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Transcript of Autism
University of Alexandria
High Institute of Public
Health
Department of Nutrition
AUTISM SPECTRUM DISORDERS
By
ORCHID ESSAM EL-DIN DARWISH
Supervisor
DR. DALIA TAYEL
1
LIST OF CONTENTS
Introduction
3
Etiology and predisposing factors
4
Clinical picture
8
Feeding problems in autism
10
Diagnosis of Autism spectrum disorders
12
Treatment options
13
References
21
2
Introduction
What Are the Autism Spectrum Disorders?
It is a lifelong complex disorder that impedes an individual’s ability to
communicate and function socially.1 Autistic spectrum disorders are set of
neurodevelopmental conditions characterized by a marked impairment in
social interaction, delayed language, and restricted patterns of behavior. In
addition to these core symptoms, autistic children frequently have serious
behavioral disturbances, such as self-injurious behavior, aggression, and
tantrums.
Usually, these behavioral problems compromise educational and
developmental progress.2 Formerly a rare condition, the prevalence of autism
has increased more than 10-fold in the past 20 years, from an estimated
prevalence of approximately5 or6 per 10,000 children to 65 per 10,000
diagnosed with ASD).1
The autism spectrum disorders are more common in the pediatric population
than are some better known disorders such as diabetes, spinal bifida, or
Down syndrome.3 A recent study of a U.S. metropolitan area estimated that
3.4 of every 1,000 children 3-10 years old had autism. 4
3
The earlier the disorder is diagnosed, the sooner the child can be helped
through treatment interventions. Pediatricians, family physicians, daycare
providers, teachers, and parents may initially dismiss signs of ASD,
optimistically thinking the child is just a little slow and will “catch up.”5
Etiology and predisposing factors:
Genetic factors:
Evidence points to genetic factors playing a prominent role in the causes for
ASD. Twin and family studies have suggested an underlying genetic
vulnerability to ASD 6 .
Recent neuroimaging studies have shown that a contributing cause for
autism may be abnormal brain development beginning in the infant’s first
months. This" growth dysregulation hypothesis” holds that the anatomical
abnormalities seen in autism are caused by genetic defects in brain growth
factors. It is possible that sudden, rapid head growth in an infant may be an
early warning signal that will lead to early diagnosis and effective biological
intervention or possible prevention of autism.7
Hypovitaminosis D and autism:
While the predisposing autistic lesion is genetic, the epidemiological
observations indicate something in the environment prenatally or
postnatally, is affecting expression of the genotype, probably through gene-
environment interactions. The environment directly influences
environmental responsive genes and they, in turn, directly influence the
genome, the neurosteroid hormones are a good example.
4
That is, while neurosteroids are under genetic organization, something in the
environment may lower neurosteroid concentrations which, in turn, fails to
signal fully the genetic expression of the neural proteins that steroid
regulates8 So it is reasonable to search for neurosteroids that have declined
over the same time autism has increased.
Of the neurosteroids involved in brain development, activated vitamin D
(calcitriol) is unique, the least understood, but, arguably, one of the most
profound. McGrath et al. alerted us to this fact in 2001, pointing out that
vitamin D is ‘‘the neglected neurosteroid’’9
In the same paper, they pointed out that calcitriol is a potent up-regulator of
nerve growth factor and that the vitamin D receptor (VDR) is found in a
wide variety of brain tissue very early in embryogenesis. They were the first
to conclude that ‘‘hypovitaminosis D should be examined in more detail as a
candidate risk factor for neurodevelopmental disorders’’
In 2006, Kalueff et al. went further, suggesting vitamin D offers
‘‘neuroprotection, antiepileptic effects, immunomodulation, possible
interplay with several brain neurotransmitter system and hormones, as well
as regulation of behaviors 10. The tissue levels of calcitriol during brain
development directly depend on maternal 25(OH)D blood levels, which, in
turn, directly depend on the amount of vitamin D the mother makes in her
skin or puts in her mouth 11.
Autistic individuals have T cell abnormalities and cytokine excesses 12that
show a striking similarity to the immune functions affected by vitamin D13.
Both the brain and the blood of autistic individuals show evidence of
ongoing chronic inflammation and oxidative stress12 , that is, the disease
5
process is probably increasingly destructive. Further hope for a nootropic
effect rests in calcitriol’s powerful anti-inflammatory properties.
