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.

 

 

 

 

 

Medicine - More Art than Science

Today's post is only indirectly about autism, it is more to do with what expectations are realistic from medical science in 2013.

I come from a family full of doctors and two engineers.  As one of the engineers, I know that engineering is a true science, and I had assumed that so was medicine.  In engineering the answers are either right or wrong, maybe or sometimes is not acceptable.  If you build 100 aeroplanes, full of maybe millions of components, you expect them work (ie not crash) everyday for 30 years.  An acceptable failure is much less than 1%, over the entire life of the planes.  So the science needs to be fully understood to the tiniest detail.

The more I am reading about medical science, the more clear it becomes how little is really understood and how trial and error is behind many breakthroughs.  Many drugs, particularly in neuroscience, work for reasons not fully understood; or there are several proposed methods of action, perhaps one of which is correct.  This really is not science.

Once you start thinking about medicine as an art rather than a science, things become clearer.  It also means that the old fashioned approach of 20-50 years ago might actually be more appropriate, than that of today.    

This also means that medicine is more about probability.  So, some new hi-tech anti-cancer drug may work in 60% of patients, but if you are one of the 40%, why suffer those horrible side effects? or indeed pay for it.  Or, for your allergy medicine, the doctor may prescribe you say, Claritin, but he probably does not tell you that in X% of patients it will not work.  Perhaps he should say, here are four antihistamines try them all and choose the two that work best, then just alternate between them.

I have been reading about thyroid hormones.  I am amazed by all the nonsense written about them, including in mass market books by experts.  The question is actually very simple, there is a prohormone called T4 with a long half-life and an active hormone called T3 with a much shorter half-life.  To optimally treat hypothyroidism you just need balance the dosage and frequency of T3 and T4 and you need to know that T3 is needed throughout the body and for it to be produced locally from T4, requires special enzymes (D1, D2, D3) to be present in sufficient quantities.  As a result, some people may need to be given T3 in addition to (or instead of) T4.   How complicated is that?

So how does this apply to autism?  Well, it means that perhaps we should not be critical of the "trial and error" approach of some US autism doctors.  "Trial and error" does need to have boundaries and safety is clearly the most important issue.  It also means that it is totally "normal" to find therapies that work in one group and yet are ineffective in another.  It means that applying complex statistical analysis, from sciences like engineering, to evaluate tiny clinical trials in autism is really a waste of time.  Not surprisingly, none of these trials stand up to scrutiny later.  Those scrutinising these mini studies are making the same mistake I did, thinking medicine is a "hard" science.  Maybe it will be in 500 years, but not in 2013.

Much can be learnt from Monty, age 10 with ASD, whose piano teacher tells me  "if a pill works, keep taking it". Hundreds of millions of people have benefited from taking statins, but as I learnt, 99% for the wrong reason.












 

Cytokine Theory of Disease & the Vagus Nerve

If you are a regular reader of this blog you will know that the key to controlling autism is reducing oxidative stress and neuroinflammation.  One of the key drivers of the on-going neuroinflammation are signalling molecules called cytokines; if you can limit the release of harmful cytokines you can reduce neuroinflammation.  This appears to be easier said than done.  I learnt that some statins limit the release of pro-inflammatory cytokines and neuroscientists in the US are researching their use, but not yet in autism.  I did some home research and found a positive effect within 24 hours.

It turns out there is an entire field of neuroscience relating to cytokines as a mediator of disease and this is all channelled through the Vagus nerve.  There is an eminent  neuroscientist, Kevin Tracey, who dominates this field; he is credited with discovering that vagus nerve stimulation inhibits inflammation by suppressing pro-inflammatory cytokine production.   Tracey is also an inventor, he is seeking to apply the science and has an interesting start-up company.  So I have found a kindred spirit and if you read his papers, you will find that often missing element, a sense of humour.

Tracy has even written a book, which explains his discoveries.

Fatal Sequence: The Killer Within

For those scientists among you, a very readable paper is:- 

Physiology and immunology of the cholinergic  Anti-inflammatory pathway

For those in a hurry, here is summary

The cytokine theory of disease is a concept that cytokines produced by the immune system can cause the signs, symptoms, and damaging aftereffects of disease.

