Prof. Dr. Vladimir Trajkovski presented topic: Health issues and health care in persons with autism spectrum disorders at international autism conference held in Krakow September 27th, 2018.

1. 1
Health issues and health care
in persons with autism
spectrum disorders
Prof. Dr. med. Vladimir Trajkovski
Krakow, September 28th 2018
University “St. Cyril and Methodius”
Faculty of Philosophy
Institute of Special Education and Rehabilitation
Macedonian Scientific Society for Autism

2. 2
What is autism?(APA,2013)
A developmental behaviorally-defined
syndrome/phenotype
Impacts social skills & communication
Associated with narrow, rigid,
repetitive behaviors
NOT A “DISEASE” !
Affects the immature, developing
brain

3. 3
Introduction (1)
Genetic research is delving into the biological causes of
autism-associated health conditions. This is part of a new
avenue of autism research aimed at identifying the many
biological subtypes of autism and developing personalized
treatments and supports.
Specialists at leading autism care centers are working with
patients and their families to improve the health and quality
of life of all those with autism by developing and
disseminating evaluation and treatment guidelines for
healthcare providers. (Perrin 2012 , Warfield 2016)
This effort also includes autism-specific medical education
and teleconferencing programs to share expertise.
(Mazurek 2017)

4. 4
Introduction (2)
These programs in USA have helped produce a sea
change in autism awareness and treatment capabilities
among the pediatricians, family physicians and other non-
specialists who provide the bulk of healthcare to the
nation’s estimated 3 million people on the autism
spectrum.
The purpose of this presentation is to summarize the
latest understanding of autism’s commonly associated
physical and mental health conditions, including how best
to identify, treat and in some cases prevent them to
improve overall health and quality of life.

5. 5
Causes of autism
Many genetic influences
in most cases multiple
most with small effects on brain
development
Interacting environmental (epigenetic)
influences
via their pathophysiologic effects on
• molecular networks
• cellular networks
• brain circuitry

6. 6
Overlapping syndromes
Autism
OCDOCD
IDID
LearningLearning
disabilitydisability,,
languagelanguage
disorder,disorder,
dyslexia, etc.dyslexia, etc.
TouretteTourette
ADHDADHD

7. 7
Current Genetic Views
Now known etiologies no longer rejected
Association with known mono-genetic disorders
PKU
Tuberous sclerosis
Fragile-X
Angelman, Cornelia de Lange, etc.
Candidate gene studies
Multiplex families
Linkage studies (cytogenetics, CNVs [microdeletions,
duplications, translocations], loci, genes)
Whole genome searches – gwas (genome-wide association
studies, microarrays)
mono- vs. heteroallelic expression
multiple genes with small effects vs. single genes with stronger
effects

8. 8
Physical/neurologic features
None present in all cases or required for
diagnosis
Abnormal head growth curve
Physical abnormalities/symptoms
Motor findings
Atypical sensory responses
Sleep problems
Language abnormalities
Autistic-language regression
Epilepsy

9. 9
Neuropathology
1980: 4 cases with severe MR: cerebellar + other
brain abnormalities (Williams et al.)
1985-2002: Cerebellum + limbic pathology (Bauman
and Kemper)
No major brain anomalies/lesions
Loss of Purkinje cells in cerebellar cortex, neurons in
deep cerebellar nuclei, inferior olive
Stunted neurons in diencephalon, amygdala
Pathology progressive in adults compared to
children?
1996: brainstem malformation in one case (Rodier
et al.)
HOXA1 gene
Thalidomide, valproate toxicity

10. 10
Cortical minicolumns in cortical area
4 lamina III in autism vs control brain
Normal
control brain
ASD brain
Casanova
2006

11. 11
Frequently reported somatic
abnormalities
Minor anomalies, dysmorphic features
Many known syndromes/genetic disorders
Middle ear infections,URIs
GI symptoms
Immunologic abnormalities

12. 12
Frequent motor findings
Stereotypies
motor, +/- object
behavioral
Dystonic postures
Toe walking
Increased joint laxity (hypotonia)
Clumsiness
Dyspraxia

13. 13
Frequent sensory findings:
hyper- & hypo-sensitivity
Touch
Pain, temperature
Proprioception
Vestibular
Audition
Vision
Taste
Smell

14. 14
Sleep disorders (1)
Difficulty falling asleep
Difficulty staying asleep
Need for less sleep time
Need for excessive sleep
Inadequate circadian rhythm

15. 15
Sleep disorders (2)
Children with ASD have a significantly high rate of sleep
disorders. Up to 80% have some issue with sleep.
The two most common problems are difficulty falling
asleep and waking up repeatedly. Some children with ASD
seem programmed to wake up early regardless of what
time they go to sleep.
One common thread is that children with ASD often have
greater anxiety and/or depression than other children.
These feelings can cause your child to lay awake worrying,
making it difficult for them to turn off their brain and fall
asleep.
If your child has a GI disorder in addition to ASD, this can
also factor into their ability to stay asleep throughout the
night.