Its administration down-regulates production of inflammatory cytokines in
the brain, which have consistently been associated with cognitive
impairment14 Furthermore, calcitriol is remarkably neuroprotective by
stimulating neurotropin release ,reducing toxic calcium levels in the brain,
inhibiting the production of nitrous oxide, and by its immunomodulating
properties – especially in reducing inflammatory cytokines15 and by
increasing brain glutathione.16
This last function of vitamin D, increasing cellular levels of glutathione 17,
may explain the purported link between heavy metals, oxidative stress, and
autism. For example, calcitriol attenuates iron-induced 18and zinc-induced19
oxidative injuries in rat brain. The primary route for the neurotoxicity of
most heavy metals is through depletion of glutathione and subsequent
generation of reactive oxygen and nitrogen species 20 .
Besides its function as a master antioxidant, glutathione acts as a chelating
agent to remove heavy metals, including mercury21 .A placebo controlled
three-month study of 20 autistic children found multivitamins with even low
doses of vitamin D (150 units or 3.75 mcg) significantly improved sleep and
gastrointestinal problems .22
Iron deficiency and autism
High prevalence of low serum ferritin concentration has been reported in
children with autism spectrum disorder (autism) 23 suggesting iron
6
deficiency. This condition could be expected to affect sleep, based on
research suggesting its impact on central nervous system functioning24.
Gluten and casein
It is hypothesized that some symptoms may be the result of opioid peptides
formed from the incomplete breakdown of foods containing gluten and
casein. Gluten is a casein-like substance that is found in the seeds of various
cereal plants—wheat, oat, rye, and barley. Casein is the principal protein in
milk.
Increased intestinal permeability, also referred to as the “leaky gut
syndrome,” allows these peptides to cross the intestinal membrane, enter the
bloodstream, and cross the blood-brain barrier, affecting the endogenous
opiate system and neurotransmission within the nervous system.25 The
resulting excess of opioids is thought to lead to behaviors noted in ASD, and
the removal of these substances from the diet parallels a change in autistic
behaviors.
Iodine deficiency and autism
Román 26 proposes maternal hypothyroxinemia as an important cause of
autism. . Maternal hypothyroxinemia can result from a number of different
pathways and etiologies, including iodine deficiency.
A diet deficient in iodine can result in a wide range of negative effects on the
developing fetus, from mild IQ loss to severe mental retardation, i.e.,
cretinism. 27 Additional support to the hypothesis posed by Román 26 includes
7
the decrease in the iodine nutrition status among women of childbearing age
in the U.S. over the last three decades 28
The pattern of decrease in the iodine nutrition status of a population and
concomitant increase in autism has been seen in other countries 29 Given the
marginal iodine nutrition status, exposure to antithyroid substances
including environmental pollutants such as perchlorate, organochlorines, and
tobacco smoke, these insults result in a deficit in thyroid hormones, and
when present during early pregnancy, result in hypothyroxinemia and most
likely cause autism and other neurologic sequelae.30
Clinical picture
All children with ASD demonstrate deficits in 1) social interaction, 2) verbal
and nonverbal communication, and 3) repetitive behaviors or interests31. In
addition, they will often have unusual responses to sensory experiences,
such as certain sounds or the way objects look. Each of these symptoms runs
the gamut from mild to severe. They will present in each individual child
differently.32
Children with ASD do not follow the typical patterns of child development.
In most cases, the problems in communication and social skills become
more noticeable as the child lags further behind other children the same age.
Oftentimes between 12 and 36 months old, the differences in the way they
react to people and other unusual behaviors become apparent.
Some parents report the change as being sudden, and that their children start
to reject people, act strangely, and lose language and social skills they had
previously acquired. In other cases, there is a plateau, or leveling, of
progress so that the difference between the child with autism and other
children the same age becomes more noticeable.33
8
The following possible indicators of ASD were identified on the Public
Health Training Network Webcast, Autism Among Us.34 :
Does not babble, point, or make meaningful gestures by 1 year of age
Does not speak one word by 16 months
Does not combine two words by 2 years
Does not respond to name
Loses language or social skills
Other Indicators
Poor eye contact
Doesn't seem to know how to play with toys
Is attached to one particular toy or object
Doesn't smile
At times seems to be hearing impaired
Social Symptoms
Most children with ASD seem to have tremendous difficulty learning to
engage in the give-and-take of everyday human interaction. They seem
indifferent to other people, and often seem to prefer being alone. They may
resist attention or passively accept hugs and cuddling. Children with ASD
also are slower in learning to interpret what others are thinking and feeling.
