Autism & Self-Injurious Behaviour (SIB)

 

For parents more severely affected by autism, one of the most difficult things to deal with is anger, aggression and self-injurious behaviour (SIB).  SIB is sometimes rather politely referred to as challenging behaviour.

In the case of Monty, aged 10 with ASD, we have overcome these problems (for now at least); but for other people have to struggle on with them, on a daily basis. 

SIB can affect any person with autism, whether they are severely, moderately or mildly affected otherwise.  Left untamed, I am reliably informed, it may return in adulthood.  

So, for those people, who do not want to follow the “novel”, but science-based, interventions discussed elsewhere in this blog, here is what the experts have to say:-

 

From the US  (an excellent paper) :-

Autism: Should My Child Take Medicine for Challenging Behavior?

  

From the UK:-

Self-Injurious Behaviour

 From Canada:-

How Do I Decide if my Child Should Have Medication?

 

 

 

 

Hypokalemic Autistic Sensory Overload

Hypokalemic Autistic Sensory Overload (HypoASO) is a condition causing distress to autistic people.  Moderately loud sounds, like those around an indoor swimming pool, or shopping mall, can cause an autistic person great irritation, leading to covering their ears, a tantrum, or even self-injurious behaviour (SIB).  The same sensory overload can be caused by light, smell or touch.  

HypoASO is a condition that can be measured and treated.

HypoASO is related to two other conditions Hypokalemic Periodic Paralysis and Hypokalemic Sensory Overstimulation.

HypoASO is an ion-channel disorder triggered by intra/extra cellular concentrations of sodium and potassium.  Calcium may also play a role.  In simple terms, sodium is bad and potassium is good.

Therapy for HypoASO

The therapy for HypoASO is a diet rich in potassium but low in sodium; magnesium will also be beneficial, since it helps maintain the level of potassium.  People with HypoASO need to maintain a high level of potassium in their blood (> 5.0 mmol/L) in order to avoid triggering this ion channel disorder;  this is at the high upper level of the reference range for potassium.   Oral supplements of potassium with magnesium will also prove useful, but need to be spread out throughout the day, for best effect.  Time release tablets should be the most effective.  Very high levels of potassium are dangerous, so care is required.

Testing for HypoASO

Diet should not be changed on a whim.  A simple test can be carried out to check whether the individual is indeed affected by the disorder. 

1.       Find a sound which the person finds disturbing, like a baby crying.

2.       Download a recording of this sound.

3.       Set up a chair in a fixed location in a room with a strong sound system / Hi Fi

4.       Sit the subject in the chair and play the annoying sound at ever greater volume and see at what point the subject reacts strongly (e.g. covers ears)

5.       Repeat the experiment over  a few days to establish a steady base-line volume, at which the subject reacts, (for example volume setting 3, when the amplifier to goes 0-10)

6.       Give the subject an oral potassium supplement (say 250 mg) and wait 20 minutes

7.       Play the annoying sound and measure the volume at which ears are covered.

8.       If the volume is markedly higher than the base-line, you established earlier, then you have established HypoASO

9.       If the subject has an NT sibling, try it on them.  They will most likely show no difference with the potassium and do not have HypoASO



 

Seasonal Autistic Mastocytosis

 

 The degranulation process in a Mast cell. 1 = antigen; 2 = IgE; 3 = FcεRI; 4 = preformed mediators (histamine, proteases, chemokines, heparin); 5 = granules; 6 - Mast cell; 7 - newly formed mediators  leukotrienes, platelet-activating factor)

Source: Wikipedia 

Some of the most popular posts on my blog refer to my investigation into the role of histamine in autism.  The investigation was productive and lead to a highly effective treatment for the wild summertime flare-ups in autistic behaviour exhibited by Monty, aged 10 with ASD. 

Since I have found a therapy it is only reasonable to give the condition a name. 

Seasonal Autistic Mastocytosis (SAM)

Seasonal Autistic Mastocytosis (SAM), sometimes known as Airborne Autistic Mastocytosis, occurs when airborne allergens like pollen, cause mast cells in the eyes, nose, mouth and lungs to degranulate.  These mast cells contain many granules, themselves containing histamine, serotonin and heparin, a naturally occurring anticoagulant.  This mast cell activation also releases inflammatory cytokines, leukotrienes and platelet activating factor (PAF).  Some of these pro-inflammatory agents enter the brain and stoke up the ever-present neuro-inflammation, starting a downward spiral with further localized cytokine release.  In behavioural terms, the result is that all the earlier bad behaviours will return, but in a magnified form.  The observer may notice swings to aggression and self-injurious behaviour (SIB).  If the subject is verbal, he may complain of unpleasant itching on arms and legs, typical of mastocytosis.  The autistic subject, not understanding the reason for the itching, is likely to react with some form of tantrum, aggression or hitting that part of his body.

