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Showing posts with label Austism flare up. Show all posts
Showing posts with label Austism flare up. Show all posts

Tuesday 13 January 2015

Cytokines from the Eruption of Permanent Teeth causing Flare-ups in Autism




A recent post looked again at inflammation in autism and some possible therapies to try.  Over Christmas and New Year, Monty, aged 11 with ASD, had occasional outbursts, more typical of his summertime raging, which was later solved using allergy /mast cell therapies.

At least it did let me establish whether Verapamil was a universal “cure” for SIB.  It is not.  It works great for allergy-driven aggressive behaviors, but had no effect on these ones.

Christmas is often a stressful period for many people with, or without, autism; but Monty likes presents and he loves food.

Having pulled out a wobbly tooth on Boxing Day and noticed an apparent behavior change, I thought that perhaps the loss of milk teeth and development of permanent teeth might cause an effect similar to that of his mild pollen allergy.  Monty, in common with many people with autism, has a high pain threshold.  While teething causes well known problems in babies, most children have minimal problems when their milk teeth are replaced by their permanent ones.

I just wondered if perhaps the underlying biological mechanism might provide an inflammatory insult to the highly inflammation-sensitive autistic brain.

Just as histamine provokes a release of inflammatory cytokines like IL-6, perhaps losing your milk teeth does something similar.


Ibuprofen experiment

I decided that I would buy some Ibuprofen, the least problematic NSAID.   A day or two later, Monty declared that another tooth was wobbly and needed to be pulled out.  This tooth was, and remains, well and truly attached.

So I decided that in advance of another, potentially stressful, Christmas event, I would give 10 ml of Ibuprofen.  I did not give it in response to any comment about pain.

It did indeed seem to work.


Skiing

A few days later we were in the Alps for skiing.

Monty can ski, but we always give him a 1:1 instructor.  On the first day, without Ibuprofen, he got agitated during the queuing at the bottom of the beginners’ ski lift.  The instructor thought it was the loud booming music.  It was clear that by the end of the lesson, it was no fun at all.

The following days, I gave 10 ml of Ibuprofen, 20 minutes before the lesson started.  He had a great time, going up by cable car to the top of the mountain and skiing along the blue/red slopes and coming down in a neighboring resort a couple of hours later.  Even a change of instructor on one day, passed without issue.

It might not be scientific proof of the effectiveness of Ibuprofen, but it was enough for me.


The Science

Since this is a scientific blog, arriving home I did some checking on the biology of what happens when you lose your milk teeth.

There is more written about “teething” when you first get your milk teeth, but there is information about “root resorption” of milk teeth and “eruption” of the permanent teeth.  The process is indeed modulated by inflammatory cytokines and transcription factors.

These cytokines will then circulate around the body and cross the blood brain barrier.





Abstract

PURPOSE:
The aim of this study was to investigate whether there are increased levels of the inflammatory cytokines IL-1beta, IL-8, and TNF alpha in the gingival crevicular fluid (GCF) of erupting primary teeth. This increase could explain such clinical manifestations as fever, diarrhea, increased crying, and sleeping and eating disturbances that occur at this time.

METHODS:

Sixteen healthy children aged 5 to 14 months (mean=9.8 months) were examined twice a week over 5 months. Gingival crevicular fluid samples were taken from erupting teeth. As a control, GCF was collected from the same teeth 1 month later. Cytokine production was measured by ELISA. Signs and clinical symptoms were listed. Pearson correlation coefficients were used in the comparisons described below. A paired t test was used to analyze the same variable at different times.

RESULTS:

Fifty teeth of the 16 children were studied. GCF samples were collected from 21 of these teeth. Statistically significant differences (P<.05) were found with regard to the occurrence of fever, behavioral problems, and coughing during the teething period and the control period. During the control period, 72% of the children did not exhibit any clinical manifestations, whereas during the teething period only 22% of the children did not exhibit any clinical manifestations. The study revealed high levels of inflammatory cytokines during the teething period, with a statistically significant difference in TNF alpha levels (P<.05) between the teething period and the control period. Correlations were found between cytokine levels and some of the clinical symptoms of teething: IL-1beta and TNF alpha were correlated with fever and sleep disturbances; IL-beta and IL-8 were correlated with gastrointestinal disturbances; IL-1beta was correlated with appetite disturbances.

CONCLUSIONS:

Cytokines appear in the GCF of erupting primary teeth. The cytokine levels are correlated to some symptoms of teething.



