Vitamin D and Fish Oil could attenuate TPH1 activity (peripheral 5-HTP->Serotonin) and also increase TPH2 (brain 5-HTP->Serotonin) activity and it is known high levels of peripheral serotonin (found in 30%-50% of those with an autism diagnosis) contribute to systemic inflammation, so perhaps this may add to some nasty inflammation feedback loop that could be reduced via drugs like Tocilizumab (used for rheumatoid arthritis) that inhibit IL-6 activity.

      On another note, I live in the states and considered Bumatenide well over a year ago after reading about the Ben-Ari initial study (it made the national news if I remember correctly) but access to it would require a shady doctor or else artificially blowing up my blood pressure to deadly levels right before a doctors visit to get a prescription for myself so I have not really pursued that path (the crazy things we do for our kids),

      Nevertheless, I have read your blog off and on for a while and would not mind sharing several novel treatments with my child that have had good success but that I don't feel comfortable discussing online due to some of them being rather unorthodox (like yours) and that since I am not a physician in the USA, that means I could get in serious trouble if I made public whatever my protocol happens to be if it were to go beyond the usual stuff you see floating around from DAN doctors involving megadoses of vitamins, herbs, and other supplements.

      If you have the time to share notes, my email address is mr_tfb@yahoo.com.

      Delete
  3. Hi Peter, I have a son with a rare form of genetic autism. I was hoping I could email you privately with some questions? Thanks so much,

    ReplyDelete
    Replies
    1. Just send me a message with your email address (which I will not publish on the blog)

      Delete
    2. Thanks for your second email.

      I do not think you need to fear discussing your protocol in public. Very many people are doing it. One reader of this blog went as far as to go to the recent Autism Conference (IMFAR 2015) in Salt Lake City and give a formal presentation of his “protocol”. he is not a doctor. I have presented my “Polypill” to the European drug agency.

      As you say, the IL-6 drugs for arthritis are interesting, but some are hugely expensive.

      If you comment on my blog using your first name or initials nobody is going to know who you are.

      I would suggest you find a way to try bumetanide, if you have a child with severe classic autism. When effective, the impact is truly profound; a child unable, or struggling, to acquire any new skills, becomes able to learn. I would hate to be without it.

      Delete
  4. Hello Peter,

    I am getting really desperate here as I am not getting any solution to my son's issues either from his paed and therapist or from this blog or other fora.

    My 4.6 year old son's learning ability has spiralled u upwards but with this cognitive enhancement has come the problems which I have already mentioned before but will be more unabashed now.

    My son tends to get irritable erections, which were earlier often associated with focussing and attention required to perform on somebody's instructions. The accompanying discomfort made it hard for him to focus on task at hand. I had considered task avoidance and performance anxiety.

    However recently, these erection episodes are occurring even during non stressful periods. Anticipating a soft drink, requesting for a puzzle..emotional hyperexcitability leading to a very bizzare physical response. He is young but in two years time this might become socially very unacceptable.

    We are approaching a festival season in October and then a winter break in December. I would like to trial whatever drugs I have at my disposal during this lean period. I am not getting bumetanide and I have not come across much feedback on benefits of spironolactone whose use I was seriously considering after reading the Bradstreet paper. On the contrary, there were reports of disruption of hormonal balance in boys.

    I have stocked fuimicil and a prescription grade potassium/magnesium syrup. Biogaia will take another ten days.
    Furosemide and acetazolamide..piratenide and torseamide. Could not find many parental opinions on positive effects on autism.

    What do you think about dosing my son on say 250 mg potassium and then observe how he behaves during a writing task..will that tell
    Us something although I do not think this will be helpful on a long term basis.

    Any suggestion, drug based or otherwise will be much appreciated. I do not really want to experiment with drugs whose side effects I will not be able to control or create bigger problems than the one they are meant to treat.

    Btw, he has suddenly developed this fear of being alone in a room or going to toilet alone , especially in the night.

    I would also value any opinion or suggestion from anybody who has experienced a similar situation.

