Autism Spectrum Disorder and Pervasive Developmental Disorders in Children

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Autism Spectrum Disorder and Pervasive Developmental Disorders in Children

By Stephen Cowan, MD, FAAP

from “Integrative Medicine for Children” edited by Dr. May Loo, 2008 Saunders


  1. Clinical Consideration in Autism

  2. Etiology :

a. Genetic Influences

b. Prenatal Influences

c. Post-natal Influences

d. Gastrointestinal Inflammation in autism

  1. Conventional diagnosis of Autism

  2. Differential Diagnosis

  3. Conventional management of Autism

  4. CAM management considerations:

    1. The "leaky gut" syndrome and autism

    2. Treating Dysbiosis

    3. Healing the Gut

    4. Strengthening Immunity and Detoxification

    5. Chelation of Toxic Elements

    6. Neuro-metabolic Fine-Tuning

  1. Holistic Management Considerations (author's experience)

  2. Summary

  3. References

Autism Spectrum Disorder and Pervasive Developmental Disorders in Children

By Stephen Cowan, MD, FAAP
Over the past 10 years there has been a significant rise in the diagnosis of Autism Spectrum disorder (ASD) in North America and Europe. What was previously felt to be a rare genetic disorder with a prevalence of 1:2000 now is estimated to be as high as 1:165 children.1,2 Initial denial by the medical community of a significant rise in prevalence has been refuted by studies that have shown this not to be due to improved diagnostics or shifts in the criteria for diagnosis.3 4 The acknowledgement that genetic syndromes do not rise epidemically has led researchers to search for possible alternative explanations for this devastating syndrome.

The term "Autism" was originally coined by Leo Kanner in 1943 and further described by Hans Asperger in 1944. They described a somewhat heterogeneous group of children with an unusual "social-communication syndrome" who appeared to be language-impaired, detached and had a number of odd behaviors. In 1967 Dr. Bernard Rimland established the Autism Research Institute (ARI), a non-profit organization, devoted to conducting research on possible causes and treatment of autism. In 1994, the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV), began referring to Autism as a "spectrum" in order to stress the wide variation in signs and symptoms. This has been further refined to include other neuro-behavioral disorders under the category of Pervasive Developmental Disorder (PDD). (See DSM IV-R Table 1) The term "PDD- Not Otherwise Specified" (PDD-NOS) has been used to refer to children who do not meet the specific criteria for Autism presented in the DSM IV-Revised but nevertheless have some social-communication dysfunction. Recently the term "Autism Spectrum Disorder" has been coined to describe this group of children.
Table 1. DSM-IV-R Diagnostic Criteria for Diagnosis of ASD5

  1. A total of six (or more) items from (1), (2), and (3), with at least two from (1), and one each from (2) and (3):

    1. qualitative impairment in social interaction, as manifested by at least two of the following:

      1. marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction

      2. failure to develop peer relationships appropriate to developmental level

      3. a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest)

      4. a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest)

    2. qualitative impairments in communication as manifested by at least one of the following:

      1. delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)

      2. in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others

      3. stereotyped and repetitive use of language or idiosyncratic language

      4. lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level

    3. restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

      1. encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus

      2. apparently inflexible adherence to specific, nonfunctional routines or rituals

      3. stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)

      4. persistent preoccupation with parts of objects

  1. Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play.

  2. The disturbance is not better accounted for by Rett's Disorder or "Childhood Disintegrative Disorder".

Clinical Considerations:

