Verapamil for a Broader sub-group of Autism and even Diabetes?

This blog is about science rather than medicine, and believe me there is a much bigger difference than you might hope for.

Many aspects of the research literature indicate the potential of certain calcium channel blockers, like Verapamil, to be useful in treating autism.  As we have seen, there are many different causes of autism and what treatment works in one type may be totally ineffective in another type.

For almost a year Monty, now age 11 with ASD, has taken Verapamil to control the behavioural effects of allergy that are driven by so called “mast cell degranulation”.  His pollen allergy makes his summertime behaviour dramatically worse; a reaction that is almost entirely reversed by Verapamil.

In my page in this blog on Allergies and Autism I raised the question as to whether Verapamil would be effective in treating the many people with autism who have food allergies leading to gastrointestinal (GI) problems.  Many people with autism have symptoms like Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD) and these are widely associated with worsening autistic behaviours.  Monty has no GI issues or food intolerance.  I was very interested to receive some lengthy comments from a mother with a son who does have autism plus GI problems.  She found Verapamil highly effective in treating both his GI problems and the autism.  This is rather significant, since while I do receive the odd comment that H1 antihistamines have an unexpected beneficial effect on autism, which supports some of my own findings and theories, the issue of GI problems is very common in autism.  Could a pill called Verapamil be the little wonder for them as well?  The science does indeed support this, even if current medicine does not.

 

How can medicine be so disconnected from science?  It does seem to happen far more often than it should.

I did wonder if I was missing something about Verapamil.  It is an L-type calcium channel blocker and in autism there is a known genetic dysfunction (CACNA1C) that affects the calcium channel (Cav1.2) blocked by Verapamil.  It also turns out that Verapamil has been shown to be a highly effective mast cell stabilizer.  I did a little more digging and found something very surprising, the effect of Verapamil on the pancreas.  The pancreas makes all kinds of enzymes as well as insulin.  In some people with an auto-immune dysfunction the body destroys its own insulin producing cells and diabetes results.  In some people with autism (also an auto-immune condition) the pancreas seems not produce some of the other enzymes and there are various DAN-type treatments for this; and the new CUREMARK drug CM-AT seems to target this dysfunction.

Science has remarkably shown that Verapamil had the potential to reverse diabetes, if intervention is early.  Given that type 1 and type 2 diabetes are becoming increasingly common and account for a substantial part of national healthcare costs, it seem odd that medicine has not taken full note.

Preventing β-Cell Loss and Diabetes With Calcium Channel Blockers

It appears that older people on Verapamil for hypertension, strangely do not develop type 2 diabetes, which supports the claim for Verapamil.

There is no mystery as to why this is happening.  Calcium channels are widely expressed in pancreas, just as they are in the heart and the brain.  The effect of aberrant calcium channel signalling does no good for the brain in autism and in some other people, with a tendency to auto-immune problems, it would appear to be the pancreas that suffers.

You will recall that autism is amongst, other things, an auto-immune condition.  If you look at the extended family you will likely notice other auto-immune conditions like diabetes, thyroid problems, and arthritis.  (I would myself add fibromyalgia and even some types of chronic headaches to this list)

Recall that several drugs that help autism have a beneficial effect in diabetes and that the key type 2 drug for diabetes seems to have a positive effect on autism.

PPAR alpha, beta and gamma in Autism, Heart Disease and Diabetes

In the above post we saw that PPAR gamma (PPARγ) is a nuclear hormone receptor which modulates insulin sensitivity.  The following autism study looked at the effect of a common diabetes drug, pioglitazone (Actos), an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile. 
 

Effect of pioglitazone treatment on behavioral symptoms in autistic children

Pioglitazone is currently in Phase 2 trials for autism.

Another comorbidity of autism that is an auto-immune condition is asthma.  Here again, Verapamil was shown many years ago to hold promise.

Verapamil in the prophylaxis of bronchial asthma

A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced bronchoconstriction in 8 out of 16 asthmatic subjects (maximum increase in PD_20FEVHi 416%). There was still significant protection (Δ PD_20FEV1Hi>100%) in the responders 5 h after the oral dose.

I also noted in earlier posts that anti-oxidants seem to reduce the insulin required by diabetics and also improves one of the big problems that occurs along with diabetes that is peripheral neuropathy.  These antioxidants, like ALA, NAC, Thioctacid etc are also chelators of heavy metals.  While the planned study of chelators in autism in the US was effectively “banned”, a large study was carried out on heart patients.  Chelation was shown to be remarkably beneficial, but chelation is really just a shock dose of antioxidants.

Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction The TACT Randomized Trial

My take on this is that in many medical conditions, oxidative stress is present and therefore any antioxidant will be beneficial, but some more so than others.  In the well-researched world of asthma they concluded that the most potent, safe antioxidant was NAC (N-acetylcysteine).  NAC is my choice for autism.

Conclusion

If you have autism and suffer from chronic GI problems, Verapamil might well offer significant relief.

If you have unexplained autism flare-ups, like aggression, in summer this may well be driven by a pollen allergy, Verapamil is likely to help.

If your older relative has hypertension already and looks likely to be heading towards type 2 diabetes, maybe suggest they talk to their doctor about Verapamil;  it may well treat both.

Incidentally, if you have a child with autism and suffer yourself from chronic headaches or fibromyalgia, you might want to try some Verapamil yourself.

Verapamil is a very cheap generic drug; one tablet cost a couple of cents/pence. 

Opinion

I continue to be surprised how far medicine is behind science.

In the case of autism there is now a great deal of “actionable” research that is available for anyone to read.  This blog is about autism, but it seems that in many other areas of medicine the same is true, for example diabetes and types of cancer.   

The idea is that you should wait for clinical trials.  But who do you think is going to do them? There is no financial incentive for drug firms to do trials on old generic drugs for new uses.  Prepare for a long wait.

The medical practitioners involved with autism, mainly psychiatrists if anyone, show little interest in any novel treatment that has not yet been approved.  With such little interest from clinicians, novel treatments will remain well kept secrets for decades to come.

The “alternative” practitioners dealing with autism, like DAN doctors, are mainly in the US; but they are not fully grounded in science and seem overly interested in unorthodox expensive lab tests and costly supplements.

So you really do have to figure out autism for yourself, if you want to control it.  

Traumatic Brain Injury and Autism, linked again, but not in a good way

It came as no surprise to me that many people involved in high profile mass shootings suffer from mild autism (Asperger’s).  What did surprise me was that so many people with TBI (Traumatic Brain Injury) also commit such crimes.  Indeed in a recent study (see later) of 239 killers, 28% appear to have autism and 21% suffered from TBI.

Indeed the name used by the Austrian, Hans Asperger, in 1943 for his newly identified condition was “Autistic Psychopathy”, it was only many decades later when his work was discovered for the English-speaking world by Lorna Wing in 1981, that the condition became known as Asperger’s.  Wing did not like the term “Autistic Psychopathy” that Asperger had chosen, because she thought it would apply sociopathic (violent) behaviour to the lay public.

Wing recently passed away and the New York Times wrote a nice article about her.

Dr. Lorna Wing, Who Broadened Views of Autism, Dies at 85

Her paper, that first established Asperger’s syndrome, is here:-

Asperger’s syndrome a clinical account

Since this paper was published only in 1981, it is hardly surprising that so few older adults have been diagnosed with Asperger’s.  Indeed it was a full ten years later, in 1991, that an authoritative English translation of Asperger's work was made by Uta Frith; before that Asperger’s Syndrome (AS) remained virtually unknown.

As we have noted before, Psychiatrists and Psychologists like to take their time; no Space Race or Manhattan Project in their little world.  Still, half a century is pretty slow.

People suggesting an autism “epidemic” might take note that only 25 years ago, absolutely nobody bothered to diagnose mild cases of autism, they did not even have a word for it.  Those of you still wondering why your doctor still knows so little about autism, might also take note.

Now I understand why there were no Aspies in my school, when I was a child.  They had not been invented.  I had assumed that Asperger’s syndrome was of the same era as the man himself, but Hans Asperger died in 1980.

I had no idea it took Psychiatrists, Psychologists, and yes, Doctors, half a century to absorb, accept, and begin to act on a new idea;  all because Asperger spoke/wrote in that “extremely rare” German language.  Incidentally, 50 million Americans claim German ancestry, not to mention that the British royal family is actually German; the House of Windsor is really the House of Saxe-Coburg-Gotha, before some image building took place in 1917 during WW1.

So don’t raise your expectations of these people too high, for the next half century.  Hopefully they have figured out Google Translate.

