Source: EpiphanyASD
There is a lot written about PANS
(Pediatric Acute-onset Neuropsychiatric Syndrome) and PANDAS (Pediatric
Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections)
which is a subset of PANS; however they are still not fully recognized as medical conditions.
I prefer to see PANS/PANDAS in the broader context of autoimmune encephalitis, a collection of related conditions in which the body's immune system mistakenly attacks the brain, causing inflammation. The immune system produces antibodies that mistakenly attack heathy receptors in the brain. Depending on which types of receptors are targeted, you will get different symptoms, plus you will get symptoms from the inflammation.
If they
are NMDA receptors, you may have hallucinations and appear to have developed
schizophrenia overnight.
It has
been suggested that the definition of PANS is too narrow and a broader term
called CANS was proposed. CANS is not exactly the same as PANS. PANS is the popular term in the US.
“A 2011 paper by Singer proposed a new, "broader concept o childhood acute neuropsychiatric symptoms (CANS)", removing some of the PANDAS criteria in favor or requiring only acute-onset. Singer said there were "numerous causes for CANS", which was proposed because of the "inconclusive and conflicting scientific support" for PANDAS, including "strong evidence suggesting the absence of an important role for GABHS, a failure to apply published [PANDAS] criteria, and a lack of scientific support for proposed therapies".”
Moving from PANDAS to CANS (pay-walled)
I do
not see why the focus is always on children, because we know that adults can
also be affected.
In
children and adults with autism it seems that quite often they may suddenly
develop verbal or motor tics, as the obvious symptom of autoimmune
encephalitis. These tics gradually
disappear when treated with a short course of oral steroids.
One
point emphasized by the likes of Susan Swedo, at the US National Institute of
Mental Health, is that PANS/PANDAS is not autism.
Non-autistic
children can develop PANS/PANDAS, but so can autistic people.
A non-autistic
child with untreated PANS/PANDAS would appear to most people as autistic, so
similar are the symptoms.
An
adult with NMDA receptors encephalitis will very likely be diagnosed as
schizophrenic.
The
autistic person who develops PANS/PANDAS appears like an autistic person who
has encountered a regression. Many of the symptoms of PANS/PANDAS are common
symptoms of autism, so the onset of PANS/PANDAS may just look like the already
present symptoms have gotten worse.
Susan
Swedo has commented that there is nothing to suggest PANS/PANDAS is more common
in children with autism. She states that PANS/PANDAS is a condition of onset in
early childhood, which is likely to reoccur when re-exposed to the same trigger,
but reoccurrence is much less of a risk after 21 years old.
I think
most cases of PANS/PANDAS in people with severe autism are never diagnosed and
so never treated. It is just put down as
an autistic regression. How many of
those adults with severe autism and extremely challenging behaviors fall into
this category? Given the enormous cost,
up to half a million dollars a year, to house this type of person in a care
facility with 24-hour support, you would think a little bit more effort should
be given to early diagnosis and treatment.
A Sceptical World
One of
our neurologist readers commented in this blog about how she successfully treated
her child’s PANS episode, even though in her country PANS does not exist as a
diagnosis and her colleagues at work had no idea how to treat it. Quick intervention
required only minor treatment.
In some
countries with free universal healthcare, you only get to diagnose and treat
PANS if you go outside that system and pay extra.
In the
US there are some pretty expensive tests proposed for PANS and CANS.
In
mainstream medicine PANS/PANDAS are not generally accepted as conditions and
yet Stanford University has had a PANS/PANDAS clinic for a decade.
https://med.stanford.edu/pans/about.html
Time for detective work
The
usual issue I have to manage in spring/summer is what I call summertime raging
and dumber in the summer. Note that a
cognitive regression is a very common symptom of PANS/PANDAS.
My
solution to summertime raging and dumber in the summer revolves around allergy,
mast cells and reducing pro-inflammatory cytokines.
