Matching Pathology with Behaviours in Autism

 
I think the wrong people are in charge of autism research; forensic scientists or even air-crash investigators might do much better.

We have seen in this blog that many drugs have a positive effect in specific types of autism. In many, but not all cases, the mechanism of that drug and its effect on the pathology of autism is understood. 

If you have followed an ABA programme, you will know that an experienced autism therapist would very easily be able to give a long list of behavioral issues that occur in varying combinations among her clients.

From reading the research, it is clear that the people who understand the biology, often do not understand the psychology and the behavioral issues they are trying to treat - but perhaps they should.  Only then can you target treatments for specific problems.  There can be no single drug for autism, but there can be a drug for obsessive behaviours, and another for self-injury.  You cannot say a low dose of X helps with social cognition, but for aggression you need a high dose of X.  To me at least, this is complete nonsense and shows a complete failure to understand the underlying psychology.

Just as most people struggle with all the jargon of biochemistry, I suppose the medical researchers fail to grasp the nuances of the psychologists’ jargon.  We need to match both sides, because we need science to solve a complex problem that presents itself in hard to describe, odd behaviours and not as nice neat equation to solve.

It is difficult to accurately describe and quantify the behavioral issues of a child with ASD.  It is very hard for a parent, but it is definitely possible for a psychologist using tools like ABBLS and others.  Then you can move towards seeing precisely what behavioral effects a drug has and stop expecting improvements in areas that are completely unrelated.

Having produced the list of deficit areas you can then try and understand the underlying pathology as to why a drug is effective.

I make no claims to have great expertise in this area, but it looks like nobody else does either.

Here are some examples:

Obsessions

Obsessive compulsive behaviours are well known to affect some people with autism.  This is a type of behaviour that most people would understand and would notice if they saw it, although they might find it hard to quantify.

Oxidative stress is a measurable pathological condition that is present in some people with autism.  Oxidative stress exists in other medical conditions and has a known therapy, an antioxidant like NAC.

By chance, it was found that treating someone with obsessive compulsive behaviours with NAC, greatly reduced those behaviours.

In the case of people with autism and obsessive compulsive behaviours, it would be good to know if other deficit areas were also impacted.  Clearly, taking away the obsessive compulsive behaviours, you would expect to see a general improvement, since the person is now much calmer and better able to function and so many behaviours should improve to a certain extent.  But does NAC reduce head banging and other SIB?  I think not.

So we can then conclude that oxidative stress triggers obsessive compulsive behaviours and NAC should be prescribed.  Oxidative stress may exist to a lesser degree in subjects that do not (yet) display obsessive behaviours.

 

Anxiety

I have not tried to treat anxiety in autism, but many people have.  Anxiety lies on the axis running from happy to depressed.  By raising the level of serotonin in the brain you move from depressed towards happy.  The antidepressant Prozac is given to many children with ASD to reduce anxiety. Prozac is a selective serotonin reuptake inhibitor (SSRI).

The problem with such drugs is their side effects and use can result in dependency.  If that was not the case, the advice would be simple.

I think a better and safer way exists to raise brain serotonin levels in autism.

Seizures and SIB

Not all people with SIB (Self-injurious Behavior) have seizures, but I expect many people with seizures have SIB.  Both conditions appear to be channelopathies (ion channel/transporter dysfunctions); but there is more to it than that, what triggers the channelopathy?  It would seem that in both cases the message comes via inflammatory signalling from the vagus nerve.  So to treat these conditions you can block the inflammatory signalling (vagus nerve stimulation), or you can treat the resulting ion channel/transporter dysfunction in the brain; doing both may be quite unnecessary.

If you have neither seizures nor SIB, then using any of the above therapies would be of little effect.

Many open questions remain

All is not clear; for example, where does hyperactivity fit in?  Where does anger fit in?  Is anger just a mild version of SIB?  It is extreme anxiety?  Is it something entirely different?

An interesting finding of mine was that showing affection appears to be pathologically related to self-confidence and lack of inhibition.  The pathology linking them appears to be neuroinflammation, or rather the control of it.

 

 

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.

