"Reprinted with permission from the July- August 2000 issue of the Autism Asperger's Digest, a 52-page bimonthly magazine on autism published by Future Horizons, Inc. www.autismdigest.com"
Introduction
During my medical training, I learned that autism and its related disorders were essentially incurable, a finding certainly confirmed by our dismal experience. Our autism clinic was an exercise in diagnosis and no treatment; what little we did for children was largely ineffective. While we had come a long way from Bettelheim's refrigerator mother theory of autism (in which a cold, unresponsive mother was the cause of the condition), we were stuck in a genetic-biochemical hypothesis allowing no possibility for cure or improvement. We were confident that the unknown genetic defect was buried deep in the biochemistry of the brain. We were excused from searching for treatments, thereby leaving this crucial journey to the parents.
The parents of autistic children convinced me that everything I learned was wrong, to everyone's benefit. Freed from the fetters of training and pessimistic professors, I discovered that children with developmental disorders are interesting, and have rich social and communicative lives, though different from their so-called normal counterparts. Attentive parents naturally learn this secret language of their autistic children without even realizing this amazing feat.
Autistic children do communicate and do respond, but as if they live in a parallel universe, which can nevertheless be accessed by those who want to reach them. They respond to many treatments, including just receiving attention and being cared for. They respond to nutritional therapies and body therapies, such as reiki or craniosacral therapy. They respond to acupuncture. They respond to biofeedback and to behavioral educational therapies. What don't they respond to?
Can autistic children become indistinguishable from so-called "normal" children? I have seen it happen sufficiently often to believe, though - in every case - the parents invested significant time and money to their child's treatment: far above what school systems and insurance carriers would have paid. To what can we attribute these successes? No one treatment seems to out perform all the others, and no clear signposts exist to tell parents what to do. Despite this, there are therapies with which I begin.
Nutritional Therapy
Nutritional therapies are first on my list. The gluten-casein free diet has helped many children and is where I begin. The diet can be difficult. Gluten, a major constituent of wheat, and several other grains, is hard to eliminate. Gluten can be found in soy sauce, for example, in the form of whey. Gluten can be found in the coatings of pills used for medicine. Eliminating dairy is almost as hard. Nevertheless, excellent cookbooks exist and are found on our web site.
The theory behind gluten-casein free diet is based on the opioid hypothesis of autism. In this hypothesis, defective intestinal enzymes (especially dipeptidyl-dipeptidase IV) allow large molecules to "leak" through the gut. Gluten, and the structurally related casein from dairy, are incompletely digested and pass through the gut as molecules with opioid-like properties. In larger doses, these molecules cause hallucinations. The effect of opioid-like compounds are, in part, the symptoms seen in autism, Asperger's, and other developmental disorders.
While the diet is difficult to follow, one month is usually sufficient to determine if following the diet will help. After one month, if any question exists, challenging the child with a grilled cheese sandwich on whole wheat bread helps to determine if symptoms will worsen after exposure to gluten or casein. Sensitive children become clearly worse after this meal. At least half of my patients improve significantly after starting the gluten/casein free diet.
Second on my list of interventions, after "GF/CF diet" or variants of it, is vitamin supplementation.
Vitamin Therapy
Enthusiasm over particular vitamins appears in waves. Recent candidates include individual B-vitamins (B6, B12, thiamin), vitamin A, and essential fatty acids. Dr. Patricia Kane has promoted awareness of fatty acid metabolism among autistic spectrum children. Through BodyBio, she offers analysis of fatty acids on the red blood cell membrane to determine their relative levels. Fatty acid metabolism can be directed toward a pro-inflammatory state or an anti-inflammatory state, the former being worse for autistic children.
Supplementation with specific fatty acids (especially omega-3 and omega-6) can alter pro-inflammatory tendencies toward anti-inflammatory. While the details of fatty acid therapy can become quite intricate, three oils provide almost all of the compounds needed: evening primrose oil, borage seed oil, and marine lipids.
