M. v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 08-284V
(To be Published)

*****************************
*
T.M. and R.R.M, *
parents and natural guardians of A.P.M., a minor, * Special Master Corcoran
*
* Filed: August 9, 2016
Petitioners, *
* Entitlement Decision; Diphtheria
v. * Tetanus and Acellular Pertussis
* and Haemophilus Influenza Type B
SECRETARY OF HEALTH AND * (“DTaP-Hib”) Vaccine;
HUMAN SERVICES, * Autism Spectrum Disorder
* (“ASD”); Cerebral Folate
Respondent. * Deficiency.
*
*****************************

Robert Joel Krakow, Law Office of Robert J. Krakow, P.C., New York, NY, for Petitioners.

Lynn Elizabeth Ricciardella, U.S. Dep’t of Justice, Washington, DC, for Respondent.

DECISION1

On April 17, 2008, T.M. and R.R.M filed a petition on behalf of their child, A.P.M., seeking
compensation under the National Vaccine Injury Compensation Program (the “Vaccine
Program”).2 T.M. & R.R.M sought to establish that the Diptheria Tetanus acellular Pertussis
(“DTaP”) vaccine that A.P.M. received on July 14, 2006, precipitated some form of cerebral folate
deficiency, which in turn caused an autistic regression manifesting as an Autism Spectrum

1
Because this decision contains a reasoned explanation for my actions in this case, I will post it on the United States
Court of Federal Claims website, in accordance with the E-Government Act of 2002, 44 U.S.C. § 3501 (2012). As
provided by 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties may object to the published decision’s inclusion of
certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party has fourteen days within
which to request redaction “of any information furnished by that party: (1) that is a trade secret or commercial or
financial in substance and is privileged or confidential; or (2) that includes medical files or similar files, the disclosure
of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the whole
decision will be available to the public. Id.

2
The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660,
100 Stat. 3758, codified as amended, 42 U.S.C. §§ 300aa-10 through 34 (2012) (“Vaccine Act” or “the Act”).
Individual section references hereafter will be to § 300aa of the Act.
Disorder (“ASD”).

A hearing was held on July 28-29, 2015, and in the months following the parties submitted
post-hearing briefs. Having completed my review of the evidentiary record and the parties’ filings,
I hereby DENY Petitioners’ request for compensation, for the reasons stated below.

I. FACTUAL BACKGROUND

A. Pre-Vaccination History

A.P.M. was born on April 16, 2005, at the Avera McKennan Hospital in Sioux Falls, South
Dakota following a mostly normal pregnancy complicated only by vaginal bleeding at fourteen
weeks gestation and fetal bradycardia.3 See generally Pet’rs’ Ex. 2; see also Pet’rs’ Ex. 4 at 11,
13, 18; Pet’rs’ Ex. 7 at 19. A.P.M. had high bilirubin levels and was treated with a phototherapy
blanket for a short time. Pet’rs’ Ex. 1 at 15, 51.

Throughout the first eighteen months of his life, A.P.M. had several well-child visits. His
pediatrician, Dr. Rick Kooima, consistently noted in the medical records that A.P.M. was
developing well. Pet’rs’ Ex. 20 at 8; Pet’rs’ Ex. 1 at 1, 12-14, 16, 41-44; Pet’rs’ Ex. 34 at 10;
Pet’rs’ Ex. 63 at 3. During this time, A.P.M. received the Hib, Pediarix, and Pneumonia
vaccinations at his two-, four- and six-month visits. Id. According to T.M., A.P.M. was “ill and
irritable” and showed obvious discomfort following the vaccinations received at his two- and four-
month visits, but the records do not indicate any significant alarming reactions requiring additional
treatment. Pet’rs’ Ex. 63 at 3. Following his six-month vaccinations, however, T.M. called Dr.
Kooima to report that A.P.M. had been “fussy” since receiving his immunizations. Pet’rs’ Ex. 1 at
12.

