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IVIG Research: Several authors have either documented the effectiveness of IVIG or speculated on its use in autism. It has shown significant benefits in Landau Kleffner Syndrome and Autism with Seizure Disorder, Knudsen etal, 1998. Dr. Gupta at the University of California, Irvine has established its potential in autism complicated by immune dysregulation.

Dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics.



Authors:
Gupta S , Aggarwal S , Heads C
Division of Basic and Clinical Immunology, University of California, Irvine, USA.
J Autism Dev Disord 1996 Aug;26(4):439-52

Serum auto antibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders.

Authors:
Connolly AM , Chez MG , Pestronk A , Arnold ST , Mehta S , Deuel RK Departments of Neurology and Pediatrics, Washington University, St. Louis Children's Hospital, St Louis, Missouri, USA.
J Pediatric 1999 May;134(5):607-13

Article Number: UI99246407



Abstract: OBJECTIVE: Etiologically unexplained disorders of language and social development have often been reported to improve in patients treated with immune-modulating regimens. Here we determined the frequency of autoantibodies to brain among such children. DESIGN: We collected sera from a cohort of children with (1) pure Landau-Kleffner syndrome (n =2), (2) Landau-Kleffner syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n = 11). None had received immune-modulating treatment before the serum sample was obtained. Control sera (n = 71) were from 29 healthy children, 22 with non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders (ONDs). We identified brain autoantibodies by immunostaining of human temporal cortex and antinuclear autoantibodies using commercially available kits. RESULTS: IgG anti-brain autoantibodies were present in 45% of sera from children with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy children and control children with NNIs. IgM autoantibodies were present in 36% of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0% of control sera. Labeling studies identified one antigenic target to be endothelial cells. Antinuclear antibodies with titers >/=1:80 were more common in children with ASD and control children with ONDs. CONCLUSION: Children with LKSV and ASD have a greater frequency of serum antibodies to brain endothelial cells and to nuclei than children with NNIs or healthy children. The presence of these antibodies raises the possibility that autoimmunity plays a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders.

High-Dose Intravenous Immunoglobulin Therapy in Three Children with Seizure Disorders and Autistic Features



Authors:
Knutsen A. and Fenton G
Division Allergy/Immunology and Neurology, St Louis University Health Sciences Center, St Louis MO., USA
Pediatric Asthma, Allergy & Immunology 1998 Vol.12 No.3: 213-216

The present report describes the clinical benefits of high-dose IVIG therapy in three children with disorders of language development and seizures.


Urinary levels of neopterin and biopterin in autism.

Authors:
Messahel S , Pheasant AE , Pall H , Ahmed-Choudhury J , Sungum-Paliwal RS ,Vostanis P
School of Biochemistry, University of Birmingham, UK.
Neurosci Lett 1998 Jan 23;241(1):17-20

Article Number: UI98161310



Abstract: The pterins, neopterin and biopterin, occur naturally in body fluids including urine. It is well established that increased neopterin levels are associated with activation of the cellular immune system and that reduced biopterins are essential for neurotransmitter synthesis. It has been suggested that some autistic children may be suffering from an autoimmune disorder. To investigate this further we performed high performance liquid chromatography analyses of urinary pterins in a group of pre-school autistic children, their siblings and age-matched control children. Both urinary neopterin and biopterin were raised in the autistic children compared to controls and the siblings showed intermediate values. This supports the possible involvement of cell-mediated immunity in the etiology of autism.



DR-positive T cells in autism: association with decreased plasma levels of the complement C4B protein.

Authors:
Warren RP , Yonk J , Burger RW , Odell D , Warren WL
Center for Persons with Disabilities, Utah State University, Logan 84322, USA.
Neuropsychobiology 1995;31(2):53-7

Article Number: UI95281107



Abstract: Autism is a developmental disorder characterized by severe communication, social and behavioral abnormalities. Over the past several years a fair amount of evidence has accumulated suggesting that some cases of autism may be associated with immune abnormalities and with products of the HLA complex including the C4B gene located in the class III region of HLA. This study sought additional evidence for an association of autoimmune processes with autism by investigating the presence of activated T cells in 26 autistic subjects. Fourteen of the autistic subjects had DR+ T cells, an indicator of activated T cells, but none of the autistic subjects had T cells expressing the interleukin-2 receptor, another indicator of T cell activation. Similar findings of incomplete or partial T cell activation have been reported in autoimmune disorders and in a recent study of autism. In the current investigation, the DR+ T cells were not found to be associated with age of the autistic patients but were inversely correlated with a decreased plasma level of the C4B protein. In conclusion, this study provides additional evidence for the involvement of an autoimmune mechanism in autism. (When all these studies are looked at as a group, it is difficult to conclude otherwise - autism is an autoimmune disorder, and with treatment for the autoimmunity - it seems unlikely they will recover fully).



Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis.

Authors:
Dittel BN , Visintin I , Merchant RM , Janeway CA Jr
Section of Immunobiology, Yale University School of Medicine,
Howard Hughes Medical Institute, New Haven, CT 06510, USA. bonnie.dittel@yale.edu
J Immunol 1999 Jul 1;163(1):32-9

Article Number: UI99316284



Abstract: Bone marrow (BM)-derived dendritic cells (DC) are potent stimulators of naïve CD4+ T cell activation. Because DC are efficient at Ag processing and could potentially present self Ags, we investigated the role of DC in the presentation of an encephalitogenic peptide from myelin basic protein (Ac1-11) in the induction of experimental autoimmune encephalomyelitis (EAE). To determine if DC could prime for EAE, we transferred DC pulsed with Ac1-11 or with medium alone into irradiated mice in combination with CD4+ T cells isolated from a mouse transgenic for a TCR specific for Ac1-11 + I-Au. Mice transferred with Ac1-11-pulsed DC developed EAE 7-10 days later, whereas mice receiving medium-pulsed DC did not. By day 15, all mice given peptide-loaded DC had signs of tail and hind limb paralysis, and by day 20 infiltration of Ac1-11-specific CD4+ T cells was detected in the brain parenchyma. We also demonstrated interactions between Ac1-11-pulsed DC and Ac1-11-specific T cells in the lymph nodes 24 h following adoptive transfer of both cell populations. These data show that DC can efficiently present the self Ag myelin basic protein Ac1-11 to Ag-specific T cells in the periphery of mice to induce EAE. (This study is impressive from the theoretical understanding of how autism may be developing, since nearly all autistics have anti-MBP activity).



Landau-Kleffner syndrome: consistent response to repeated intravenous gamma-globulin doses: a case
report.