Children on the Autistic spectrum share a common dysfunction in "relatedness". This is a core feature that accounts for many of their odd behaviors. Though often subtle and frequently missed by parents and clinicians in very young children, the incapacity to "socially connect" may carry more predictive weight than delays in verbal expression. Problems with relatedness are linked to receptive language dysfunction. Parent and clinicians often concentrate more on the number of words a child can say rather than what he/she can understand. To new parents or inexperienced clinicians, it may not be obvious that a child does not comprehend. Asking a child to use a finger to point at a specific object in response to a command is a simple exercise that can elicit receptive language problems . An extreme form of receptive language dysfunction involves the inability to recognize facial expressions. It is important to recognize that a child who confuses a smile for anger may appear to respond quite bizarrely. Receptive language dysfunction impacts on a child's ability to "read social cues". This may be the only clue that there is a problem in high-functioning children such as Aspergers Syndrome. Relatedness also manifests as the inability to "reciprocally interact". Typically, autistic children will have great difficulty "taking turns". A simple exercise to assess this skill is to ask a parent to roll a ball to the child and observe if and how many times the child will "get the game", rolling it back and forth. Limited ability to "pretend play" also reflects this restricted social-communication ability in autism. These children are often unable to "symbolically" represent the world with language. This greatly limits the capacity to mentally transform an object or mimic adult behavior. The spontaneous development of imagination, imagining a pencil as a rocket-ship or feeding a bowel of pretend soup to a doll (pretend person) does not occur unless relatedness and receptive language develop. The clinician must additionally be keenly aware of the quality of a child's sense of humor. "Getting the joke" implies sophistication of social-language abilities that is often lacking in the autistic child. Lastly the clinician needs to observe the degree to which the child's repertoire of activity is restricted. Due to the inability to understand the unpredictable world of human language and behavior, many children develop a rigid set of routines as self-defense. They often show intense resistance to change that can harden into obsessive compulsive behaviors. Many self-stimulatory behaviors develop as a way of "blocking out" the chaos of the world. An autistic child may choose sensory input that "feels" good and withdraw into it when they are being overwhelmed. Some children with autism seem to get caught in the details of things, spinning shiny objects, studying the electrical circuitry of a room, etc. They appear to be hyper-focused, studying the basic mechanisms of their environment. Self-stimulation, (hand-flapping, spinning etc.) may also be the result of an apparent heightened sensory awareness. Many children with autism will demonstrate extraordinary sensory abilities. These may result from a compensatory reaction to the limitations on the "social senses". One observes analogous abilities in the heightened visual acuity of the hearing impaired child and the heightened sense of smell or touch seen in the visually-impaired child.


The etiology of autism at present is unknown. This may be largely due to the fact that Autism is a "symptom complex" and not a single entity. No single cause has as yet been identified but recent research is beginning to reveal pieces to the puzzle.

1. Genetic and Metabolic Factors: Chromosomal abnormalities account for less than 1% of children with autistic features6,7. These involve aberrations in chromosome 15q (15q11-q13)8,9 Conventional texts report that less than 5% of autistic children show evidence of in-born metabolic disorders.10 Family studies in children with autism have noted an increased prevalence of autoimmune disease, inflammatory bowel disease, depression, obsessive–compulsive disorder, anxiety disorder, bipolar disorder, social phobia and language disorders.11 12 13 14 There is some evidence that relatives of autistic children show mild social, communicative or repetitive behaviors that may place them on the "normal end" of the autistic spectrum. There is a 3:1 predilection for males over females in autism, which may indicate some genetic influence or may be related to the relative strength of social/empathy skills generally demonstrated by girls. Twin studies of autistic children show a 60-90% incidence of autism in monozygotic twins.

Recent research has shown important evidence that multiple gene-loci may be involved in the expression of autistic characteristics.15 Studies have shown an increased number of genetic variants (polymorphisms) associated with the enzyme activity of Methylenetetrahydrofolate Reductase (MTHFR) in children with Autism.16 This enzyme is essential in the Methionine Synthase reaction, a major biochemical component of the detoxification process associated with production of glutathione, methylB12 , folate/follinic acid activation and dopamine formation. This may have great importance in understanding the etiology of Autism as a spectrum related to potential neuro-toxic exposures. Current thinking in genetics understands the complexity of human neuro-social development to result form the "organic" nature of genes which are turned on and off by various environmental stressors.