Because of their concern about A.P.M.’s reactions to the vaccinations he previously
received, T.M. & R.R.M asked their pediatrician to defer additional immunizations at the 12-
month well-child visit in April 2006. Pet’rs’ Ex. 1 at 11, 40. T.M. & R.R.M did not want A.P.M.
to ever have the varicella vaccine, but informed A.P.M.’s treaters that they would consent to the
Prevnar vaccination at the next well-child visit. Id. Prior to his July 2006 15-month well-child visit,
T.M. & R.R.M brought A.P.M. back to see Dr. Kooima because of their concern that A.P.M. was
breaking into a rash whenever his skin encountered a milk-based product. Pet’rs’ Ex. 1 at 9, 48.
Dr. Kooima tested A.P.M. for allergies, but all testing was negative, and he instead diagnosed
A.P.M. with rhinitis/conjunctivitis. Id. At this time, A.P.M. was again noted to be “well-
3
Bradycardia means slowness of the heartbeat, with the pulse rate slowing to less than 60. Dorland’s Illustrated
Medical Dictionary (32d ed. 2012) at 245 (“Dorland’s”).
2
developed.” Id.

B. Vaccination and Subsequent Medical History

At his 15-month well-child visit on July 14, 2006, A.P.M. received the combination DTaP
and Haemophilus influenza type B (“Hib”) and measles, mumps, and rubella (“MMR”) vaccines.
Pet’rs’ Ex. 1 at 1, 16, 38; Pet’rs’ Ex. 63 at 3; Pet’rs’ Ex. 34 at 10. In the interim period until
A.P.M.’s next pediatric visit three months later (when he was 18 months old), almost no medical
records shed light on his post-vaccination condition – and even fewer before his two-year visit, at
which time the record first sets forth the most detailed initial questions about A.P.M.’s
development. However, Petitioners have offered declarations intended to fill in those blank periods
in the record.

Thus, twelve days after the vaccinations (or on July 26, 2006), T.M. avers that she called
Dr. Kooima, alerting him that A.P.M. had a low-grade temperature and a rash. Pet’rs’ Ex. 1 at 8.
Then, according to her, “within weeks” of the July 14, 2006, vaccinations A.P.M. “began to lose
some of the words he had been using.” Pet’rs’ Ex. 63 at ¶ 9. He also became socially withdrawn
and stopped playing with his toys. Id. at ¶¶ 11-12. But with the exception of an additional phone
call from T.M. reporting that A.P.M. was experiencing watery eyes and congestion, T.M. & R.R.M
had no further contact with his pediatrician until A.P.M.’s 18-month well-child visit on October
18, 2006. Pet’rs’ Ex. 1 at 8.

The contemporaneous medical records largely do not corroborate T.M.’s statements. The
medical records from that 18-month well-child visit include notations of parental concerns about
“talking,” but also characterize A.P.M. as “very healthy” in growth and development. Pet’rs’ Ex.
1 at 8, 37; Pet’rs’ Ex. 21 at 32. T.M. testified, however, that in the ensuing months her concerns
about A.P.M.’s speech loss intensified, as did A.P.M.’s gastrointestinal issues. Pet’rs’ Ex. 63 at 4.
But concerns about A.P.M.’s development were not thoroughly documented until his two-year
well-child visit six months later, on April 17, 2007. Pet’rs’ Ex. 1 at 7, 36. In response, Dr. Kooima
referred T.M. & R.R.M to the “Birth to Three” Program and to Dr. Jerome Blake, a developmental
pediatrician, at the Sanford Children’s Specialty Clinic in Sioux Falls, South Dakota. Id.