Authors:
Fayad MN , Choueiri R , Mikati M
Department of Pediatrics, American University of Beirut School of Medicine, Lebanon.
Epilepsia 1997 Apr;38(4):489-94

Article Number: UI97258798



Abstract: PURPOSE: Although several treatments have been tried for Landau-Kleffner syndrome (LKS) too many patients are refractory to known therapies. We report an 8-year-old girl who failed other therapies but who had a consistent response after treatment with intravenous (i.v.) gamma-globulin. METHODS: We monitored the girl from the age of 6 years, when she presented with a 6-month history of loss of language with normal hearing, normal brain magnetic resonance imaging (MRI), increased cerebrospinal fluid (CSF) IgG index, and an EEG showing almost continuous, predominantly left-sided spike- and slow-wave complexes. She had no clinical seizures and did not respond to consecutive trials of valproate (VPA), clonazepam (CZP), prednisone, and carbamazepine (CBZ). She received three courses of intravenous (i.v.) gamma-globulin; after each course, clinical and electrographic improvement lasted a few months. After each of the initial two courses, clinical improvement lasted 3-4 months but was followed by recurrence of the spikes on the EEG and by speech deterioration. RESULTS: However, her last remission has been continuous for the past 16 months. Her CSF IgG index became normal after the first i.v. gamma-globulin infusion. CONCLUSIONS: Based on our experience with this patient and on other investigators' experience, we believe that further research into immunologic mechanisms and therapies of this syndrome are warranted.

IVIG is believed to act through inhibition of cytokines and the removal of autoantibodies. Our current research into IVIG is designed to do several things. We are treating children with known autoimmune disorders. In particular, we are interested in the use of IVIG for children with Anti-MBP and/or Anti-NAFP, especially if they also have immune dysfunction or deficiency. We will be following their autoimmune titers and their progress in association with Dr. Singh at the University of Michigan. We want to see if IVIG is working through removal of Anti-MBP activity. Another part of our research will be to follow the effect of IVIG on plasma serotonin. Unfortunately, our research is not funded so parents are paying for their child's treatment. Some insurance companies are reimbursing parents for children with IgG subset deficiencies. We do not know yet if they will reimburse for LKS treatment. We are not financially able to buy the IVIG and wait for insurance companies to maybe pay. The study allows parents to opt for 400mg/kg, 1Gm/kg or 2Gm/kg. Our cost for IVIG is significant. It varies in price depending on availability and like secretin, is in short supply. Each gram costs about $100. But there are other costs, so this study is unfortunately expensive. Just purchasing the IVIG can cost $3000 or more per treatment on the high dose regimen. We usually ask parents to pay for IVIG when we order it. Money must be wired the day of the order, because IVIG weekly orders for us can run $30,000. I know that is uncomfortable for many people. But if research like this succeeds, insurance companies and the FDA may consider it routine care in the future.

We have a TV/VCR in each room and the kids generally do not need sedation after the first treatment. We recommend parents bring their child's favorite videos (as you know autistic kids tend to be fussy about what they watch).

Insurance and IVIG: To help parents with their insurance we will fill out the standard HCFA form. I am including excerpts from the NIH consensus statement on IVIG use. If your child has any of those indications (subset immunoglobulin deficiency with recurrent infections, total IgG deficiency, persistent seizures or other indicated neurological indications) your insurance company is bound under ERISA rules to pay for the treatment, regardless of their initial complaints about doing so. Federal employment rules (assuming your policy is an ERISA policy) mandate that standard care cannot be refused unless specifically excluded by prearranged contract. You are not claiming in the examples given that your child needs IVIG for autism. They need it for their immune or seizure disorders. If your child's only reason for IVIG is autoimmune encephalopathy (AKA – autism) we expect you will have great difficulty educating the insurance company as to the necessity of this treatment.



INTRAVENOUS IMMUNOGLOBULIN: PREVENTION AND TREATMENT OF DISEASE
National Institutes of Health Consensus Development Conference Statement
May 21-23, 1990



This statement was originally published as:
Intravenous Immunoglobulin: Prevention and Treatment of Disease. NIH Consens Statement 1990 May 21-23;8(5):1-23.


For making bibliographic reference to the statement in the electronic form displayed here, it is recommended that the following format be used:
Intravenous Immunoglobulin: Prevention and Treatment of Disease. NIH Consens Statement Online 1990 May 21-23 [cited year month day];8(5):1-23.
ABSTRACT
The National Institutes of Health Consensus Development Conference on Intravenous Immunoglobulin: Prevention and Treatment of Disease brought together biomedical scientists in immunology, infectious disease, and pediatrics, as well as health care providers, patients and their families, and the public to address the safe and effective uses of intravenous immunoglobulin (IVIG) preparations. Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared a consensus statement.
Among their findings, the panel concluded that all currently available IVIG preparations are safe and effective in treating the conditions for which they have been licensed; however, their efficacy in treating other conditions remains to be established. Effective regimens have been developed for primary immunodeficiencies and secondary immunodeficiencies, idiopathic thrombocytopenic purpura, and Kawasaki syndrome. However, optimal dosages and treatment schedules still need to be established for patients who may benefit from IVIG therapy. The panel also concluded that the risks of IVIG therapy are minimal, and adverse events, which are rare, can often be alleviated by reducing the rate or volume of infusion. Future research is also important, particularly studies to discern the mechanisms of action of IVIG, to compare the effectiveness of IVIG preparations, and to determine their long-term effectiveness and their effect on quality of life for patients receiving IVIG. The edited for relevant content text of the consensus panel's statement follows.

INTRODUCTION
Immunoglobulins are proteins produced by cells of the B lymphocyte lineage that are the major effector molecules of the humoral immune system. Immunoglobulin molecules are antibodies that react with specific antigens, although in many circumstances, the specificity of a given immunoglobulin antibody is unknown. Immunoglobulin preparations from human blood were first used in clinical medicine in 1952 to treat immune deficiency conditions. At that time, the only available preparations required intramuscular administration. In the past decade, several immunoglobulin preparations for intravenous administration have become available. Although initially used for immune deficiency states, intravenous immunoglobulin (IVIG) has also been utilized as a prophylactic and therapeutic reagent in a variety of other conditions. The use of IVIG has undergone tremendous growth in the past several years. This rapid growth in use is the result of improvements in the preparations of IVIG, which have led to reduced morbidity and reports of its benefits in a number of unexpected circumstances. IVIG has been used in such diverse diseases as primary immunodeficiencies, pediatric AIDS, infections in low birth weight infants, bone marrow transplantation, chronic lymphocytic leukemia, idiopathic thrombocytopenic purpura, Kawasaki syndrome, and demyelinating polyneuropathies. However, important questions regarding its use still remain. To assess the usefulness of IVIG in diseases where substantive data existed, the National Institute of Allergy and Infectious Diseases and the Office of Medical Applications of Research of the National Institutes of Health convened a Consensus Development Conference on Intravenous Immunoglobulin: Prevention and Treatment of Disease on May 21-23, 1990. Cosponsors were the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Child Health and Human Development, National Institute of Neurological Disorders and Stroke, and the Food and Drug Administration.