    Regards

    ReplyDelete
    Replies
    1. Kritika, he is very young and does not have a severe type of autism.

      Potassium does affect sensory issues in some people and might give benefit. A small daily dose of potassium has proved totally without problems for my son, even after nearly 4 years.

      If you give your son homeopathic or other substances they may also have side effects. Perhaps something is affecting NO (nitric oxide) that would be one explanation for your son's issue.

      Delete
    2. Hello Peter,

      First, I do not know what you mean by severe autism..how autism is graded. Functionality, intellect, sensory issues or lack thereof, crippling obsessions or anxieties. My son has huge issues with language and I suspect he compensates for this deficit by cleverly mapping out situations and intelligent guesswork.

      I have attempted to inform myself a little about nitric oxide and uncannily things are repeatedly pointing out towards vasodilation, hypertension, inflammation and androgens. I would have found this fascinating..such a precarious and delicate equilibrium..issues of identity..who are we really. A little tweaking of hormone here, ingesting a bacteria there and you have a different person.

      So Peter, involvement of vasopressin and androgens in bringing about erections via the nitric oxide pathway could direct us to one area of intervention..endocrine imbalanced. In fact spironolactone could be one option to be tried out as it's a diuretic with regulatory effects on androgens apart from immunologic and anti inflammatory impacts. I do feel that my son has high testosterone levels, a thick mop of hair that interestingly is somehow also linked to nitric oxide levels.

      Nitric oxides involvement in critical biological processes but neurotransmission and cytokinin activity/inflammation in particular would have implications on autistic traits if it's levels are elevated as you suspect. Nitric oxide synthase antagonist, specifically the arginine types have been postulated to be of therapeutic value. So directly regulating nitric oxide synthesis could be the second alternative.

      But this is all theoretical. How does one go about it practically..consulting an endocrinologist could be the first step.

      Since nitric oxide is involved in neurotransmission and penile erection it seems logical to consider it. But ultimately, the aberration is in imbalanced or aberrant neuronal signals.. actually I am getting sort of confused now.
      Please elaborate and advise if possible.






      Delete
    3. Hello Peter,

      I was wondering if an NMDA receptor antagonist could help my son. As activation of NMDA receptor by glutamate and and glycine induces NO synthesis, simply regulating glutamate levels.. NAC could be helpful here..
      could also have some benefits.

      NAC, NMDA receptor antagonists..I feel could be helpful. Actually everything is so interconnected but I feel using safe interventions which affect the E/I balance (and I know it's skewed towards excitory in my son) could be the simplest and most sensible step.

      Please give your opinion.



      Delete
    4. Hello Peter,

      I think I am lost now. If we are considering nitric oxide disregulation for my son's hyper excitation leading to his disruptive erections, we should concentrate on the endothelial isoform of NO.

      Actually, at my ignorance levels, implicating NO for my son's issue is as good as telling me that he has a neurodevelopmental disorders!

      I mean, it's all so interconnected that identifying a specific aberration in terms of process as well as location seems beyond my comprehension right now. Nitric oxide seems to be controlling both gaba as well as glutamergic signalling and there seem to be lots of feedback and lots of ion channel issues.

      I think I am back to square one.

      Delete
  5. Kritika, you might want to add the GABA B agonist Baclofen to your list. In one post I showed that it corrects some NMDA dysfunction. It is effective in >50% of people with Asperger's based on anacdotes at doses of about 5mg two or three times a day.

    ReplyDelete
  6. Hello Peter,

    I believe baclofen will be effective in those cases where the glutamate receptor, NMDA is hypoactive.

    In my son's case it seems to be just the opposite. I was thinking more on the lines of nac to regulate glutamate, magnesium for blocking NMDA R channels, and then probably NMDA antagonist like amantadine. I will have to read up more on dopamine and serotonin. It's too complicated and I think even the GABA E/I imbalance, aberrant functioning again has to be looked at.

    My son does not have asperger. He has early onset autism, is probably not functioning too badly in areas of daily living activities and Adaptive behaviour but in terms of language and social skills might be functioning at a much lower level. It's kind of sad ..he is a beautiful child.