 

 

 

 

 

Autism, a Dynamic Encephalopathy, Indeed

 

With a title like that, not many people will stumble upon this post with Google.

So, for the hard-core of readers, today I am going to develop an idea of Martha Herbert, the pediatric neuroscientist from Harvard, who writes a lot about autism.

Incidentally, most researchers do not like publicity, and particularly those looking at autism.  Martha, herself makes some side remarks as to why this is; as I suggested in earlier posts it dates back 10+ years to a certain Dr Wakefield.

“A further barrier to considering the body’s impact on the brain was the reaction to the work of Wakefield, who argued not only that there was a link  between  autism  and  vaccines  but  also  that  this  link was mediated through the gastrointestinal system. For the better part of a decade any attempt to discuss gastrointestinal or immune issues with autism was construed as a support of Wakefield’s vaccine hypothesis, and it was difficult to discuss, let alone get funding for, clinical or research observations about these problems.  One way around the essentially taboo character of somatic problems in autism was to treat them as coincidental symptoms. For example, one could  talk about gut problems provided one made  it clear that they did not cause the autism in the brain. Improvement after treatment of gut problems, which is often observed, would then be explained as a consequence of reduction of pain and discomfort, but not of any direct impact on core brain mechanisms generating autistic behaviors.”

Another fearless autism researcher, not shy to voice his opinions by blog and tweet, is Paul Whiteley, in Sunderland.   Paul is very much a believer in the role the gut/diet in autism, he and Paul Shattock are the driving force behind the gluten and casein free diet as a therapy for autism.  Given what Martha writes above, and the association between Shattock and Wakefield, is it surprising that the GCF diet remains on the fringes?  I know some parents who wholly endorse it.

Here is a link to one of Martha’s recent works, for Herbert fans:-

From Static Genetic Brain Defect to Dynamic Gene- Environment- Modulated Pathophysiology

Dynamic Encephalopathy

It was Martha who called autism a dynamic Encephalopathy.  Encephalopathy just means a brain disease.

What she means is that over time autism changes, day to day and year to year.  Just as during fever, autism symptoms may wane, other environmental provocations may cause flare ups.  With age come hormonal changes that will inevitably change the central hormonal homeostasis, I hope for the better, as generally is the case.

Other than being a fancy word, Encephalopathy, is probably a much better word than autism.  There are many types of Encephalopathy and there are multiple causes, it refers to a syndrome of global brain dysfunction; this syndrome can have many different organic and inorganic causes.  As with autism the hallmark of encephalopathy is an altered mental state.

 
Forget Autism think Encephalopathy

If you have not already opened up Wikipedia, I suggest you do.

http://en.wikipedia.org/wiki/Encephalopathy

From my desk research and primary research, I know that one factor behind this encephalophy is chronic inflammation, otherwise known as neuroinflammation.

At this point, we should look at what neuroscience can tell us about neuroinflammation

The Dana Foundation is a private philanthropic organization committed to advancing brain research.  Founded in 1950 and with $230+ million in assets I think they should be a good source.  Here  is an excellent paper, that is written for non-scientists. 

 Consequences of the Inflamed Brain

Among the many interesting insights are these:- 

 “Until recently the CNS and peripheral immune sys­tem were thought to operate independently.”

“However, new research has led to important advances in our understanding of how immune-related events in the periphery can influence CNS processes, thereby altering cognition, mood, and behavior, and these advances are suggesting that inflammation may have important long term implica­tions for the brain.”

 “Inflammation in the body can lead to inflammation in the brain”

“The same cytokines that participate in produc­ing the inflammatory response in the body also initiate the communication process to the CNS. They accumu­late in the bloodstream and thereby travel to the brain”

“They cross into the brain in regions where the barrier is weak, and they bind to receptors on the insides of the cerebral vascular blood vessels, thereby inducing the production of soluble mediators within the epithelial cells that can cross into the brain.”

“In addition, there are neural as well as blood-borne communication routes. For example, there are cytokine receptors on nerves, such as the vagus, that innervate peripheral immune organs, and these nerves communicate to the brain and are activated during infection.”

