Autism Treatment in the Evidence Gap · 2009-02-16 08:45

“After careful consideration of all of the evidence, it was abundantly clear that petitioners’ theories of causation were speculative and unpersuasive… Although C.’s condition markedly improved between his diagnosis and the hearing, the experimental treatments he received cannot be logically or scientifically linked to the theories of causation.

“Sadly, the petitioners in this litigation have been the victims of bad science, conducted to support litigation rather than to advance medical and scientific understanding of ASD.”

The recent ruling in the Omnibus Autism Proceeding test case Snyder v. HHS (Case No. 01-162V; U.S. Court of Federal Claims Office of Special Masters, February 12, 2009) gives renewed cause to question the efficacy of various pharmaceutical and quasi-pharmaceutical treatments marketed to parents seeking to mitigate their autistic children’s physical, developmental and behavioral problems, by those who promulgate and profit from the hypothesis that autism is a consequence of vaccine injury. The decision discusses at length the professional credentials, research and medical practice of one such entrepreneur, Dr. James Jeffrey Bradstreet — the petitioner’s treating physician, National Autism Association Advisory Board member, and a prominent member and clinician educator in the Defeat Autism Now! organization.

The passages that follow offer a troubling glimpse into the extensive, often invasive diagnostic testing and questionable clinical judgment used to justify the protracted administration to autistic children of proprietary nutritional supplements, secretin, chelation drugs, intravenous immune globulin, and other pharmaceutical products, on the rationale that they harbor persistent measles virus, or have become “mercury toxic” through exposure to thimerosal-containing vaccines.

This material graphically illustrates the extent to which Dr. Bradstreet’s interpretations of diagnostic test results and subsequent treatment recommendations diverge from the professional opinions and recommendations of many highly-qualified, knowledgeable, conscientious gastroenterologists, immunologists, virologists, medical toxicologists, pediatric neurologists, and child psychiatrists. Readers may draw their own conclusions as to whether his lucrative departures from evidence-based practice reflect an unmatched grasp of research methodology, exclusive access to superior sources of data, and a heroic willingness to employ novel means to nurture autistic children’s potential, or an uncommon hubris, a talent for salesmanship, and an unconscionable eagerness to expose disabled children to unnecessary medical and research risk.

For ease of reading, I have removed references to case exhibits and hearing transcripts, and have incorporated experts’ first names, specialties and selected footnotes into the text within brackets. Although the decision was issued unredacted, since many of the following passages discuss specifics of medical treatment, and since my intention is not to call attention to the child or his parents but to the medical care furnished to them, I have chosen to redact the child’s first and family names from the text. All links and instances of bold type are added.

Excerpts from
Decision, Snyder v. HHS
(No. 01-162V; filed February 12, 2009)

Treating Physician: Dr. J. Jeffrey Bradstreet (pp. 34-35)

Although Dr. Bradstreet was identified as a treating physician rather than as an expert witness for the hearing, he filed six expert reports before C.’s case became part of the OAP. Additionally, his publications were discussed and critiqued during the course of the trial. Prior to beginning his testimony, he corrected a mistake in one of his publications which had listed him as an adjunct professor at Stetson University. Although he believed he was so appointed, at the time of the article’s publication, he subsequently learned that the appointment was not properly processed.

Dr. Bradstreet is licensed to practice medicine in Florida and Arizona. He is a family physician who has chosen to limit his practice to children with ASD and ADHD. He is not board certified in any medical specialty, although he was one of the experts in the U.K. MMR litigation. Dr. Bradstreet thus presented as a blend between treating physician and expert. As the reports he filed as an expert were not withdrawn as exhibits, it is appropriate to consider his qualifications to opine on the cause of C.’s condition. His credentials are less robust than most expert witnesses, even those who testify under the relaxed evidentiary requirements in Vaccine Act cases. I note that two courts have refused, based on Daubert, to permit him to testify as an expert witness in cases alleging that vaccines cause or contribute to ASD. See Redfoot v. B.F. Ascher & Co., 2007 U.S. Dist. LEXIS 40002, *38-40 (N.D. CA 2007) (although a treating doctor, Dr. Bradstreet’s testimony on matters related to TCVs and autism was excluded as to matters about which he was not a percipient witness), and Easter v. Aventis Pasteur, Inc., 358 F.Supp.2d 574 (E.D. TX 2005) (Dr. Bradstreet found not qualified to opine on vaccine causation).

Nevertheless, I considered Dr. Bradstreet’s six reports and the medical journal articles he authored, in addition to his medical records and testimony pertaining to C. in rendering my opinion on the specific causation claim in C.’s case.

Dr. Bradstreet’s Research on Mercury Excretion Disorders in ASD (pp. 101-103)

[Immunologist] Dr. [Jeffrey] Brent testified that there is no study in the peer reviewed English language scientific literature that reports a difference in blood or urinary mercury levels in autistic children as compared to controls. These are the easiest levels to measure. Two of the three studies that petitioners relied upon to demonstrate aberrant mercury excretion patterns in children with ASD involved hair and teeth. The third, Dr. Bradstreet’s 2003 study [A Case-Control Study of Mercury Burden in Children with Autistic Spectrum Disorders], did involve urine, but the paper was not published in a peer reviewed and indexed journal. All three of these studies have significant flaws that adversely affect the scientific reliability of their conclusions.

In the Bradstreet study, autistic children were matched for age, sex, and vaccination status with eight, non-randomly selected controls. Mean urinary mercury excretion after three days of chelation was 6.42 µg/g of creatinine for the ASD children and only 1.08 µg/g of creatinine for the control children. No pre-chelation levels were determined for either group. [The failure to ascertain pre-chelation levels of urinary mercury is contrary to standard practice, as petitioners’ own expert conceded.] The authors conceded that they could not determine whether the higher mercury excretion levels in the ASD children were the result of higher mercury intake or a reduced ability to excrete it without chelation.

Other problems with the Bradstreet 2003 article, as noted by Dr. Brent, involve the huge and overlapping range of values for urinary mercury levels, the failure to control for diet between the two groups, and the statistical methodology employed. A chart on page 79 of the study reflected the urinary mercury ranges from zero to 60 µg/g of creatinine in the ASD children and from zero to 6 µg in the control group. The standard deviations exceeded the actual values reported, rendering the data essentially meaningless. Dr. Brent also noted that, given the large standard deviations, it was unlikely that the differences between the two groups were statistically significant. Based on the methodology described in the paper, Dr. Brent was unable to find a statistically significant result.

Additionally, the control group of children was selected based on parental concerns about environmental mercury. Dr. Brent testified that parents concerned about mercury are likely to restrict seafood in their children’s diets, which would contribute to lower urinary mercury levels in the control children. However, the investigators failed to control for diet in the study.

The urinary excretion rates for the children with ASD reflected urinary mercury rates consistent with the general population. Although no study was filed to indicate what post-chelation mercury excretion rates are typical, Dr. Brent based his testimony on his experience with normal mercury levels.

Another problem with the Bradstreet 2003 study was that the authors failed to state whether individuals who had undergone prior chelation were excluded. Given that the study subjects were individuals treated by Dr. Bradstreet, who used multiple rounds of chelation with C., the possibility that some of the children studied had previous rounds of chelation therapy cannot be excluded.

Another group of researchers attempted to duplicate Dr. Bradstreet’s study. The Soden study failed to find evidence that the autistic subjects had excess levels of mercury or other heavy metals. This study did not suffer from the defects noted by Dr. Brent in the Bradstreet 2003 study, although the numbers of test subjects with autism diagnoses and controls were smaller than in the Bradstreet 2003 study. To correct for one of the flaws noted in the Bradstreet 2003 study, dietary restrictions were imposed, pre-chelation (baseline) urine levels were measured, diagnoses of autism were confirmed, and those with previous chelation were excluded. Only one of the autistic children had a post-chelation urinary mercury level above the limits of detection. None of the typically developing control children showed post-chelation urinary mercury levels above the limits of detection (which was 1 µg). Because of the small number of control subjects, no statistically significant comparison could be made. The authors considered it highly significant, however, that only one of the ASD subjects demonstrated a detectable level of mercury after chelation.

Treatment by Dr. Bradstreet (pp. 231-234)

Dr. Bradstreet began treating C. on July 28, 1999, and was still treating him at the time of the hearing in November, 2007. C.’s medical records with Dr. Bradstreet encompass over 650 pages over more than eight years, including over 160 office visits, telephone consultations, and email contacts, regarding C.’s condition, symptoms, treatments and response to those treatments. These records reflected office visits every four to eight weeks throughout most of the period between mid-1999 and August, 2007, the date of the last medical record filed. [These records do not include Dr. Bradstreet’s hyperbaric oxygen treatments. Although the hyperbaric oxygen treatments are referenced occasionally in the other medical records, they were not furnished with the rest of the records from Dr. Bradstreet.]