One example is the case of TNF, a cytokine implicated as a necessary and sufficient mediator of lethal septic shock. Administration of TNF to healthy humans reproduces the metabolic, immunological, and pathological manifestations of the disease and the gene knockout or pharmacological blockade of TNF activity prevents the development of lethal septic shock. Other pathophysiological activities ascribed to TNF are the capacity to cause fever and localized inflammation. Clinical successes in the 1990s using drugs that specifically inhibit TNF for patients with inflammatory bowel disease or rheumatoid arthritis directly implicated a pathogenic role of this cytokine in other diseases and validated in humans the fundamental premise of the cytokine theory of disease.

 

 

The cholinergic anti-inflammatory pathway

Tracey reasoned that, since the CNS coordinates major physiological responses via innervated circuits, it might also use neural input to control a potentially deadly cytokine response. In classical physiological systems, the sensory projections of the autonomic nervous system provide input to brain networks about essential bodily functions. These elicit a coordinated neural output from the CNS to maintain homeostasis for parameters as varied as heart rate, blood pressure, digestion, body temperature, organ perfusion, and blood glucose levels. Accordingly, it seemed possible to posit the existence of a comparable mechanism to control cytokine release that could, at least in theory, function as an extremely fast, reflex-like anti-inflammatory pathway controlled by brain networks.  Stimulation of vagus nerve signals was shown to significantly inhibit TNF release in animals receiving lethal amounts of endotoxin. Subsequent work established that vagus nerve signaling inhibits cytokine activities and improves disease endpoints in experimental models of sepsis, schemia/reperfusion, hemorrhagic shock, myocardial ischemia, ileus, experimental arthritis, and pancreatitis. The cellular molecular mechanism for inhibition of cytokine synthesis is attributable to acetylcholine (ACh), the major vagus nerve neurotransmitter. Macrophages and other cytokine-producing cells express acetylcholine receptors (AChRs), which transduce an intracellular signal that inhibits cytokine synthesis. The best characterized of these cholinergic receptors that suppress cytokines is the α7 subunit of the nicotinic AChR (α7 nAChR).

 

 

It takes nerve to restrain cytokines: anatomy of an innervated cytokine system

Recent studies of the physiology, functional anatomy, and cellular molecular mechanisms of the cholinergic anti-inflammatory pathway indicate that the principal components for cytokine suppression by the vagus nerve converge in the spleen. Endotoxin localizes to macrophages primarily in the spleen and liver, thereby activating an immediate early cytokine response. The spleen is the major source of both hepatic and systemic TNF during endotoxemia; it releases newly synthesized TNF into the splenic vein, which drains into the liver, and from there, TNF crosses into the systemic circulation.

 Vagus nerve stimulation, or administration of α7 nAChR agonists, inhibits not only TNF but also IL-1, IL-6, IL-8, and high mobility group box 1 (HMGB1)

 

Preclinical efficacy of experimental therapeutics

Preclinical studies are in progress to determine whether it may be possible to develop therapeutics based upon either devices that stimulate vagus nerve activity or drugs that activate the cholinergic anti-inflammatory pathway to suppress cytokine damage. A significant number of studies indicate that the cholinergic anti-inflammatory pathway is a robust regulator of cytokine-mediated damage in local and systemic experimental disease.

The role of exercise

Exercise reduces levels of TNF and other cytokines, confers protection against cardiovascular disease and type 2 diabetes, increases vagus nerve activity, and confers protection against the development of atherosclerosis. It is possible that the mechanism of these exercise effects is at least in part attributable to exercise-induced increases in cholinergic anti-inflammatory pathway activity. Obesity, on the other hand, is characterized by diminished vagus nerve output and elevated cytokine levels, which have been implicated in mediating insulin resistance and atherosclerosis. Since weight loss and exercise are each associated with increasing vagus nerve activity, one can consider whether enhanced activity in the cholinergic anti-inflammatory pathway might decrease cytokine production and reduce the damage and metabolic derangements mediated by chronic, low-grade systemic inflammation that is characteristic of the metabolic syndrome

His conclusion:-

“It is bemusing to think that one of the fundamental premises of the ancient Greeks was that dietary manipulation controlled humoral balances. This concept is now, at least in principle, supported by new evidence of a direct link between dietary composition and the regulation of cytokines by the cholinergic anti-inflammatory pathway. Modern clinical studies have advocated supplementing diet with fish oil, soy oil, olive oil, and other fats to significantly increase vagus nerve activity, reduce inflammatory markers, and improve disease severity in inflammatory bowel disease, rheumatoid arthritis, and cardiovascular disease. These clinical anti-inflammatory responses may be linked to the fat-induced stimulation of the cholinergic anti-inflammatory pathway, as is the case in rats. And now it appears that a major source of systemic TNF during lethal challenges is the spleen, the source of Galen’s black bile. One can’t help but wonder: How did the ancient Greeks know?”