We can broadly speak of an inflammatory theory of autism, in which nerve cell membranes are irritated and nerve transmission is affected. The inflammation can come from a variety of sources, including viral infections, auto-immune phenomena (in which the body's immune system attacks its own nervous system), post-vaccine reactions, abnormal molecules in the nervous system (coming from the leaky gut and deficient enzyme activity in the gut), and abnormal fatty acid metabolism. The inflammatory theory can explain the role of some vitamins as anti-oxidants (preventing and reversing cellular damage from inflammation) and as direct anti-inflammatory agents (vitamin C, omega fatty acids).
Vitamin supplementation alters metabolism of the nervous system and provides an abundance of resources for healing within the brain. Getting children to take vitamins can be difficult, but can be overcome by blending vitamins into palatable drinks or by mixing the vitamins into foods that the children will eat. Stevia is a sweetening herb that makes these concoctions more palatable without causing the adverse side effects sometimes associated with simple sugars. My basic supplement program includes vitamin C, trace minerals (vanadium, germanium, selenium, tungsten, tin, etc.), common minerals (zinc, manganese, magnesium, calcium), B vitamins (with extra thiamin, B6, and B12), vitamin A, evening primrose oil, marine lipids, OPC-3's, and vitamin E. Recent enthusiasm has centered around vitamin A followed by doses of urecholine. I have not yet tried the urecholine, but suspect that urecholine may not be the essential element of the treatment.
Pygmalion Effect
A major problem in autism treatment is separating what could be called the "Pygmalion Effect" from true biological efficacy. The problem is complicated by the possibility that true biological activity without an emotional and environmental context for a treatment doesn't really exist. The Pygmalion Effect is named after George Bernard Shaw's play in which a lower class, "uncultured" woman from the slums of London is trained to be a "lady," and becomes every bit as sophisticated as one born to this position.
The effect has been demonstrated in elementary school classrooms. In the classic experiment, children's IQ's were measured and the children were ranked as higher or lower IQ. Teachers were told the opposite from what was found. High IQ children were presented to teachers as lower IQ. Low IQ children were presented to teachers as high IQ. One year later, the teachers' expectations were much more important in determining children's performance than their actual IQ. Knowing this, we could never ethically repeat this experiment, for we are so much more aware of how people's expectations for others determines performance.
A confounding problem in evaluating any therapy for autism, including vitamins, is this Pygmalion Effect. Because of this, many conventional physicians dismiss the potential value of alternative therapies in favor of pharmaceutical treatments. Drugs are always better studied than alternative treatments, because 1): they are easier to study, 2): more money exists to study drugs because of the potential profitability, and 3): it is more respectable as a researcher and a physician to study drugs.
Until sophisticated clinical trials are completed, any of the alternative therapies I will discuss could be explained partially or completely by the Pygmalion Effect. What is exciting about this is the realization that expectations can alter behavior. If parents expect strongly that their autistic child will improve, the child does. I am not afraid to try safe therapies that may only work because they activate this Pygmalion Effect. This type of healing is just as real as that produced by drugs, and probably much safer!
While we struggle to find biologically active treatments for autism, we cannot err too greatly by supporting parents' enthusiasm for safe, new treatments. We know from research on the placebo effect that an enthusiastic doctor whose patients believe in him or her has a 70% success rate regardless of the effectiveness of the treatment. An unenthusiastic doctor has only a 30% success rate with an ineffective treatment. Therefore, we should never discount enthusiasm.
I continue to believe that vitamins are an important part of treating autism, the above considerations aside. Nevertheless, the Pygmalion Effect may be very important in another popular therapy - that of secretin.
Secretin
Secretin is a 27 peptide hormone, produced in the intestines, and commercially marketed as an aid to endoscopy. The interest in secretin began in 1996, when Dr. Karoly S. Horvath, director of the pediatric gastrointestinal and nutrition laboratory at the University of Maryland, Baltimore, administered intravenous secretin while examining an autistic child with chronic diarrhea. Several weeks later, the child's mother, Victoria Beck, called with surprising news: her 3-year-old son, Parker, had started to talk and had good eye contact 1. Subsequent infusions, obtained by the parents - against medical advice - led to further gains.