Dr. Bradstreet’s treatments included a wide variety of dietary supplements, secretin infusions, immunoglobulin therapy, chelation, glutathione, and prednilisone. He ordered numerous laboratory tests, many of which were non-standard tests not approved by the FDA, or ones performed outside the U.S. He performed several lumbar punctures to draw C.’s CSF to test for measles virus and measles antibodies, and referred C. to a gastroenterologist for a colonoscopy and gut biopsy. His reported diagnoses varied throughout C.’s treatment. He began with a diagnosis of autism, yeast overgrowth, and a fungal infection in July, 1999. [I note that [petitioner’s previous treating doctor] Dr. [Nancy] Wenk concluded that C. did not meet the diagnostic criteria for autism, giving him a PDD-NOS diagnosis shortly after C.’s first visit to Dr. Bradstreet. Dr. Bradstreet’s records do not reflect the use of any of the autism rating scales, such as the ADI-R, CARS, or ADOS; his diagnosis appeared to be based solely on his own observations and parental reports.] Subsequent diagnoses included autoimmune encephalopathy; autoimmune disease not elsewhere classified and immune mechanism disease not elsewhere classified; allergic gastroenteritis and autoimmune disease; unspecified urticaria, unspecified encephalopathy, and allergic gastroenteritis; encephalopathy unspecified, unspecified disorder of immune mechanism, gastroenteritis, and colitis; disturbance of sulphur-bearing amino acid metabolism, unspecified disorder of immune mechanism, unspecified disorder of metabolism, and encephalopathy unspecified; the same diagnoses in July, 2004, with the addition of “rule out epilepsy, unspecified”; autoimmune disease not elsewhere classified, unspecified disorder of metabolism, unspecified disorder of immune mechanism, and encephalopathy not elsewhere classified; and toxic effect of mercury and its compounds, autoimmune disease not elsewhere classified, and unspecified disorder of immune mechanism. Dr. Bradstreet testified that the recorded diagnoses varied, depending on the nature of the problem being treated at that particular time. [This list is not exhaustive of the various diagnoses assigned to C. throughout Dr. Bradstreet’s treatment of him.]

Dr. Bradstreet’s treatment of C. overlapped with C.’s speech therapy from July, 1999 through April, 2003. C. also saw his primary care provider and occasionally saw specialists during this time frame.

Exactly how Mrs. S. was referred to Dr. Bradstreet is unclear. [C.‘s speech therapist Ms. Kathy Timlin] testified that she referred Mrs. S. to another mother whose child was seeing Dr. Bradstreet. She admitted that she “made suggestions that he was available,” but did not recall any direct referrals to Dr. Bradstreet. Mrs. S. testified that C.’s speech therapist told her that she “needed to see Dr. Bradstreet” and that she obtained his contact information from the therapist. The questionnaire she completed for Dr. Bradstreet mentioned an Orlando conference where Dr. Bradstreet suggested certain testing, and it also stated that Ms. Timlin “educated her on the different causes of autism” and prompted her to see Dr. Bradstreet while C. was still young. Ms. Timlin’s notes did not mention a referral to Dr. Bradstreet.

C.’s Initial Testing and Assessment (pp. 233-235)

Although C. did not see Dr. Bradstreet until July 28, 1999, his mother completed a screening evaluation form for treatment on May 11, 1999. A number of laboratory tests were performed at the initial screening visit. In her parent questionnaire, Mrs. S. described C. as having early speech and a large vocabulary, which he lost at approximately 18 months of age. She described his vocabulary exclusively in terms of names (grandma, Krista, mama, dada). She indicated that he stopped playing with his siblings and had delayed motor skills after 16 months of age. She listed chronic “loose stools” as a concern, but noted communication and behavior problems as her primary concerns. She had removed gluten and casein products from his diet after a recommendation by his speech therapist, with a “very good response.” Mrs. S. described her belief that C.’s problems were linked to his milk allergy, a lot of antibiotic use, and his MMR shot. [Mrs. S. responded to a question on the form: “Do you believe your child’s symptoms are vaccine related?” by circling “yes.” She then wrote in the comments about the MMR vaccine, milk allergy, and antibiotic use. Dr. Bradstreet testified that this question had been on his intake form for 10 years, and about 40-60% of his patients answered it “yes.”] She recorded that C. was hospitalized two weeks after the MMR vaccination. [The hospitalization actually occurred 33 days after the MMR vaccination.]

C. had a number of tests during May, 1999, including antifungal sensitivity, stool analysis, and bacterial sensitivity testing. An immune system panel test was also performed which showed normal IgG levels, low IgA subclass levels, and a very high IgE level. [The laboratory report actually listed the IgA results in the “within” range column. Subsequent studies in other laboratories, including the Shands Medical Center laboratory at the University of Florida, showed normal IgA levels.] Allergy testing demonstrated extreme reactivity to trees, grass, weeds, and mold. As [petitioner’s previous doctor] Dr. [Steven] Sahai later characterized C.’s allergy test results: “C. is allergic to the Florida environment.”

During his initial examination of C., Dr. Bradstreet found him to be combative and agitated. He was unable to obtain vital signs or to check his height and weight. While C. made good eye contact, it was fleeting. He had social interest in his mother, but not in anyone else. He was hyperactive, toe walking, and engaged in self-stimulatory behavior. His speech was limited to two or three words. In physical appearance, he was thin with dark circles under his eyes. Dr. Bradstreet’s working diagnosis was autism, overgrowth of yeast in his digestive tract, and clostridia bacteria in his urinary tract. His later testimony confirmed that his diagnosis was autism, in terms of the DSM-IV-TR, 299.00, diagnostic criteria, rather than the PDD-NOS diagnosis he was later given by Dr. Wenk.

He began treating C. initially with intravenous secretin and Diflucan, and a variety of dietary supplements. He referred to C.’s yeast overgrowth as “dysbiosis,” meaning that atypical, and possibly pathogenic, organisms were residing in his gastrointestinal tract. […] The secretin treatment seemed to improve his [diarrheal] symptoms, as noted by his mother, Dr. Bradstreet, family members, and his speech therapist. According to Dr. Bradstreet, in April, 2000, when C. first began receiving IVIG treatments, he began to make “remarkable dramatic improvements.” Dr. Bradstreet prescribed the IVIG treatments based on the work of Drs. [Sudhir] Gupta and [Jane] El-Dahr. According to Dr. Bradstreet, C. met the selection criteria for IVIG treatments based on his long history of “immunological dysregulation” and his high level of antibodies to MBP. Dr. Bradstreet testified that, based on C.’s ongoing gastrointestinal problems, his immunologic history, and his regression after 15-16 months of age, C. appeared to fit the regressive subset of children with autism. Dr. Bradstreet variously described C.’s condition as “autoimmune related encephalopathy” and “post-measles encephalopathy.”

Types of Treatment Provided (pp. 235-236)

Dr. Bradstreet testified that C. made a dramatic, and highly unusual, level of improvement while under his care. By six years of age, C. had normal language scores, which represented a remarkable recovery from the levels he displayed at two and one-half years of age. The progress continued. Although C. started the first grade classified as developmentally delayed and language impaired, at seven and one-half years of age, C.’s vocabulary and sentence structure was that of a nine year old. C. was released from the developmental delay classification on August 10, 2004.

Dr. Bradstreet based his treatment modalities on his view of what caused C.’s condition. He noted that C. was exposed to mercury in TCVs, both prior to, and at the time of, his MMR vaccination. Based on the immunological records, the hospitalization, the subsequent treatment, and on other laboratory testing, he believed the MMR vaccination dysregulated C.’s immune system. The dysregulated immune system permitted gut and brain inflammation. The evidence for gut inflammation came from biopsies taken during an endoscopy and a colonoscopy in May, 2002. The evidence for brain inflammation was “his overall cognitive abilities and his response to therapies that are anti-inflammatory in nature.” He believed that C. had oxidative stress, and was certain that he had persistent measles virus in his CSF and gastrointestinal tract. His immune dysregulation, exposure to antibiotics, and persistent virus led to an inability to manage pathogens in his gut. His therapies for C. were designed to address all of these issues. A more detailed account of the testing performed or ordered by Dr. Bradstreet, the results, and interpretations of those results is immediately below, followed by an account of Dr. Bradstreet’s treatment regimen.

(1) Testing (pp. 236-245)

(a) Low IgA Levels

One and one-half months after his MMR vaccination, C. had a low serum IgA (24.9, with a reference range of 36-163 mg/dL as normal). According to Dr. Bradstreet, the level was still low in July, 1999, when he retested C.. The actual test results showed that C.’s total IgA was within normal limits (38 mg/dL, with a reference range of 24-121 as normal). However, IgA subclasses (IgA1 and IgA2) levels were low (31 mg/dL of IgA1, with a reference range of 48-378 and 6 mg/dL of IgA2, with a reference range of 13-91). [Internist and immunologist] Dr. [Burton] Zweiman testified that this was a “modestly decreased” serum IgA level, not an IgA deficiency.