16. 16
Sleep disorders (3)
Sleep disorders can affect the entire family but can be
especially disruptive to the child, causing additional
behavioral issues. Parents can establish routines to
promote optimal sleeping conditions.
Some common practices include:
Keep the bedroom dark and cool;
Keep the wake and sleep schedule consistent – even on
weekends;
Do not allow your child to have caffeine, coca cola;
Establish a bedtime routine and stick to it;
Make sure your child gets exercise each day.

17. 17
Seizure disorders (1)
Related to the severity, location, type
of brain pathology/cognitive level
Related to type of language disorder
Rare in high functioning children
Peaks in early childhood and in
adolescence
Rarely the cause of autistic
regression.

18. 18
Seizure disorders (2)
Seizures and epilepsy are one of the most common
medical conditions associated with ASD. Statistics show
that the rate of epilepsy in children with ASD can vary
from 5% to 38% in contrast to 1-2% of the rest of the
population.
Another source shows that statistic even higher at 10%
to 30%.
Majority of seizure activity occurs in children with
ASD after 10 years of age with the average age being
13.3.
While there are still not enough studies to conclusively
determine why seizures are so common, scientists have
found some evidence to support various scenarios.

19. 19
Seizure disorders (3)
The risk for seizures or epilepsy appears to be higher in those
children who experienced a regression of language skills before
the age of three.
The largest group at risk for seizure disorders appears to be
those individuals diagnosed with intellectual disability in addition
to ASD.
Seizures appear to be more common in children who have used
antipsychotic medications as part of their ASD treatment.
Though diet has not been shown as a factor causing seizures,
some doctors have used a ketogenic diet to significantly reduce
and even eliminate seizures. This diet consists of increasing fat
intake to four times the intake of carbs and proteins.
Doctors still aren’t sure why this works but according to the
Epilepsy Foundation, up to 2/3 of patients have found some
success with the diet.

20. 20
Autistic Regression and Epilepsy
Relation to Landau-Kleffner syndrome
(language regression with either
seizures or a subclinical epileptiform
EEG)?
Relation to status epilepticus in slow
wave sleep (ESES)?
Limited value of all-night EEG
monitoring

21. 21
Gastrointestinal disorders (1)
Gastrointestinal disorders can include chronic
diarrhea and constipation.
46% to 85% of autistic children suffer from these GI
issues.
Common symptoms include vomiting, constipation,
abdominal pain, acid reflux and diarrhea.
When a child is experiencing these problems, it can
further contribute to behavioral problems, limit
learning and interrupt sleep.

22. 22
Gastrointestinal disorders (2)
Researchers have still not been able to clearly define
why these children are more susceptible to GI problems
but some studies suggest dietary allergies may play a
role in some cases.
Some children have been found to fare better when
removing dairy and gluten from their diets.
Others do better when processed foods with dyes are
eliminated.
Still others have added probiotics to their diet to offset
symptoms.
Researchers from Columbia University believe that early
treatment of GI symptoms can result in the reduction of
behavioral problems.

23. 23
Gastrointestinal disorders (3)
Children suffering from GI problems may not exhibit typical
symptoms so in some cases parents may not even know
there is a problem. Some behaviors that can indicate a
problem may include:
Coughing excessively
Refusing to swallow food or difficulty swallowing
Hitting self in jaw or fisting the jaw
Chewing excessively
Chewing on clothes
Sleep problems
Eating to relieve symptoms
Unexplained changes in behavior

24. 24
Autism and the microbiome
Since the late 1990s, researchers have been adding to the
evidence that unhealthy changes in the intestinal tract’s
normal community of digestive bacteria (the microbiome)
drive both behavioral and GI problems in some people on
the autism spectrum.
The first reported person to make this gut-brain connection
was the mother of a child with autism, Ellen Bolte, who
saw a parallel between her son’s symptoms and infant
botulism.
Dr. Finegold and others showed that spikes in toxin-
producing bacteria in the intestines could directly affect the
brain via the vagus nerve that runs between the digestive
tract and the brain. (Finegold, 2002)

25. 25
Food allergies (1)
It may be no coincidence that in the 1990’s not only was
there a huge uptick in reported autism diagnoses but a
vast increase in food allergies in children as well. Food
allergies, like autism, have an underlying link to the
immune system, which is why it’s possible that they may
go hand in hand. In most cases the food allergies are not
life-threatening for children with ASD however certain
foods may cause worsening of autistic symptoms.
Inflammation caused by a reaction to certain foods can
cause the brain of an autistic child to be even more
overactive than usual. Toxins in other foods may decrease
the brain activity in other children who have under-active
brain activity.