“During a normal infection, neuroinflammation and the resulting adaptive sickness behaviors persist only for several days. However, if these responses become exaggerated or prolonged, the outcomes may well become estab­lished, leading to cognitive impairment instead of brief memory disruption,”

 “… physiology can become pathology when a set of processes designed to be rela­tively brief becomes prolonged.”

“However, peripheral inflammation is highly complex and involves many immune cells and their products. Existing anti-inflammatory drugs often target only one of these. For example, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, inhibit only a hor­mone, prostaglandins, leaving other actors in inflam­mation (cytokines, chemokines, etc.) untouched.”

“A second way that central neuroinflammation could be prolonged is less obvious. The CNS may come to over-respond to the same signal from the peripheral immune system. As noted above, microglia and the cytokines they produce when activated are at the core of the neuroinflammatory response that pro­duces sickness behaviors. If microglia were to become “sensitized,” which means they respond in exagger­ated or prolonged fashion, then sickness behaviors would become intensified and prolonged—pathology instead of physiology.”

“Most encouragingly, studies in numerous animal models show that the development and expression of chronic pain can be blocked with drugs that inhibit either microglial activation within the spinal cord, or the inflammatory cytokines that microglia produce.”

“In addition, microglia also can become sensi­tized without a prolonged peripheral inflammation. For example, aging appears to sensitize microglia so that microglia, particularly in the hippocampus, respond in exaggerated fashion to input. Thus, neuroinflammation produced by surgery, peripheral infection, and the like, is greatly exaggerated in aged subjects. Correspond­ingly, aging also augments the chances of depressive behaviors, cognitive impairments, and pain produced by peripheral inflammatory events. Encouragingly, however, some human studies show that inhibition of microglia and cytokines in the brain blunts such patho­logical outcomes.”

“Blockade of inflammation in the periphery and microglial activation/cytokine action in the CNS, may well become important therapies for a range of disorders not often thought of as mediated by these factors.”

Conclusion

There is nothing new to me in the Dana paper; this in itself is rather a shock.  If you have followed my blog from the start, you should also not be surprised; but I have never seen quite so much scientific good sense written in just four pages.  It tells me a lot and reassures me that I am on the right track with my cytokine blocking therapies, mast cell stabilization and somewhat far fetched, vagus nerve stimmulation ideas.

There are other science-based "inflammation control" therapies and I will be writing about them later.

P.S.  Why no Dean’s List for Martha?

Regular readers of my blog may have noticed that a small number of the several hundred researchers, whose papers are discussed here, are given a pat on the back and moved to the Dean’s List.  Why not Martha?

There is a good reason.  For many years Martha keeps going on about the “Fever Effect” in autism.  This is the strange phenomenon where autistic behaviours abate during fever, i.e. sickness associated with high temperature.  I myself witness this every time Monty, aged 10 with ASD, has a high temperature.  I think that conclusively solving this, might indeed tell us something profound about this wide phenotype of autism.

I think with the resources of Harvard, she should be able to figure this out.  Her TRANSCEND Program gives her a pool of research subjects.

Peter has just one mouse model of autism and, at the age of 10, he is getting a big to be called a mouse.

So Martha, put aside the MRIs and the calcium channelopathies, if you figure it out before me, you get on the Dean’s List.

If I can prove the underlying reason, I will put myself on the Dean’s List.

 

Pregnenolone - an effective OTC anti-inflammatory therapy for autism?

Pregnenolone is the true mother hormone, being derived from cholesterol and the precursor of all steroid hormones. 

It is a potent anti-inflammatory agent.  It is  also claimed that supplementing with Pregnenolone will increase IGF-1, which I found interesting, given my very recent post on IGF-1 therapy in autism.  

In the late 1940’s and 1950’s successful studies were carried out into the use of Pregnenolone in the inflammatory condition of arthritis. 

As we found in recent posts regarding the vagus nerve, all inflammatory conditions (autism included) share much in common.  A treatment that is effective against neuroinflammation in one condition should be tested in the others.

Interest was high in Pregnenolone because it was cheap and free of troubling side effects.  Alternative steroid treatments, for example with Prednisone, can have major side effects.