This year
some new symptoms developed after summer:
·
Sensory amplification,
in the form of sound sensitivity
·
Clinginess to Mum/Mom and separation
anxiety
·
Hair twirling, using fingers to twist
hair
·
Nail picking, the
medical term is Onychotillomania
·
General anxiety
·
Increased urinary frequency, not due to a
UTI (urinary tract infection)
·
Aggression and reactive rage (as
opposed to predatory rage)
· Mood disorder, crying for no apparent reason at school and home
All the
above symptoms can be passed off as autism.
Sound
sensitivity is a common problem in autism, but Monty was getting so sensitive
to sounds that he could not tolerate sitting next to someone eating at home. At
school, where it is very noisy, this was not a problem.
Clinginess
to Mum/Mom rather merged with the aggression and reactive rage symptoms. Aggression is a very common problem in severe
autism and it is usually directed mainly at Mum. This time it was not just behaviors, but talking in
advance about potential aggressive behaviors, this was new and got worse and
worse.
Hair
twirling has occurred before and is a common expression of anxiety, which then
just becomes a habit, like a stim or tic.
This was previously resolved by a haircut. This time the short hair did not solve the
issue.
Nail picking (Onychotillomania) is when use your index finger to pick at the cuticle on your thumb and end up tearing the skin. This is rather like compulsive hair pulling (Trichotillomania) which is a common feature of OCD (obsessive compulsive disorder). NAC is used to treat Trichotillomania.
Anxiety is nearly always an issue in all levels of autism.
The urinary symptoms of PANS/PANDAS are something that I had not paid attention to earlier.
We covered polydipsia, drinking too much water, in a special post. This is a big problem for some readers of this blog.
Thirst – Too much or too little (Polydipsia and Hypodipsia) Vasopressin and Angiotensin
People taking Bumetanide for autism will drink a lot, but should do so only in the few hours after taking the therapy, not all day long.
Autistic
people with polydipsia are at risk of death due
to low sodium levels (hyponatremia).
Monty
was drinking so much I was giving him additional sodium and potassium.
Children
with autism often use toilet breaks as an escape from whatever task they have
been given. Monty’s assistant had
commented on how he seemed to be trying to escape from her.
The
mood disorder was very marked and on one occasion Monty cried at school; his
classmates were worried about him and did their best to comfort him. This had never happened before and there was
no apparent trigger. The same thing happened at home a few times, normally in
the evening.
After a
gradual worsening of the above symptoms, Monty had a viral infection, and he informed us that he had a sore throat. Behaviors then got significantly worse
and he had a week off school, more for the behaviours than for the mild flu-like
symptoms. Having then announced that his
ear was hurting, we took him to the Ear Nose and Throat doctor. To get to see
the doctor you first have to go and get a negative Covid test. The diagnosis was a mild
ear infection that might not need an antibiotic, but if it got worse take the
antibiotic (Cefpodoxime).
This is a β-lactam antibiotic.
We did cover the non-antibiotic properties of this class of antibiotic in a dedicated post, since many antibiotics have profound anti-inflammatory and other effects not related to killing bacteria. You can never know with 100% certainty which effect is giving you the benefit.
Autism and Non-Antibiotic Properties of Common Beta-lactam
Antibiotics
For anyone interested in trivia. The aerobic mold which forms the basis of this antibiotic, cephalosporin C, was found in the sea near a sewage outfall by Cagliari harbour in Sardinia, by the Italian pharmacologist Giuseppe Brotzu in July 1945.
If you like sandy beaches
like Monty, Sardinia is a great place to visit. Cagliari is in the south, the famous
part of Sardinia is Costa Smeralda, on the northern coast, where the celebs go to
be seen.
Since Monty’s
problem was more behavioral than due to pain in his ear, we started the
antibiotic without delay.
Over 5
days, the behaviors began to improve and on day 6 the hair twirling vanished
entirely for a day, so clearly something new was going on in his brain.
The
mood disorder switched to occasional extreme laughter/happiness, rather than the
previous tears.
The
behavioral regression started well before the viral infection and ear infection,
so it is not just a simple case of a sore throat and a strep infection.
Are all
the above symptoms due to PANS/PANDAS?