Here is the Pediatrician, Professor Hans Asperger at work in Austria; nice drawing on the black board:-

  

Die„Autistischen Psychopathen“ im Kindesalter (1943)

Autistic Psychopathy in Childhood  1943 (translated from Germanin 1991)

Asperger and his Syndrome, by Uta Frith

  

Asperger’s (Autistic  Psychopathy) and  TBI among Mass Murderers

In the recent study of 239 mass murderers almost 50% had either ASD or head injury /TBI, the other half suffered from “psychological stresses”.

Neuro-developmental and psychosocial risk factors in serial killers and mass murderers

At least the author has clearly read about Hans Asperger, he suggests a new diagnosis, Criminal Autistic Psychopathy, as a subcategory of Asperger's syndrome.

I will not dwell on the murder angle, other than to say that perhaps if people with Asperger’s were actively included at school, they would ultimately lead happier and more successful lives.  The percentage that currently go on to have very violent thoughts, might not then do so, and the tiny percentage of those might not act on those very thoughts.

I should point out that I do not find it odd at all that the boy with Asperger’s in my elder son’s class keeps telling him “I will kill you and your parents”, to which Ted, now 14,  says “but I won’t let you” and the response is “but I will wait until you are not there”.  I am not seriously worried that he will do this, but if I was his parent, I would be very concerned that he says/thinks such things.

Fortunately there are no serial killers with Classic Autism, so no need to lock up Ted’s brother.

ASD, TBI & PTSD

We have come across TBI several times in this blog, and I note that many people coming to this blog are TBI sufferers.

Both ASD and TBI are associated various degrees of mood disorder.  These feelings are driven by neurological changes that are usually ignored, or treated rather crudely with drugs that rarely seem to work entirely as intended. 

I think the world of autism could learn much from the mood disorders that follow TBI.

Epilepsy occurs very frequently in both ASD and TBI.

The third condition that we might usefully consider is Post Traumatic Stress Disorder (PTSD).  This condition is also associated with severely affected mood.  Army veterans returning from recent conflicts can be greatly affected by PTSD.  We came across the military type of PTSD in the post about the hormone TRH.  One of the many roles of TRH in the body seems to be linked to mood, and very specifically suicide.  The US military is funding development of a TRH nasal spray to reduce the incidence of suicide.  They cannot give antidepressants, like Prozac, because a well-known side effect is suicidal thought.  TRH is included in my autism PolyPill.

People with Asperger’s do have an elevated risk of suicide, another reason to sniff some TRH, perhaps?

The Link between ASD, TBI and PTSD

The above conditions are very different, but they share some similar symptoms relating to mood disorders.  By understanding the neurological underpinnings of the mood disorder in one condition, we might well learn something useful for the others.

The research into TBI seems to focus on better surviving the first few hours.  We saw in earlier posts that by giving intravenously either statins, or the female hormone progesterone, in the Emergency Room, there was a marked increase in survivability.  Progesterone and statins are both highly neuroprotective.

When Michael Schumacher had his TBI in a recent skiing accident, I was saying to myself “give him progesterone”, I very much doubt the French neurologists did.  They probably do not read American/English research.

In the case of autism, very recent research has shown an excess of male hormones in the amniotic fluid of mothers who give birth to a baby that will later be diagnosed with autism.  We also have seen how some people with mild autism treat themselves with progesterone to feel better.

Many years ago pregnant women were often prescribed progesterone and/or estrogen, now it seems to be limited to some women undergoing infertility treatment.  Perhaps giving progesterone might reduce the incidence of autism?

Statins are a known treatment for cytokine storms and are included in my autism PolyPill.

Once back home, people recovering from TBI and PTSD do seem to face similar treatment to adults with autism; they get ignored.

Due to all the recent conflicts in Iraq and Afghanistan, we do hear quite frequently about the consequences of untreated PTSD.  There are also very many cases of TBI, resulting from motor vehicle accidents (cars, bikes, quad bikes etc), sports accidents (skiing) and shootings (particularly in the US).  It seems that in many cases there can outwardly be a physical recovery, but personality has altered.  As we have seen in this blog, all the various hormones and neurotransmitters are interrelated and so any neurological damage will have multiple knock-on effects.  This will consequently transform, for better or worse, someone’s personality.  I used to know a person once, who was about to marry for the third time.  The second wife had been hit by a bus while crossing the street, and I remember how odd it sounded what he said next, “when she got better, she was a different person and I had to divorce her”.  The change in personality makes perfect sense, we are all the result of the particular homeostasis our brains settled at.  So some people are gregarious, others are loners, and a very small number become psychopaths.