Rebecca Morke, a certified nurse practitioner working with Dr. Blake, subsequently
evaluated A.P.M. on May 10, 2007 (at which time A.P.M. was 25 months old), and diagnosed him
as having “mixed developmental delays,” having lost the approximately 6 to 10 words he had
previously acquired and used between 18 and 20 months of age. Pet’rs’ Ex. 13 at 17; see also
Pet’rs’ Ex. 8 at 6; Pet’rs’ Ex. 7 at 24. A.P.M. was administered the Rockford Infant Developmental
Evaluation Scales (“RIDES”), and the results were not encouraging: although now more than two
years old, A.P.M. demonstrated expressive language in the 6-9 month range; receptive language
3
skills at the 9-12 month range; personal social/self-care skills in the 9-12 month range; gross motor
skills in the 18-24 month range; and fine motor skills in the 12-15 month range. Pet’rs’ Ex. 26 at
184-90. In response, Dr. Blake recommended a hearing evaluation, speech therapy, occupational
therapy, and a genetics workup. Id.

A week later that same May, the Sioux Falls School District administered an education
assessment, giving A.P.M. the Battelle Development Inventory. Pet’rs’ Ex. 13 at 17-18. The results
showed that A.P.M. was more than two standard deviations below average in the areas of person-
social, adaptive, motor, cognitive, and communication. Id. Other tests demonstrated that he had
difficulty with language and fine motor skills. Id. As a result, A.P.M. qualified for special
education. Id.

In the ensuing months, A.P.M. began routinely going for sessions with a chiropractor and
also began speech and occupational therapy. See generally, Pet’rs’ Exs. 9, 28; see also Pet’rs’ Ex.
35, part 1 at 33-34; Pet’rs’ Ex. 8 at 6-8. T.M. provided such treaters with a variety of dates about
the onset of A.P.M.’s symptoms. To some treaters seen in October, May, and June 2007, T.M. &
R.R.M reported onset at anywhere from 18 to 24 months. Pet’rs’ Ex. 7 at 9, 18; Pet’rs’ Ex. 8 at 6.
Frequently they identified the MMR vaccine (which, as discussed below, is no longer a component
of Petitioners’ case) as an aggravating factor. Pet’rs’ Ex. 8 at 6. To others, T.M. identified 19
months as the time when A.P.M. began losing skills. Id. at 11. She also more broadly defined the
period between 15 and 18 months as when she became concerned about his loss of skills. Pet’rs’
Ex. 12 at 6. Notably, however, no treater associated A.P.M.’s developmental problems with his
vaccinations, and thus all references to onset in this portion of the medical records contain only
T.M. & R.R.M’ recitation of when developmental problems began, rather than a physician’s
informed diagnosis.

C. A.P.M.’s Autism Diagnosis

On June 25, 2007, when providing a pediatric health history for A.P.M.’s chiropractor,
T.M. noted that A.P.M. had “developmental disability – possibly autism.” Pet’rs’ Ex. 28, part 1
at 5-6. She reported therein that A.P.M. had a “tough time” with vaccinations and had lost speech
within four to six weeks after the last round of vaccinations he had received in 2006. Id. She also
reported breastfeeding A.P.M. until 18 months, at which point A.P.M. began to drink cow’s milk.
Id. The next month, A.P.M.’s chiropractor noted in a record that A.P.M. had normal development
until his 15-month immunizations, at which point he developed autism. Pet’rs’ Ex. 10 at 4, and
Ex. 12 at 6.

However, on October 15, 2007, Sioux Falls School District administered an Autism
Screening and found that A.P.M. did not meet the eligibility criteria for an ASD. Pet’rs’ Ex. 13 at
4
18. A few days later on October 18, 2007, A.P.M. was again administered the RIDES, which
showed some improvement particularly in the receptive language category. Pet’rs’ Ex. 7 at 10-15.
A.P.M. was thus diagnosed with mixed developmental delays. Pet’rs’ Ex. 13 at 18.

Shortly thereafter, in November 2007, A.P.M. first went to Thoughtful House in Austin,
Texas where he saw Dr. Byran Jepson, a DAN!4 doctor. Pet’rs’ Ex. 11 at 7-11. The medical history
contained in these documents (consistent with the prior medical record discussed above) notes that
after A.P.M.’s “15 month [vaccinations] not a lot of reaction:” he was “just sore and fussy for a
few days. Then 3 weeks later stopped speaking, completey [sic] gone in 3 to 4 mnths [sic].” Id. at
8. Upon visiting with Dr. Kooima later that month, Dr. Kooima again “reinforced the fact that
[A.P.M.] should be seen by an autistic specialist as soon as possible.” Pet’rs’ Ex. 21 at 7.