 

Anti-inflammatory activities of vagus nerve stimulation

The discovery by Tracey that vagus nerve stimulation inhibits inflammation by suppressing pro-inflammatory cytokine production has led to significant interest in the potential to use this approach for treating inflammatory diseases ranging from arthritis to colitis, ischemia, myocardial infarction, and congestive heart failure. Action potentials transmitted in the vagus nerve activate the efferent arm of the Inflammatory Reflex, the neural circuit that converges on the spleen to inhibit the production of TNF and other pro-inflammatory cytokines by macrophages there. This efferent arc is also known as the Cholinergic anti-inflammatory pathway Because this strategy targets the release of TNF and other pro-inflammatory cytokines, it may be possible to use vagus nerve stimulation instead of anti-inflammatory antibodies (e.g., Remicade or Enbrel) to treat inflammation. SetPoint Medical, Inc. is an early-stage medical device company, set up by Tracey, developing an implantable  neurostimulation platform for the treatment of inflammatory diseases.

Remicade and Enbrel are ultra-expensive drugs, costing about $20,000 per year.  Not surprisingly, some US autism doctors are wondering what they would do in autism.

My Conclusion

I was wondering if Kevin Tracey might be related to Jeff Tracy, in which case, can Brains please make Monty, aged 10 with ASD,  a vagus nerve stimulation device, preferably with a built-in nuclear power pack.  (I refer to a cult British TV series from the 1960s called Thunderbirds, a favourite of both Monty and his big brother, Ted.)  

 

 

IBS, IBD and Autism, leading to Cholinergic Signaling and the Vagus Nerve

This post is all about those stomach problems typical of many kids with ASD and some of their neuro-typical close relatives. Since Monty, aged 10 with ASD, does not have any of these problems, it is not something I have looked into earlier.  As you will see later in this post, by understanding the underlying science, we can move another step towards inhibiting systemic inflammation, which affects all people with ASD.
 

Irritable bowel syndrome (IBS) and Inflammatory Bowel Disease (IBD),

First of all we need to differentiate two common conditions with very similar symptoms.  IBS is the less serious condition, though it causes lots of discomfort.
 

Irritable Bowel syndrome - IBS

Irritable bowel syndrome (IBS) sufferers show no sign of disease or abnormalities when the colon is examined.

IBS does not produce the destructive inflammation found in IBD. It does not result in permanent harm to the intestines, intestinal bleeding, or the harmful complications often occurring with IBD. People with IBS are not at higher risk for colon cancer, nor are they more likely to develop IBD or other gastrointestinal diseases

The exact cause of IBS is unknown.   The most common theory is that IBS is a disorder of the interaction between the brain and the gastrointestinal tract, although there may also be abnormalities in the gut flora and immune system.

Inflammatory Bowel Disease -  IBD

Inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis

Crohn’s disease has a strong genetic component and is far more prevalent among smokers.  The usual onset is between 15 and 30 years old.

Ulcerative colitis is an auto-immune disease with no known cause.  The symptoms are very similar to Crohn’s disease, but there are some stark differences.  Ulcerative colitis is far less prevalent among smokers

Autistic Colitis / Ulcerative Colitis

The Inflammatory Bowel Disease (IBD) that seems to be relevant in Autism is ulcerative colitis, so much so that Wakefield and Krigsman sought to name a sub-type Autistic Enterocolitis.  Due to all the furore about vaccinations and autism, the research of these two gastroenterologists has been blacklisted.

Dr Krigsman has an informative website and has published some interesting research.

If you spend all day looking via the endoscope  at children with ASD, you are bound to notice a thing or two.  Ignoring what Krigsman observes is bizarre.