In the various disease states in which IVIG has been used, the following questions were considered:


What are the data to support the efficacy of IVIG in these circumstances?

are the appropriate dosage and treatment schedules?

all IVIG preparations equally efficacious?

are the risks involved in the use of IVIG?

are the mechanisms of action?

What are the directions for future research?

After a day and a half of presentations by experts in the field and discussion by the audience, a consensus panel drawn from specialists and generalists from the medical profession and related scientific disciplines, clinical investigators, and public representatives considered the evidence and came to the conclusions on the following pages.


WHAT ARE THE DATA TO SUPPORT THE EFFICACY OF IVIG IN THESE CIRCUMSTANCES?


Primary Immunodeficiencies
The beneficial effects of intramuscular (IM) injection of immune globulin (IG) in the prophylactic treatment of patients with primary immunodeficiency syndromes have been well established. Early studies based on small sample sizes have indicated that almost any desired blood level of IgG can be obtained by use of intravenous immunoglobulin and that infection rates are reduced by use of IVIG as compared with IM IG. IVIG has been shown to ameliorate chronic sinopulmonary disease that developed in patients on long-term IM IG. There is a suggestion that chronic enterovirus meningoencephalitis in patients with X-linked agammaglobulinemia may be less frequent in those receiving prophylactic IVIG as compared with historical data in which IM IG was used. Hence, IVIG has become the current standard in clinical practice for replacement therapy of patients with primary immunodeficiencies (e.g., X-linked agammaglobulinemia and common variable immunodeficiency and immunoglobulin subclass deficiency in which deficiencies of antibody production to common pathogens can be demonstrated). Studies have shown that maintenance of a trough level of 500 mg/dL is beneficial. Dose ranges of 200-800 mg/kg/mo have been shown to be effective, but dose or frequency of infusions must be tailored to the individual patient, because half life of infused IVIG varies widely.

Chronic Inflammatory Demyelinating Polyneuropathies
Several small studies have shown positive responses to IVIG in the majority of treated patients. Treatment needs to be periodically repeated to prevent relapse. When considered in comparison with customary treatments, IVIG may be easier to use and associated with fewer complications than repeated therapeutic plasma exchange and long-term glucocorticoids, respectively.

Intractable Seizure Disorders
A number of uncontrolled studies and anecdotal reports have indicated benefit of IVIG administration in children with intractable seizures. The absence of randomized, double-blind studies does not allow specific recommendations to be made regarding such treatment. The panel emphasizes the need for controlled human studies in this area.


WHAT ARE THE APPROPRIATE DOSAGE AND TREATMENT SCHEDULES?


Effective doses of IVIG have been demonstrated in primary immunodeficiencies, ITP, and Kawasaki syndrome. Whether alterations in amount, frequency, or duration of administration will improve efficacy is not known. Specific details of dosage regimens are discussed in detail in the response to the previous question.


WHAT ARE THE RISKS INVOLVED IN THE USE OF IVIG?


The incidence of adverse events associated with the administration of IVIG is reported by the manufacturers to be in the range of 1 to 15 percent, usually less than 5 percent. Most of these reactions are mild and self-limited. Severe reactions occur very infrequently and usually do not contraindicate further IVIG therapy. Neither HIV nor hepatitis B infection has been transmitted to recipients of products currently licensed in the U.S. The various IVIGs are manufactured from large numbers of donors whose plasma has been tested and found to be negative for hepatitis B surface antigen and HIV antibody. A number of adverse events have been recognized. These include the following:


pyrogenic reactions marked by high fever and systemic symptoms;

systemic reactions with headache, myalgia, fever, chills, lightheadedness, nausea and/or vomiting;

and/or cardiovascular manifestations, marked by changes in blood pressure and tachycardia. These may be related to occasional reports of shortness of breath and chest tightness; and

and anaphylactic reactions.


Risk factors
Patients with primary antibody deficiency syndromes may be at increased risk for reactions. Anaphylactic reactions induced by anti-IgA can occur in individuals who have a total absence of circulating IgA and antibodies to IgA. These are extremely rare in panhypogammaglobulinemic individuals and potentially more frequent in patients with subclass deficiencies. Frequency of reactions may be correlated with volume and/or rate of infusion. Seriously ill patients with compromised cardiac function may be at increased risk of vasomotor or cardiac complications manifested by elevated blood pressure and/or cardiac failure.

Prevention and management
Adverse reactions often can be alleviated by reducing the rate or the volume of infusion. For patients with repeated severe reactions unresponsive to these measures, hydrocortisone, 1-2 mg/kg, intravenously, can be given 30 minutes before IVIG infusion. In those rare instances when reactions related to anti-IgA antibodies have occurred, use of IgA-depleted preparations will reduce the likelihood of further reactions. Avoidance of anaphylactic reactions may require the use of material completely devoid of IgA. Because the combination of the absence of IgA and the presence of anti-IgA antibodies is infrequent and reactions are rare, screening for IgA-deficiency is not routinely recommended for potential recipients of IVIG.
As with any biologic or pharmacological product, the potential for new or previously unrecognized adverse events should be anticipated. With IVIG these include the following:


transmission of blood-borne pathogens, such as the newly identified hepatitis C virus.

example, administration of IVIG has been associated with

transient effects on immune response that do not appear to have clinical significance. However, with increased dosage of IVIG or new products for the treatment of specific infections, the possibility of adverse outcomes from immunosuppression should be considered. After nearly a decade of experience, the safety of IVIG has been established. For any potential recipient, the small risk of adverse reactions must be weighed against the likelihood of significant benefit. For those patients who require repeated courses of IVIG such as those with a primary humoral immunodeficiency home infusion by the patient or a family member after adequate training has been effectively utilized and is cost-effective.


WHAT ARE THE MECHANISMS OF ACTION?


At the present time, we assume that all effects of IVIG are related to the quantity and quality of IgG in the product. Various mechanisms may be important in the different therapeutic uses of IVIG, including (1) replacement therapy for primary and secondary immunodeficiencies, (2) specific passive immunotherapy, and (3) management of specific inflammatory and/or immunologic disorders.
Efficacy of IVIG infusions in primary immunodeficiency diseases is probably related to replacement of antibodies to environmental pathogens. Despite variations in the titer of specific antibodies, all licensed preparations are apparently efficacious in the treatment of these diseases. In addition, pooled antibodies may have physiologic activities other than pathogen recognition that may contribute to the beneficial effects of replacement therapy.