Dr. Zweiman did not think these levels were of concern. Another physician, Dr. [Steven] Von Elten, who replaced Dr. Sahai as C.’s primary care provider, did not think that these IgA levels were of any clinical significance. He spoke with Dr. Bradstreet about Mr. and Mrs. S.’s request that he order the IVIG product. With regard to this conversation, Dr. Von Elten’s notes stated “mild IgA subtype deficiency not clinically significant.” The note does not reflect who made the conclusion regarding the lack of clinical significance. Although the context suggests it was Dr. Bradstreet (a conclusion also reached by [virologist] Dr. [Brian] Ward upon reading these notes), Dr. Bradstreet testified that he did not so conclude. As these laboratory tests do not appear in Dr. Von Elten’s records, the information concerning the IgA levels must have come from Dr. Bradstreet.

An IgA test performed in January, 2006, ordered by Dr. [Suzanne] Skoda-Smith, an immunologist to whom C. was referred, was normal. C.’s IgA levels were also normal in July 2007, in the only other serum IgA test ordered by Dr. Bradstreet.

(b) High IgE Levels

Dr. [Ayodeji] Otegbeye [another treating immunologist] did not test C.’s IgE levels. Initial testing initiated by Dr. Bradstreet showed an extremely high IgE level (2471 IU/mL with a reference range of 0-164), indicative of an allergic process. Dr. Zweiman characterized this result as a strikingly elevated serum IgE level, which C.’s doctors should have followed up with testing to ensure that there was no parasitic infection, which might have caused his diarrhea. There was no evidence that Dr. Bradstreet conducted such follow up. Although he did stool testing at the initial visit, the analysis did not include testing for parasites.

Dr. Zweiman testified that another explanation for C.’s elevated IgE level was eosinophilic gastroenteritis, which is seen in children who have food allergies or other reactions to certain foods, something C. clearly demonstrated, both clinically and on the gut biopsies taken in May, 2002. The only other IgE testing, conducted on July 16, 2007, showed a level of 820 with the upper range of normal at 328.

(c) Lymphocyte Levels

Dr. Bradstreet characterized C.’s lymphocyte levels as evidencing a persistent lymphocytosis, or too many white lymphocytes, which indicated immune dysregulation. Dr. Otegbeye’s testing in June, 1998, showed 67% lymphocytes, with a normal range of 18-56. The June, 1999, results showed 62% lymphocytes, with a reference range of 50-56%. C.’s lymphocyte levels were consistently high. They were low only on one test.

(d) Myelin Basic Protein Autoantibodies

Dr. Bradstreet ordered MBP autoantibody testing at C.’s initial visit in July, 1999, and had Mrs. S. sign a consent form for such testing, but the sample was not drawn until January, 2000. Specialty Laboratories reported his result on January 25, 2000, as 46 EIA units, with a reference range for normal of less than 10. Mrs. S. could not recall why the MBP test was performed.

Dr. Bradstreet characterized C.’s initial MBP autoantibody level as “very high.” Dr. Zweiman concurred with this assessment. Dr. Bradstreet recommended a course of IVIG treatment to clear the antibodies and to treat C.’s elevated IgE level. According to Dr. Zweiman, IVIG would not be an appropriate therapy to treat an anti-MBP antibody level of 46.

Dr. Zweiman also noted that measuring antibodies against MBP can be difficult. It is also difficult to compare findings from one measurement technique to another. Testing for MBP has not been standardized, as the primary use for anti-MBP tests is in research, rather than clinical care.

Anti-MBP antibodies have been reported in patients with ASD and in patients with neurodegenerative diseases or epilepsy, with varying frequency. Some reports indicate that 50-60% of ASD patients have such antibodies. Anti-MBP antibodies have been found in 62% of individuals with multiple sclerosis and in about 50% of those with active rheumatoid arthritis. However, anti-MBP antibodies have also been found in about 25% of individuals without any clinical disease, and thus elevated anti-MBP levels are not always a sign of neurologic dysfunction. There is no evidence that anti-MBP antibodies are associated with any pathology in ASD patients. Since injecting anti-MBP into experimental animals does not induce neurologic disease, there is no consensus on the clinical relevance, if any, of anti-MBP antibodies.

An MRI can show demyelination in conditions like multiple sclerosis, but demyelination is not seen in autism. C.’s MRI, performed in January, 2006, showed no evidence of demyelination. Because normal individuals may have antibodies against MBP, and such antibody levels are highly variable, it is difficult to draw conclusions from C.’s test results.

On the date C. began IVIG therapy, March 8, 2000, Dr. Bradstreet ordered another test of his anti-MBP level. The report was negative. It included the comment: “There was no sign of autoimmunity to brain myelin….”

Over the next six years, C.’s blood anti-MBP antibodies remained within the normal range of 10 or below, except for one test on October 9, 2002, when the level was 14. Dr. Zweiman noted that anti-MBP levels are variable. The only test for MBP in C.’s CSF, drawn on April 17, 2002, was also negative. Antibodies against MBP in the CSF would be more direct evidence of damage to the white matter of the brain than finding such antibodies in blood serum.

In spite of repeatedly normal anti-MBP tests, apparently C.’s parents still thought his anti-MBP antibodies were high in March, 2007. At his 10 year check up, they reported that he had anti-MBP antibodies to his primary care physician, and attempted to get his IVIG treatment for them restarted. Apparently Dr. Bradstreet thought they were still high as well, because a note, dated in March, 2007, in the records of C.’s family practice physician commented: “IVIG referral treatment by Dr. Bradstreet for myelin protein antibody.” A later-dated note recorded that a request for the IVIG had been sent to another office for processing.

Dr. Bradstreet ascribed the need for IVIG therapy to C.’s anti-MBP levels. However, there is no evidence that either the wild-type measles virus or the vaccine strain measles virus induces the formation of anti-MBP antibodies, despite extensive study. It is not a reliable marker for measles infection in the brain.

(e) Mercury Testing

[The petitioners present] a table that captures the mercury testing performed on C. over more than six years, measuring mercury in the hair, blood, and urine. For reasons set forth below, I conclude that none of these tests demonstrated excess mercury in C.’s body.

(i) Hair Mercury Test

C.’s first mercury test was a hair test, conducted on April 29, 2000. Hair tests measure exposure to organic mercury, primarily ethyl or methylmercury. The hair closest to the scalp captures the level of mercury in the blood within a month of the time the hair was cut. The remainder of the hair strand provides information regarding historical exposure. Hair mercury levels reflect circulating blood levels of mercury at the time of hair growth, not the level of mercury in tissue (body burden).

The April 29, 2000 hair test for mercury demonstrated a low level of mercury in C.’s hair, but one within the reference range of normal for the laboratory, and one well below the 90th percentile for U.S. children ages six to eight. Although C. was a little over three years of age at the time of the test, the U.S. norms for older children help to place this result in context.

Given C.’s exposure to mercury through TCVs, Dr. Bradstreet expected this hair mercury level to be higher. He thought the low test results reflected a problem in excreting mercury, rather than low body levels of mercury. This inverse correlation between hair mercury and mercury body burden was based on Dr. [Amy] Holmes’ work.

[Immunotoxicologist] Dr. [Michael] McCabe disagreed with Dr. Bradstreet, testifying that this result would be expected from C.’s diet (which did not include fish), and from the small amount of thimerosal contained in C.’s vaccines. He also noted that it was consistent with the levels of mercury found in C.’s blood.

(ii) Urine Mercury Levels

C.’s first urine test for mercury exposure was a post-provocation challenge test conducted on July 21, 2000. Prior to collecting the urine, C. was administered 100 mg of DMSA, a chelating agent. The results were reported by Doctor’s Data laboratory as “very elevated,” at 11 µg/g creatinine. Converting this figure to parts per billion (µg/L) would yield a result of 2.2 µg/L of urine. No baseline urinary mercury level was determined before administration of the chelating agent.

However, the reference ranges for this test were based on subjects who were not chelated before measurement of their urinary mercury levels. Based on Dr. [James] Woods’ research, urinary mercury levels in adults not occupationally exposed to mercury were 3.0 µg/L, pre-chelation; C. had a lower result, post-chelation. Although the Doctor’s Data laboratory reported C.’s results as “very elevated,” applying the correct reference range placed C.’s post-chelation mercury level in the range of normal pre-chelation levels.

Dr. McCabe’s testimony was also supported by an article filed [to Cedillo v. HHS]. This study looked at chelation as a method to assess “body burden” of mercury. Healthy adults were tested for mercury levels, and then took a chelating agent. Baseline urinary mercury averaged 2.2 µg/L of mercury. Post-chelation mercury levels were an average of 13.7 µg/L. Based on this small study, C.’s post-chelation mercury level appeared to be low, not elevated. The study also demonstrated why no post-chelation norms have been established for children. One of the 15 adults recruited for this study suffered a serious reaction to the chelating agent, and the study was terminated after only one round of chelation.

A post-chelation urine sample, taken on April 24, 2006, reported that any mercury present was below the detection limit. Another post-chelation urine sample, taken on June 26, 2008, was reported by another laboratory as well below the reference range for mercury. Another post-chelation urine sample, taken on September 25, 2006, found no detectable mercury.