2. Prenatal Influences: Over the past 5 years, the term "Regressive Autism" has begun to be used to differentiate a subtype of children who are developmentally normal until 1-2 years of age and then begin to lose milestones or plateau in developmental progress.17 18 19 20 21. Retrospective studies have found a number of associations with the development of Autism. These include: exposure to epidural anesthesia, the older age of parents at the time of conception, elective or emergency caesarian section, use of pitocin for labor induction, and threatened abortion, 22 23

3. Post-natal Influences: In order to explain the apparent exponential rise in prevalence of autism in recent years, researchers have been looking at a number of potential environmental causative factors. Over the past decade, many articles have suggested a possible role of mercury exposure in autistic-like neurologic disorders. Remarkable similarities between mercury toxicity and autism have been noted. 24 25 26 Mercury has been shown to compromise the detoxification mechanism mediated by glutathione and methionine synthase. 27 28 29 It has also been noted that mercury toxicity causes impairment of the immune system and increased risk of autoimmunity.30 31 A significant source of methyl-mercury has been found in Thimerisol-containing vaccines and there is some evidence that cumulative exposures have the potential for neurologic sequelae.32 33 34Based on the VAERS and US Department of Education data, Geier demonstrated a linear statistical relationship between the incidence rate of neurodevelopment disorders after childhood immunization and increasing thimerisol in vaccines. 35 36 37. In light of the literature acknowledging the potential risks to the infant exposed to mercury during infancy in the context of the increasing prevalence of autism spectrum disorder, pharmaceutical companies have begun removing thimerisol from vaccines. 38 39 40

4. Gastrointestinal Inflammation in Autism: In 1999, Horvath published evidence of an apparent inflammation of the gut in children with Autism.41 The following year Wakefield demonstrated biopsy evidence of chronic enterocolitis in autistic children.42 Recent studies have shown abnormal gut mucosal immune infiltration and impaired intestinal permeability in autistic children. 43 44 45 46 Emerging research ofver the past twenty years has generated a new field of study linking brain and gut function. Much of this has concentrated on the immune effects of stress on the gut.47 48 49 The reverse relationship, where inflammation of the gut affects brain dysfunction has also been found in children with autism and the term "Autistic Entero-colonic Encephalopathy" has begun to be used. 50 51 52 53 54 Evidence of impaired gut immunity associated with Candida overgrowth in children with autism has been demonstrated with increased excretion of urinary arabinose and analogs of Krebs cycle metabolites.55 56 57 58

In 1998, Wakefield published the highly controversial findings of a possible link between Measles virus and the gut-inflammation found in children with Autism. This was based on biopsy identification of genomic measles RNA in lymphoid follicles of gut mucosal in children with regressive autism. 59 Based on previous studies that have demonstrated a known relationship between measles infection and Crohns disease and other inflammatory bowel diseases60 61 62 , he proposed that live measles virus vaccines such as the MMR may play a role in the immunologic etiology of autism. Other studies have failed to confirm this association.63 64 65. Singh et al have recently published a number of articles showing evidence, however, of an abnormal hyper-immune response to measles in children with autism which may represent a mercury-induced autoimmune response to live virus exposure.66 67 68 There is mounting evidence of increased autoimmunity in Autism. 69 70 71 72 73 Clearly further studies are needed to clarify the relationship between viral immunity and autism.
The Conventional Diagnosis of Autism

There is no doubt that the earlier a child is evaluated for possible Autism Spectrum Disorder, the better the prognosis. The American Academy of Pediatrics has recently highlighted the need for early diagnosis with the A.L.A.R.M. policy which encourages early evaluation, diagnosis, referral and parent education. 74 The diagnosis of autism spectrum disorder is typically based on the criteria described by the DMS-IV-R. (see table1). With the recent increase in the prevalence of Autism, the American Academy of Pediatrics has adopted recommendations made by the American Academy of Neurology and the Child Neurology Society which developed practice guidelines to help the clinician.75 (This information has been endorsed by the American Academy of Audiology, the American Occupational Therapy association, The American speech-Language-Hearing association, the Autism National Committee, Cure Autism Now, the National Alliance of Autism Research and the Society of Developmental Pediatrics). The initial assessment of a child suspected of having Autism begins in the clinician's office where routine developmental screening should be a part of general health supervision. There are a number of developmental screening tools available that have some sensitivity in picking up children with developmental problems. These include: The Ages and Stages Questionnaire, the BRIGANCE screens, the Child Development Inventories and the Parents' Evaluations of Developmental Status.76 Of note, the Denver-II (DDST-II), which is widely used by pediatricians as a screening tool has been shown to detect only 30% of children with language impairments and 50% of children with mental retardation.77 78. The importance of listening to parents' concerns about developmental issues cannot be overstressed and there have been studies demonstrating the high sensitivity and specificity this carries in detecting global developmental deficits.79 80 Optimum screening combines attention to parents' concerns and observations coupled with appropriate screening tools. Important signs that raise suspicion of a autism and require immediate evaluations include:

