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Monday 4 August 2014

Allergies, Autism and Cognitive Impairment

Previous posts showed how pollen allergies can lead to summertime flare-ups in autism; most noticeable are violent/aggressive behaviours, but there is actually much more going on.

I established that Verapamil, the calcium channel blocker, and surprisingly also a mast cell stabilizer, can very effectively extinguish the aggression, but without really solving the usual allergy symptoms like itchy eyes.  As a result, you need to use a convention anti-allergy treatment as well.


Asthma/Pollen Hot Spots

Any asthma suffer will be able to tell you about the places that make them feel worse and the places that places that reduce their symptoms.  It seems that pine forests high in the mountains and on certain coastlines are best.

Forested areas around cities are not good for asthma, Berlin being an example. So you can easily check if you live in an asthma hot spot, or in a better place.


Cognitive Impairment

We just spent two weeks under the olive trees beside the sea in Greece, which I would classify as a low pollen location.  Having returned home to a big city and a house directly opposite a forest, we could see the effect of an asthma/pollen hot spot.

Monty, aged 11 with ASD, mild pollen allergy and mild asthma, did change his behaviour almost immediately.

The Verapamil does continue to block aggressive behaviour, but what changed was an immediate return of mild atopic dermatitis (red patches behind knees) and what Monty’s brother Ted, aged 14, described as Monty became “more stupid”.  It is not a nice way to describe it, but when you look closely, it is there.  The allergy has effectively lowered his cognitive function.  It is very easy to check, just ask some simple maths questions or memory questions (what did you have for breakfast?).  It is as if he is very mildly intoxicated (drunk), he is not staggering around, but he is not as sharp as he was in Greece, or at home in the spring.

Faced with an aggressive child, the last thing you would bother about is how good he is at mental maths, and so you would probably never notice it.  But having solved the aggression we are left with the observation that the allergy causes some temporary cognitive impairment.  I say temporary, because if you take away the allergens, everything improves and returns to where it was.


What is going on?

We know that allergens cause mast cell degranulation, which releases histamine, IL-6, and other pro-inflammatory substances in a chain reaction.  We know that these cross the BBB (blood brain barrier) where there are several types of histamine receptor.  The body has at least 4 types: - H1, H2, H3 and H4, and maybe more not yet identified.

Typical anti-histamines only block H1, and the newer ones are specifically designed not to cross the BBB, so as not to make you drowsy.  We later discovered that most H1 anti-histamines have moderate mast cell stabilizing properties, meaning they do reduce the release of histamine itself.

Calcium channel signaling is known to be disturbed in autism and there is excess physical calcium found in the autistic brain.  This did suggest that modifying calcium channel behaviour might be of benefit.  A known genetic variation in autism does affect the L-type calcium channels.  This suggested that blocking the L-channels might be helpful.  This was shown to be true in Timothy syndrome and I showed it to be true in Monty.

Other research has shown that Verapamil is an effective mast cell stabilizer, which did come as a surprise.

Now we come back to the effect of the allergy.  If untreated, it will “dumb down” the child and also lead to extreme behaviours like aggression, but also even odd physical tics, like moving the head forwards and backwards like a pigeon.

Perhaps there is a two stage process going on, which ultimately leads to the aberrant signaling of the L-type calcium channels and aggression.  Or is it just a progression from mild to severe?

Is it a coincidence that a calcium channel blocker can stabilize mast cells?  I think it unlikely.


Autism as an Allergy of the Brain

The idea put forward by Professor Theoharides, that autism is, at least in part, an allergy of the brain, looks more and more valid.  It was the subject of an earlier post.


I do wonder how much mental retardation (MR) / cognitive impairment is also caused by the same mechanism.  Depending on how you define “autism” and whose figures you use, between 20% and 50% of people with autism have MR.  MR is defined as an IQ of 70 or less.

·        Mild retardation: Mild retardation: IQ level 50-55 to approximately 70 (85% of people with mental retardation are in this category)
·        Moderate retardation: IQ level 35-40 to 50-55 (10% of people with mental retardation)
·        Severe retardation: IQ level 20-25 to 35-40 (3 - 4% of people with mental retardation)
·        Profound retardation: IQ level below 20 or 25 (1 - 2% of people with mental retardation)

I would suggest that many people with autism might be “cognitively impaired” by allergies, be they caused by pollen, cats, dust, food, detergents, pollution or anything else.  Maybe they just dropped from a potential IQ of 120 to 110, or maybe they dropped from 80 to 35 and are now known as severely retarded.


Verapamil treats more than aggression and SIB

Based on my sample of one, it would be conceivable that Verapamil merely treats aggression and self-injurious behaviour (SIB), and that allergies are a side issue.  But thanks to the feedback on this blog, it is clear that Verapamil is treating the allergy.  One reader gave very extensive feedback showing how Verapamil greatly reduced her child’s GI problems (caused by food intolerance/allergies) and improved behaviour.  So based on a sample of two, Verapamil’s effect does seem to be related to mast cell degranulation and allergies.


Conclusion

I am very happy to have discovered the benefits of Verapamil, but I will continue to look into how further to reduce the “brain allergy effect”.  Perhaps the allergy is somehow affecting the excitatory/inhibitory balance of the Neurotransmitter GABA, I say this because Monty’s behaviour somehow resembles life without Bumetanide.  

Bumetanide’s role in autism is to lower brain Cl- concentration and to switch GABA to be inhibitory.  A recent comment on one of my Bumetanide posts was from somebody highlighting a paper that questioned whether enough Bumetanide crosses into the brain to switch GABA to be inhibitory.  