In an earlier post I referred to the successful use of the steroid Prednisone in ASD in the US.  Wider adoption, and the lack of clinical trials, are held back by the fear of side effects.

Promoting Speech in a 7 year old Non-verbal Child with Autism

"... Dr Michael Chez, of the Pediatric Neurology and Autism Neurodevelopmental Program, Sutter Neuroscience Institute in Sacramento California.  He wrote a paper I have already referred to in this blog called:-

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

In that paper he talks of his knowledge of the effects of prednisone on children with autism and he mentions the dosage used.

Treatment was usually prescribed with daily prednisone doses of 2 mg/kg/day for 3 to 6 months. Limitations to therapy were usually Cushingoid side effects. As in other chronic conditions requiring steroids, pulse dosing was tried with steroids in the form of prednisone or prednisolone at 5 to 10 mg/kg twice per week.

Long-term success with no dependence or minimal Cushingoid effects has been noted in several hundred patients treated in this manner (Chez, unpublished data, personal communication).

In all, 17 of 32 patients showed response to prednisone after 2 to 4 months of treatment (53%). Improvements were seen on EEG and in language skills of the patients. Other steroid treatment series of regressed language in autistic spectrum patients diagnosed with LKS variant showed improved language with pulse-dose steroids."

 Pregnenolone Studies

Pregnenolone in the Treatment of Rheumatoid Arthritis

Pregnenolone in Rheumatoid Arthritis

If effect, Pregnenolone seems to be a weaker, but much safer, alternative to Prednisone.  Some people with arthritis currently take it. 

Pregnenolone is indeed already one of hundreds of fringe treatments for autism.  There are some very good reasons why it should be effective. 

Stanford University are currently running a clinical trial of Pregnenolone on adults with autism. It is the same researcher that worked on their study on NAC in children with autism.  It is nice to know that the adults with ASD have not been forgotten; after all, children have a habit of growing up.

A Study of Pregnenolone in the Treatment of Individuals With Autism

Conclusion

The next time I receive a question on this blog asking for a potentially effective OTC anti-neuroinflammatory “supplement” for autism, I will know what to suggest trying.

Fibromyalgia and, perhaps, What Happened to the Missing Females with Autism

This post is about a condition about Fibromyalgia, a condition that affects 2-4% of the population. It affects women eight times more often than men, but it does, bizarrely, appear to be related to autism and is seen by some as a comorbidity.  I would go further and suggest that perhaps I have stumbled upon the missing females with autism. 

When you look at all the proposed drugs and supplements, there is a 90% overlap between the two conditions, even things like low dose naltrexone and flavonoids, like quercetin, crop up.

As we have seen earlier in this blog, autism is a disease related to the auto-immune system and inflammatory pathways.  There are many other diseases with similar origins, one example being arthritis.  Fibromyalgia tends to get lumped together with arthritis.  Families with autism present tend to have higher levels of arthritis and there are even some overlapping therapies, such as vagus nerve stimulation.

Fibromyalgia caught my attention, because it seems to be uncannily closely related to autism, but there are some distinct differences.  Classic “full-on” fibromyalgia is a disease about pain, whereas in autism people tend to have a high pain threshold.  Nonetheless, if you Google “Fibromyalgia with Autism” you will find no shortage of people suffering from both and pondering a connection.

Comorbidities are interesting, because they can indicate possible new therapies.  The people researching fibromyalgia are not generally the same people as the autism researchers.  The underlying pathologies though are very likely overlapping, even though neither is fully understood.

Fibromyalgia is neither degenerative nor curable, but it is treatable.

Here is a link to an article by a US doctor who came to the same conclusion.  (The article itself is not great)

Symptoms of Fibromyalgia

We can split these into two categories, pain-related and pain-unrelated.  In the case of autism we should look at pain-unrelated, but in the case of relatives we should look at both.  You will probably be able to diagnose a non-autistic family member with symptoms of this syndrome.

 
Pain-related:-

·        Widespread muscle pain and joint pain, the effects of these symptoms varies from person to person and from day to day.  Many people have flare-ups.  There are specific pain areas, and these are shown below:

 

·        Long-term studies suggest that it is not progressive, it does not cause permanent damage to your muscles, bones, joints or organs.