(iii) Blood Mercury Levels

C.’s blood mercury levels were tested on five occasions, all with findings in the normal range. A blood sample drawn on September 21, 2000, was tested for mercury on September 26, 2000. The mercury level of 3 µg/L was well within the reference range. C.’s blood mercury levels were measured on December 10, 2004, April 29, 2005, and June 26 and December 11, 2006. All of the results were lower than the reference limit of 10 µg/g, even though they were all post-chelation tests. The blood mercury levels measured recent exposure, which, in C.’s case, would have been very limited due to his diet and his parents’ refusal to administer any additional vaccines.

(iv) Urinary Porphyrin Testing

According to testing done at the Laboratoire Phillippe August in France, C. had abnormal urinary porphyrins consistent with mercury exposure. Dr. Bradstreet interpreted C.’s porphyrin test results as consistent with his other observations that C. demonstrated low levels of thiols, cystine, and glutathione, and he was probably not a good excreter of mercury. Dr. Bradstreet explained that the ratios between certain types of porphyrins were important, and C.’s precoporphyrin level was greater than his uriporphyrin level, an atypical presentation. He based this interpretation on work by Drs. Wood, [Robert] Nataf, and [Mark] Geier.

Urinary porphyrin testing represents a “work in progress,” according to Dr. McCabe. Precoproporphyrin appears to be a marker of urinary mercury in those occupationally exposed to high levels of elemental or methylmercury, but there is no data on those with intermittent exposure to TCVs.

C.’s precoproporphyrin test results were somewhat inconsistent. On September 15, 2006, his level was 31.7 nmol. On July 27, 2006, his precoproporphyrin level was 24.6, with a reference range of 2-5. On July 26, 2007, the level had risen to 30, in spite of several rounds of chelation between the latter two tests. These test results conflicted with the urine, hair, and blood tests, all of which showed low or undetectable levels of mercury.

Dr. McCabe noted that Dr. Woods found two porphyrins, precoproporphyrin and pentacarboxyporphyrin, that appeared to equate to other measures of mercury exposure (comparing porphyrins to urinary mercury levels). C.’s urine was high in both. However, C. was also high in two other porphyrins, heptacarboxyporphyrin and hexacarboxyporphyrin, giving him an unusual profile. Given C.’s many rounds of chelation, Dr. McCabe was highly skeptical that C.’s porphyrin testing represented residual mercury in his body. He noted that Dr. Woods’ work demonstrated that chelation lowered urinary precoproporphyrin levels “precipitously.”

(f) Measles Virus Antibody Testing

Measles virus antibody testing measures exposure to measles virus whether from natural infection or from vaccine. A positive test result for measles IgG antibody would be expected in someone who had been vaccinated within the prior two years, and would be indicative of an appropriate immune response to the vaccine. From a blood sample drawn on March 8, 2000, C. tested positive for both measles virus and herpes virus-6 IgG, reflecting his MMR vaccination two years earlier, and some natural exposure to herpes virus.

However, by March, 2002, C. did not have detectable levels of antibodies to measles virus, MMR, or herpes virus in his CSF, which Dr. Bradstreet attributed to two years of IVIG treatments. Later, Dr. Bradstreet elaborated on this testimony, stating that the absence of measles virus antibodies in C.’s CSF in 2002, “needs to be interpreted in the light of his previous therapy.” He agreed that most batches of IVIG would have significant levels of anti-measles virus antibodies.

According to Dr. Ward, Dr. Bradstreet’s explanation that IVIG treatments caused the negative result for measles antibodies was not persuasive. If C. had a persistent measles infection and manufactured antibodies to the measles virus as a result of either that infection or his vaccination, he would not cease manufacturing them simply because he had an IVIG treatment. A negative measles antibody test would be inconsistent with an active, persistent measles infection.

(g) Endoscopy and Colonoscopy Results

In May, 2002, Dr. Kerry Thek performed an upper endoscopy and colonoscopy on C. for “poor weight gain, weight loss, chronic diarrhea, and emesis.” In a letter to Dr. Bradstreet, Dr. Thek noted that C. had a history of gastrointestinal complaints, including chronic intermittent diarrhea. Her letter also indicated that the pathologist found no colitis or ileitis on the biopsies, but did find several intraepithelial eosinophils in samples taken from C.’s lower esophagus.

The operative report noted that, on endoscopy, C. appeared normal from his esophagus through his duodenum. On colonoscopy, Dr. Thek found lymphonodular hyperplasia and ileitis with mild hemorrhage in his terminal ilium. Her assessment was “possible ileitis in terminal ileum,” pending biopsy report. The pathology report on the endoscopy samples showed several intraepithelial eosinophils; the report on the colonoscopy samples was entirely benign, finding “no significant histopathology.”

Dr. Bradstreet wanted a second opinion on the biopsy samples and arranged to send the tissue blocks to a Dr. Andrew Anthony. Dr. Anthony’s report was not filed prior to trial, with the rest of Dr. Bradstreet’s records. Dr. Anthony’s findings were different from those of the first pathologist. He found more eosinophils in the duodenum. In the terminal ileum, he found “prominent lymphoid tissue” with a hyperplastic follicle with a large germinal center on one sample. He also found two large collections of eosinophils. In the cecum, he found “a mild focal excess of mucosal chronic inflammatory cells with an eosinophil component.” He commented that the changes raised “the possibility of an allergic process,” and commented that they were “similar to those seen previously in children with autism.” Dr. Bradstreet interpreted this pathology report as a “diagnosis of eosinophilic gastroenteritis or enteritis that certainly matches up with his high IgA’s and some of his other observations and is consistent with his immune disregulation. And when combined with the measles virus report from the biopsy, is concerning about the persistence of that virus triggering some of these changes.” I note that C.’s IgA levels were never high, and it is likely Dr. Bradstreet simply misspoke, meaning instead C.’s high IgE levels.

(h) Testing for Measles Virus RNA

Based on reports from Dr. [John] O’Leary’s laboratory, Unigenetics, that measles virus had been detected in the gastrointestinal tract of some children with autism, Dr. Bradstreet thought it was logical to confirm his suspicion of a causal relationship between the MMR vaccine and onset of C.’s symptoms. He traveled to Dublin to meet Dr. O’Leary to ask if CSF should be tested for the presence of the measles virus, and to find out whether Unigenetics could detect it, if present. Dr. O’Leary gave him a tour of the laboratory and explained the collection, shipping, and testing procedures. He thereafter arranged for C.’s blood, CSF, and gut tissue to be tested for the presence of measles virus RNA.

C.’s CSF and blood samples were drawn in Dr. Bradstreet’s office on April 17, 2002, and shipped to Unigenetics. The CSF sample was reported back as positive for measles virus at 3.7 × 10 copies per nanogram of total RNA. C.’s blood sample tested negative for the presence of measles virus. Both reports were dated June 5, 2002. These reports are what [virologist] Dr. [Bertus] Rima called “headline reports” in that they simply reported the results without explaining how the copy numbers were computed. A terminal ileal biopsy, collected during Dr. Thek’s endoscopy and colonoscopy of C. on May 30, 2002, was received by Unigenetics on December 12, 2002. It also tested positive for the measles F gene RNA by PCR testing performed by Unigenetics. The copy number was very low, 7 copies per nanogram of total RNA. Petitioners’ expert, [virologist] Dr. [Ronald] Kennedy, testified that this result was quite low, and was only comfortable with calling the gut biopsy results “indeterminate.”

To Dr. Bradstreet, the positive test result from the CSF sample meant that the virus was reproducing in the brain. Viral replication explained C.’s dependence on IVIG to relieve his autism symptoms and why his symptoms returned when he was withdrawn from IVIG.

(i) Other Tests

Dr. Bradstreet testified that C.’s adenosine deaminase level [an enzyme] was high, reflecting immune dysregulation. Although his TNF-α level was reported as normal by the laboratory, and there is a handwritten notation on the laboratory report of “good,” Dr. Bradstreet testified that “subsequent literature” indicated it was actually high. Subsequent testing, on January 12, 2006, showed a normal TNF-α level. Dr. Bradstreet also noted that C.’s neopterin levels [a compound typically excreted a low levels in the urine] were high in September, 2006, in spite of the years of IVIG treatment. Testing in July, 2007, reflected normal neopterin levels.

C. had several antinuclear antibody [“ANA”] tests. This is the primary test used to diagnose systemic lupus erythematosus and other autoimmune diseases. All of the tests were negative.

(2) Treatment (pp. 246-256, 262)

(a) Dietary Supplements

According to Mrs. S., Dr. Bradstreet recommended various supplements and “de-yeasting.” The supplements included CoQ10, flax, SuperNuThera, and others that Mrs. S. could not recall. C. began taking at least some of the recommended supplements almost immediately. He did fine on some, but would then “bottom out” and those supplements would be discontinued.