Note that a recently published comprehensive review on the use of bumetanide in the treatment of neonatal seizures indicates that theres is no evidence to support the use of this drug in the treatment of central nervous system disorders via the NKCC1-dependent mechanism described above, as at the very low doses that are given to infants and children bumetanide does not reach sufficient levels in the brain.

direct link to the original review:
http://onlinelibrary.wiley.com/doi/10.1111/epi.12620/pdf

It is conceivable that allergies affect the blood brain barrier (BBB), although you might expect allergies to weaken the BBB, rather than strengthen it; but the body does plenty of strange things.  So a second daily dose of Bumetanide just might help.  In France, the autism researchers working with Bumetanide do give it twice a day.

The simplest method to reduce the “brain allergy effect” would be to just avoid the allergen(s).  In the case of Monty, this would be to go and live in a low pollen environment, and perhaps even avoid cats.

Since 30+% of people with autism apparently suffer from asthma, then 30% of people with autism might also find behavioral relief by avoiding pollen.  Those suffering from aggression and SIB would very likely benefit dramatically from Verapamil.

This might also suggest that residential facilities for people with severe autism should be in low pollen areas.

Incidentally, our local special needs school used to be surrounded by a rampant overgrowth of ragweed/ambrosia.  This is one of the most notorious plants for causing allergies in humans.  The current number 1 in the ATP world tennis rankings then gave them some money to tidy up the grounds.  Coincidentally, like many of the “inmates”, he also favors a gluten free diet.






11 comments:

  1. Hi peter ,
    I have bought verapamil but I have read that it is not compatible with diuretucs,statins,carbamazepin...
    Isla it true?have you notice any interaction betweenthe drugs?thanks

    ReplyDelete
    Replies
    1. I have noticed no interactions between the drugs I am using.

      I am using a low dose of statin, at higher statin doses the verapamil can increase their effect.

      Delete
  2. Can you please share your research sources?

    ReplyDelete
    Replies
    1. Search the blog to find posts on what you are interested in and you will find many links to research papers.

      Delete
  3. So, this is the comment I did not expect to write.
    The reason for being here is my youngest daughter, 2 years old and autistic.
    I also have a girl who is 5 years old who except for being superactive (hyper?) and intelligent, seems pretty “normal”. She has been very allergic to pollen for most of her life. She uses Aerius (levocetirizin) which does help, but not to the extent needed. I am giving her the dose for a 6-year old which is double the dose for a 5 year old, still not happy with the results.
    Anyway, pollen time is here yet again and to my surprise she is having some unexpected reactions beside the more common ones (sneezing, runny nose, red eyes). Readers of this blog might not find them as unexpected… This is what I have noticed:
    -Aggressiveness, tantrums, explosive mood for non-existent issues, features like obedient defiant disorder (ODD)
    -Clumsiness, both fine and gross motor skills seems affected
    -Saying out isolated words and phrases loud, probably things she has heard recently
    -Inattention, which manifests itself as inability to “hear” that we are talking to her or what we are saying.
    -Hyperactiveness
    -Almost unable to eye contact even at will
    -Loudness
    -Need to go to the toilet very often (psychological issue or yeast?)
    The thing is I don’t know what to get out from this. Sharing genes with her little sister I am starting to suspect she also may have some diagnose. But on the other hand, these are issues that came along the allergy. So is it the pollen who makes her slightly autistic? Or is it side effects of Aerius?

    /Ling

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  4. Sadly I have no way to try verapamil this year to see if it affects my NT daughters "brain allergy". But I have a strong feeling that Agnieszkas request for reports on verapamil use in autism might be of concern to a bigger group of people than those affected with classic autism.

    All those extra suicides during pollen highs could eventually be prevented with the same method...

    What I did now was to stop medicine completely and replaced it with quercetin (4*200 mg a day). Might be too early to report effects, but I have had a very much happier daughter today who is more like herself.
    /Ling

    ReplyDelete
    Replies
    1. Ling, you are correct about the link, as this Danish Study demonstrates.

      Suicide risk in relation to air pollen counts: a study based on data from Danish registers
      https://www.researchgate.net/publication/241693877_Suicide_risk_in_relation_to_air_pollen_counts_A_study_based_on_data_from_Danish_registers

      The good thing is that there are very many allergy therapies.

      Quercetin is a natural substance that really does have an effect. In some people, like me, it has side effects after a while. It gave me tendonitis in one ankle, which went away after I stopped taking it.

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    2. I don't know about levo cetrizine but cetrizine gave crying episodes in my grandson. Last month he had severe viral diarrhea which lasted for two weeks. Along with regression he developed itching. Allegra helped but not much. We tried cetrizine and itching was better but he will cry uncontrollably for even an hour. We stopped cetrizine and crying was gone.

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    3. Just to add some information on the case:

      The "brain allergy" reaction was not a side effect of Aerius - it did not stop when we removed Aerius. Looking at a case list on suspected adverse effects of this type for Aerius I actually found that some of the cases had ASD...

      As pollen time is over here all the reactions listed above are greatly minimized or gone.
      Quercetin helped a lot, but not 100% so I'll have to find alternatives until next year. Seeing an immunologist soon, are there any other substances than verapamil that I should read up on?

      /Ling

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    4. Ling, the other drugs are cromolyn sodium, azelastine, rupatadine.

      Supplements include histidine, Biogaia Protectis and even high bioavailable forms of curcumin.

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    5. Thanks Peter for that quick tip! :)

      /Ling

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