Mechanism of Human Tooth Eruption: Review Article Including a New Theory for Future Studies on the Eruption Process



Physiologic root resorption in primary teeth: molecular and histological events


Root resorption is a physiologic event for the primary teeth. It is still unclear whether odontoclasts, the cells which resorb the dental hard tissue, are different from the osteoclasts, the cells that resorb bone. Root resorption seems to be initiated and regulated by the stellate reticulum and the dental follicle of the underlying permanent tooth via the secretion of stimulatory molecules, i.e. cytokines and transcription factors. The primary root resorption process is regulated in a manner similar to bone remodeling, involving the same receptor ligand system known as RANK/RANKL (receptor activator of nuclear factor-kappa B/ RANK Ligand). Primary teeth without a permanent successor eventually exfoliate as well, but our current understanding on the underlying mechanism is slim. The literature is also vague on how resorption of the pulp and periodontal ligament of the primary teeth occurs. Knowledge on the mechanisms involved in the physiologic root resorption process may enable us to delay or even inhibit exfoliation of primary teeth in those cases that the permanent successor teeth are not present and thus preservation of the primary teeth is desirable. (J. Oral Sci. 49, 1-12, 2007)


Nonsteroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, work by inhibiting the enzyme COX which converts arachidonic acid to prostaglandin H2 (PGH2). PGH2, in turn, is converted by other enzymes to several other prostaglandins ,which are mediators of pain, inflammation, and fever.


Prostaglandin E synthase


Prostaglandin E2 (PGE2) is generated from the action of prostaglandin E synthases on prostaglandin H2 (PGH2).

PGE2 has various known effects, but one known effect is to increase the pro-inflammatory cytokine IL-6.  The same one that is increased by histamine released from mast cells during allergic reactions.

Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2.


Abstract

Injection of mineral oils such as pristane into the peritoneal cavities of BALB/c mice results in a chronic peritonitis associated with high tissue levels of interleukin 6 (IL-6). Here we show that increased prostaglandin E2 (PGE2) synthesis causes induction of IL-6 and that expression of an inducible cyclooxygenase, Cox-2, may mediate this process. Levels of both PGE2 and IL-6 are elevated in inflammatory exudates from pristane-treated mice compared with lavage samples from untreated mice. The Cox-2 gene is induced in the peritoneal macrophage fraction isolated from the mice. A cause and effect relationship between increased macrophage PGE2 and IL-6 production is shown in vitro. When peritoneal macrophages are activated with an inflammatory stimulus (polymerized albumin), the Cox-2 gene is induced and secretion of PGE2 and IL-6 increases, with elevated PGE2 appearing before IL-6. Cotreatment with 1 microM indomethacin inhibits PGE2 production by the cells and reduces the induction of IL-6 mRNA but has no effect on Cox-2 mRNA, consistent with the fact that the drug inhibits catalytic activity of the cyclooxygenase but does not affect expression of the gene. Addition of exogenous PGE2 to macrophages induces IL-6 protein and mRNA synthesis, indicating that the eicosanoid stimulates IL-6 production at the level of gene expression. PGE2-stimulated IL-6 production is unaffected by addition of indomethacin. Taken together with the earlier finding that indomethacin diminishes the elevation of IL-6 in pristane-treated mice, the results show that PGE2 can induce IL-6 production in vivo and implicate expression of the Cox-2 gene in the regulation of this cytokine


Indomethacin is another NSAID, like Ibuprofen.



Implications

If, as seems likely, many incidents of anxiety, aggression, explosive behavior, or "meltdowns" are made possible by elevated levels of the pro-inflammatory cytokine IL-6, then the occasional use of drugs known to inhibit IL-6 makes a lot of sense.

Ibuprofen is an NSAID and it is known that some people respond much better to certain NSAIDs and suffer side effects from others.   NSAID drugs work by affecting both COX-1 and COX-2.  It appears that desired effect of NSAIDs comes from their effect on COX-2, while the side effects come from changes made to COX-1.  So it is logical that some NSAIDs are better tolerated than others and for some people a different NSAID may be more appropriate.

Other common drugs also lower IL-6;  leukotriene receptor antagonists like Montelukast (Singulair)  being an example.  This drug is used in autism, but a known side-effect in typical people is to worsen behavior, sometimes severely.  There are plenty of reports of Singulair in autism, some good and some bad.  Since almost all drugs have multiple effects, this is not surprising.

Interestingly, one of the drugs in my Polypill, NAC, is also known to reduce IL-6; but it also reduces the “good” anti-inflammatory cytokines like IL-10.  Perhaps this is why NAC is not beneficial to some people with autism?

Occasional use of Ibuprofen at times anticipated to be stressful makes a lot of sense. 


Conclusion

While it is well known that Ibuprofen relieves pain from teething, low level pain is often completely ignored by people with ASD.  The cytokine release associated with the resorption of the milk teeth and the eruption of the permanent tooth appears to be much more problematic.

Ibuprofen, available OTC, limits the production of pain mediators, called prostaglandins, which in turn stimulate production of the inflammatory cytokine IL-6.

Ibuprofen will reduce both pain and the level of cytokines like IL-6.

In earlier extensive posts on mast cell degranulation in autism, I concluded that the resulting elevated levels of IL-6 likely produced behaviors ranging from anxiety, through aggression, all the way to self-injury.




Wednesday 16 July 2014

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.



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. 
 

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 PD20FEVHi 416%). There was still significant protection (Δ PD20FEV1Hi>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.  



Saturday 21 June 2014

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). 



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   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.


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.