Although not universal, it is common for people with ASD also to have
difficulty regulating their emotions. This can take the form of “immature”
behavior such as crying in class or verbal outbursts that seem inappropriate
to those around them. The individual with ASD might also be disruptive and
physically aggressive at times, making social relationships still more
difficult35
9
Communication Difficulties
Some children diagnosed with ASD remain mute throughout their lives.
Some infants who later show signs of ASD coo and babble during the first
few months of life, but they soon stop. Others may be delayed, developing
language as late as age 5 to 9.
Those who do speak often use language in unusual ways. They seem unable
to combine words into meaningful sentences. Some speak only single words,
while others repeat the same phrase over and over. Another difficulty is
often the inability to understand body language, tone of voice, or “phrases of
speech.” 36
Repetitive Behaviors
Although children with ASD usually appear physically normal and have
good muscle control, odd repetitive motions may set them off from other
children. Some children and older individuals spend a lot of time repeatedly
flapping their arms or walking on their toes. Some suddenly freeze in
position.
As children, they might spend hours lining up their cars and trains in a
certain way, rather than using them for pretend play. If someone accidentally
moves one of the toys, the child may be tremendously upset. A slight change
in any routine—in mealtimes, dressing, taking a bath, going to school at a
certain time and by the same route—can be extremely disturbing. Repetitive
behavior sometimes takes the form of a persistent, intense preoccupation.
Often there is great interest in numbers, symbols, or science topics37
Feeding problems in autism
10
It should be noted that feeding problems are much more frequent than what
is observed with other children with disabilities that have some similarities
to ASD such as language impairments.38 In fact, the atypical eating styles are
so common that at one time they were considered symptomatic of ASD 39
There are a number of target areas for autistic children that are particularly
problematic compared to typical and atypically developing children.
Among these problems are:
1. Prefers food of a certain texture or smell;
2. Will eat only certain foods;
3. Eats things that are not meant to be eaten;
4. Eats too quickly; and
5. Eats too much.
The first two items could be categorized as food selectivity. These items are
generally a target for intervention due to concerns over their high frequency
in ASD.40
The latter three items could be characterized as eating style, and are
potentially very serious, even life threatening. Eating inedible items (pica)
can result in serious injury or death, through choking or intestinal blockage.
Similarly, rapid eating can be and is a life threatening behavior in some
contexts for persons with ASD.
These problems are further compounded by the fact that attempts to redirect
the child can result in greater rates of challenging behaviors. 38 Thus, early
identification of these problems, is nonetheless extremely important.
11
An approach to evaluate food problems is described by Lukens &Linscheid41
.They describe the Brief Autism Mealtime Behavior Inventory (BAMBI),
which they note to be the first standardized measure of mealtime behavior
for children with autism. The authors concluded that the BAMBI had good
internal consistency, test–retest reliability, and good construct and criterion-
related reliability.
The Diagnosis of Autism Spectrum Disorders
Although there are many concerns about labeling a young child with an
ASD, the earlier the diagnosis of ASD is made, the earlier needed
interventions can begin. Evidence over the last 15 years indicates that
intensive early intervention in optimal educational settings for at least 2
years during the preschool years results in improved outcomes in most
young children with ASD3
In evaluating a child, clinicians rely on behavioral characteristics to make a
diagnosis. For the diagnosis, problems in at least one of the areas of
communication, socialization, or restricted behavior must be present before
the age of 3. The diagnosis requires a two-stage process. The first stage
involves developmental screening during “well child” check-ups; the second
stage entails a comprehensive evaluation by a multidisciplinary team.42
Screening for ASD
A “well child” check-up should include a developmental screening test by
the pediatrician 42 Several screening instruments have been developed to
quickly gather information about a child's social and communicative
development within medical settings. Among them are the Checklist of
12
Autism in Toddlers (CHAT),43 the modified Checklist for Autism in
Toddlers (M-CHAT),44 the Screening Tool for Autism in Two-Year-Olds
(STAT),45and the Social Communication Questionnaire (SCQ)46(for children
4 years of age and older).
Screening instruments do not provide individual diagnosis but serve to
assess the need for referral for possible diagnosis of ASD.