The effectiveness and the mechanism of action of IVIG in secondary immunodeficiencies such as indolent lymphomas is presumed to be similar to that in primary immunodeficiencies. In these diseases, a reasonable correlation between rates of systemic infection and concentrations of serum immunoglobulins supports this presumption. The benefit of prophylactic replacement of IgG in very low birth weight infants is not established. Attempts to replace antibodies may be rational in this situation. However, it is possible that administration of immunoglobulin from large donor pools could adversely affect the development of the infant's immune system, as there is substantial evidence in mice that anti-idiotypic antibodies may profoundly affect immune responsiveness. For conditions such as bone marrow transplantation and pediatric HIV infection, the complexity of immunologic abnormalities will make determination of mechanisms extremely difficult. IVIG is also being used for specific passive immunotherapy. In these instances, the titers of specific antibodies are of paramount importance. Moreover, consideration must be given to the possibility that large amounts of apparently irrelevant antibodies may block receptors on the surface of phagocytes and thus interfere with effective disposal of microbial pathogens.

In the treatment of ITP, there may be multiple mechanisms of IVIG action. The platelet count increase occurring within several days of the initiation of therapy appears to be caused by diminished sequestration of autoantibody-sensitized platelets. This may be caused by interference with Fc receptors on the cells of the monocyte-macrophage system. A similar mechanism may operate in other autoimmune and alloimmune cytopenias. Sustained responses to IVIG may represent spontaneous remissions or may be related to an immunosuppressive effect of IVIG.
There are several possible mechanisms by which the infusion of large concentrations of immunoglobulins may have an immunosuppressive effect. The presence of IgG dimers in immunoglobulin preparations, a result of pooling samples from a large number of individual donors, likely represents the occurrence of idiotype-anti-idiotype complexes. There is evidence that anti-idiotype antibodies in IVIG react with epitopes on the autoantibodies in patients with thyroiditis or spontaneous factor VIII inhibitors. Alterations of T-cell subsets and of in vitro B cell function, both spontaneous and mitogen driven, have been reported in patients treated with IVIG. It is unknown if these observations are related to a mechanism of therapeutic effect.
A striking anti-inflammatory effect of IVIG has been observed. This phenomenon is most apparent in Kawasaki syndrome, where reductions in fever, neutrophil counts, and acute phase reactants regularly occur within a day or so of initiation of treatment. This effect is not unique to Kawasaki syndrome but has been seen in other inflammatory disorders. The mechanisms are unknown but may be distinct from those that mediate immunosuppression. One possible mechanism demonstrated in experimental animals is the inhibition of complement-dependent tissue damage caused by binding of IVIG to active C3 fragments.

There is a great need for an understanding of the mechanisms of IVIG in the various conditions in which it is used. A variety of mechanisms have been suggested but none proven. Mechanistic hypotheses such as the provision of anti-idiotype antibodies, Fc receptor blockade, and alteration of reticuloendothelial cell system function should be rigorously tested. Utilization of appropriate animal models would provide an efficient way to test these hypotheses.


ARE ALL IVIG PREPARATIONS EQUALLY EFFICACIOUS?


Seven IVIG preparations have been licensed in the U.S.: all seven for use in primary immunodeficiencies, five for idiopathic thrombocytopenia, and one for chronic lymphocytic leukemia. For these disease groups, the limited comparative data available reveal no differences in efficacy among the licensed preparations. For the other uses of IVIG, there is insufficient information to choose one product over another or to know whether each has comparable activity. Given the large number of conditions for which IVIG may have potential value, the prescribing physician should be aware of the demonstrated efficacy of each IVIG preparation to treat a specific disorder. The products and their quality are under the control of commercial firms who must meet general regulatory guidelines of the Center for Biologics Evaluation and Research of the Food and Drug Administration. These include tests for sterility, pyrogenicity, purity, and safety. It is required also to measure antibody levels against polio, measles, hepatitis B, and diphtheria. At the present time, there is no requirement to identify hepatitis C virus in IVIG preparations. Epidemiologic data support the quality and safety of current products. However, guidelines and monitoring methods must be developed as information about transmission of hepatitis C virus and other infectious diseases becomes better defined. Consideration should be given to screening donors for hepatitis C.

Confidence in the capacity of a given preparation to accomplish the desired end result would be enhanced if a more rigorous procedure were established for using IVIG to prevent or treat infections caused by specific microorganisms. The availability of antibody titers to a wider range of pathogens would permit a more rational basis for the choice of a specific product in situations where immunotherapy is directed to a restricted number of infectious agents. Because the factor essential for the effectiveness of IVIG in a number of disorders, such as ITP and Kawasaki syndrome, is unknown, it is not possible to predict efficacy of a given preparation of IVIG for any of these disease processes.


Transfer Factor Research: Dr. Fudenberg has established the effectiveness of transfer factor from leukocytes of household contacts in the treatment of autism. Approximately 40% of children had dramatic responses. We are attempting to develop a study in conjunction with/or based on Dr. Fudenberg's recommendations. I expect this to start after November 1999. Transfer factor is an exciting area of promise for autism. Transfer factor works through cellular immune mechanisms, and we do know that cellular immunity is altered in some cases of autism. The off-the-shelf transfer factor available in health food stores is unlikely to reproduce Dr. Fundenberg's results. In talking to Dr. Singh (neuroimmunologist at the University of Michigan) and Dr. Fundenberg about this, fresh lymphapheresis derived TF, from household contacts or selected donors would be necessary to obtain good results (see below).


Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot study.

Author:
Fudenberg HH
Neurolmmuno Therapeutics Research Foundation Spartanburg,
S.C., USA.
Biotherapy 1996;9(1-3):143-7

Article Number: UI97146917



Abstract: 40 infantile autistic patients were studied. They ranged from 6 years to 15 years of age at entry. 22 were cases of classical infantile autism; whereas 18 lacked one or more clinical defects associated with infantile autism ("pseudo-autism"). Of the 22 with classic autism, 21 responded to transfer factor (TF) treatment by gaining at least 2 points in symptoms severity score average (SSSA); and 10 became normal in that they were main-streamed in school and clinical characteristics were fully normalized. Of the 18 remaining, 4 responded to TF, some to other therapies. After cessation of TF therapy, 5 in the autistic group and 3 of the pseudo-autistic group regressed, but they did not drop as low as baseline levels. (Regression can be avoided by continuation of therapy).