If we more fully understood how the brain works, most types of mood disorder would likely be treatable.  Since people with TBI and mild autism are now easily identifiable, there is yet another reason to accelerate this research.  A frequent justification for the low expenditure on autism research is that “you don’t die from autism”.  Well, the above research shows that plenty of people do die from autism, just not the ones you expected.

Just to give the full picture, sadly people with severer types of autism have substantially elevated risk of mortality in their early years, due to seizures, drowning and other accidents.  There is research showing this, but it also shows up any time you see cause of death on the samples from brain tissue banks, used in autism studies.  This is why it is very important to teach people with severer autism to be confident swimmers, however hard it might seem.

NAC and Rotten Eggs – Where to draw the line?

One effective intervention in autism, particularly to reduce stereotypy, is N-acetylcysteine (NAC).  Here NAC is being used as an anti-oxidant in its own right and as a precursor to the body’s own main anti-oxidant, called GSH.  Classic autism is associated with oxidative stress and so NAC should be beneficial.

In much of Europe, NAC is seen primarily as a pharmaceutical, in North America, and much of the rest of the world, NAC is primarily just another supplement.

As a drug, it is mainly used as a so-called mucolytic agent, and as such is used as a cough medicine, because it breaks down mucus and liquefies it, making it easier to cough up.  It is frequently prescribed by doctors for children, but only in some parts of the world.

The problem with NAC, and all supplements, is quality control.  There is pressure to drive down prices and so quality will vary.  NAC is not particularly stable (it is labile) and so it tends to break down and release some foul smelling compounds.

For those who remember chemistry from school, the chemical formula is C₅H₉NO₃S and the following chemical structure:

The smell of rotten eggs is associated with H₂S, hydrogen sulphide/sulfide.  The ‘S’ in NAC is sulphur/sulfur and so when it breaks down or oxidizes you get a nasty smell.

The question is how much of a smell is normal and how much means your cheap NAC capsule has spoiled to the point of being worthless?

There is plenty of online discussion on this subject among regular users of NAC.  As usual, much is nonsense; some people are even saying that NAC has to stink and that it is a sign that it is good.

When it is freshly produced, there should be very little smell.  When you open the pharmaceutical NAC from its blister pack there is no smell whatsoever.

Cheap NAC

Since you need large amounts of NAC for treating autism, I found a brand of the cheap NAC capsules, but I always open the individual capsules and mix them in juice.  I never had any stinky bad egg smell until recently.  Now as soon as I open the jar, let alone the capsule, there is a potent smell.  Try a jar from a different batch, same smell.  More to the point, I have noticed small signs of stereotypy when Monty, aged 10 with ASD, goes for a swim.  He is swimming in the water and then starts wiggling his fingers and looking at them.

So I have decided to switch to the pharmaceutical NAC, which where we live is called Fluimucil and is made in Switzerland.  You buy it in the pharmacy over the counter, but without a prescription.  The cheap NAC does not say where it is made, or even have a use by date.  I suspect that different batches are made by totally different producers, whichever offers the lowest price.

The well-known expensive brand of NAC sold in the US is actually produced in Europe, if it turns out to be Swiss, we can probably guess who is making it for them.

It is clear that when the cheap NAC is very fresh, it works fine, but I want a product that functions as it should, 100% of the time.

I will see if the small re-emerging signs of stereotypy disappear with the Swiss NAC.

PANDAS, PANS, Penguins and Autism

Anyone with a serious interest in autism should also be aware of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome).  These are two syndromes which have acute onset of symptoms very similar to some of those found in autism.  It is claimed to affect 1 in every 200 children in the US.

The good news is that a very thorough and dedicated doctor called Susan Swedo has worked logically through from starting to identify the syndrome, all the way through to treating it.  Good job Susan.

Though she insists that PANDAS and PANS are distinct from autism, one can only wonder how many other distinct, but yet to be identified, syndromes exist that also present with autism-like symptoms.

Thanks to the efforts of Dr Swedo and the US NIMH (National Institute of Mental Health), these two conditions have been remarkably well investigated, in a very short period of time.  It shows what medical science can achieve when the right people are in charge.  It is odd that such effective clinical attention has not been focused on autism itself.

Here is a very recent presentation given by Dr Swedo, which really covers all the important aspects of both PANS and PANDAS.  For those with a serious interest, have a look though this post and then watch the presentation, to get the most from it.