SAM should be considered even when only very minor symptoms of an allergy are visible, like red eyes or runny nose.  

The most effective therapy is to use mast cell stabilizers, but even a standard OTC H1 antihistamine will provide some relief within 20 minutes.  The dosage required to have an effect, may be much higher than the recommended dose for allergic rhinitis (hay fever), but should still be within safe limits.

 

An alternative therapy is simply to move to somewhere that is pollen free, even just for a weekend and observe the effect.

Depending on where you live, SAM may be possible for about 5 months of the year.

Mast cells are particularly present in the digestive tract, the lungs, skin, eyes, mouth and nose.  They undoubtedly also play a major role is asthma.

Mastocytic enterocolitis is a related condition.  This condition is acknowledged in the medical community.  I am not a gastroenterologist, but I think Messrs Wakefield and Krigsman may have really stumbled upon cases of Mastocytic enterocolitis, when they came up with their diagnosis of Autistic enterocolitis.  Incidentally, Krigsman recently published an interesting paper on genes and colitis in ASD.

Some of the frequently reported cases of GI problems in autism may also be caused by mast cell degranulation.  Some of the DAN doctors treat GI problems with mast cell stabilizers and allergists routinely prescribe them.

Note on Serotonin

Approximately 30% of people with autism have high blood serotonin; perhaps a contributing factor is serotonin released by the degranulation of mast cells.  We have already seen that there often appears to be central hypo-function of serotonin in autism (i.e. low brain serotonin).  The endocrine system functions using feedback loops, so high blood serotonin sends a signal to lower serotonin; thus you could get low brain serotonin but high blood serotonin.  Remember that serotonin does not cross the blood brain barrier.

Piracetam for Autism, Comrades

Piracetam was first synthesized in 1964 by a Romanian scientist called Corneliu Giurgea, who was highly unusual.  He was educated in then communist Romania, followed by research in Russia and then at the University of Rochester in the US, before ending up in Belgium, eventually as the Head of Research at drug firm UCB and being a Professor at a Belgian university.  How this was possible under the strict form of communism followed in Romania,  I do not really understand.

Anyway, Giurgea was clearly very resourceful and he decided to invent a new class of drugs, to be called Nootropic.

He stated that Nootropic drugs should have the following characteristics:

1.     They should enhance learning and memory.

2.     They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).

3.     They should protect the brain against various physical or chemical injuries.

4.     They should increase the efficacy of the tonic cortical/subcortical control mechanisms.

5.     They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.

Piracetam was soon followed by other drugs developed by competitors.

This class of drug seems never to have been licensed in the US, but was used widely in the Soviet Union, Eastern Europe and some western European countries.

As seems all too common in medicine, nobody knows for sure how Piracetam works.  There are many proposed mechanisms and I was attracted by one of them.

Autism in Ukraine

The internet does give the impression of giving you all the answers.  Often it gives you far too much information, much of it of dubious quality.  In reality, you are only seeing what is written in English, and although it is the international language of science and medicine, you will never see the majority of Russian, Japanese and Chinese knowledge/research.  Medical practice varies widely between Western medicine and the others.

In Japan for example, the MMR vaccination has been banned since 1993 and Prozac, the anti-depressant prescribed in huge quantities in the US, is a banned substance.  

So it was not a surprise to find only passing references to apparently widespread use of Piracetam for autism in the Ukraine, going back for decades.  I have no doubt if you could access the Russian research you would find studies on this.

Side Effects

There is no shortage of drugs prescribed in the US for autism, such as Ritalin, Prozac and Risperidone.  I have no doubt that they have some very good qualities; however they all have very real side effects, some of which are permanent.  Giurgea was very wise to only consider drugs with very few side effects and low toxicity.

In the 50 years since he synthesized Piracetam, one thing everyone seems to agree on, is that either it has no side effects, or it has very minor side effects.

Does Piracetam work?

In the 1970s there were numerous studies on Piracetam in a wide range of neurological conditions.  Today Piracetam is extensively used “off label” as a treatment for many of those conditions.  Does Piracetam work in autism?

I guess the doctors in the Ukraine must think it works.  Dr Akhondzadeh, a researcher into autism, ADHD, and other mental health conditions in Iran, found it to be effective.  Kelly Dorfman of the Development Delay Resources in Pittsburgh thinks it is effective for learning disabilities and dyspraxia, but less so for autism.