Vaccines and Autism: This is an area doomed to remain controversial for years or even decades. While experts line up on both sides of the controversy, children are still lining up for their compulsory vaccinations prior to daycare and school. We have excerpts from the Congressional hearings May 1999, and tapes of Dr. Wakefield's lectures on MMR vaccine available. (Order). Congressman Dan Burton is taking up the vaccine issue in full committee as I write this. The US Today made it front page news. None of this helps our kids today, but we may prevent a few children from getting autism if their parents avoid certain vaccines early in life.

And the vaccine issue is not without embarrassing retractions from the CDC and the American Academy of Pediatrics. Recently the CDC pulled the Rotavirus vaccine off the market because of near fatal side-effects in 18 children. And the decades old policy of using live Polio has been changed and no live Polio is to be given anymore. That won't help the scores of children with vaccine polio, but it will prevent future polio from vaccines, because all polio will be inactivated before injection. And last month the AAP decided it was wrong in its recommendations regarding Hepatitis B vaccine prior to discharge from the nursery. They are now recommending delaying the vaccine until 6 months. But babies are at extremely low risk of hepatitis B unless they live in very unusual circumstances (like a "crack house" or bordello). So, this vaccine certainly can be delayed in most cases.

I do not have time for full discussion of the controversy, but here are my current recommendations. If you think your child is a vaccine induced autistic, report it to VAERS (Vaccine Adverse Event Reporting System), a federally mandated program. Get MMR titers from Specialty Labs or Dr. Singh. Check viral titers to vaccine components prior to any further vaccines. Decide as the parent if the risk/benefits of vaccines are justified for your child. Please note both the MMR vaccine and the Hepatitis B vaccine are under Congressional review. Here's the rub. Experts of similar fine reputation radically disagree about vaccine safety, when they should be given and to whom they should be given. Given these opposite positions should the government be in the mandating business? Tough issue. I do not want to see polio epidemics - and fortunately as of today the recommendations are for all killed polio vaccines. Live measles vaccines work better than killed ones, but there does appear to be a risk of autoimmune disorders from MMR and Hepatitis B. Consider delaying MMR until after 2 years of age. If you are concerned about measles (as I am, having seen 3 children with wild measles induced autism), consider giving the Measles (Rubeola) vaccine by itself, without mumps and rubella. Rubella (German measles - the mild one unless you are an unborn child) is only required for women of reproductive years. Children would be better served and develop better immunity by getting German Measles. Boys have no need of rubella vaccines ever, and I do not understand the policy on an MMR vaccine. Mumps is occasionally a bad actor, causing infertility and encephalitis, but the incidence of that severe a disease is unlikely without immune deficiency. It is likely, if Wakefield and Singh are correct, that MMR vaccines are more likely to cause disease, than Mumps infection in the wild state. See Below:


Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children [see comments]

Authors:
Wakefield AJ , Murch SH , Anthony A , Linnell J , Casson DM , Malik M , Berelowitz, M , Dhillon AP , Thomson MA , Harvey P , Valentine A , Davies SE , Walker-Smith JA
Inflammatory Bowel Disease Study Group, University Department of Medicine, Royal Free Hospital and School of Medicine, London, UK.
Lancet 1998 Feb 28;351(9103):637-41

Article Number: UI98159956



Abstract : BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI),electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers. (Since this study was published, Dr. Wakefield's group, and a highly respected virology DNA/RNA sequencing scientist in Japan, have identified the vaccine Measles virus in the ileal lesions in children with autism, leaving no doubt in my mind that the vaccine itself, precipitated the disorder.)


Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism.

Authors:
Singh VK , Lin SX , Yang VC
College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109-1065, USA.
Clin Immunol Immunopathol 1998 Oct;89(1):105-8

Article Number: UI98434745


Abstract: Considering an autoimmunity and autism connection, brain autoantibodies to myelin basic protein (anti-MBP) and neuron-axon filament protein (anti-NAFP) have been found in autistic children. In this current study, we examined associations between virus serology and autoantibody by simultaneous analysis of measles virus antibody (measles-IgG),human herpesvirus-6 antibody (HHV-6-IgG), anti-MBP, and anti-NAFP. We found that measles-IgG and HHV-6-IgG titers were moderately higher in autistic children but they did not significantly differ from normal controls. Moreover, we found that a vast majority of virus serology-positive autistic sera was also positive for brain autoantibody:

90% of measles-IgG-positive autistic sera was also positive for anti-MBP;
73% of measles-IgG-positive autistic sera was also positive for anti-NAFP;
84% of HHV-6-IgG-positive autistic sera was also positive for anti-MBP; and
72% of HHV-6-IgG-positive autistic sera was also positive for anti-NAFP.
This study is the first to report an association between virus serology and brain autoantibody in autism; it supports the hypothesis that a virus-induced autoimmune response may play a causal role in autism.

Three monoclonal antibodies against measles virus F protein cross-react with cellular stress proteins.

Authors:
Sheshberadaran H , Norrby E
J Virol 1984 Dec;52(3):995-9

Article Number: UI85033974



Abstract: In a group of 11 monoclonal antibodies specifically reacting with the measles virus fusion protein, three antibodies also immunoprecipitated other proteins, in particular a 79,000-molecular-weight protein from virus-infected cells. The cross-reacting 79,000-molecular-weight protein was shown to be a virus-induced host stress protein. This protein could be induced by (i) different paramyxoviruses, (ii) heat shock of uninfected HeLa cells, and (iii) 2-deoxyglucose, tunicamycin, or L-canavanine treatment of different mammalian cell lines. Immunofluorescence of stressed HeLa cells localized the cross-reacting host protein(s) mainly in the cytoplasm. The significance of these results in relation to autoimmunity is discussed.


Autoimmunity caused by host cell protein-containing viruses.

Authors:
Rott O , Herzog S , Cash E
Institut fur Virologie, Justus-Liebig-Universitat Giessen, Germany.
Med Microbiol Immunol (Berl) 1994 Sep;183(4):195-204

Article Number: UI95147804



Abstract: Autoreactive T cells specific for myelin basic protein (MBP), a major component of central nervous system (CNS) protein, are frequently found in blood and cerebrospinal fluid of patients with postinfectious encephalomyelitis. This autoimmune syndrome is a CNS complication after infections with a number of different enveloped viruses, e.g. mumps, measles, rubella, influenza and varicella. However, the pathophysiological mechanism leading to this breaking of natural self tolerance in the course of viral infection remains an enigma. A long-lasting hypothesis has suggested that incorporation of cellular (self) proteins into the envelope of budding viruses might be a possible mechanism leading to autosensitization. In a model study we demonstrate here that vesicular stomatitis virus (VSV), grown in myelin protein-expressing cell cultures, is highly efficient in triggering T cell responses to MBP in vitro and can prime autoreactive T cell immune responses in vivo. On the basis of these findings, we suggest that incorporation of CNS membrane components into the viral envelope and subsequent priming of self-reactive immune responses might be the common pathogenic mechanism underlying the postinfectious encephalomyelitis syndrome. (This is exactly what we are seeing in autism when we look at the immunological status of the children).