    Well..coming to the treatment part have I made some mistake in comprehending the likely to be affected pathways as what you are telling me is contrary to what I am understanding regarding NMDA dysfunction.

    Regards

    ReplyDelete
  7. Hello Peter,

    I just wanted to briefly describe a few behaviours of my child so that you can probably better understand his issues
    He started off as zoned out happy child, so typical of infantile autism, to the point that I was considering using naltrexone.

    With increased awareness and cognitive improvements came hyperexcitability and then bursts of hyperactivity. Amazingly yesterday he straightened out a bedsheet, pulling the corners snd adjusted my shirt unprompted. If you tell him to clean up, if he is in the right mood he will put his books and toys in their right places. But his hyperactivity and energy and constant exploring is getting very tiring and irritating. He will adjust tables and climb on chests to get to the wall clock, haul himself up the kitchen slab, cycle with eyes closed or feet in the air like an adrenalin junkie. He has excellent memory and will remember places and where objects of his interest are located in those places. If he wants water he will rush to the kitchen, drink fast and rush back. If I tell him to put the plates away, he will run and throw the plates in the basin with a bang..lot of stomping, banging. I am at my wit's end.

    In this last month, he has started telling us to pat him hard on his feet, legs, chest and back before he goes off to sleep. Good thing is he conveys and points to where it hurts and itches. If he has a reflux and we asked him to show where it hurts he pointed to his throat, nose and head in that order.

    But now I feel this hyperexcitability will become a big hindrance to instructional learning.. experiental learning will only get better I feel.

    One more important observation..he seems to have two modes of learning, a suppressed neurotypical one and the dominant autistic one. You may find it odd butveven his teachers have told me that he learns fast, sometimes in the first attempt only to either lose interest or shift back to autistic learning mode. This has happened while teaching him qualitative concepts and most significantly meaningful counting. He did it, silently counting on his mind and writing the correct answer only to lose this ability and now it's back to autistic repetitive teaching.

    What is happening..split personality!

    Sorry for the long account but is this a normal feature of autistic kids?

    And about the NMDA R antagonist, magnesium taurate might act as a mild one although many doubt it's efficacy. Epsom salt baths do nothing for my son in calming him down. He loves the bathing part, though.

    If you feel Mg taurate might help, it can be trialled immediately. Also, I was interested in ZMA that Tyler mentioned but the testosterone elevating effects are something I am wary of as my son Already seems to have high androgen levels.

    I feel I have to try something potent, his supercharged state is really getting on my nerves. And do consider his need for deep, hard pats in order to be able to unwind.

    Regards







    ReplyDelete
    Replies
    1. Hi Kritika,

      My daughter at your son's age was a whirlwind! We used to call her crouching tiger hidden dragon, because it felt like her feet never touched ground. A lot of asd kids are this way, it will pass. What helped my daughter was lots of exercise, as in roller blading, swimming, riding, bicycling etc.

      About the learning, people in general tend to conserve cognitive processes, since learning something new uses a lot of energy. This is called cognitive sparing and we tend to use memory or approximations to understand and solve a problem. I also think this is what we all do when trying to learn something new. As adults, we might bring discipline and rules, motivated by intrinsic rewards, to make ourselves pay attention for, say, 45 minutes or an hour. Much harder as a child. A trick that I use, and that is a cornerstone of ABA is rewards. I use frequent rewards, might be praise, a high five etc, to constantly compensate for the effort. So, the activity of learning is not only associated with effort and pain, but also a feel good reward. Over time, in spite of the effort, she loves to learn. The best part is that later, she loves to practice what she has learnt, because its such a wonderful feeling to get good at something and be praised.

      Most people with neurological and psychiatric disorders have problems with attention span because it seems like there is simply not enough energy available for the brain. Glucose transport in the brain is one of the most finely controlled processes and the first to take a hit in brain injury. This is the reason the ketogenic diet/ mct oil, nasal insulin, trh are important to try. It might be that this is what's happening with your son. He expends some energy learning and then goes into low power mode.