If following the screening process or during a routine “well child” check-up,
the child's doctor sees any of the possible indicators of ASD, further
evaluation is indicated.
Comprehensive Diagnostic Evaluation
The second stage of diagnosis must be comprehensive in order to accurately
rule in or rule out an ASD or other developmental problem. This evaluation
that entails neurological and genetic assessment may be done by a
multidisciplinary team that includes a psychologist, a neurologist, a
psychiatrist, a speech therapist, or other professionals who diagnose children
with ASD.
In addition in-depth cognitive and language testing42and measures developed
specifically for diagnosing autism are often used. These include the Autism
Diagnosis Interview-Revised (ADI-R)47 and the Autism Diagnostic
Observation Schedule (ADOS-G).48The ADI-R consists of four main factors
—the child's communication, social interaction, repetitive behaviors, and
age-of-onset symptoms. The ADOS-G is an observational measure used to
“press” for socio-communicative behaviors that are often delayed, abnormal,
or absent in children with ASD.
13
Two other tests that should be used to assess any child with a developmental
delay are a formal audiologic hearing evaluation and a lead screening.
Children with an autistic disorder usually have elevated blood lead levels.42
Treatment Options
Behavioral Management
There is no single best treatment package for all children with ASD. One
point that most professionals agree on is that early intervention is important;
another is that most individuals with ASD respond well to highly structured,
specialized programs.
Among the many methods available for treatment and education of people
with autism, applied behavior analysis (ABA) has become widely accepted
as an effective treatment49. The goal of behavioral management is to
reinforce desirable behaviors and reduce undesirable ones.50 Effective
programs will teach early communication and social interaction skills. In
children younger than 3 years, appropriate interventions usually take place in
the home or a child care center.
These interventions target specific deficits in learning, language, imitation,
attention, motivation, compliance, and initiative of interaction. Included are
behavioral methods, communication, occupational and physical therapy
along with social play interventions51Children older than 3 years usually
have school-based, individualized, special education.
Dietary Intervention
Dietary interventions are based on the idea that:
Food allergies cause symptoms of autism, and
14
An insufficiency of a specific vitamin or mineral may cause some
autistic symptoms.
If parents decide to try for a given period of time a special diet, they should
be sure that the child's nutritional status is measured carefully. A diet that
some parents have found was helpful to their autistic child is a gluten-free,
casein-free diet (GFCF diet).
Since gluten and milk are found in many of the foods we eat, difficulty for
parents to follow the diet modification, the extra cost of the food, and extra
time in preparing the meals, following a gluten-free, casein-free diet is
difficult. In addition, some data suggest that children following the GFCF
diet may have increased prevalence of essential amino acid deficiencies and
bone loss 52
Some autistic children consume self-restricted diets due to sensory
limitations and may limit the number of foods to five or fewer 52. Autistic
children tend to be deficient in minerals such as sulphur, zinc, magnesium,
iodine, lithium and potassium. A supplement that some parents feel is
beneficial for an autistic child is Vitamin B6, taken with magnesium (which
makes the vitamin effective). The result of research studies is mixed; some
children respond positively, some negatively, some not at all or very little.53
The central nervous system is rich in highly unsaturated fatty acids (HUFA),
principally docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid
(20:4n-6, ARA), which cannot be synthesized by the human body but must
be supplied by nutrition.
Highly unsaturated fatty acids are essential for normal brain development
and function 54 There is also increasing evidence that fatty acid deficiencies
15
or imbalances may contribute to childhood neurodevelopmental disorders,
including attention-deficit/hyperactivity disorder, dyslexia, dyspraxia, and
autistic spectrum disorders55.
Parents of children with autism who supplemented their children with
omega-3 rich fish oils reported improvements in general health, sleeping
patterns, cognitive and motor skills, concentration, eye contact, and
sociability, as well as reductions in irritability, aggression and
hyperactivity56.
The underlying mechanism of action is not understood but may be related to
modulation of serotonergic and dopaminergic neurotransmission.57
Management of feeding problems
A variety of food-related problems have been treated in ASD children such
as eating compliance, rapid eating58, inadequate food consumption, and food
packing. 59 However, food selectivity has been the most frequently studied
feeding problem60. Applied behavior analysis has been the treatment model
of choice in most instances.61
Furthermore, existing measures such as the Screening Tool of fEeding
Problems (STEP), which have been developed for persons with intellectual
disability, could be easily adapted to the ASD population 62. Functional
assessment and direct observational methods should also be included in
comprehensive assessment .63
Nutritional assessment
16
Nutrition is also a treatment modality for some autistic symptoms. With an
increasing incidence rate and proposed nutrition connections, more dietitians
will be contacted with referrals for nutritional assessment of children with
autism. The core components of autism, direct resulting behaviors expressed
in the children, and coexisting medical conditions related to autism can be
problematic to conduction of a nutritional assessment.