Measles virus-directed responses of CD4+ T lymphocytes in MS patients and healthy individuals.

Authors:
Pette M , Liebert UG , Gobel U , Grosse-Wilde H , Hartung HP , Toyka KV
Department of Neurology, University of Wurzburg, Germany.
Neurology 1993 Oct;43(10):2019-25

Article Number: UI94020230



Abstract: To analyze the antigen specificities of measles virus (MV)-reactive CD4+ T cells in multiple sclerosis (MS) patients as compared with those of healthy donors, we established 492 MV-reactive short-term T-cell lines (TCL) from blood of 12 MS patients (n = 243 TCL) and 12 healthy subjects (n = 249 TCL). We determined antigen specificities of these TCL by proliferative responses to optimal concentrations of recombinant MV structural proteins (MV-SP) and human myelin basic protein (MBP). In both donor groups, there was a dominant reactivity against the MV fusion protein and the MV nucleocapsid protein. However, there was a substantial heterogeneity of T-cellular polypeptide specificities among MS patients as well as among healthy individuals, which was true even in subjects sharing identical HLA-DR and HLA-DQ haplotypes. By comparing the T-cell antigen specificity patterns obtained in both donor populations, we found decreased percentages of TCL reactive with the MV fusion protein, the hemaglutinin, and the phosphoprotein in MS patients, but these differences failed to reach statistical significance. None of the 492 MV-specific TCL, nor an additional 276 TCL, showed any reactivity to MBP. Therefore, we did not detect any MS-specific pattern of T-cell responses to MV-SP. Furthermore, our study suggests that mechanisms other than molecular mimicry between MV-SP and MBP may cause myelin-directed autoimmunity.


This next study is interesting from the vaccine induced autoimmunity issue, even though it is not related to autism.

Are viral studies indicated in juvenile-onset diabetes?

Authors:
Bartsocas CS , Lab M , Spyrou N , Krikelis N , Serie C , Papadatos, CJ
Padiatr Padol 1982;17(3):603-6

Article Number: UI82273649


Abstract: Recent observations have shown that insulin-dependent diabetes (JOD) may be the result of autoimmunity causing more or less rapid pancreatic isle cell destruction. This autoimmune process may be initiated in individuals who are genetically vulnerable to specific virus action. Several viruses have been implicated as causing JOD. Rubella and mumps viruses were the first viruses to be proved diabetogenic.


CSF antibody to myelin basic protein. Measurement in patients with multiple sclerosis and subacute sclerosing panencephalitis.

Authors:
Panitch HS , Hooper CJ , Johnson KP
Arch Neurol 1980 Apr;37(4):206-9

Article Number: UI80152831



Abstract: A solid phase radioimmunoassay was used to detect antibodies to myelin basic protein (MBP) in the CSF of patients with multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE). F(ab')2 fragments prepared from SSPE IgG retained their activity, which showed that the assay measures a true antigen-antibody reaction rather than nonspecific adherence to IgG to MBP. Samples of CSF from 48 patients with MS and 30 patients with SSPE were tested and, in both conditions, antibody activity was significantly greater than in controls, when tested at identical IgG concentrations. In MS, levels of antibody were highest in patients with acute exacerbations and lower in patients in remission, which supported the hypothesis that autoimmunity to a myelin antigen may play a role in the pathogenesis of the disease. The reaction with MBP was consistently more pronounced in SSPE than in MS. In view of the association of SSPE with measles virus and the presence of high titers of measles antibody in the CSF, antibodies to measles and to MBP may be directed against similar antigenic determinants. (My note here: elevated MBP is typically present in over 95% of Autistic Children, but essentially no controls, as reported by Singh and others.)


Paramyxovirus membrane protein enhances antibody production to new antigenic determinants in the actin molecule: a model for virus-induced autoimmunity.

Authors:
Anomasiri WT , Tovell DR , Tyrrell DL
Department of Biochemistry, University of Alberta, Edmonton, Canada.
J Virol 1990 Jul;64(7):3179-84

Article Number: UI90279044


Abstract: Paramyxovirus membrane (M) protein specifically binds to cellular actin but not to bovine serum albumin or myoglobin, as determined by affinity chromatography and enzyme-linked immunosorbent assay. The binding site for M protein on actin is different from the binding sites for antiactin antibodies. The interaction of M protein with actin resulted in production of antibodies to several new antigenic sites on the actin molecule. Five rabbits immunized with actin alone produced antibodies against the N-terminal sequence (residues 1 to 39). Another five rabbits immunized with a mixture of M protein and actin produced antibodies against a C-terminal fragment and a central region as well as the N-terminal fragment. By immunoblotting with proteolytic fragments of actin, the new antigenic sites were located between amino acid residues 40 to 113, 114 to 226, and 227 to 375. Antisera taken from some patients with recent measles virus infections demonstrated antiactin antibodies to sites other than the N-terminal fragment of actin (amino acids 1 to 39). The interaction of paramyxovirus M protein with actin and the subsequent production of antibodies to new antigenic sites may serve as a model for one of the mechanisms of virus-induced autoimmunity. (Again a note from me: Dr. Singh and others including our research have documented a high titer to NAFP in most autistics).

Vaccine in general childhood population and associated risks: We don't know enough yet about vaccines, despite widespread use. The longest safety trial on vaccine was only 3 months prior to release of vaccine. Here is another article to ponder.


The timing of immunization affects the development of diabetes in rodents.

Author:
Classen JB
Classen Immunotherapies, Inc., Baltimore, MD 21212, USA.
Autoimmunity 1996;24(3):137-45

Article Number: UI97172322



Abstract: BACKGROUND: Insulin-dependant diabetes mellitus (IDDM) is an autoimmune disease that can be altered by immune modulation. NOD mice and BB rats have been used as models of spontaneous IDDM. The development of diabetes in these animals has been altered by several different immune modulators using relatively high doses for the size of the animal. The effect of pharmaceutical doses of vaccines on the development of diabetes in these rodents has not been adequately studied. CONCLUSIONS: Animal studies have demonstrated the timing and content of human vaccines can affect the development of diabetes. Clinical trials of new human vaccines are not designed and generally not powered to detect an effect of immunization on the development of IDDM. These animal toxicology studies indicate that the effect of vaccines on human insulin dependent diabetes needs to be examined.