      It may also be that there are certain things that he is able to learn in the usual way, yet others that he needs repetitive teaching on.

      I agree with Peter, your son does seem to be high functioning, since he is able to both follow directions and learn inspite of the hyperactivity.


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    2. Hello RG,

      You got it. It's cognitive sparing which I meant although I did not know the terminology.

      My son's lead therapist has told me that my son's IQ might be higher than mine or his so rather than restraining him too much, he be allowed to explore and taught simultaneously. As if I can restrain him!

      I do not want to complain too much but he is getting himself into danger by his adventurous pursuits. Today he tried to operate the microwave to cook popcorn. He hardly ever walks straight
      ..in the park he will try and walk balancing himself on the raisings rather than walk on the track. He will try to pour water from glass bottles instead of plastic ones. Hr will run with four eggs precariously balanced in his handd. Few days back he was trying to run scissors through his hair. He stuck all his cars inside the AC. He has destroyed two TVs and when I rebuke him loudly he will often take my hand and slap himself saying 'no' as if he is sorry but cannot control his impulse.

      Till six months back he was sitting and learning wonderfully, copying basic patterns that I drew. Now it's a whirlwind. Tabletop learning
      Hhas become a pain although other kind of learning, learning through experience and exploration has increased. I am worried this problem is going to become worse and without an ability or willingness to learn through instructions, he will remain stuck.

      Another problem, which probably you are not aware of is that this unwillingness to learn and perform on instruction is accompanied by or probably caused by penile erections which he gets on being excited..this is now occurring even during non learning but excitory moments like when he really wants something bad and has to wait for it or is denied an activity or object.

      I know it's hyperexcitability because a few times when he was holding onto his erections and whining while writing, handing him some play dough or allowing him to eat munchies during the task diverted and diluted the focus and he was able to perform. But it is always not so easy.

      I do not as much mind the hyperactivity, although it's difficult with me being the only caretaker, as I am worried about roadblocks to learning.

      Thanks for your suggestions. I have to now note down all the drug based treatment information I have accessed from this blog somewhere and makeva beginning. Enough of testing the waters.

      Regards






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    3. RG,

      As far as positive reinforcement and rewards is concerned, my child was earlier performing just for the praise and the smiles and probably the novelty of learning.

      Going back to more tangible or basic rewards like giving spins, or eatables or dramatic high fives will be one step backwards. But yes, we have to keep changing strategies with the varying developmental profile of our kids.

      ABA is a principal on which all of us function. I was hoping that my son develops a more evolved concept of rewards but I think it will take time.

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    4. RG,

      Sorry for pestering,

      But are you hinting towards mitochondrial dysfunction. In that case, I move towards carnitine, Co q 10, galantamine.

      I have to consolidate all this information.

      Thanks

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    5. My understanding is that mitochondrial dysfunction is about cellular energy production and output. I am talking about input, fuel. Its likely that lack of adequate fuel in the form of glucose or ketones would lead to mitochondrial dysfunction.

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  8. Peter,

    Wanted to add another piece of information..either because of anxiety but more probably in order to map and understand continuity of routines, he will keep one book or puzzle next to himself before going to sleep and on waking up he will look for the same. This also happens when he goes to school. But it's not obsessive or attachment to a single object as he keeps on varying them. Is he trying to understand permanence in his own way?

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    1. Many people with autism like the feeling of pressure, so people have weighted bankets etc. Many people aged 4 or 5 with classic autism really are unable to learn much at all. This is why I think your son is much higher functioning and therefore it is quite possible that baclofen will help, even though you may think it will have the opposite effect biologicallly to what you think he needs. I would just start making short trials of these drugs that do help some people and see what helps. Then you will have some good data with which to plan your next steps.

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    2. Peter,

      I think you are right..have to begin somewhere. Probably it's a barrier.. foray from one unknown of autism to another unknown of chemicals to alter my son's issues.

      Your blog and it's readers have provided me with sufficient information to initiate short trials as you say.

      Regards

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