Dr Susan Swedo (click for IPad users)

Penguins and PANDAS

One of the reasons I was so impressed by how PANDAS has been addressed, as opposed to the much more common autism, is the before and after data.  For example, many people talk about regressive autism, but nobody quantifies from what, to what.  Some children went from a spoken vocabulary of 10 words to 2 words, while others went from 500 words to zero; there is a profound (and relevant) difference.

In the case of PANS and PANDAS we have the before and after artwork from the affected kids. As usual, a picture is worth a thousand words.

I have no great panda pictures, but Monty aged 10 with ASD, brought back his artwork from school last week and pride of place goes to his picture of two penguins.  We were all more than a little taken aback to see it.  Did he really draw this? Unassisted?  It looks much more like the work of his big brother.  Even his assistant was surprised and confirmed that this was the result of his work in the art room for a double lesson.  I never expected to be displaying Monty’s artwork to the world.

Later in this post you will see the before and after PANDAS artwork.

PANDAS and PANS

When I first came across a condition known as PANDAS or PANS, I did not take that much notice; with such a name I assumed it was nonsense.   Researchers should give a serious syndrome a serious name/acronym.

I imagine that with the ever widening of the diagnosis of autism, some people with PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) /PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) have been misdiagnosed as autistic and vice versa.

When you look at the symptoms and apparent cause of PANDAS/PANS you may wonder how many other similar conditions exist within the myriad of conditions leading to autism.

The shocking regression in cognitive function (illustrated by children’s drawings further down the page) produced by this condition and the fact that it can be reversed, should really be carefully evaluated in comparison to regressive autism.

It would be appear that all of this is caused by an immune system gone “haywire”.  I wonder how many other immune dysfunctions leading to regression and odd behaviours will be identified in future decades.

The treatment for all these current, and future, conditions are likely to revolve around immunomodulatory therapy, ranging from very cheap steroids (prednisone) to the very expensive, like IVIG (Intravenous immunoglobulin)

If you have a case of regressive autism and the expert says it does not fit the definition of PANDAS/PANS, he might think the case is closed.  Perhaps it should not be.

I suggest that immune over-activation is involved in both groups of autism:-

Early onset autism

In these cases the immune activation is secondary; when it occurs the existing autism just gets much worse.  In some cases these flare-ups are evidently caused by food allergies/intolerance or pollen allergies.

Regressive Autism

I think that in mild cases, some autism may be solely an over-activation of the immune system, without any of the channelopathies and other dysfunctions common in classic autism.  I would put PANS/PANDAS is this category.  I suggest that many other cases of regressive autism could be traced back to allergies and food intolerance, which triggered an immune over-response.

It does seem that many regressions followed a viral infection, and of course, many people believe their regression was triggered by vaccines.  I expect in most cases the vaccine is just a scapegoat, but I very much doubt it is in every case.   

I do not expect there will be any research in this area, because the results would inevitably be misinterpreted by the public.  What a pity.

If we better understood what events could radically disrupt brain function, we might be able to better understand how to treat the resulting neuropsychiatric phenomena, known as regressive autism, PANDAS, PANS and other, yet to be invented, acronyms.

A serious condition with some serious followers

Many people’s knowledge of autism seems to come from sound bites from scientific luminaries like Oprah, Jenny McCarthy and even Donald Trump.  Somewhat remarkably, the PANS doctors are actually a very serious bunch, under the umbrella of the International OCD Foundation (and the NIMH).  This foundation is a serious organisation with a scientific advisory board loaded with people from top US Medical Schools.

Not only have they concisely explained the symptoms, but they have also found therapies; albeit, they do not really know why they work.

The US National Institute of Mental Health has great information.

There is also a very serious parent run organisation called PANDAS Network.

About PANDAS and PANS

In the early 1990s, 50 years after Kanner noticed autism, researchers in the US noticed what they thought was an odd acute-onset type of Obsessive Compulsive Disorder (OCD).  At first it was thought that only streptococcal infections and Scarlet fever triggered this abrupt regression in the child’s behaviour and cognitive performance.  The first name they came up with was PANDAS, (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections); when reports came in that many other infections caused acute regression the name got changed to PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). 