Dietitians must be aware of several factors when counseling a family with a
child with autism including:
o Multiple medications with serious nutritional implications,
o Serious sensory integration issues that make obtaining anthropometric
measurements difficult,
o Specialized diet patterns containing foods often not covered in standard
dietary analysis software, and
o Impaired communication skills that require reliance on parents for
information64
Medications Used in Treatment
Attempts to treat autism with medications in various chemical classes have
had limited success. Some of the better-studied medications (including
haloperidol and risperidone) often are efficacious in treating associated
symptoms of autism but also can cause unacceptable adverse effects 65 .
Medications are often used to treat behavioral problems, such as aggression,
self-injurious behavior, and severe tantrums that keep the person with ASD
from functioning more effectively at home or school. Many of these
17
medications are prescribed" off-label” This means they have not been
officially approved by the FDA for use in children and further research
needs to be done to ensure not only the efficacy but the safety of
psychotropic agents used in the treatment of children and adolescents.
A child with ASD may not respond in the same way to medications as
typically developing children. It is important that parents work with a doctor
who has experience with children with autism. The child should be
monitored closely while taking a medication.
Anxiety and depression
The selective serotonin reuptake inhibitors (SSRI's) are the medications
most often prescribed for symptoms of anxiety, depression, and/or
obsessive-compulsive disorder (OCD). Only one of the SSRI's, fluoxetine
has been approved by the FDA for both OCD and depression in children age
7 and older.
In addition, fluvoxamine (age 8 and older); sertraline (age 6 and older); and
clomipramine (age 10 and older).34Treatment with these medications can be
associated with decreased frequency of repetitive, ritualistic behavior and
improvements in eye contact and social contacts. The FDA is studying and
analyzing data to better understand how to use the SSRI's safely, effectively,
and at the lowest dose possible.
Behavioral problems
Antipsychotic medications have been used to treat severe behavioral
problems. These medications work by reducing the activity in the brain of
the neurotransmitter dopamine .Haloperidol was found in more than one
18
study to be more effective than a placebo in treating serious behavioral
problems.66However, haloperidol, while helpful for reducing symptoms of
aggression, can also have adverse side effects, such as sedation, muscle
stiffness, and abnormal movements.
Other atypical antipsychotics that have been studied recently with
encouraging results are olanzapine and ziprasidone
Seizures
Seizures are found in one in four persons with ASD, most often in those who
have low IQ or are mute. They are treated with one or more of the
anticonvulsants. These include such medications as carbamazepine
lamotrigine ,topiramate and valproic acid . The level of the medication in the
blood should be monitored carefully and adjusted so that the least amount
possible is used to be effective.
Inattention and Hyperactivity
Stimulant medications such as methylphenidate, used safely and effectively
in persons with attention deficit hyperactivity disorder, have also been
prescribed for children with autism. These medications may decrease
impulsivity and hyperactivity in some children, especially those higher
functioning children
New treatment modalities
A. Hyperbaric Oxygen Therapy (HBOT)
HBOT has produced remarkable results in supplying more oxygen-rich
blood to the cells, including the brain cells. And this has led to vast
improvements in the behavior of autistic kids. Children with autism who
received hyperbaric treatment at 1.3 atm and 24% oxygen for 40 hourly
19
sessions had significant improvements in overall functioning, receptive
language, social interaction, eye contact, and sensory/cognitive awareness
compared to children who received slightly pressurized room air.67
B. Stem cell therapy
The combined use of mesenchymal stem cells (MSC) and cord blood
CD34+cells may be useful in the treatment of autism. The treatment of
immune deregulation in autism is expected to not only cause amelioration
of intestinal and systemic symptomatology, but also to profoundly
influence neurological function 68 .
C. Secretin
The use of secretin, a substance approved by the Food and Drug
Administration (FDA) for a single dose Reports have shown
improvement in autism symptoms, including sleep patterns, eye contact,
language skills, and alertness 69.
20
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25
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