Dramatic improvement has been reported for some autistic children who receive secretin. Typically a dose of 2-3.5 International Units per kilogram of body weight is administered intravenously every 3-7 weeks, depending upon the child's response and when the effects of the secretin appear to wear off. Victoria Beck switched to transdermal administration for her child in which the secretin is applied daily to the skin and soaks into the body through a vehicle such as DMSO. Typically a dose of 3 to 7.5 International Units is used each day.
Dr. Horvath and associates gave secretin while assessing gastrointestinal complaints in two other autistic children, and reported "a dramatic improvement in their behavior, manifested by improved eye contact, alertness, and expansion of expressive language," in the next several weeks along with relief of gastrointestinal symptoms 2.
In December 1999, Dr. Bernard Rimland of the Autism Research Institute in San Diego, California, reported that one-half of 100 treated children improved in behavior, sleep, and/or digestive symptoms - based on questionnaires returned by self-selected parents.
In another series, 70% of 200 children responded positively, according to the treating physician, with a dramatic effect among 10%. These reports did not control for concurrent treatment, nor was diagnosis rigorously established.
The results of a randomized, controlled trial of one dose of secretin was reported in the New England Journal of Medicine's December, 1999, issue by Dr. Sandlin and colleagues. Children were randomized to receive either secretin in an appropriate dose or placebo. Change was measured on the Autism Behavior Checklist. Both placebo and treatment group improved equally over the course of one month. Opponents of secretin have used this study to argue that secretin is ineffective in autism. Secretin proponents have argued that the study was of insufficient length to draw serious conclusions and that important variables that change in response to secretin were not measured.
The Autism Behavior Checklist, for example, changes more slowly than one month. We administer it every six months. This study showed no adverse reactions to secretin, which was suspicious to me, since I see about 15% of children reacting to secretin infusion with increased hyperactivity or aggression. Reducing the dose or giving the secretin at longer intervals usually corrects this.
I have presented a case series of secretin infusions lasting over one year among 35 patients. About 70% of patients improved - some quite dramatically - again, a figure within the range of what could be expected with enthusiastic placebo. What is more remarkable to me is how much some of these children improved. If secretin is working only because of a change in parental expectations, we have good news. Such a finding could open a new awareness for the need to expect more from autistic children.
If secretin is not biologically active, then what do parents do who believe in secretin to foster such dramatic improvements in their child? Knowing this and being able to train parents in how to influence the course of autism would be as significant as finding an active biological agent. Unfortunately, the developmental disorders community tends to overlook behavioral therapies, much as most illness communities. We modern 21st century people are still searching for pills that will change everything. While autism may respond in this way, it is as likely that it is a complex illness that requires multiple, synergistic treatments, not all of which are biological.
Secretin may open the pathway for searching for other neurohormonal therapies that activate brain receptors. We know that secretin receptors are found in the brain, especially in the temporal lobe speech areas. Brain-imaging studies in one of Horvath's original cases showed a "marked" post-infusion increase in cerebral blood flow to these areas. Secretin may also activate receptors for a related hormone, vasoactive intestinal polypeptide or VIP, which is more widely distributed in the brain. Secretin also stimulates pituitary adenylate cyclase which increases intracellular cyclic adenosine monophosphate (cAMP), a messenger molecule for brain biochemical reactions. Opioid-like peptides are known to lower levels of cAMP. Perhaps secretin prevents this or replenishes the missing cAMP.
Lectins may also be important in explaining the mechanism of action of secretin. Lectins are molecules that bind to cholecystokinin (CCK) receptors and other glycosylated (meaning: attached to long-chain sugars) membrane proteins. CCK is another gut hormone with receptors in the brain. Lectins inhibit CCK-8-induced alpha-amylase secretion by the pancreas. This inhibition does not occur after administration of secretin.