Sphingolin in theory and practice: I have used Sphingolin (myelin basic protein or MBP) to reduce autoimmunity to MBP in children with autism. The results are mixed. Some children get worse, some get better, and dosing is key. I do not yet know enough about sphingolin and autism to give you wise advice. Here's what I do suspect. Oral tolerance probably plays a role in those children helped by sphingolin. We do not know the right dose yet. If you do this, start at little doses before trying to work your way up. The second article below would indicate high doses are necessary (but our experience is that some children do poorly with MBP, especially if concurrently on secretin). We do have this item in stock as several families swear by it. Here is an article to point to where the research is headed:


Oral tolerance: a biologically relevant pathway to generate peripheral tolerance against external and self antigens.

Authors:
Friedman A , al-Sabbagh A , Santos LM , Fishman-Lobell J ,
Polanski M , Das MP , Khoury SJ , Weiner HL
Center for Neurological Diseases, Brigham and Women's Hospital, Boston, Mass.
Chem Immunol 1994;58():259-90

Article Number: UI94280607



Abstract: OT is a relevant biological pathway for generating peripheral tolerance against both self and external antigens with minimal side effects (fig. 3). This route might, therefore, contain promising potential for the treatment of autoimmune and allergic diseases in the human (fig. 3). Thus, oral administration of autoantigens suppresses experimental autoimmune diseases (EAE, EAU, AA, collagen-induced arthritis, NOD diabetes) in a disease- and antigen-specific manner, and oral administration of alloantigens has led to increase of allograft survival. OT might be important in treatment of immune complex diseases and food allergies. OT is mediated by T lymphocytes using at least two known mutually exclusive mechanisms: suppression and anergy. Suppression can be adoptively transferred by CD8+ T lymphocytes which act by releasingTGF-beta and IL-4 following antigen-specific triggering. Antigen-driven tissue-directed suppression occurs following oral administration of an antigen from the target organ, even if it is not the disease-inducing antigen (bystander suppression). Thus, synthetic peptides can induce OT, and tolerogenic epitopes of antigen may be different from the autoreactive epitope. Due to the promising results in animal models, OT is being tested in clinical trials in multiple sclerosis (this is with sphingolin- my note), rheumatoid arthritis and uveitis [193, 194].


Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis.



Authors:
Benson JM , Stuckman SS , Cox KL , Wardrop RM , Gienapp IE
, Cross AH , Trotter JL , Whitacre CC
Department of Medical Microbiology and Immunology, Ohio State University College of
Medicine and Public Health, Columbus, OH 43210, USA.
J Immunol 1999 May 15;162(10):6247-54

Article Number: UI99248213


Abstract: Oral administration of a myelin component, myelin basic protein (MBP), induces immunological unresponsiveness to CNS Ags and ameliorates murine relapsing experimental autoimmune encephalomyelitis (REAE). However, a recent clinical trial in which multiple sclerosis patients were treated with repeated doses of oral myelin was unsuccessful in reducing disease exacerbations. Therefore, we directly compared the tolerizing capacity of myelin vs MBP during REAE in B10.PL mice. Oral administration of high doses of myelin, either before disease induction or during REAE, did not provide protection from disease or decrease in vitro T cell responses. In contrast, repeated oral administration of high doses of MBP suppressed established disease and MBP-specific T cell proliferation and cytokine responses. The frequency of IL-2-, IFN-gamma-, and IL-5-secreting MBP-specific T cells declined with MBP feeding, implicating anergy and/or deletion as the mechanism(s) of oral tolerance after high Ag doses. We have previously shown that the dosage and timing of Ag administration are critical parameters in oral tolerance induction. Studies presented here demonstrate that Ag homogeneity is also important, i.e., homogeneous Ag (MBP) is more effective at inducing oral tolerance than heterogeneous Ag (myelin). (This study is so close to what we suspect is the pathophysiology in autism that it deserves special attention).

SUPPLEMENTS AND MEDICATIONS
There exists abundant anecdotal and medical evidence that certain supplements help some or many children with autism. It is easy to become overwhelmed by supplements. The following is a general discussion of things I use on a case by case basis. Dosing of these vitamins is a little complicated. You can learn all about the procedures in the FAQs from the www.autism.com/ari website and I encourage you to go there rather than make me repeat Dr. Rimland's fine efforts. A word about medications for autism. One grave concern I have is the temptation to chemically restrain our children. Psychotropic (anti-psychotic medications) are generally so powerful as to be reserved for the most extreme cases where children are a hazard to themselves. Having said that, I do not believe that scenario is a likely reality if you follow the general recommendations made above and in the DAN! protocol. In addition, the strong chemicals often used to treat autism prevent observing the improvements caused by treatments for gluten/casein removal, allergy and the use of secretin. The medications I generally use are:


Rx Tenex: (an alpha adrenergic blocker which was originally designed to control blood pressure). It seems to lower anxiety, tension and stereotypic behaviors. It also has resulted in significant language gains for my son and others. Dr. Hunt at Vanderbilt has investigated it in ADHD and finds it very effective (published data). It also has beneficial effects in autism.

Clonidine: (Catapres) this is like Tenex, but it has a shorter half-life in the body. It is nice for sedation and control of hyperactivity if tenex is not effective.

Risperdal: Risperidone (generic) has been studied in autistic adults and is still in investigational use in children. Despite a lack of specific FDA approval, many autism experts find it very useful in children with autism. I use this drug for children who are a danger to themselves or others. It has been generally well tolerated in our population. Weight gain and sedation are the most common effects. Extrapyramidal (hard muscles, etc) side-effects are not a common problem and in the Arch Gen Psychiatry 1998;55:633-641 article they were comparable to placebo. It is a bitter tasting suspension and we generally mix it with Tylenol Suspension for flavor. Dose varies, but 0.5 to 2mls per day are generally effective.

ReVia or Naltrexone (50 mg tablets): This drug works by competing with other opioids (presumably gluten and casein derived ones) for the binding at the mu-opioid receptor in the brain. This is the receptor that pain-killers work through. It can help increase appetite for a wider variety of food making the transition to a GC free diet easier. It occasionally helps general autism symptoms, but I use it for GC free transitions. The dose is variable but 1/8 twice daily is where I start.

Yeast: Medications are based on sensitivity data derived from the stool culture reports. Diflucan, Sporonox, Nystatin and Fungizone are the most common forms of medical treatments I use. Because candida can invade the lining of the GI tract and protect itself from Nystatin, I rarely rely on it for eradication of yeast. It can be helpful in decreasing the total yeast burden. ALWAYS FOLLOW REPEAT CULTURES TO ASSURE ERADICATION.