[One petitioner’s exhibit] contains a list of the dietary supplements C. received between 1999-2004. Syclovir, a nutritional supplement, was recommended by Dr. [Jerrold] Kartzinel, one of Dr. Bradstreet’s partners, to treat inflammatory changes in the digestive tract. During cross-examination, Dr. Bradstreet identified some of the other supplements and explained why they were prescribed. He identified alpha lipoic acid as an antioxidant; flax as containing essential fatty acids; and Primal Defense as a probiotic. He explained that NAC was n-acetylcysteine, an orally absorbable form of a thiol amino acid, critical to the development of glutathione, the body’s main antioxidant, and one required by the brain. He identified taurine as a neutral amino acid essential for the formation of bile salts, and explained that it had been observed to calm and ease behavioral symptoms. He indicated that he prescribed it fairly frequently. Without his permission, a company that manufactured it (Kirkman Laboratory) used him as a testimonial for its efficacy. Dr. Bradstreet acknowledged that Kirkman Laboratory was promoting taurine for use in treating autistic patients without any scientific support for the claim, and ran into problems with the FDA as a result. C. took taurine for a considerable period of time, although laboratory tests in November, 2000, showed that C.’s taurine levels were actually high.

The nutritional supplements prescribed by Dr. Bradstreet were also sold by Dr. Bradstreet. His testimony on whether this was a profit-making enterprise was somewhat equivocal. After first testifying that his corporation made “approximately nothing” from the sale of supplements, with “essentially no mark-up at all”, he gave a non-responsive answer to the next question, concerning any profit from the sale of dietary supplements. Rather than answering yes or no, he commented that he often “gave supplements away to families in need.”

C.’s experiences with nutritional supplements were not always benign. On October 26, 1999, what appears to be a telephone consultation with a nurse in Dr. Bradstreet’s office recorded that C. was irritable, throwing temper tantrums, not sleeping through the night, and having recurrent diarrhea. C. saw Dr. Sahai that same day. Mrs. S. reported that he was having tics at night that Dr. Sahai suspected were myoclonic jerks related to the medications C. was taking. Dr. Sahai commented that C. was on “quite a few medications for his pervasive developmental disorder which I am quite unfamiliar with,” and suggested they be discontinued. Mrs. S. refused, based on the improvement she saw in C.. Dr. Sahai’s observation was that C. was unchanged neurologically, and still showed signs of a pervasive developmental disorder.

[In view of Mrs. S.’s praise of Dr. Sahai on the initial questionnaire that she completed for Dr. Bradstreet, I expressly reject her testimony that she mentioned C.’s behavior to Dr. Sahai earlier and that he was not responsive to her concerns. In this regard, I note that Dr. Bradstreet was quite critical of Dr. Sahai’s care of C., and his negative opinions may have influenced Mrs. Snyder’s later accounts.]

Mrs. S. frequently commented on problems after the addition of a new supplement. This encounter note indicated that every time C. was placed on a supplement, he would respond with incontinence or poor behavior; the health care provider’s response was to recommend a decrease in the dose of supplements to one-fourth and to start them one at a time.

(b) Secretin

Secretin therapy appeared to be the intervention C. received the longest, beginning on C.’s first visit with Dr. Bradstreet in July, 1999. He took several forms of secretin, beginning with intravenous secretin, and, in April, 2005, he began to use nasal secretin in combination with intravenous secretin.

According to [pediatric neurologist] Dr. [Max] Wiznitzer, secretin does not work as a treatment for autism. In controlled studies, some children improved while taking secretin, which he attributed to a combination of the placebo effect and the natural history of autism. Secretin might have some positive effect on bowel problems, but not on the core symptoms of autism.

His testimony was buttressed by [child psychiatrist] Dr. [Edwin] Cook’s in Cedillo. Dr. Cook testified that he was one of the researchers involved in clinical trials of secretin as a therapy for autism. Three case reports suggested that secretin might be effective, and he was very excited about the prospect of a drug treatment for autism. Secretin was tested against saltwater in a blinded study. The initial data indicated that the children were better after the study. When the study was unblinded, however, those receiving saltwater actually did slightly better than the children receiving secretin. The study itself provided hope to families struggling with this illness, but secretin therapy proved less effective than the placebo.

Nevertheless, Mrs. S. was adamant that the secretin therapy helped C.’s autistic symptoms, as well as his gastrointestinal ones. She testified that, after beginning secretin, C. began sleeping through the night. His diarrhea did not entirely go away, but it was much better, and she began to see more eye contact and fewer tantrums. Most of Mrs. S.’s comments in C.’s records about secretin’s effectiveness concerned C.’s digestive issues. However, she also attributed good behavioral effects to secretin. Dr. Bradstreet noted in August, 2006, that C. “seems to require secretin to stay on target – with it he does very well in school.” [I note that Dr. Bradstreet made virtually identical claims for IVIG’s efficacy for C..]

(c) Chelation

Dr. McCabe testified no good data demonstrates that chelation therapy works to treat autism. Nevertheless, approximately 30-40% of Dr. Bradstreet’s patients were chelated during his treatment of them, a figure that remained consistent over the five years preceding the hearing. Dr. Bradstreet testified that chelation was clinically indicated in patients with a history of significant exposure to a heavy metal; elevated current blood levels of mercury or lead; high levels of porphyrin in the urine, combined with oxidative stress; high hair levels of mercury; or a very strong result to a provocation challenge. He used chelation challenge to diagnose whether a child had excessive levels of mercury, and did not routinely test for mercury or other heavy metals prior to beginning chelation. In spite of the fact that none of C.’s tests for mercury was high, and C. responded poorly to chelation, Dr. Bradstreet ordered numerous rounds of chelation therapy.

C. was initially chelated with Chemet, the brand name for succimer, or DMSA, in July, 2000. Based on the results from this test, Dr. Bradstreet prescribed 100 mg of Chemet to be taken three times a day for three days, followed by an 11 day break, repeated for 10 cycles of chelation. Apparently Dr. Kartzinel reduced the dose by half, to 50 mg of Chemet three times a day, according to nursing notes in the records. Although the date C. began taking Chemet was not recorded, the prescription was dated August 3, 2000, and a message regarding the recommended dosage change was left on August 4, 2000.

A nursing note reflected that C. became very agitated and noncompliant five days after chelation, but that his behavior was back to normal by August 14, 2000. On August 16, 2008, Dr. Bradstreet’s records reflected that C. was experiencing myclonic jerks at night. Dr. Bradstreet recorded temporary setbacks with the chelation and decreased C.’s dose that same day.

The second round of chelation did not go nearly as well. A nurse’s note dated August 21, 2000, reflected that, upon restarting the Chemet on August 20, C. was going “beserck.” He was described as aggressive and noncompliant, with repetitive behaviors and tantrums.

Nevertheless, another round of chelation began in October, 2000. Chemet was to be compounded “per new chelation protocol,” at a dosage of 200 mg, three times a day for three days, followed by an 11 day break, repeating as directed.

This round of chelation also did not go well. C. visited HFHC with complaints of back pain on October 3, 2000, the day after beginning chelation. His primary care provider, Dr. Von Elten, noted that 5% of children taking Chemet developed back or flank pain.

The S.‘s called Dr. Bradstreet’s office on October 5, 2000, to report that C. was up all night with high-pitched screaming, and that he was more constipated since the last IVIG treatment. Dr. Bradstreet recommended Epsom salt baths and an enema. The next day, Dr. Bradstreet asked to see C.. On October 9, 2000, Mrs. S. called to report that, since starting glutathione, C. was vomiting and complaining of a backache. Dr. Bradstreet recommended waiting until C. was stable before restarting chelation.

C. returned to Dr. Von Elten’s office on October 12, 2000, with continuing complaints of back pain. All tests conducted were normal, but Dr. Von Elten wrote: “I am concerned regarding the treatment that he is getting from Dr. Bradstreet that (sic) would like to rule out serious cause for the child’s back pain.” He ordered additional tests, including renal and abdominal ultrasounds. C.’s creatinine, sodium, and carbon dioxide levels were low, but the other tests were all normal.

C. returned to Dr. Von Elten on October 24, 2000. Mrs. S. told Dr. Von Elten that C. had made a dramatic improvement, reporting that “[h]is personality has come back and he has not complained of back pain since stopping the Chemit (sic).” Dr. Von Elten recommended against restarting Chemet.

At Dr. Bradstreet’s office three days later, Mrs. S. reported that it took a month to get C. back to normal after chelation, and that he had been self-injurious, noncompliant, and aggressive. However, on November 10, 2000, Mrs. S. reported that C. “did fine while on DMSA, when off is when regression occurred (sic).”

Chelation therapy continued in February, 2005, with a prescription for DMPS, another chelating agent. He developed incontinence while using DMPS. In spite of this adverse reaction, another DMPS prescription was written in June, 2005. This time, reactions included “meltdowns,” night sweats, and agitation. Dr. Bradstreet’s physician’s assistant ordered a reduction to a half dose of DMPS.