There actually is a 100% overlap between Monty’s recent symptoms and a list of possible
PANS/PANDAS symptoms. Every symptom I listed is on the doctor’s checklist below:
-
Description of PANS Symptoms
1) OCD
Traditional OCD presents with mild obsessions
and compulsions that become more involved and burdensome over time. In
traditional OCD, symptoms tend to be persistent with minor variance in symptoms
(often referred to as a waxing and waning). In contrast, PANS OCD presents with a sudden
onset typically from mild or no symptoms to debilitating in an abrupt amount of
time. Often, parents recall the exact date of symptom onset, and
frequently report “it just came on out of the blue.”
Many compulsions are either mental rituals (and
therefore difficult to observe) or appear as extremes of an acceptable behavior
(e.g., compulsive handwashing). Common OCD rituals in children include:
washing/grooming, checking (locks, door), counting, ordering/symmetry,
hoarding, restrictive eating, and repetitive questioning.
Emerging research suggests different treatment
options are available for children with PANS OCD than for children with non-PANS
OCD. Understanding the difference between the two forms of OCD allows
appropriate interventions to be implemented.
2) Eating Restriction
PANS children describe various reasons for not
eating normally or adequately, such as: fear of vomiting, sensitivity to taste,
smell, and texture, fear food is spoiled, or fear of being poisoned. In some
cases, the restricted eating is directly related to body image distortions,
including concerns about being overweight (even when the child is normal weight
and was previously satisfied with their body habitus.)
3) Anxiety
Anxiety
frequently presents as constant, generalized anxiety or age-inappropriate
separation anxiety.
4) Sensory Amplification
PANS children may become uncharacteristically
and intensely bothered by smells, tastes, sounds, and textures, causing difficulties with
daily routines, such as brushing teeth, riding in a car, eating, and dressing.
5) Motor Abnormalities
PANS
children may exhibit motor and vocal tics, handwriting changes and/or clumsiness.
6) Behavioral Regression
PANS
children may display regressed behaviors, such as: baby talk, refusal to carry
out age-appropriate grooming activities, tantrums, clinginess, and/or
separation anxiety.
7) Deterioration in School Performance
Psychological testing of children with PANDAS,
a subset of PANS where strep is the infectious trigger, has found impairments
on a visual-spatial recall test, on measures of executive function, and on a
dexterity test. PANS children may also experience a decreased processing speed,
memory issues, and/or difficulty in math and calculation.
8) Mood Disorder
Depression, mania, irritability, hypersexuality, emotional lability, and rage
have been noted during a PANS exacerbation. Moods may change from happy
to sad to angry in moments. Reactive
rage (as oppose to predatory rage) may start instantaneously and stop as
quickly, leaving the child remorseful and confused.
9) Urinary Symptoms
An
initial complaint may be urinary frequency. A careful history will often expose additional
symptoms. PANS children may develop polyuria (up to many times per hour),
frequent urges to urinate, and/or day and night secondary enuresis. These
urinary symptoms are not due to UTI, anxiety or OCD type worries.
10) Sleep Disturbances
Polysomnography has demonstrated a variety of
sleep abnormalities in children with PANS, including initial and middle
insomnia, REM behavior disorder, parasomnias, and/or sleep phase shifting.
Since I did introduce the term CANS, here is a comparison of PANDAS, PANS and CANS from a recent Italian paper:-
CANS:
Childhood acute neuropsychiatric syndromes
Table 1 - Criteria for PANDAS, PANS, and CANS
PANDAS
1. Presence
of OCD and/or a tic disorder
2. Pediatric
onset (Symptoms of the disorder first become evident between 3 years of age and
the puberty.)
3. Episodic
course of symptom severity Abrupt onset of symptoms or dramatic symptom
exacerbations. Often, the onset of a specific symptom exacerbation can be
assigned to a particular day or week, at which time the symptoms seemed to
‘‘explode’’ in severity. Symptoms usually decrease significantly between
episodes and occasionally resolve completely between exacerbations.
4.
Association with Streptococcal infection Symptom exacerbations must be
temporally related to Streptococcal infection
5.
Association with neurological abnormalities During symptom exacerbations,
patients will have abnormal results on neurological examination. Motor
hyperactivity and adventitious movements
PANS
1. Abrupt,
dramatic onset of OCD or severely restricted food intake
2.