In case you are wondering what he does, he is going through the mouth to do an Upper Endoscopy; for the Colonoscopy he goes in from below.  He does both procedures under general anaesthetic.  That will be painless; I once had an endoscopy under general anaesthetic and you have no bad effects.  I had the misfortune to have another one without any anaesthetic, which was one of the most unpleasant experiences of my life.

Ulcerative colitis looks like a nasty condition but Krigsman finds it is generally treatable with some combination of anti-inflammatory medication, antimicrobials, probiotics, digestive enzymes and dietary restriction.

One thing he does not mention is nicotine, more of that later.

GERD

Gastroesophageal reflux disease (GERD) is a very common disease.  The acid within the stomach rises up into the esophagus and in doing so, damages its lining.

Most children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition. This is particularly true when a family history of GERD is present.   It is estimated that 15% of adults of adults are affected by GERD.

Krigsman find that in kids with ASD and their siblings, GERD is relatively common.

 

Mechanisms linking IBS and IBD to Autism

I have already written about the link between food allergies, autism and behaviour.  In those posts it was histamine released from mast cells (along with cytokines and other nasties) that was the culprit.  The treatments included antihistamines and mast cell stabilizers (Ketotifen, Intal etc).  I would presume this would fall into the IBS category.

When it comes to IBD, things get interesting.

In 1936 the Nobel Prize for Physiology was awarded to Sir Henry Dale and Otto Loewi.  One had identified the neurotransmitter acetylcholine and the other had shown how the vagus nerve releases acetylcholine to control heartbeat.

It later became apparent how important the vagus nerve is.  The vagus nerve is a modulator of inflammation throughout the body.  Acetylcholine, the principle neurotransmitter released by the vagus nerve, can exert its anti-inflammatory effect via binding to nicotinic acetylcholine receptors (nAChRs), which are expressed on macrophages and other immune cells.

 
In a recent post I showed that autistic brain samples have diminished acetylcholine and nicotinic receptor activity.  I showed how this could be corrected either by drugs that mimic acetylcholine (eg nicotine or acetylcholine) or with an acetylcholinesterase inhibitor (Galantamine or Donepezil).

I found it very interesting that IBD can be successfully treated by mild smoking (3 cigarettes a day) or with nicotine patches. 

This then connects various comorbidities in a very useful way and opens up therapeutic directions.  The vagus nerve is also key to epilepsy.  Vagus nerve stimulation is currently used to treat epilepsy and depression.

Experimentally, vagus nerve stimulation is already used in autism.  

Vagus nerve stimulation therapy inpatients with autism spectrum disorder and intractable epilepsy: results fromthe vagus nerve stimulation therapy patient outcome registry.

CONCLUSIONS:

Patients with ASD and intractable epilepsy respond as favorably as all other patients receiving VNS therapy. In addition, they may experience a number of QOL improvements, some of which exceed those classically observed following placement of a VNS device.

 

Kevin J. Tracey

A neurosurgeon and inventor, Kevin Tracey, is the man behind the inflammatory reflex.  The inflammatory reflex is a neural circuit that regulates the immune response to injury and invasion. All reflexes have an afferent and efferent arc. The Inflammatory reflex has a sensory, afferent arc, which is activated by cytokines, and a motor, or efferent arc, which transmits action potentials in the vagus nerve to suppress cytokine production. Increased signaling in the efferent arc inhibits inflammation and prevents organ damage.

We will be looking at his research and the Cholinergic anti-inflammatory pathway, in later posts

 

Epilepsy, Autism & EEGs

It is widely known that autism and epilepsy are comorbid with each other. Statistics are not very consistent, but it appears that up to 35% of people with autism will develop epilepsy and something like 30% of people with epilepsy already have autism.

My interest in epilepsy is currently just as a comorbidity, since Monty, aged 10 with ASD, has not exhibited any signs of it.  I will refer back to epilepsy in later posts when I attempt to “validate” potential autism interventions.  My logic is that if something has a positive effect across the majority of comorbidities, then I may be on to something.  For example, I found it insightful to read in a small study that nicotine patches reduced the incidence of epileptic attacks by 50%.

I recently came across an excellent, highly readable, paper that I think all parents interested in ASD should read.  It is written by an Israeli lady who is also doing some other very thoughtful research into treating autism.  The research itself is a retrospective study of EEG (Electroencephalography) tests on 56 children done in the US.