There are two divergent opinions on secretin - one that high doses are necessary to obtain binding of secretin to receptors in the brain; the other, that only small concentrations are required. The final verdict on secretin is not yet out.
Anti-virals
Returning to the inflammatory theory of autism brings us to anti-viral therapy. Proponents of this theory argue that signs of long-term or chronic viral infection exist among autistic children, and that treatment with anti-viral agents can improve autism. The most commonly used agent is Valtrex, though some also have used Zovirax, which is known best for its use in treating herpes virus infections. Some parents have even reported improvements in their autistic children from the use of antibiotics.
At this time, I know of no trials that show true biological efficacy of anti-virals for autistic children. Nevertheless, we can't yet discount this therapy. It may also be that autistic children have immune defects and are more prone to chronic viral infections. Treatment of these viral infections could relieve some of the physiological stress of infection and result in an improvement.
Chronic illnesses (including autism) are so much more complex that most physicians would like to acknowledge. Once a disease process is started, effects follow upon many other organ systems. Even if viral infection is not the precipitating insult of autism, it may be important once autism is established, and treating chronic viral illness may be helpful. If this is so, however, it would only be helpful for thosechildren who have a chronic virus.
There are risks to anti-viral medications, and there are herbal alternatives. Herbs boost the immune system instead of attacking the virus directly. Common immune boosting herbs include echinacea, astragalus, garlic, plant tannins, uva ursi, and berberis. These herbs can also treat Candida, again by strengthening the immune system.
Immunotherapy
Regarding immunotherapy and IVIG, we know that autistic children have defects in their immunity, especially cellular immunity (the kind that involves the direct action of cells - opposed to humoral immunity which involves immunoglobulin molecules released into the blood stream). The white blood cells (lymphocytes, macrophages, natural killer cells) of autistic children can be sluggish and weak. Antibodies to brain proteins (especially myelin basic protein) are also more prominent among autistic children, suggesting an auto-immune process, in which the body is attacking itself. Autistic children show decreased activation of lymphocytes in response to mitogens (substances known to attract lymphocytes to stream into action) 3, 4.
Other immunological abnormalities found among autistic children include weakened macrophages and natural killer cells 5, 6, circulating auto-antibodies to brain proteins7-9, and elevation of agents which activate immune T-cells (interleukin-2 and soluble CD8) 10, along with increased levels of other activated cells (DR+) cells 11, 12. (Plioplys et al., 1994; Warren et al., 1995).
Levels of substances which indicate excess immune activity directed at the self have been found elevated among autistic children. These include gamma-interferon, alpha-interferon, interleukin 6 and 12, alpha tumor necrosis factor and others.
Immunological studies of autistic patients have revealed features also found in patients with other autoimmune diseases. Autoimmune diseases, including Grave's thyroid disease, rheumatoid arthritis, and insulin-dependant diabetes, show some genetic predisposition. Similarly, autism is higher among identical twins than in the normal population. Autism is four to five times more prevalent in boys than in girls - a gender factor also found in other immune diseases, including systemic lupus erythematosus, Grave's disease, and ankylosing spondylitis.
Autoimmune disease may be triggered by infections with bacteria or viruses. In autism, coincidental findings indicate infections with congenital rubella and cytomegalovirus.
Treatment is more difficult. The most popular treatment is intravenous immunoglobulin G, given in varying protocols. The most aggressive protocol gives the immunoglobulin approximately every other day, in progressively increasing dosages, starting at 1 gm/kg, and increasing to 5 gm/kg. The more conservative protocol begins with 1 gm/kg, increasing to 2-7 gm/kg at monthly doses. An intermediate intensity protocol is 5 gm/kg, administered monthly.