Concurrent presence of additional neuropsychiatric symptoms, with similarly
severe and acute onset, from at least two of the following seven categories
1) Anxiety
2) Emotional lability and/or depression
3) Irritability, aggression and/or severely oppositional
behaviors
4) Behavioral (developmental) regression
5) Deterioration in school performance
6) Sensory or motor abnormalities
7) Somatic signs and symptoms, including sleep disturbances,
enuresis or urinary frequency.
3. Symptoms
are not better explained by a known neurologic or medical disorder (Such as
Sydenham's chorea, systemic lupus erythematosus, Tourette disorder, or others).
Idiopathic CANS
Acute onset
before age 18 of behavioral and motor signs encompassing
1. Primary
criterion OCD
2. Secondary
criteria
1) Anxiety
2) Psychosis
3) Developmental regression
4) Sensitivity to sensory stimuli
5) Emotional lability
6) Tics
7) Dysgraphia
8) Clumsiness
9) Hyperactivity
3. Mono- or polyphasic cours
Treatment
Susan Swedo advises to treat PANDAS with 3 weeks of
antibiotics.
Monty’s 2 previous cases of sudden onset motor/verbal tics were
resolved by 5 days of Prednisone. This
is a common therapy for a PANS flare-up.
There is a study from Stanford on its benefit. The sooner you use this therapy, the greater
the benefit.
The most important thing with all forms of autoimmune
encephalitis seems to be speedy treatment so the condition does not become
chronic. Then you have to use much more
invasive and expensive therapies like IVIG and Plasmapheresis.
It is clear that PANS/PANDAS is likely to reoccur.
In Monty’s case the first two instances were very
similar. They were both acute onset
tics. The third instance was very different.
Given that Monty’s antibiotic very obviously had a
behavioral benefit, we will follow Swedo’s advice and continue for 3 weeks,
which is 2 weeks longer than the standard ear infection therapy.
The
short course of Prednisone will hopefully complete the therapy and life will go
back to normal.
I recall that our neurologist reader, with those sceptical colleagues, did not even need steroids to
resolve her child’s problems, NSAIDs were sufficient. The sooner you treat the symptoms, the less
potent the therapy needs to be and the more effective it seems to be. Some people commence treatment years after the
symptoms emerge.
Conclusion
One
conclusion to this post might have been along the lines of “My god, whatever
next?” as if autism brings never-ending problems.
I
rather see it as, why did it take me so long to recognize the symptoms?
The
answer to that one is that PANS/PANDAS/CANS, or indeed the broader Autoimmune
encephalitis, is a family of conditions.
Just because you saw one set of broad symptoms earlier, does not mean
you will not face a different subset of symptoms next time.
The urinary
symptoms of PANS were a surprise and worth highlighting.
Autistic
regressions should be investigated and treated.
On the
one hand, doctors, particularly in the US, do like expensive diagnostic tests. They want certainly and often struggle to
treat ill-defined conditions that they have not been taught about. They prefer not to tinker around, in fact
tinkering is frowned upon.
On the
other hand, when very expensive testing is done and it identifies in someone a
combination of rare genetic dysfunctions associated with autism, nobody thinks
to look up each gene and see how to compensate for the usual loss of function - that does not seem to count as medicine. The genetic
diagnosis is crystal clear, but the therapy would definitely require some
tinkering around, to perfect it. But, such tinkering is so
frowned upon that the “specialist” just stands well clear and moves on to the
next patient.
Tinkering
around is an essential part of fixing practical problems.
In my
case of autism, I have not paid $925 for the Cunningham Panel of PANS/PANDAS tests, or even a strep test, or a urine culture test.
The
cost of treating the 2 apparent PANS episodes in previous years was about $5
dollars each time. The cost of the
current episode was more, about $15, plus the cost of a visit to the ENT
doctor and the required Covid test. Our
neurologist reader likely spent even less for her NSAIDs.
PANDAS,
PANS, CANS or just autoimmune encephalopathy, it does not really matter what
you call it, prompt intervention will likely resolve the symptoms.