C. began getting an intravenous form of chelation in April, 2006, using a chelator called CaEDTA. He received additional treatments of CaEDTA in May and June, 2006. The day after the May chelation, his parents reported that he was easily irritated and having headaches and stomachaches. Four days after the June chelation, he had headaches and his arms and legs hurt.

In August, 2006, after C.’s first urinary porphyrin test, Dr. Bradstreet again prescribed DMPS. His mother reported that, after three suppositories of DMPS, C. became incontinent, paranoid of the dark, and easily irritated. She described him as more withdrawn, and said he complained of bone aches, headache, and fatigue. C. had another CaEDTA treatment that same day. This was apparently C.’s last chelation.

Dr. Bradstreet conceded that C. did not respond well to chelation. The medical records, including reports from Mrs. S., reflected that C. did poorly after every round of chelation therapy, although the effects from CaEDTA appeared to be milder than those from DMSA or DMPS. The more disturbing question is why chelation was performed at all, in view of the normal levels of mercury found in the hair, blood, and urine, its apparent lack of efficacy in treating C.’s symptoms, and the adverse side effects it apparently caused.

(d) Immunoglobulin Therapy

During the course of his treatment by Dr. Bradstreet, C. received oral immunoglobulin [“OIG”], intravenous immunoglobulin (Gamunex or Gamimune) [“IVIG”], Baygam, subcutaneous immunoglobulin, and intramuscular gamma globulin [“IMIG”]. Gamunex and Gamimune are brand names for intravenous gammaglobulins. Baygam is an injectable immunoglobulin.

C. actually began immunoglobulin therapy on November 2, 1999, with intramuscular immunoglobulin. A recent history provided by Mrs. S. on the date of his first immunoglobulin treatment noted that C.’s speech was improved and he was using more words. He was jumping and running, and had increased socialization and social functioning. His eye contact was not improved, and he was still banging his head and having some behavioral problems, including more than three weeks of screaming. The office notes from C.’s next visit, a month later, reflected similar recent behavior with the exception of increased eye contact. He received OIG at this visit as well as IMIG.

Sometime in early 2000, Dr. Bradstreet recommended that C. begin IVIG treatment. The IVIG treatments began on March 8, 2000. Dr. Bradstreet noted the earlier discussion with Dr. Von Elten, saying: “We discussed this with the Residency Program at Halifax and all are in agreement to try to help C. with IVIG to remove the antibodies,” referring to the IgE and anti-MBP antibodies. Reviewing Dr. Von Elten’s own notes, this “agreement” with the proposed treatment appears to be an overstatement. At the time C.’s IVIG treatment began, Dr. Bradstreet considered IVIG therapy to be clinically indicated if a patient had evidence of a dysregulated immune system, preferably with evidence of autoantibodies, such as anti-myelin antibodies or dysregulation would include IgA deficiencies, subclass IgG and IgM deficiencies, defects in cell-mediated immunity, or autoimmunity.

According to Dr. Bradstreet, C. had significant titers of autoantibodies to MBP, a positive rheumatoid factor, IgA deficiency, and very high levels of IgE. The anti-MBP titer, in the presence of C.’s history and symptoms, was of the greatest concern to Dr. Bradstreet in the decision to begin IVIG therapy. His treatment objective was to improve the child’s behavior to the point of recovery or near recovery. Thus, although laboratory values would be monitored, treatment efficacy would be measured by C.’s behavior–in Dr. Bradstreet’s words, “what’s going on with the patient”–rather than strictly on laboratory values. Dr. Bradstreet was also concerned about C.’s ongoing gastrointestinal problems, his immunological history, and his regressive history. He believed that C. had an autoimmune-related encephalopathy, a condition that would benefit from IVIG.

[The administration of IVIG, according to Dr. Bradstreet’s records, was a time-consuming and labor-intensive process. To illustrate, C.’s 6th IVIG treatment, administered on August 16, 2000, began at 8:30 AM, with application of a topical anesthetic. The IV was established at 9:30 AM, and infusion of Gamimune began at 9:50 AM, followed by SoluMedrol (a steroid), Benadryl (an antihistamine), and Nubain (an opiate pain medication prescribed as a sedative). More Gamimune was administered at 12:30 PM. A nurse noted C.’s condition every 15 minutes, until 3:30 PM, when the IV was discontinued.]

Respondent’s experts were highly skeptical of Dr. Bradstreet’s treatment rationale and its efficacy. Dr. Zweiman testified that the available studies on IVIG therapy for ASD had such significant design flaws that it was impossible to extrapolate an effect on ASD’s core features. He commented that both a group of Canadian experts and the American Academy of Pediatrics have found insufficient data to support the use of IVIG in treating autism. In his report, [pediatric neurologist] Dr. [Andrew] Zimmerman also noted that there was no evidence that administration of immunoglobulins improved autistic symptoms.

Dr. Ward testified that IVIG is not a treatment commonly used for wild-type measles virus infections and, thus, it was unlikely to be effective in treating a persistent measles infection of any type. Since C. was already manufacturing IgG against the measles virus at the time his IVIG treatments began, the measles antibodies in the IVIG treatments would not do anything his immune system was not already doing.

Both an immunologist and a pediatric neurologist who evaluated C. in 2005-06 were also skeptical about the IVIG treatments. Dr. Skoda-Smith, an immunologist who evaluated C. in November, 2005, commented: “I do not know of an immunologist that uses titers of [anti-MBP] antibodies to guide IVIG therapy at this time.” She noted that C.’s family attributed his dramatic recovery to the IVIG therapy and commented: “There are children with poorly described inflammatory diseases of the central nervous system that have responded to IVIG therapy. However, most of these children have some significant marker, physical finding, or neurologic finding related to this underlying inflammation.” She did not note any such significant marker in C.. She stated: “I think it would be important for us to find some clear marker that IVIG is benefitting this young man. It is difficult to know without structured or validated behavioral scales, whether we can use behavioral measures alone to guide our therapy in his case.” The pediatric neurologist who examined C. in January, 2006 (the only time C. actually saw a pediatric neurologist), commented: “At this time, we have no explanation why these symptoms should be responsive to IVIG. Clearly, his behavioral disturbances are cyclical.” The examiner recommended a referral to a neuropsychologist who specialized in developmental disorders, but the family declined. The opinions of both specialists were based on the reports of C.’s family concerning onset, cyclic nature of the symptoms, and efficacy of the IVIG treatments.

Mrs. S. testified that prior to C.’s third birthday, there were brief periods when they saw “the old C..” After the IVIG therapy began, C.’s personality “started” to return. His language improved, with parts of words instead of just sounds. His facial expressions returned. Although he still engaged in repetitive play, he began responding to his name and interacting with his family. The more he received IVIG, “the more he came back to us.” By the time he was in pre-kindergarten, he was doing well. Mrs. S. deliberately chose not to tell his pre-kindergarten teacher about his ASD diagnosis, and received good reports from her. Mrs. Noonan also testified that after the IVIG therapy began, C. played better in groups and was more a part of the family. His speech slowly returned. He interacted with her and began to participate in story time.

In the medical records, Mrs. S. generally noted improvements after IVIG therapy, although there were times when the therapy itself (or some component thereof) caused C. to be ill or to miss school afterwards. However, she also recorded improvements at the office visits on the date of the IVIG therapy, presumably when C.’s symptoms would have been at their worst. She noted when gaps in the IVIG therapy caused problem behavior. There were times he did well when not receiving IVIG.

Dr. Bradstreet could not explain why IVIG therapy was effective in treating C., although he had theories. He testified that IVIG was “an anti-inflammatory,” and that it was used in LKS, a condition he described as similar to autism. He was aware that most batches of IVIG contained anti-measles virus antibodies, but the titers of antibodies in the IVIG he administered were not important to him, as long as the treatment was effective. It was effective in C.’s case, and in the cases of many people with ASD, based on his empirical evidence. According to Dr. Bradstreet, C. did remarkably well on the treatment, going from severe delay to becoming an A/B student, with excellent language, and a charming and social personality.

In the 2002 time frame, Medicaid withdrew approval for IVIG treatment, so C. received it less frequently over that period. Both Dr. Bradstreet and Mrs. S. reported that if he went longer than 30 days between IVIG treatments, C. became more irritable, squinted or closed his eyes during conversations, displayed more obsessive behavior, and was less socially interactive. Because C. regressed when he didn’t get IVIG treatments, Dr. Bradstreet concluded that he had immunological dysregulation that was autoimmune in nature. He did not reference any tests objectively measuring autoimmunity in C..

During the period from April 29, 2005, to May 19, 2006, the pace of IVIG treatments substantially slowed. C. had an IVIG treatment on April 29, 2005, a subcutaneous IG treatment on September 15, 2005, a subcutaneous IVIG treatment on October 4, 2005, and an IVIG treatment on May 19, 2006. In spite of the length of time between the last two treatments, Dr. Bradstreet described C. as having done “amazingly well.” During this same time frame, C. had excellent grades, was described as communicating well by both Dr. Evers and Dr. Skoda-Smith, and was working above grade level as reflected on the Florida Comprehensive Assessment Test administered in the spring of 2006. His individual educational program assessment evaluation reported that he was doing well in all academic areas and was loved by many of the students in his regular classroom, but he continued to need remediation and instruction in oral communication.