From Research Subgroup to Clinical Syndrome: Modifyingthe PANDAS Criteria to Describe PANS (Pediatric Acute-onset NeuropsychiatricSyndrome)

Symptoms of PANS

It is pretty clear to me that some people diagnosed with regressive autism actually have PANS.  I have from two sources a list of symptoms:-

International OCD Foundation

• Acute sudden onset of OCD
• Challenges with eating, and at the extreme end, anorexia
• Sensory issues such as sensitivity to clothes, sound, and light
• Handwriting noticeably deteriorates
• Urinary frequency or bedwetting
• Small motor skills deteriorate - a craft project from yesterday is now impossible to complete (see images below)
• Tics
• Inattentive, distractible, unable to focus and has difficulties with memory
• Overnight onset of anxiety or panic attacks over things that were no big deal a few days ago, such as thunderstorms or bugs
• Suddenly unable to separate from their caregiver, or to sleep alone
• Screaming for hours on end
• Fear of germs and other more traditional-looking OCD symptoms

US National Institute of Mental Health

• Severe separation anxiety (e.g., child can't leave parent's side or needs to sleep on floor next to parent's bed, etc.)
• Generalized anxiety. which may progress to episodes of panic and a "terror-stricken look"
• Motoric hyperactivity, abnormal movements, and a sense of restlessness
• Sensory abnormalities, including hyper-sensitivity to light or sounds, distortions of visual perceptions, and occasionally, visual or auditory hallucinations
• Concentration difficulties, and loss of academic abilities, particularly in math and visual-spatial areas
• Increased urinary frequency and a new onset of bed-wetting
• Irritability (sometimes with aggression) and emotional liability. Abrupt onset of depression can also occur, with thoughts about suicide.
• Developmental regression, including temper tantrums, "baby talk" and handwriting deterioration (also related to motor symptoms)

In case you want to see what they mean by regression, look at these pictures drawn by a child with PANDAS before and after treatment.  Panel A is before and Panel B is after.   Source International OCD Foundation

  

Treatment

Compared to Autism, a very refreshing approach is taken to treating PANS.

The treatments include:-

·        Treatment with antibiotics to eradicate the infection, if it is still present.

·        Immune-based therapies such as

o   Plasmapheresis

o   intravenous immunoglobulin (IVIG)

o   corticosteroids (such as prednisone).

The good news about the immune therapies is that the treatment gains were maintained long-term, which is exactly what you would want to see. 

Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood

Implications for Autism

In spite of what your doctor might tell you, if your child has regressive autism, you would be well advised to check and re-check that he/she does not have PANS or a (yet to be identified) variant thereof. 

The immune-based therapies that ultimately are proved to be successful in PANS are highly likely to be helpful in treating the kind of autism in which the immune system remains in a state of over-activation.  Also the immune-therapies being trialled for autism, if successful, might very likely be helpful alternative therapies for PANS; the therapy I have in mind is TSO.

Classic early-onset autism, as researched in post-mortem studies at the Courchesne lab and elsewhere, is associated with physical brain abnormalities, that should be irreversible.  It would seem that PANS is something entirely different and should be treatable and potentially fully recoverable.

For those of you unaware of Courchesne, here is a short video; he is quoted by many of the leading autism researchers, so I hope he has got things right.

Eric Couchesne &Karen Pierce from University of California at San Diego

Where does regressive autism fit in?  I really doubt that all those people with regressive autism have the physical brain abnormalities of classic autism.  Research has shown that regressive autism has even higher bio-markers of neuroinflammation than classic autism.  Perhaps regressive autism is neuroinflammation, without physical brain abnormalities?

Just as PANS is a mini-spectrum of conditions, pathologically distinct from early onset autism, I suspect that regressive autism is equally pathologically distinct from early onset autism.

Why does it matter?  Well if you want to treat something, it helps to know what you are dealing with.

PANS looks like it has some clever people working on it.  Regressive autism, which may indeed be the most prevalent type, is in need of some similarly clever people.

Conclusion

If regressive autism is your area of interest, I would suggest you look very carefully at PANS/PANDAS and the therapies that have been shown to be effective.

If you have PANS/PANDAS, taking a look at the experimental immunomodulatory therapy used in autism might be very worthwhile, for example the TSO therapy from Coronado Bioscience.

We know that PANS/PANDAS is caused by an ongoing inappropriate immune response, but we do not know how this is mediated into the odd behaviours.  One possible mechanism would be via a weakening of the blood brain barrier (BBB).  

It has been shown that the similar mechanism controls the BBB and the gut immune barrier.   Clever research into Celiac Disease has resulted in the discovery of Zonulin, which is now known to be the only physiological modulator of both these barriers.  Using a type of laboratory test called ELISA, it is now possible to measure Zonulin levels.  If people diagnosed with PANS/PANDAS were shown to have low Zonulin levels, we could assume that the BBB was compromised; this would certainly advance understanding of the condition. It would of course point the way to new therapies.