26. 26
Food allergies (2)
Research has shown that there are 5 foods that tend to
increase ASD symptoms:
Gluten
Dairy
Sugar
Corn
Artificial ingredients like dye, preservatives and artificial
sweetening agents
Parents should not eliminate all foods at once, but
systematically to better understand which foods affect their
child and how. It is also important to note that behavior
changes may take time so be ready to wait a few weeks or
more to see any differences.

27. 27
Headaches (1)
One of the less common ASD symptoms is headaches.
One reason may be because ASD can be associated
with pain insensitivity. This means that the child may just
not feel the pain of a typical headache the same way a
child without ASD would.
Research has however indicated a link between migraines
and ASD.
One study found that children with sensory hyperactivity
were more likely to experience migraines. Additionally
those children with higher levels of anxiety are more likely
to have migraines or cluster headaches than others.

28. 28
Headaches (2)
Children with ASD may also suffer from headaches if they
are head bangers.
Children who bang their heads may be doing so in an
attempt to limit the pain signals that are being delivered to
their brains. Inflammation caused by GI disorders can also
cause headaches in your child.
Nutritional changes, behavioral therapies and other
treatments to reduce anxiety can play a significant role in
reducing these symptoms.

29. 29
Asthma
It is still unclear how much ASD is related to asthma
because asthma is such a common respiratory disorder.
The association between the two however, is increasingly
being acknowledged as research reveals some correlation.
Asthma is considered an immune-mediated disorder that
inflames the lungs.
Individuals with ASD are considered to have an imbalance
of the immune and inflammatory processes.
The connection of both disorders to the immune system
may suggest that they are related in some instances.

30. 30
Eczema and Other Skin Issues
Children with autism are 1.6 times more likely to have skin
conditions like eczema. Studies have shown a possible link
between autism and autoimmune disorders.
More research needs to be done but one study
suggests that parents with autoimmune disorders may be
more likely to have children with autism.
When autism is accompanied by a skin condition, it may
be the result of an autoimmune disorder passed on by a
parent or an existing food allergy that is causing dry skin,
rashes or other skin issues.

31. 31
Immune Disorders
Due to the connection between the immune system and
autism as described in other conditions, autism is often
accompanied by another immune disorder.
Current research points to a family history of immune
disorders when autism is present in a child.
Other research suggests that expectant mothers
who experience infections or inflammation during
pregnancy may be more likely to have a child with autism
or other disorders of brain development.
This again falls back to the connection of the immune
system and its link to autism.

32. 32
Tuberous Sclerosis
Tuberous Sclerosis (TSC) is defined as a rare genetic
disease that causes noncancerous tumors to grow all over
the body.
It is estimated that 25% – 50% of children diagnosed with
TSC will develop ASD compared to only 1% of the general
population.
This connection suggests that TSC symptoms show before
ASD symptoms. Often times ASD is not diagnosed until a
child with TSC is older because of the other developmental
disabilities that accompany TSC.
More studies need to be done to narrow the risk factors for
TSC among those with ASD.

33. 33
Feeding Disorders (1)
Children with sensory issues due to autism may be at risk
for feeding disorders including difficulty eating or
swallowing food based on the smell, texture or color.
These children tend to be picky eaters and may even
throw tantrums when asked to eat certain foods.
Up to 70% of children with ASD may present symptoms of
feeding disorders.
Parents dealing with these picka eaters are encouraged to
offer choices while still having their child stick to the rules.
Let them know they have to eat one vegetable at dinner,
but allow them to choose which one. It is also important to
ensure that your child isn’t avoiding a food because of an
allergy.

34. 34
Feeding Disorders (2)
Chronic overeating is a common issue among both children and
adults on the autism spectrum. Some people with autism have
poor sensitivity to internal cues such as feeling full.
Autism-related aversions to strong flavors, textures and smells
can lead to overconsumption of high-calorie, low-nutrient foods.
In addition, increased appetite is a common and serious side
effect of the only FDA-approved medicines for autism-associated
challenging behavior (agitation) – risperidone and aripiprazole.
(Maayan 2011, Scahill 2016)
The result is a high incidence of obesity – often combined with
nutritional deficiencies – in both children and adults on the autism
spectrum.
(Shmaya 2015, Croen 2015, Hill 2015)