  1. No babbling, pointing or gesturing by 12 months of age

  2. No single words by 16 months of age

  3. No two-word spontaneous phrases (not echolalia) by 24 months

  4. Any loss of any language or social skills at ANY age

Following the identification of a child "at risk" for a developmental disorder like autism, it is recommended that the child be referred for formal audiologic evaluation and lead testing if pica is present. Because there are no biologic markers for autism, a number of screening tools have been developed to look "specifically" for signs of Autism Spectrum Disorders. These include: "The Checklist for Autism in Toddlers" (CHAT), and the "Autism Screening Questionnaire (ASQ)". Newer screening tools are currently being developed to increase specificity such as the PDDST-II-stage 1 and the Australian Scale for Aspergers syndrome. It is recommended that a clinician experienced in the diagnosis and treatment of autism be consulted for an accurate diagnosis. The formal evaluation of a child for autism should include:

  1. A family history

  2. A Parent interview (Gilliam Autism Rating scale, the Parent Interview for Autism, the PDDST-Stage 3, The Autism diagnostic interview, Revised, The Childhood Autism Rating Scale, the Screening Tool for Autism)

  3. Past medical history (birth history, milestones, regressions, seizures, pica)

  4. Physical/neurologic evaluation: head circumference (there is an increased prevalence of macrocephapy in autism), presence of dysmorphic features, gait disturbance, hypotonia, and presence of focal neurologic signs.

  5. Genetic evaluation for Fragile X syndrome and Tuberous sclerosis (children with these syndromes may exhibit autistic characteristics)

  6. Verbal and Non-verbal communication assessment

  7. Cognitive Assessment of adaptive skills

  8. Sensory-motor and occupational therapy evaluation

  9. Neuropsychological and behavioral assessment

  10. Selective metabolic testing: (inborn errors of metabolism may be associated with autistic behaviors though the prevalence is less than 5%)81

  11. EEG studies: the prevalence of seizures in autism is estimated at 7-14%.82 Electrophysiologic studies should be reserved for children who demonstrate clinical or subclinical seizures and have a history of regression in development.

  12. CT and MRI studies: inconsistent findings in neuro-imaging studies of children with autism make these studies unwarranted as routine unless there are specific neurologic concerns83

Differential Diagnosis:

AS a child develops, the nervous system is constantly being remodeled by environmental stimulae through a process known as Apotosis or "neurologic pruning". This permits the most efficient neural pathways to be fortified while those that are inefficient are destroyed.84 The constantly changing nervous system may present the clinician with a confusing picture when diagnosing a child with autism. Early on, many developmental problems may present with similar characteristics of autism but as the nervous system matures characteristics may change or subside. This is in no way a reason to delay evaluation and treatment but it is wise to remember that a diagnosis of autism can only be taken as a "snapshot" of a moment in the constantly adapting child's life. Odd behaviors such as "self-stimulation" and "echolalia" may not be specific to children with autism but may be non-specific signs of other developmental language disorders. Careful evaluation and tracking is essential to determine the accuracy and prognosis for each child. See Table 2 for examples of related syndromes to consider.