Autism and epilepsy: Cause,consequence, comorbidity, or coincidence?

EEG testing is known to be very insightful, but due to cost and availability, is rarely used in autism.  Some children, diagnosed with autism, turn out to have something different.

 Here are some highlights:

·        About 10% of children given a diagnosis of autism are found to have either a paroxysmal EEG pattern, as seen in acquired epileptic aphasia (Landau–Kleffner syndrome), or electrical status epilepticus during sleep, as seen in some children with childhood disintegrative disorder. 

·        None of the children who presented with ‘‘unlikely symptoms,’’ such as febrile convulsions, breath holding spells, and rage episodes, were diagnosed with epilepsy  

·        As many as 40% of the total group with autism had epilepsy, which was symptomatic in most children. Half of the children presented with convulsions, and they all had abnormal electroencephalograms (EEG) and were diagnosed with epilepsy.  

·        About one-quarter of the children presented with staring episodes, half of whom had epilepsy. 

·        None of the children with episodes of rage or breath holding spells had epilepsy 

o   This is the opposite of what many experts assume 

·       Our results, which indicate that clinical suspicion for epilepsy should be high if there is a history of convulsion and staring episodes, are in agreement with other studies showing that nearly all autistic children with seizures also exhibit epileptiform activity on electroencephalograms

 

A short film

Here is a parent-made film, showing the EEG procedure.

Conclusion

If you live in an area where EEGs are on offer, (California seems to be one good place to live) then it looks like a very smart test to have done.  If you were thinking your child’s tantrums and raging were indicative of future epilepsy, you can breathe again. 

 

Autism - Drugs and Supplements that actually do work

Following requests for more information about supplements and drugs that really do seem to help with autistic behaviours, I have updated my "Top Tips" page.  Here is the updated information for anyone who is interested.

You will find links to the science behind all these ideas in various posts on my blog.  Many of these are "off label" applications, since there are no treatments yet  licensed for autism.

From comments received, it is clear people want "supplements" because they are available without prescription.  The rules vary widely from country to country.  A supplement in the US may be a drug in the UK and vica versa.  Or even a drug in UK is a supplement in Germany.  Just do some research on the internet.

 

Since I am not a doctor, this is not medical advice.  Since your doctor does not read the autism research, he/she will probably not be able to help you.



Anti-oxidants

Science established some time ago that oxidative stress plays a central role in autism.

There is one widely available antioxidant that is highly effective. It is called NAC  (N-Acetyl Cysteine) and is available without prescription via the internet (from Amazon for example) or many pharmacies.

The result is very dose dependent.  Some people take time to adjust to it, due to mild stomach irritation.  Most supplements come in 600mg capsules.  Two capsules has an effect, but the effect becomes larger as you increase to about 3g per day (i.e. 5 capsules per day).  You should observe a great reduction in obsessive behaviours within a few days.  Then new good behaviours should emerge quite rapidly.  Speech increases.

To read about this on the blog, go to the list of labels and click on GSH.


Neuroprotection and anti-inflammatory

The research is conclusive that there is chronic neuroinflammation in autism.  The anti-oxidant will contribute to managing this, but an anti-inflammatory agent that can reach the brain will give additional benefit.

This blog has highlighted research to show that widely used drugs called Statins have a secondary effect that reduces neuroinflammation.

The Statin I choose is Atorvastatin, but Simvastatin also looks a good choice.  In the UK Simvastatin is available without prescription.

I use 10mg Atorvastatin.  The behavioural improvement was visible within two days.  New behaviours involving initiative emerge.

To read about this just click on statins in the list of labels.


GABA Neurotransmitter

Research going on for 10 years in France has shown that the widely used diuretic Bumetanide reduces the level of chloride in the brain.  The high level of chloride causes the brain neurotransmitter GABA to malfunction in autism and babies with neonatal seizures.

The effect of taking 1mg of Bumetanide has a dramatic behavioural effect.  It improves the child's ability to control himself.  He appears more "present" and not in his own world, this results in more interaction with his peers and an improvement in mood and a general increase in happiness.  Speech increases.

To read about this just click on bumetanide in the list of labels.