Rather than attributing C.’s obvious improvements in speech, language, socialization, and behavior to the effects of IVIG, secretin, chelation, and/or dietary supplements, Dr. Wiznitzer noted that C.’s developmental pattern was consistent with the natural history of autism in that those with the disorder are at their worst at the second or beginning of the third year of life. Speech therapy improved his speech, and C.’s normal intelligence permitted him to benefit substantially from speech and language therapy.

Dr. Bradstreet’s Opinion (pp. 256-259)

Based on all of the test results, his care and treatment of C., and C.’s medical history, Dr. Bradstreet opined that C. had “measles virus induced encephalopathy from persistence of the measles virus in his CNS.” [Dr. Bradstreet believed that vaccines caused between 10-50% of the cases of autism he has treated.] He also opined that C. had immune dysregulation, presumably secondary to the viral persistence, and caused, in part, by his TCV exposure. Dr. Bradstreet believed that C. was still suffering from a chronic encephalopathy at the time of the hearing, although C. had improved because of the treatment he had provided.

He opined that C.’s regression began by May 6, 1998, when he began to become irritable and fussy. Those symptoms, plus the crying and sleep disorder, were all part of his encephalopathic symptoms. He testified that there was no way to distinguish between these manifestations of ASD and the language regression he later developed. Dr. Bradstreet did not explain why these symptoms marked the beginning of his encephalopathy, but the earlier and similar symptoms did not.

Based on Mrs. S.’s reports and his interpretation of C.’s medical records, Dr. Bradstreet opined that C.’s visit to Dr. Sahai on May 6, 1998, was “the first evidence of a low-grade encephalitis condition.” He also opined that C. had an autoimmune disorder at the time he saw Dr. Otegbeye. He concluded that “C.S. is suffering from what remains a well-described measles phenomena — that being a post-vaccinal encephalopathy.” Retreating from the diagnostic conclusion of autism that he reached upon his initial examination of C., Dr. Bradstreet went on to say, “we are not speaking of autism, we are describing a post-vaccinal encephalopathy that has some autistic features associated with it.”

In essence, Dr. Bradstreet presented a theory based on direct and circumstantial evidence. The direct evidence was the presence of measles virus in C.’s CSF and gut, as detected by Unigenetics. The circumstantial evidence was the improvement C. made based on treatments designed to counter a persistent measles virus infection. He did not identify which of the therapies he provided were specifically targeted toward treating the measles virus persistence. He also failed to explain the relationship, if any, between MBP antibodies and measles virus.

In addition to challenging the scientific bases for, and reliability of, Dr. Bradstreet’s opinions, respondent pointed to inconsistencies in Dr. Bradstreet’s reasons for therapies and C.’s test results, the scientific evidence concerning the efficacy of such therapies, and challenged his qualifications to offer opinions. Respondent also raised questions concerning Dr. Bradstreet’s biases and motives for proffering opinions supporting vaccine causation.

During cross-examination, Dr. Bradstreet identified C. as one of the three children he described in the article (Bradstreet 2004) that he co-authored with Dr. [Andrew] Wakefield. C. was identified as Case No. 3 in the article, which indicated that C.’s immune system dysregulation began after the administration of his MMR vaccination. He acknowledged that the conflict of interest statement filed in connection with that article stated that C.’s Vaccine Act claim was filed after the receipt of positive test results for measles virus in his CSF. C.’s petition for compensation was actually filed over a year before the CSF testing was conducted. He acknowledged that at the time he published both his 2003 and 2004 articles, he had two claims, filed on behalf of his son and daughter, pending under the Vaccine Act. [He later withdrew the claims filed on behalf of his children.] He also filed a civil suit against several vaccine manufacturers, a power company, and the American Dental Association, but did not disclose these pending claims or lawsuits in the conflict of interest statements included in the articles. [The lawsuits were later withdrawn, according to Dr. Bradstreet’s testimony.]

Respondent also explored Dr. Bradstreet’s financial motivations for advocating alternative medical treatments for autism. Dr. Bradstreet testified that, over the period of his involvement in C.’s case, he was associated with a number of different corporations or foundations. They included the Autism Research Center, International Autism Resource Center, the International Child Development Resource Center [“ICDRC”], the Good News Doctor, and Creation’s Own. The ICDRC is a non-profit corporation. Creation’s Own is a for-profit company owned by Dr. Bradstreet. Part of his medical practice is conducted under the auspices of Creation’s Own. The Good News Doctor is a foundation; the ICDRC is a component of that foundation. The foundation is designed to raise health awareness, foster personal responsibility for health care, and fund health care for the needy. This foundation raises hundreds of thousands of dollars to care for needy kids, providing them with supplements, medical equipment, and whatever else may be necessary for their treatment. Some of the funds raised also provide for Dr. Bradstreet’s treatment or for treatment provided by other physicians. Funds have been provided for endoscopies, for example. Creation’s Own corporation received funding from the non-profit ICDRC, meaning that Dr. Bradstreet could directly benefit from medical services paid for by the ministry for some of his 3,000 autism patients. When Mrs. S. testified that some of C.’s therapy was funded through a ministry, she was referring to the Good News Doctor non-profit corporation. C.’s medical records also reflected that some of his treatments were funded by the ministry. Respondent also elicited evidence that Dr. Bradstreet sold the nutritional supplements he prescribed or recommended.

Three well-qualified specialists examined Dr. Bradstreet’s opinions on the nature of C.’s illnesses, post-vaccination, and all disagreed with his autoimmune reaction/post-vaccinal encephalopathy conclusions.

Dr. Wiznitzer, a pediatric neurologist, noted that the contemporaneous medical records of C.’s hospitalization were inconsistent with an encephalopathy. He pointed out inconsistencies between Dr. Bradstreet’s own records of the history of the onset of C.’s symptoms and the facts Dr. Bradstreet cited in his report as evidence of an encephalopathy. Using the contemporaneous records, Dr. Wiznitzer documented evidence of a neurologic examination and nursing assessments describing C. as alert. Dr. Wiznitzer noted that Dr. Bradstreet’s own references did not support his claims. Quoting one of those sources, Dr. Wiznitzer noted that C.’s condition was not “marked by seizures, altered behavior or consciousness, and ataxia,” all symptoms common to encephalopathy after measles vaccine.

Dr. Ward, a specialist in infectious diseases with specific expertise in measles virus and vaccine, also noted that C. received neurologic examinations during his hospitalization, with no indication of any encephalopathic condition, other than the lethargy that prompted the hospitalization. The lethargy resolved upon rehydration and reduction of his fever. He found no laboratory evidence of any autoimmune condition or immunosuppression. He noted that Dr. Bradstreet’s opinion that C.’s febrile illness “was likely measles” was nonsensical, because C.’s white blood cell counts were evidence of a bacterial, not viral infection.

Dr. Zweiman, an immunologist, opined that Dr. Bradstreet’s opinion that C. had an autoimmune measles encephalitis was unclear, because it was uncertain if he was referring to ADEM (PIEM) or SSPE. In either case, Dr. Zweiman found no clinical support for Dr. Bradstreet’s opinion. Dr. Zweiman found Dr. Bradstreet’s reliance on the positive RF test, serum IgA, and anti-MBP tests to be misplaced, as none of these tests were reliable indicators of an autoimmune process or an encephalopathic illness. He called Dr. Bradstreet’s opinion “seriously flawed” and noted that the evidence Dr. Bradstreet cited in support was either irrelevant or involved wild-type measles infections and an entirely different clinical picture.

I found the opinions of Drs. Ward, Zweiman, and Wiznitzer to be more persuasive than Dr. Bradstreet’s. Their opinions are based on C.’s medical records and have the weight of scientific authority behind them.

On the Efficacy of Dr. Bradstreet’s Treatment

Dr. Bradstreet’s opinions on causation informed his treatment of C., and for that reason, if for no other, they warrant consideration. It is clear that C.’s condition materially improved between the time he began speech therapy in April, 1999, and the time of the hearing. However, it is far from clear that C.’s improvement was due to Dr. Bradstreet’s treatment. It is even less clear that the treatments were designed to remove a dangerous virus from his body, and the evidence that any of the treatments were capable of doing so is nonexistent.