Table 2: Differential Diagnosis

Rett's Disorder;
Childhood Disintegrative Disorder
Asperger's Disorder
Selective Mutism

Expressive Language Disorder
Mixed Receptive-Expressive Language Disorder

Semantic Pragmatic Language Disorder

Verbal Apraxia

Non-Verbal Learning Disability
Mental Retardation
Stereotypic Movement Habit Disorder

The Conventional Management of Autism :

Early diagnosis is imperative in order to start treatment as early as possible. As with other developmental disorders, prognosis is improved with early detection and treatment. 85 86 The first-line of management is referral to early intervention services for neuro-development support. Controversy over treatment has changed through the years. 10 years ago, conventional neurology/psychiatry considered treatments such as Applied Behavioral Analysis (ABA) and Sensory Integration Therapy (SI) to be "alternative therapies" but these have now become standards of care in many areas. Early intervention services for autism typically include: Special education, Speech therapy, Occupational therapy, Physical therapy and Social skills therapy. Based on evaluation of a child's particular deficits and sensitivities, additional therapies may include: Auditory Integration Therapy, Sensory Integration Therapy, Visual Training Therapy, Music Therapy, Cranio-Sacral therapy.

At present there are no specific indications for the pharmacologic treatment in autism. Conventional medicine has relied on the pharmacological management primarily for the management of aggressive or compulsive behaviors in autism. Medications such as Risperidone, Abilify, Prozac, Paxil, Adderall, Depakote, Propranolol and other psychotropic medication are currently being used on an experimental basis by the psychiatric/neurology specialists.
Complimentary and Alternative Management Considerations:

Because of the unknown nature of autism, parents and practitioners have explored a wide range of CAM practices over the years. Since 1967, The Autism Research Institute has been supporting research in alternative treatments in autism. The ARI recognized that many parents may feel significant desperation in their search for a "cure" which puts them at particular risk for trying many treatments simultaneously which can lead to exorbitant expense as well as confusion as to what is actually working. In the past ten years, a number of clinicians and researchers have developed the "D.A.N. protocol" (Defeat Autism Now!) in an attempt to assess the efficacy of various alternative and nutritional therapies in autism.87 Parents should be advised to seek qualified, informed professionals such as clinicians who have been trained in the D.A.N. protocol and are listed on the ARI website.

Based on the accumulating etiologic evidence in the scientific literature, the D.A.N. protocol has proposed that autism results from the cumulative effects of repeated toxic exposures in genetically predisposed children.88 Recent evidence of impaired gut immunity and function in autism has led CAM practitioners to treat this disorder as a toxic inflammation of the neuro-digestive system. Understanding the etiologic sequence (see table 3) that leads up to the full blown expression of Autism is essential to developing a treatment strategy for each child: (see table 4). The sequence and dosages of supplements listed below are meant only as a general guide to practitioners and are by no means specific for one particular patient. Variations in clinical presentation, laboratory data and responses to interventions must always be taken into consideration by the CAM practitioner when choosing an intervention.

Table 3. Etiologic Sequence of Autism

Genetic Predisposition

Perinatal Factors

Impaired Detoxification

Gut Inflammation

Yeast overgrowth

"Autistic Enterocolitis, Encephalitis Syndrome"