Autsim flare-ups  -  over activated mast cell response to allergens

Violent episodes may sometimes be provoked by an allergic reaction caused by so-called, mast cells.  What in a typical child might just cause a runny nose or sneezing, may cause violent/aggressive behaviour in a child with ASD.

A cheap over the counter drug drug called Claritin, acts as an anti-histamine H1 antagonist, it will subdue the allergic reaction within a few tens of minutes.

Many people do not respond to a particular anti-histamine, if one does not work just try a different one.  Your pharmacist can suggest an alternative (levoceterizine for example).  The brand names vary by country.

If the child complains about creepy feelings on his/her legs this would be an indicator or this type of allergic reaction.

There are other serious behavioural causes of self injury, but if the child is normally well behaved and under self control, sudden outbursts may be being triggered by mast cells.  Read all about mast cell research here.


Lower Serotonin Levels 

High serotonin levels are a known biomarker of autism;  lowering them does indeed appear to reduce autistic behaviours.   

You can do this via diet.  Avoid food known to raise serotonin, for example bananas and caffeine.  A low carbohydrate, high protein diet is known to lower serotonin levels.  The Atkins (induction phase) diet and the Ketogenic diet are also known to lower serotonin levels.  You will know if it is working because lowering serotonin increases appetite, your child should put on weight.

The easier way is with a serotonin antagonist like Periactin, often prescribed in the US to underweight children.  Periactin is a first generation antihistamine drug, so it will cause drowsiness.  It is known to be antiserotonergeric.  It is available OTC in some countries.

Read the post on Serotonin here.

Increase acetylcholine levels

The story about acetylcholine is quite complex, and the full post about it is here.

To increase acetylcholine there are various options.  The drug options shown to be effective work by affecting the enzyme acetylcholinesterase.  The two drugs shown to be effective in autism are Galantamine and Donepzil.  These are prescription drugs.

The same effect is possible using a nicotine patch, or even potentially by using nicotine gum.  One quarter of a 7mg patch applied for 6-8 hours is suggested by one US doctor.

The other method, that is sometimes combined with Donepzil, is to give the dietary supplement choline, which is widely available.

 

High potassium diet reduces sensory overload

If your child with ASD, like most, has a problem with sensory issues like sound, light, smell etc, there is a dietary solution.  Increase potassium in his/her diet - eat more bananas, oranges, kiwis, potatoes etc.  You can also use potassium + magnesium supplements.  If you live in the US, beware of these supplements, they are very weak.  A banana has 500mg of potassium,  US supplements contains up to 100mg, UK supplements are up to 200mg.  Magnesium plays a role as well, it is needed to maintain potassium levels.  I use a cheap French supplement with 500mg Potassium and 150 mg Magnesium, taken half AM and half PM.  Potassium supplements can irritate the stomach, but they do modify autistic behaviours for the better.

Potassium ion channels (like Kir 4.1) play a role in the brain in both ASD and epilepsy.  It is very complicated and still not fully understood, but it WORKS! 

 

 

Parental Placebo Effect in Autism

I have not met that many parents of kids with ASD; from those that I have met it, is clear that often the therapies applied are limited by the more skeptical parent.  There really are no therapies that everyone agrees on.

So it is no surprise that sometimes my wife doubts the value of the therapies I am sharing in this blog.  She would far rather have a homeopathic wonder cure, than use drugs or ABA.  I saw today as an opportunity.  Monty, aged 10 with ASD, had been up half of the night with a virus and his Mum said "don't give him any of your medicines"; "OK" I replied.

By 2pm Monty was in an increasingly bad mood, frustrated,  exhibiting obsessive repetitive behaviours and showing warning signs of mild self injury.

So I mixed him up a Peter cocktail (1.2g NAC, 10 mg atorvastatin and 1mg of bumetanide) in orange juice.  Within 10 minutes things started to change.  Facial expression switched from anger to contented and, most telling of all, he sat at the piano and started to play.  I could not have hoped for a better result. 

After an hour I asked Mum, if she noticed the transformation.  Yes she had and agreed it was remarkable.


Placebo Effect

It is clear that the more involved the parent becomes, the greater is the risk of seeing what you want to see, rather than what is there.  This why nobody generally listens to parents and indeed why doctors are not supposed to treat their children.

It is always good to have a reality check.

I can now move forward to my serotonin and acetylcholine interventions, in the knowledge that previous interventions have past their critical test.