C.’s parents clearly believed in Dr. Bradstreet’s treatment regimen. They saw evidence of behavioral responses to IVIG and secretin therapy, and reported their observations to health care providers, including those other than Dr. Bradstreet. Their subjective beliefs also warrant careful consideration. However, the objective evidence regarding Dr. Bradstreet’s therapies is not particularly persuasive. C. got worse when chelated. Secretin may have helped with bowel symptoms, and even with behavior, but, objectively, secretin has been shown to be ineffective in autism treatment. As Dr. Wiznitzer noted, C. had digestive and allergy problems that may have been helped by dietary restrictions. C.’s parents clearly believed that IVIG therapy helped C.. Although my detailed review of C.’s medical records, and a comparison of those records against objective measures of his performance in school and speech therapy makes me, like Dr. Skoda-Smith, less sanguine about IVIG’s effectiveness, even accepting their assessment does not advance C.’s claim for causation. IVIG therapy has not been shown to be effective against measles virus. It has not been shown to be effective in treating anti-MBP antibodies, a problem that had disappeared by the time the treatment was initiated, and which did not appear to resurface during those periods when IVIG therapy was suspended. The many dietary supplements may or may not have helped C., but, again, there were no reasons advanced to connect them to countering persistent measles virus.

I am unconvinced that Dr. Bradstreet’s treatments span the gap between the theory of measles virus persistence and C.’s PDD-NOS. Dr. [Marcel] Kinsbourne’s conclusions regarding causation in C. are ultimately based on the presence of a persistent measles virus in his brain. However, the absence of any credible evidence that C. actually had measles virus in his brain eliminated the connector between Dr. Kinsbourne’s theory and C.’s condition.

Conclusion (p. 278)

To conclude that C.‘s condition was the result of his MMR vaccine, an objective observer would have to emulate Lewis Carroll’s White Queen and be able to believe six impossible (or, at least, highly improbable) things before breakfast. The families of children with ASD and the court have waited in vain for adequate evidence to support the autism-MMR hypothesis. Although I have the deepest sympathy for families like C.‘s, struggling emotionally and financially to find answers about ASD’s causes, and reliable therapies to treat ASD’s symptoms, I must decide C.‘s case based on the evidence before me. That evidence does not establish an adequate factual basis from which to conclude that C.‘s condition was caused by his vaccines.

Comments


  1. How much do you think the family paid Bradstreet to “treat” the child? Instead of pursuing a claim in vaccine court, they should file for malpractice. I wonder if one of the PSC lawyers might take the case? It’s much stronger.

    They put that child through hell and agony. Reading this account sickens me. What the hell were his parents thinking?

    — Tom    2009-02-16 11:12    #

  2. I, for one, am appalled by the medical care provided by Dr. Bradstreet to this boy.

    He ordered invasive and expensive tests (how many lumbar punctures – “spinal taps” – did this poor boy endure?) and yet made little if any rational use of the information he obtained. Many of the tests he ordered were uninterpretable (e.g. the urinary porphyrin tests) because there was no data about “normal values” in children (or in adults) or what “abnormal” results might indicate in this clinical setting. Other tests were more well-defined, but he did not appear to know how to interpret them.

    Dr. Bradstreet’s treatments appear to have been dictated more by his beliefs than by any objective science. How else can we explain his perseverative use of chelation in the face of persistently low urine, blood and hair mercury – not to mention the severe reactions reported by his mother? His use of IVIG to treat an ephemeral “persistent measles infection” appears to be directed more by magical thinking (“other children got better after IVIG”) than by any scientific rationale.

    Dr. Bradstreet claims to be “treating the patient”, but a physician who ignores the laboratory results from his patient (or “spins” them to support his pet hypothesis) is ignoring part of what the patient is trying to tell them. When I was in medical school, I was repeatedly told to ask myself if a test would change my management before ordering it. I don’t see that sort of thought process in the records above.

    I am also concerned by the clear conflict of interest Dr. Bradstreet has, since he is selling the “supplements” and other materia medica that he prescribes. In my state, physicians require a special license (and receive extra monitoring) in order to dispense (i.e. sell) the drugs they prescribe, yet this does not appear to be the case for “supplements” and “herbal remedies”.

    I also wonder about the ethics of Dr. Bradstreet setting up a charitable organization that pays for treatment he provides.

    While I recognize that medicine remains a bit of an art as well as a science, ignoring the “science” of medicine in favor of the “art” is not responsible medicine.

    Jim Laidler

    — James Laidler, MD    2009-02-16 13:28    #

  3. The treatment history of the petitioners is a good illustration of why it’s important to look critically at the vaccines cause autism idea because, as Special Master Vowell points out, this idea has informed the treatment of autistic kids. Autistic kids and their families have a right to ethical medical treatment. The treatment of C., described in this decision, was not only unethical, it looks like battery.

    Thanks for taking a closer look at this important aspect of the OAP decisions.

    — Anne    2009-02-16 15:05    #

  4. The kid survived the “treatments”. He’s a fighter allright.

    — _Arthur    2009-02-16 17:21    #

  5. Anne, kid C is not the only biomed kid subjected to a pharmacopea of supplements, drugs, invasive procedures, and strange treatments, like, say, hyperbaric chambers.

    Any suspected GI anomaly can be caused by any the supplements, or the Diflucan/Vermox/Nystatin, no way to tell.

    The next kid, YH, was “treated” with Lupron, his mother testified how it helped the kid.

    — _Arthur    2009-02-16 19:29    #

  6. This poor child was medically tortured.I also have a child w/autism but as much as I would love to see a cure I don’t believe anyone, let alone a child, should have to go through all of that trial and error. I think this doctor benefited from these so called treatments more than the child.

    — violet    2009-02-16 22:58    #

  7. “The belief in magic can do no harm”
    I could not read all of it . It makes me ill that frauds or mentally ill people are free to do this to children.
    Thank you for doing this work for us.
    Robert

    — Robert estrada    2009-02-17 01:11    #

  8. Thanks again, Kathleen, for an excellent objective review of the facts here.

    As others have pointed out, the treatment of C falls somewhere between bumbling ineptitude by an unqualified practitioner and torture for profit.

    It’s a shame that obvious malpractice like this goes unpunished.

    Joe

    — Club 166    2009-02-17 08:47    #

  9. Getting through the entire story left me cold. These “physicians” need to answer for what they did and what they’re doing right now.

    These children are being treated with less respect than lab animals.

    — JKW    2009-02-17 15:42    #

  10. Treament regimes like this are well documented in McCarthy’s book, which is why it’s a fairly shocking read. The scary thing is the reasonable tone in which the tale is told as if something like 40 supplements a day is anything extraordinary for a six year old. Or the horrific reactions to anti-virals is just something that has to be got through. It’s this closed environment where anything biomed goes because that’s the discourse that carries weight. Stan Kurz is responsible for quite a lot of it and he’s a complete ignoramus. Bradstreet keeps the Kurz characters going.

    — alyric    2009-02-18 11:35    #

  11. Kathleen, thank you for providing this. I feel sick to my stomach after reading it. The incompetence and malpractice that Dr. Bradstreet subjected this child to is unconscionable. I wonder if this record could be sent to the Florida Board of Medicine to try to stop this monstrous treatment of autistic children. This child was tortured. For absolutely no reason and no benefit. I’m going to look up the Medical Board in Florida right now, I am so outraged.

    — storkdok    2009-02-18 15:36    #

  12. The exhaustive list of the supplements, drugs and “biomed” treatments kid C was subjected to is not part of the hearings. The list here on Neurodiversity, is merely a subset. Possibly a more complete list will turn up if and when the written expert reports are disclosed.

    — _Arthur    2009-02-18 22:21    #

  13. This is an interesting description of a case decision relating to treatment of a child with autism as it relates to MMR vaccination. It saddens me however, to read the off-the-cuff comments by unknown persons, obviously learned people, who apparently have no concept of what it is like to try to treat autistic children for whom mainstream medicine offers little or no hope for recovery. Those who ridicule caring physicians, such as Dr. Bradstreet and others who devote all of their energies to trying to find an answer to this disorder are betraying their lack of knowledge about the many non-mainstream treatment stratagies that, in spite of the lack of controlled studies, do seem to offer, some relief of the devastating symptoms of autism.

    — Amos    2009-02-20 18:08    #

  14. Amos, what you call “caring physicians”, I call “greedy quacks”, who give false hopes to the parents, attribute any progress the child will make to their experimental —and multiple— “treatments”, while shrugging off all the side-effects on the hapless kid, and make a great living out of it.

    My “lack of knowledge” on the quack treatments may stem from the fact that those “caring physicians” don’t bother to write scientific papers about their speculations, or even useful case histories.

    What the Petitioners presented before the Autism Omnibus Court was their best scientific evidence. It is quite damning.

    “Some relief” ?!?? Ha!

    — _Arthur    2009-02-21 11:52    #

  15. Horrifying.

    — trrll    2009-02-23 16:40    #

  16. As always, a very thorough blog entry.
    My heart goes out to C and children like him who have undergone such treatment.
    My sympathy goes out to the families whose desperation and lack of knowledge causes them to seek out these treatments for their children.
    My anger goes out to these so-called “doctors” who take advantage of families and subject undue suffering to children.

    — camercad    2009-02-24 15:28    #

  17. I’ve had to turn off comments on this piece because it’s in the crosshairs of a spambot. If anyone wants to leave a comment, please send it to me at anima@neurodiversity.com and I’ll post it ASAP.

    — Kathleen Seidel    2009-03-09 09:23    #