35. 35
Autism and mental health (1)
Epidemiological studies suggest that between 54 and 70%
of people with autism also have one or more other mental
health conditions.
(Simonoff 2008, Hofvander 2009, Croen 2015, Romero 2016)
Attention deficit and hyperactivity disorder (ADHD)
affects an estimated 30 to 61% of people with autism.
(Goldstein 2004, Lee 2006, Gadow 2006, Romero 2016)
Anxiety disorders affect an estimated 11 to 42% of
people with autism.
(Vasa 2016, White 2009, Croen 2015, Romero 2016)

36. 36
Autism and mental health (2)
Depression affects an estimated 7% of children and 26%
of adults with autism.
(Greenlee 2016, Croen 2015)
Schizophrenia affects an estimated 4 to 35% of adults
with autism.
(Chisolm 2015)
Bipolar disorder affects between 6 and 27% of people
with autism.
(Munesue 2008, Rosenberg 2011, Vannucchi 2014, Guinchat 2015,
Croen 2015)

37. 37
Depression, Autism and Suicide
In 2012, researchers at Penn State College of Medicine
reported the disturbing finding that 14% of children with
autism age 16 or younger “sometimes” or “very often”
contemplated or attempted suicide – a rate 28 times
higher than for similarly aged children with typical
development (Mayes, 2013).
This increase in suicidal tendencies became significant
after age 10, with signs of depression being the strongest
predictor. Neither autism severity nor IQ altered the
frequency.
Healthcare providers should screen all children with autism
for suicidal thoughts or attempts in addition to raising
awareness of the issue with parents.

38. 38
Autism and premature death (1)
As a group, people who have autism are more than twice
as likely to die prematurely.
For some subgroups, the risk can be up to 10 times that of
the general population.
Among the most disheartening results of autism research
is the persistent finding of premature mortality. There is an
evidence base of more than 15 years of small studies
suggesting premature mortality rates to be 2 to 10 times
higher than normal among various groups with autism.
(Isager 1999, Mouridsen 2008, Gillberg 2010, Pickett 2011, Bilder 2013)
Two new, large studies provide compelling evidence that,
as a group, people with autism die younger – as much as
36 years younger – than those in the general population.
(Hirvikoski 2016, Guan 2017)

39. 39
Autism and premature death (2)
This research also makes clear that autism alone is not driving
the premature mortality. Rather, leading causes of death include
many of the medical and mental health conditions described in
this presentation – further highlighting the urgent need to
recognize and address them.
The most recent study involved the analysis of more than 32
million U.S. death certificates, including those of 1,367 people
with autism who died between 1999 and 2014 (Guan 2017).
This study found that the average lifespan of someone with
autism was half that of the general population – an average of
36 versus 72 years.
Accidental injury was the leading cause of death, at a rate 3
times higher than in the general population.
Further analysis revealed that children with autism were 160
times more likely to drown than were children across the
general population.

40. 40
Where to go: biology
Elucidate pathophysiology, i.e., what
goes on in the brain
(neurotransmitters, neuromodulators,
epilepsy, etc…)
Pathophysiology more likely to lead to
new drugs than genetics
Elucidate basis of autistic regression
Devise a rational treatment for autistic
regression

41. 41
Where to go: genetics
In the clinic:
Limited referral based on family history &
phenotype
Probability of a specific genetic diagnosis
low
Always discuss recurrence risk !
Lack of prenatal diagnosis unless etiology
known
For research (paid for by research funds !)
Strongly encourage enrollment in a funded
comprehensive study.

42. 42
Conclusions (1)
Autism can affect the whole body.
Seizures, disturbed sleep and painful gastrointestinal
disorders are some of the health conditions commonly
associated with autism.
Autism is also frequently accompanied by mental health
conditions including anxiety, depression, and ADHD.
Autism-associated health problems extend across the life
span – from young children to senior citizens.
32% of 2 to 5 year olds with autism are overweight and
16% are obese.

43. 43
Conclusions (2)
23% of 2 to 5 year olds in the general population are
overweight and only 10% are medically obese.
Likelihood of being overweight or obese increases with the
number of behavioral medicines a child is taking.
Significant weight gain is a common side effect of behavior-
calming medications such as risperidone and aripiprazole,
the only FDA-approved medications for autism-associated
agitation and irritability.
On average, autism costs an estimated $60,000 a year
through childhood, with the bulk of the costs in special
services and lost wages related to increased demands on
one or both parents. Costs increase with the occurrence of
intellectual disability.

44. 44
Call for papers
https://jrtdd.com
October 30th, 2018

45. 45
THANK YOU
+389-2-3116-520 (234)
+389-2-3118-143
vladotra@fzf.ukim.edu.mk
http://vladotra68.blogspot.com
Prof. Dr. Vladimir Trajkovski
@vladotra
http://www.linkedin.com/profile/VladimirTrajkovski