Table 4. Treatment Sequence in Autism

1. Treat Dysbiosis

2. Heal the Gut

3. Strengthen Immunity and Detoxification

4. Chelation of Toxic Elements

5. Neuro-metabolic Fine-Tuning.

1. "The Leaky Gut Syndrome" and autism: A major component of the immune-regulatory system in the infant is located in the digestive tract. In genetically-predisposed children, repeated exposures to toxins results in a chronic inflammation of the intestinal wall with subsequent "hyper-permeability" that allows increased absorption, ("leaking in"), of macromolecules, diasaccharides, antigens and toxins resulting in neuro-immune dysfunction.89 90 91 A viscous cycle of gut mucosal damage is set up by repeated mercury exposure or antibiotic use which leads to abnormal gut-flora overgrowth "dysbiosis" (yeast, pathogenic bacteria like clostridia etc.). This further damages the gut mucosa leading to absorption of the toxic by-products of abnormal gut flora (lactic acid, organic acids, arabinose, biologically active peptides etc.) which aggravate brain function leading to progressive neurologic damage.92 93 94 95 96 A host of non-specific symptoms may be early signs of "leaky gut". These include eczema, bloating, colic, hives, reflux, wheezing, diarrhea, and constipation. Treatment of "leaky gut" syndrome is an essential component of the CAM management of autism although its presence is not specific to autism.
2. Treating Dysbiosis: One of the first steps in the CAM management of a child with Autism is to treat abnormal gut flora (dysbiosis) if present.97 Organic acid tests are available to determine the presence and degree of dysbiosis98. An IgG Food Sensitivity test will give indirect evidence of "leaky gut syndrome" and serve as a guide to what foods to avoid. Often simply "lightening the load" of foods that are "toxic" to a leaky gut will have a beneficial effect on behavior. 99 Placing a child on a Gluten-free, Casein-free diet reduces the burden on the digestive system.100 In some cases, the reduction of casomorphin absorption is enough to improve developmental progress.101 102 The treatment of Candida yeast overgrowth may require pharmaceutical antifungals such as Nystatin or Diflucan. Although this will often have a significant effect on developmental progress, antifungal drugs can have a compromising effects on liver function and must be used with great care. Natural antifungals include Garlic, Grapefruit seed extract and Saccharomyces Boulardii. Parents should be counseled to watch for symptoms of "die off" (the effects of absorption of toxins from killed yeast). These may include behavioral regressions, loose stools, increased self-stimulation, abdominal pain, and rashes. The addition of probiotics is essential to gut health, replacing pathogenic organisms with "good bacteria".103 A trial of Elaine Gottshalts's Specific Carbohydrate Diet (SCD) has proven to be beneficial in treating dysbiosis. The basic premise of the SCD is to limit the availability of carbohydrates that pathogenic intestinal microbes require for energy. By depriving their food source, the bacteria will gradually decrease in number. As the number of microbes decreases so do the toxic by-products they create.104

3. Healing the Gut: In addition to probiotics, the gut lining can be strengthened with some basic nutritional supplements that include: (Approximate dosages based on DAN protocol, individual considerations are required)105 106

Zinc: picolinate form is most absorbably 10-50mg/day

Calcium: 250-1000mg/day

Magnesium: glycinate form is most absorbable, 100-300mg/day)

Vitamin B6: in activated P5P form 50mg < 5 years old

Vitamin C: up to 1000 mg /day

Vitamin A: as cod liver oil or as supplement 1000-5000 iu/day

Selenium: 50-150mcg high doses may be toxic

Supplements that reduce inflammation of the gut include:

L-Glutamine: up to 3500 mg/day

Licorice root: in deglycyrrhized form up to 500 mg/day

Aloe barbadensis: up to 50mg/day

Omega 3 Essential Fatty Acids (EFA): 750-1200mg/day

Coenzyme Q 10: 30-60mg/day,

Grape seed extract,

Vit B12 as methylcobalamin 750-2500mcg as subcutaneous injection

DMG (Dimethylglycine): 125-250mg/day

Digestive enzymes improve absorption and should be given with meals.

Authors note: It is this author's experience that it is wise to start autistic children at lower doses for all supplements because of heightened sensitivities. Often in fact, lower doses may give paradoxically better responses than higher doses.

4. Strengthening Immunity and Detoxification Support : Reducing the oxidative stress on the body has been shown to improve both gut and neurologic function.107 Reduced Glutathione (oral 150 mg BID, topical 125 mg BID or IV 300-600 mg)108 has both anti-inflammatory functions as well as being supportive in the detoxification mechanism. It is available in both oral form and as a topical gel which may be better tolerated and better absorbed. In addition, high dose Vitamin C, Carnosine, Vitamin B6, Magnesium, Zinc, Selenium, and Folinic acid support biochemical pathways involved in the protection against oxidative damage.