 

Pain-unrelated:-

This is a long list and typically only some will apply to any one person:-

·        Cognitive dysfunction, such as:

o   Difficulty following directions when driving

o   Losing your train of thought in the middle of a sentence

o   Difficulty paying attention

o   Memory problems

o   Difficulty expressing ideas in words

·        Depression, anxiety, irritability,  overreaction, anger outbursts, unpredictable mood swings, phobias and personality changes

·        Difficulty swallowing

·        Headaches

·        Restless leg syndrome

·        Sensitivity to the cold, and/or having cold hands and feet

·        Palpitations

·        Chest pain and costochondritis    

·        Sensitivity to light and noise intolerance.

·        Clumsy walking, dropping things

·        Hair loss

Fibromyalgia vs autism

There are some other similarities/differences with autism.

·        It often takes years to get a diagnosis and some doctors do not believe the condition exists

·        There is a specialist doctor that should know about it – the Rheumatologist, although Neurologists sometimes get involved

·        It is not curable, but it is treatable

·        It is usually diagnosed on very subjective measures

·        A blood test does now exist in the US  - the FM/a test  

The firm with the blood test is called, interestingly, “Epigenetics”.  If you make a blood test for Fibromyalgia, there is a good chance that the same researchers could develop one for autism.  They are measuring the level of pro-inflammatory cytokines.

The test is expensive, about $750.  Who knows how accurate the result is; they claim 99%.

In the UK, the National Health Service maintains that no test for Fibromyalgia exists.

A Neuro-immuno-endocrine disorder

Evidence exists that fibromyalgia is a neuro-immuno-endocrine disorder. Elevations in substance P, IL-6 and IL-8 as well as corticotropin-releasing hormone have been found in the cerebral spinal fluid of fibromyalgia suffering individuals. Increased numbers of mast cell numbers have been found in skin biopsies of some individuals with fibromyalgia.

Theoharides, who I have quoted extensively in early post on mast cells and autism, appears here too:- 

Fibromyalgia--new concepts of pathogenesis and treatment.

Lucas HJ, Brauch CM, Settas L, Theoharides TC.

Abstract

Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.

Treatment

Classic treatment involves tricyclic antidepressants, which are actually very closely related to the early antihistamine drugs. 

Even though low brain serotonin is a feature of the disease, counter-intuitively, it has been found that serotonin-3 receptor antagonists are effective; this is the opposite of what was expected.  Tropisetron is a favoured antagonist, but there are several others.  Tropisetron is also a α₇-nicotinic receptor agonist, which you may recall, I highlighted as interesting in posts on the cholinergic system and autism.

Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.

This blog is about autism, so let us go back to a previous paper I looked at.

Nicotinic Acetylcholine Receptor Alterations in Autism Spectrum Disorders – Biomarkers and Therapeutic Targets

 

In that paper tropisetron is put forward as a potential autism treatment.

 

10.1.2 ᾳ7 nAChRs

It is possible to use ᾳ7 nAChR agonists to treat neuroinflammation in ASD. There is strong evidence that activation of the ᾳ7 nAChR expressed on monocytes and macrophage, by inhibiting NF-kappaB nuclear translocation, suppresses cytokine release by them, and that this cholinergic anti-inflammatory pathway that provides a bidirectional link between the nervous and immune system, inhibits the innate immune response. Hence, a reasonable case can be made for the use of ᾳ7 nAChR agonists to treat neuroinflammation in ASD.

A second candidate drug, Tropisetron is a partial agonist of the ᾳ7 nAChR. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. In a clinical trial with 33 schizophrenic patients administration of tropisetron, without placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. In mice, the early postnatal period represents a critical time window essential for brain development. The administration of tropisetron from postnatal days 2-12

(P2-P12) in mice did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays.

 

It is the non-conventional treatments that overlap with autism, things like GH, IGF-1 and low dose naltrexone etc.  The interesting therapies relate to treating the non-pain symptoms. There are many such therapies and some have been used for decades, one or two may be interesting for autism; they may indeed be more effective in autism that in fibromyalgia.  There is even an overlap with therapies I am already investigating.