Diflucan or fluconazole: (antiyeast medication that has the best CNS penetration). Whether the brain absorption is important or not, this drug really puts an end to yeast. I recommend using the 40mg/ml variety to keep the volume easier to manage. Follow standard dose for weight guidelines.

Nystatin is another option for many patients. In speaking with Dr. Shaw and Dr. Crook about yeast, we all agree that the non-prescription remedies run the risk of failure to irradiate yeast, and that is very dangerous for autistic children. Yeast sugar (arabinose) can cause permanent damage to the brain. If you want to, try oregano oil, Uva Ursi, citrus seed extract. Please follow urinary arabinose and tartaric acid levels as well as stool cultures to make sure your treatment is working. All children with documented urinary abnormalities of significance get repeated urine assays to make sure we are on track. It can be compounded by a special pharmacist to avoid sugar and artificial colors.

Fungizone (amphotericin oral suspension): This is a nasty drug if given IV, but a very safe one orally. It is given at 1 ml four times daily (regardless of weight) for one to three months.

Sporonox Suspension: Itraconazole is a great antifungal and one of the few things that eradicate Candida Parasipilosis, a dangerous pathogen. It does taste yucky and needs determined parenting to get it in. (Follow standard guidelines for weight).

Metronidazole (Flagyl- gross tasting) or Metronidazole Benzoate (good tasting and can be compounded any flavor you like), is my drug of choice for Clostridia bacteria problems. We see these when the DHPPA analog is elevated on the urine studies. It is very serious. DHPPA-a interferes with normal brain chemistry. We have used this without side-effects in hundreds of children. It also treats many of the common parasites we find in their stool. We can get information to your doctor (if we aren't) about proper compounding. The ratio is 400mg of Metronidazole Benzoate = 250mg of Flagyl or generic metronidazole.

ALLERGIES: * Claritin for allergies is well tolerated and tested on kids- most children need 5-10 mgs and it is very safe even with Diflucan use. I prefer the RediTab which dissolves on the tongue. Since most children with autism are also children with allergies this can help restrain some of the symptoms. Nasal steroids do have a place and I have the parents observe night-time sleeping to see if the children are nasally obstructed. If they are or if severe allergic-eosinophilic nasal discharge is a problem, consider Rhinocort (1 puff each nostril per day.)

* Other medications may require a pediatric psychiatrist or neurologist as I would use them so infrequently that I am not confident in my own understanding of potential harm to the children from these powerful drugs. I do not treat seizure disorders, but I am very willing to work with the treating physician when these are present.


or Child Essence by Creation's Own: These similar products are designed to give your child most essential nutrients lacking in their diet. It provides the maximum dose of vitamin A along with magnesium, B-6 and other vitamins and minerals. It is the foundational starting point. Most children need little doses at first so they can adjust to the new input of vitamins. Work your way up as fast as your child tolerates to the maximum recommended doses. Dr. Rimland (one of the World's most knowledgeable sources of vitamin therapy) has excellent references on vitamin therapy on his Autism Research Center website.

or TMG: Dimethylglycine and trimethylglycine have a tremendous safety record. I think it works best if applied directly to the tongue. Dosing is tricky as some kids need a lot and others a little. Some children get hyperactive with it. I always recommend folic acid (also known as folate) with it. TMG generates SAMe methyl donor activity, so don't us both.

Acid: Wayne Matteson and Bernie Rimland educated me about this in autism. High dose folic acid is necessary because of mitochondrial stress in our kids. 800 to 3200 mcg per day in divided doses.

is a neurotransmitter available at health food stores. It is a calming to inhibitory amino acid. It should be given on an empty stomach and start at 500 mgs a few times a day if the child is very anxious. IN STOCK ITEM.

is an amino acid that has a stabilizing effect on brain cell membranes. It may help prevent seizures, and it has shown benefits in several children with autism. I use 1000 mgs several times a day with my own son and it truly helped his aggression, and obsessive behavior. It should be used for 3 to 6 months then discontinued for a period of time for reassessment. IN STOCK ITEM.

or SAM (S-adenosylmethionine): numerous published medical reports show that SAM is comparable to prescription antidepressants. It may work through regulation of serotonin or other neurotransmitters. We are currently researching this issue. It is one of the things we do for children with depressed serotonin levels and while this is very early in our observations it is well tolerated and seems to be helping. Children can take 100 to 400 mgs four times a day depending on size. As with every new supplement - start low and work up. HEALTH FOOD STORE ITEM.

or 5 hydroxytryptophan the precursor of serotonin. Consider this only under a doctor's supervision when serotonin levels are low. It is available as a prescription through compounding pharmacies. Small amounts like 5 to 20 mgs are day are probably safe. Rx preferred.

Picolinate: this is the important co-factor for insulin to manage blood sugar. The more carbos you eat the more you need. Most autistics are carbo junkies. See Carbohydrate Excess in Autism below. 100 to 200 mcg per day. IN STOCK ITEM.

Gluconate: 20 mg per day. HEALTH FOOD STORE ITEM.

(Twin Labs makes a good calcium for kids) 400 to 800 mgs per day, HEALTH FOOD STORE ITEM.

I prefer to get these from Super NuThera or soon our formula called Child Essence which will provide all the magnesium and B6 required along with a bunch of other things. You can adjust other supplements down based on SNT or CE. P5P or active B6 is preferred over B6. IN STOCK ITEM.

Fatty Acids: I prefer to use fatty acid testing to guide how much and of what to provide. Most children could take several teaspoons of Flax Essential Oils (Michael Murray ND) as formulated by Enzymatic Therapy or Phytopharmica. IN STOCK ITEM.

but important minerals (Krebs Chelates) along with major minerals, can be ground and given for trace and essential minerals. One or two per child per day. IN STOCK ITEM.

from Nutricology contains glutathione, n-acetyl-cysteine and alpha lipoic acid. It is a good way to treat the carbohydrate metabolism errors found so often in autism. I use it when citric acid or other factors in the Kreb's cycle are abnormal. It is a good all around antioxidant as well. 500 to 1000 mgs per day. (Not cheap) Order from Nutricology directly or from us. (Stock Item). Nutricology phone number is (800)782-4274.

Fuel (Twin Labs) is a great tasting predigested liquid amino acid liquid that provides nutritional support for growth and health. It can be taken for kids with poor digestion, poor intake of protein and bad allergies since it is hypoallergenic. Several tablespoons per day. IN STOCK ITEM.

10: nearly all children are deficient. CoQ10 drives the mitoc