5. Chelation of Toxic Elements: The removal of heavy metals has been utilized in the treatment of lead poisoning for many years. Based on evidence that children with autism may have faulty immune function, it has been hypothesized that they cannot handle the increased exposure to heavy metals known to have neurologic effects such as mercury found in vaccines and environmental pollutants. With this in mind, provoking an excretion of these metals with a chelating substance such as DMSA would determine the need for removal by chelation.109 Since chelation is a potentially dangerous procedure, support of both the digestive and immune systems is essential before trying to remove potentially toxic elements. Careful monitoring for adverse reactions from both the chelating agents and the mobilization of toxic elements is required. Hematologic and liver function monitoring is recommended and the procedure often requires mineral supplementation. Bone marrow suppression and impaired hepatic function although rare have been reported during the chelation process.110 Allergic reactions and seizures have also been reported. 111 A single-dose challenge of a chelator like DMSA (10mg/kg) followed by measurement of urinary metal excretion will determine the need for chelation. (Authors note: It has been this author's experience that many parents seek quick treatment solutions and rushing into chelation should be avoided because it can result in making a child sicker if the child is not adequately prepared and monitored by an experienced clinician.) Natural detoxing agents such as Garlic, Cilantro, Chlorella, Chitosan and Hyaluronic acid have been used in the treatment of heavy metal toxicity. Allithiamine (a synthetic form as thiamine tetrahydrofurfuryl disulfide: TTFD) is a garlic derivative that may potentiate removal of heavy metals and has been recommended as a topical application.112

6. Neuro-Metabolic Fine-Tuning: Impaired function of methionine synthase impacts on the bio-activity of SAMe, B12 and glutathione, all of which play a role in the chemical mediators of brain function. Supplementation with DMG (dimethylglycine), TMG (betaine), Methyl B12, Amino Acids, DMAE, L-theanine, Acetyl-L-Carnitine, Coenzyme Q10, and specific neurotransmitter precursors like tyrosine and 5 HTP and Tryptophan can support proper brain function. Tests are available to indirectly assess relative imbalances in neuro-transmitters113.

Other Holistic Management Considerations:

It has been this author's experience that the challenges facing a clinician in the treatment of children with autism require a holistic perspective that takes into consideration the complex interactions of both internal and external environments. Chinese medicine offers a complete system of medicine that provides a novel model for understanding autism in the framework of disharmonies and imbalances. Although there are no published studies on the use of Chinese medicine in autism, the author has found practical applications in conceptualizing etiology and designing treatment options through TCM.

In traditional Chinese Medical texts, children with mental disorders that bear similarities to Autism are described as resulting from "phlegm misting the mind".114 The origin of this phlegm is thought to be internal trauma, excessive wetness, inappropriate diet, and food stagnation. Stagnation in the spleen network is a common source of phlegm in children due to intense activity during the formative years of growth. The Spleen's importance in transforming food into qi and differentiating "clear" and "dirty" fluids in the digestive processes cannot be overstated in children.115 Spleen dysfunction corresponds well with the "leaky gut" model described above. Furthermore, the spleen is considered to be the residence of thought, influencing introspection, and focus, factors that are impaired in autism.

In the Five Phase Model (see diagram) described in Chinese medical texts116, 117 118 there is a regulatory (ke) relationship between the Spleen and Kidney (Jing which is responsible for the inherited capacity to develop and thrive). This is well-illustrated by the etiologic relationship between causative environmental agents and genetic predisposing factors found in autism.

When the spleen network is weakened or stagnant, phlegm begins to "mist the mind". Consequently it cannot support the Lung/Large Intestine system (sheng cycle) with resultant signs of constipation, diarrhea and eczema. With further toxic exposures and damage, the kidney network decompensates, leading to an "ungrounding" of developmental drive with apparent plateaus and regressions in development. As the five-phase system uncouples, the Liver network show signs of dysfunction resulting in motor-planning problems, balance issues and agitated "fight or flight" behaviors. Ultimately, with "rebellion of the Liver", the Heart network, the so-called "Emperor" loses rule over the governing of physical, emotional, and spiritual aspects of the being. Speech, which is governed by the Heart is blocked and shen is unstable. Thus autism can be understood as a multi-system failure, resulting in the unpredictable and disconnected nature of the child.