Olga Bogdashina, President of the Autism Society of Ukraine, notes that piracetam is widely used as an autism treatment in the Ukraine. Having conducted her own small-scale study, she found that piracetam improved the attention spans and mental capabilities in the majority of participating children. She also says that her autistic son became more sociable and flexible and less aggressive on the supplement. She does warn that during the initial phase of treatment, hyperactivity and tantrums may increase. However, researcher Stephen Fowkes notes that these side effects are only common with high doses, and asserts that they are rare with standard doses (both cited in “Letters to the Editor, Autism Research Review International, 1996).

I thought Bogdashina’s name was familiar.  I read her book on sensory issues in autism.  It is a good read, but it does not really tell you what to do.

Piracetam’s claimed possible methods of action

·        It is NOT a sedative or a stimulant

·        Piracetam is a positive allosteric modulator of the AMPA receptor.

^·         It is hypothesized to act on ion channels or ion carriers; thus leading to increased neuron excitability

^·         GABA brain metabolism and GABA receptors are not affected by piracetam.

^·         Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors, which are implicated in memory processes

·        Furthermore, piracetam may have an effect on NMDA glutamate receptors, which are involved with learning and memory processes.

·        Piracetam is thought to increase cell membrane permeability

·        Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na⁺, K⁺).

·        It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains.

·        Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria.

·        But in the brain, it also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.

In 2005 there was an interesting review carried out in Poland; it is very readable.

Piracetam - An old drug with novel properties? 

"Piracetam is generally reported to have minimal or no side effects. It is interesting to note, however,  that piracetam is occasionally reported side effects of anxiety, insomnia, agitation, irritability  and tremor are identical to the symptoms of excessive acetylcholine/glutamate neuroactivity. In spite of these effects, piracetam is generally not considered to be a significant agonist or inhibitor of the synaptic action of most   neurotransmitters. The piracetam-type nootropic drugs might exert their

effect on some species of molecules present in the plasma membrane. It would seem that they act as potentiators of an already present activity, rather than possessing any neurotransmitter-like activity of  their own."

It would seem to me that we have come back to the vagus nerve and the Cholinergic system

http://epiphanyasd.blogspot.com/2013/10/biomarkers-in-autism-cholinergic-system.html

I learnt in that post that there are two main classes of acetylcholine receptor (AChR), nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR).  Mostly it seems to be the nicotinic type that is targeted by medical science, but piracetam has an effect on the other type of receptor.  This would explain excessive use of piracetam causing symptoms of too much acetylcholine.

If this is indeed the case, that would add yet another method of “correcting” the known biomarker of autism that is “diminished acetylcholine and nicotinic receptor activity”.  Of all the methods I have so far investigated, this might actually be the safest;  it is certainly inexpensive.

Effect on Comorbidities

My method of separating fact from fiction in autism now includes looking at the effect of therapies on the principal comorbidities of autism.  Most genuinely effective drugs seem to work across many comorbidities.  Epilepsy is the most prevalent comorbidity.
 

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

"CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage. "

Note:  Unverricht–Lundborg disease is the most common form of an uncommon group of epilepsy called the progressive myoclonus epilepsies.

Conclusion

Piracetam seems to be a safe supplement/drug that improves mood and reduces aggression (and SIBs).  I thought it was worthwhile testing and indeed I was not disappointed.  The dosage suggested is 50-100 mg/kg, but the optimal dose seems to vary by child.  If you follow my vagus nerve/neuroinflammation/ cholinergic way of thinking, then Piracetam would be acting (via acetylcholine) to reduce pro-inflammatory cytokines and hence reduce inflammation in the autistic brain.  This would mean that Piracetam would be a useful tool to control autism flare-ups, be they triggered by pollen allergy, intestinal inflammation, or even stress.  I shall use it as such.

As for why Piracetam seems more effective in the Ukraine than in Pittsburgh - that I can answer.  Much of what passes as autism in Pittsburgh, would be completely ignored in Kiev.  It would not be diagnosed as autism; only if it is disabling would it be called autism.  If you have "autism-lite", the symptoms are mild and you probably do not need Piracetam and it would likely have little effect.   The same would apply for the majority of ADHD/ADD cases, outside of the US they would not be diagnosed as such.

If you are on Ritalin for your severe ADHD, you might want to try Piracetam.  If you Google ADHD and Piracetam, you will find adults using Piracetam to avoid the side effects of Ritalin.

If your child suffers from SIBs (self-injurious behaviours) then Piracetam, along with nicotine patches, would be well worth investigating.