Several studies have shown benefit to treating children with immunoglobulin, though it is uncertain if all children would benefit, or only those with chronic viral infections, frequent bacterial infections, fungal infections, or other immune deficiencies. Dr. Gupta at the University of California, Irvine, is conducting clinical trials on the use of immunoglobulin therapy for autistic children, and will have more data soon.
Other immune enhancing therapies include vitamin C, oligoprocyanthocyanidins (OPC-3), and anti-inflammatory fatty acids, along with the herbs already discussed.
Homeopathy
I have also used homeopathy to treat the symptoms of autism. Homeopathy is controversial among conventional physicians, but is occasionally very effective in my experience. Is this effectiveness due to the remedy, to the placebo effect, or to the Pygmalion Effect? I cannot say, but have especially used sulfur for hyperactive and aggressive behavior, along with a variety of other remedies as appropriate to homeopathic theory.
Homeopathy has the advantage of having minimal risk. It either works or it doesn't. When it doesn't work, it doesn't harm. The debate will continue for some time about whether homeopathy works, though a recent analysis published in The Lancet, reviewed all of the recent clinical studies of homeopathy and concluded that it is significantly more effective than placebo. The downside noted by the review was that homeopathy was not as reliable as some other treatments. This has also been my clinical experience. When it works, it's wonderful, but it isn't always predictable whether or not it will work.
Homeopathic detoxification is popular with some parents and physicians. In this approach, small amounts of toxic substances are used to stimulate the body to heal itself from these substances. The approach may be combined with dietary modifications to faciliate the release of toxins. For example, alkaline diets seem helpful for agitated children, at times, and are thought to aid detoxification. Alkalinizing agents in the diet include spinach, cucumber, carrot, beet, and celery. These are juiced and used alongside food or used instead of food in an alkaline fast. Avoiding acidic foods can also be helpful. These foods include tomatoes, red meats, and simple carbohydrates, to name a few.
Allergic Theories and Treatments
Lurking in the background throughout complementary and alternative medicine lies the question of allergies. Though some physicians feel allergies are over-stressed, the concept is important.
I typically use the ELISA/ACT Test from Serammune Physicians Laboratories in Virginia, to test for food allergies. The acronym stands for Enhanced Lymphocyte Immunostimulation Assay. Blood is drawn and the patient's lymphocytes are incubated with various substances to determine what cell-mediated reactions the patient is having. Cell-mediated reactions are more important for food allergies than humoral reactions (immediate antibody reactions in the blood stream).
Some more alternative physicians use applied kinesiology or an off-shoot called Neuro-emotional technique, or N.E.T., to test for allergies. Others place the substances within the patient's "energy field," and test for changes in Chinese Meridians using pulse diagnosis. Offending substances are identified and eliminated from the diet or the environment. Nambuprihad Allergy Elimination Technique (N.E.A.T.) aims to reduce the patient's allergic reaction by balancing the energy meridians with the offending substances in the patient's energy field.
I have seen these approaches work and not work. We are all impressed when they work. We are not so impressed, when they are ineffective. I know of no rigorous clinical studies of the role of allergy treatment in autism, but suspect that some will some be forthcoming. Certainly eliminating foods and other substances that produce allergic responses in the autistic child can't be harmful, and may be helpful in other ways, even if these approaches show no effect on autism in rigorous trials. These approaches can help the gastrointestinal problems of autistic children, which is no small feat. Perhaps that will be where their utility will lie.
Body Therapy and Manipulative Therapies
A recent study from the University of Miami showed effectiveness of craniosacral therapy, a form of osteopathic manipulation, for autistic children. In craniosacral therapy, the bones of the skull are adjusted along with subtle adjustments of the spine, all the way to the sacrum. Craniosacral therapy, or CST, is different from chiropractic manipulation in that the adjustments are very subtle and are aimed at improving the flow of cerebrospinal fluid down the spinal canal. This fluid has been demonstrated to cycle with a pulse of 12 beats per minute. This pulse can be felt in the area of the sacrum (near the tail bone).