Treatment is aimed at first re-establishing harmony between the Spleen qi and Kidney/jing, (dietary management, treating dysbiosis, supporting the immune system), strengthening the Lung/Large Intestine (re-establishing membrane boundaries, healing the gut) followed by strengthening the Liver/hun (detoxification and chelation) and ultimately comforting the Heart/shen (support of neuro-metabolic fine-tuning). A treatment plan which incorporates this model allows the practitioner to integrate chinese dietary principles, herbs and acupuncture/acupressure into the D.A.N. protocol.

Having treated a large number of children with autism over the past 10 years, this author has found this method very effective. It is important to note, however, the dangers of doing "too much too fast". "Too much" acupuncture may be overstimulating to the overly sensitive autistic child and making changes too fast can have a destabilizing effect on the delicate balance of development. It is the author's experience that Laser acupuncture also tends to provide excess stimulation while tuning fork stimulation of particular acupuncture points and the use of gold-plated magnets has a beneficial effect. In particular, the treatment of "Shen Men" ear points with magnets, foot massage (tui na) of K1 and LV3 and gentle acupuncture at K3, SP6, St 36, LI11, TB5 have beneficial regulatory effects and appears to work synergistically with some of the other treatments outline above. Herbs that promote harmony between Spleen and Liver (such as Bluperium root, cyperus, licorice root, unripe citrus peel etc.) and Kidney and Heart (such as rehmannia root, sciszandra, salvia root, and lotus seed) have been particularly helpful. 119

CAM treatments can be of great benefit in the management of Autism. In light of the rising prevalence of this disorder and the limited treatment options offered by conventional medicine, practitioners should be encouraged to explore alternative treatment options that have proved successful. Developing a holistic treatment plan requires an understanding of autism as a cumulative series of insults to the neuro-immunologic system. The complex relationship between genetic predispositions and toxic exposures may account for the wide variations in symptoms encountered in this syndrome. This may have great importance in preventive management when counseling siblings of children with autism. Early non-specific symptoms such as eczema and chronic loose stools associated with language delays may be subtle signs of impending developmental dysfunction. Since no single cause of autism has been found, research must be aimed at considering multiple variables together. A careful history and tracking of symptoms is essential for diagnosis, management and prognosis. An approach to management that respects the highly sensitive nature of children with autism can result in profound improvements in behavior and development.

1 Bertrand J, et al: Prevalence of autism in a United States population: the Brick Township, New Jersey investigation. Pediatrcis 108: 1155-1161, 2001

2 Newschaffer CJ, et al: National autism prevalence trends from United States special education data. Pediatrcis 115:e277-e282, 2005

3 Byrd, RS, Report to the Legislature on the Principal Findings from the Epidemiology of Autism in California: A Comprehensive Pilot Study. San Diego: MIND Institute, University of California, Davis; 2002. The Epidemiology of Autism in California: A Comprehensive Pilot Study

4 Yeargin-Allsopp M, et al: Prevalence of autism in a US metropolitan areas. JAMA 289:49-55,2003

5 Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Revised (DSM-IVR), American Psychiatric Association, 2000

6 Weidmer-Mikhail E et al, Chromosomes in autism and related pervasive developmental disorders: a cytogenetic study. J Intellect Disabil Res 1998;42:8-12

7 Schroer RJ et al. Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998;76;327-336

8 Cook Eh et al. Autism or Atypical autism in maternally but not paternally derived proximal 15q duplication. AM J Hum Genet 1997;60:928-934

9 Weidmer-Mikhail E et al. Chromosomes in autism and related pervasive developmental disorders: a cytologic study. J Intellect Disabil Res 1998;42:8-12

10 Dykens EM, Volkmar FR. Medical conditionsassociated with autism. In: Cohen DJ, VOlkmar FR, eds. Handbook of autism and pervasive developmental disorders, second edition. New York, NY: John Wiley & sons, 1997:388-410.

11 Comi AM, Zimmerman A et al, 'Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism', Journal of Child Neurology, 1999, Vol. 14, pp. 388-394
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