The goal of craniosacral therapy is to improve the ease with which the cerebrospinal fluid circulates and to help hold the skull bones and the spine in adjustment. The study showed improved concentration, socialization, and less self-stimulation behavior after a course of craniosacral therapy. This has been my experience, as well, watching children receive the therapy.
Chiropractic manipulation has been used for autistic children. I know of no formal clinical studies on its effectiveness, but have referred children for this therapy and been pleased with the results. Naturally, without clinical studies, the results could be due to the parents expecting it to work, so we cannot say for sure that the technique works of its own.
Sometimes techniques work by giving opportunities for natural healers and patients to interact. Unlike drugs,which can be more obviously separated from the prescriber, body therapies are more fused with the person administering the treatment. Some body therapists are more inspired than others. Nevertheless, a developing literature is finding body therapies very effective for many medical conditions.
We have been doing a pilot study of reiki massage for autistic children. The preliminary results are encouraging, especially when the parents are taught to do the reiki along with visualization in between formal appointments with the therapist. The use of reiki by parents and therapist appears to encourage communication, especially non-verbal communication. Children are more calm and have less self-stimulation.
Important to remember with healing methods that are non-pharmacological, is that their effectiveness is a complex mixture of technique, therapist, expectation, and communication.
Naturalistic Behavior Therapy
Most practitioners in the autism world have heard of Lovass' technique of applied behavioral analysis. This approach is based upon teaching the child skills through interaction in discrete trials in which the child is rewarded for the correct response. Rewards often include food, sometimes, unfortunately, foods to which the child may be allergic (M & M candies are frequently used!).
Studies from the Autism Research Center at the School of Education at the University of California at Santa Barbara, have shown that naturalistic behavior therapies are better than the applied behavioral analysis at changing autistic behaviors. This approach incorporates natural situations in which the child is already interacting and rewards the child through creating opportunities to do more of what the child already enjoys doing.
Non-autistic children may be recruited to be part of the therapeutic process. Examples of therapies in the classroom include a teacher developing a game for the entire class when her autistic student was obsessed with maps. The game consisted of the children dividing into teams and drawing states on sidewalks with chalk as fast as possible, including locating the capitol of the state. The autistic student was excellent at this game and was soon desired as a team member, thereby improving his opportunities for interaction with other children.
A book has been published about this approach, entitled Teaching Children with Autism. We are more excited about this method than the applied behavior analysis, though ABA as it is often called, has helped many children.
Other more permission therapies exist such as those offered by the Options Institute in Western Massachusetts, in which parents are helped to appreciate the special talents and uniqueness of the autistic child, and to learn to love the child as he or she actually is. These are often healing for families, especially when coupled with naturalistic behavior therapy and the other therapies mentioned here.
Conclusions
Many options exist within complementary and alternative medicine for the treatment of autistic children. We have not discussed drugs that can help autistic children, but rather have focused upon non-drug therapies. This is not to say that medications cannot be helpful, because they can. But many parents are interested in alternatives to medications, especially when there are side effects, and other parents have found that the medications are not helpful or that alternative therapies can add much benefit beyond what medications can do.
My approach is to present this menu to parents, suggesting that they decide what makes the most sense to try first. If parents don't know or can't decide, I proceed in an orderly fashion through nutritional therapies, to body therapies (craniosacral and reiki, especially), through educational and behavior therapies, and through Chinese medicine. By thetime we have reached Chinese medicine, parents have learned more about these alternatives, and typically have definite opinions about what will work. I monitor the outcomes of treatments carefully, asking parents to record daily counts of desirable behaviors (eye contact, appropriate use of language, etc.) and undesirable behaviors (self-stimulations, non-responsiveness, aggression). I use the Achenbach Child Behavior Checklist and the Autism Behavior Inventory on a regular basis also to document progress.
With any therapy, conventional or alternative, accurate data are needed to prove that the treatment is worth the expense and the side effects (if there are any). Fortunately, the majority of the alternative therapies have no side effects.
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