On November 8, 2007, the T.M. & R.R.M returned to Sanford Children’s Specialty Clinic,
where Dr. Tracy J. Stephens, a psychologist, performed a psychological evaluation of A.P.M.
Pet’rs’ Ex. 13 at 19. At this time, A.P.M. was diagnosed with “autistic disorder” because he
demonstrated many characteristics of an ASD, including expressive and receptive language delay.
Id. Dr. Stephens drew this conclusion from A.P.M.’s score of 32.0 on the childhood autism rating
scale (“CARS”), which indicated that he had “mild to moderate” autism. Pet’rs’ Ex. 7 at 27-29.

That same day, A.P.M. also saw Alison Kringstad, a special education specialist at
Behavior Care Specialists, who confirmed A.P.M.’s autism diagnosis using the nine DSM-IV
criteria. Pet’rs’ Ex. 12 at 6-9. She noted that A.P.M. had lost skills after his 15-month vaccinations
and currently had skill deficits in the areas of cognitive development, communication,
socialization, and adaptive behavior. Id. Notably, she independently performed a CARS evaluation
and rated A.P.M. at 23.0, a significantly lower score than what is required for an autism diagnosis.

4
DAN! was composed of doctors and medical professionals who believed, among other things, that autism could be
caused by vaccines. See Dwyer v. Sec’y of Health & Human Servs., No. 03-1202V, 2010 WL 892250, at *165 (Fed.
Cl. Spec. Mstr. Mar. 12, 2010). The Autism Research Institute (“ARI”), which was founded by Bernard Rimland, MD
in 1967, created the DAN! Protocol in 1995. Moving Forward: The Expanding Mission of ARI, Autism Research
Institute, http://www.autism.com/expanding_2014 (last visited Aug. 9, 2016). “DAN! Doctors [were] trained in an
approach to autism treatment that begins with the idea that autism is a biomedical disorder caused by a combination
of lowered immune response, external toxins from vaccines and other sources, and problems caused by certain foods.”
DAN! PROTOCOL, Autism Services and Resources Connecticut, http://www.autismconnecticut.org/dan-protocol
(last visited Aug. 5, 2016). Accordingly, DAN! “doctors may recommend treatments including nutritional
supplements, special diets, testing for hidden food allergies, treatment of intestinal yeast or bacterial overgrowth, and
detoxification of heavy metals.” Id.

However, ARI discontinued the DAN! Protocol in 2011, noting that individuals included on the list of providers were
merely doctors who attended training seminars, and there was therefore no way to assure that such practitioners were
providing high quality services. Lisa Jo Rudy, What Was the DAN! (Defeat Autism Now) Protocol?, Very Well
(updated Dec. 30, 2015), https://www.verywell.com/dan-defeat-autism-now-is-no-more-3971489 (last visited Aug. 5,
2016).

5
Id. However, she still recommended developmental therapy at a minimum of 25 hours per week.
Id.

The Sioux Falls School District altered their determination about A.P.M. a week later, after
administering the Bayley Scales of Infant Development, which put him at a developmental age of
19 months, even though he was 31 months old. Pet’rs’ Ex. 14 at 20-24. The School District also
administered the Gilliam Autism Rating Scale, which put A.P.M. in the average to high probability
range for autism. Id. Ultimately, they concluded that he was eligible for special education as a
result of his autism. Id. at 1-16.

D. Efforts to Treat A.P.M. and Identify the Cause of his ASD

Over the next several years, T.M. & R.R.M continued to pursue treatment for A.P.M. On
November 19, 2007, T.M. & R.R.M took A.P.M. back to Thoughtful House, where he was seen
by Kelly Barnhill, a nutritionist. Pet’rs’ Ex. 11 at 2-7. At this time, T.M. & R.R.M informed Ms.
Barnhill that at 18 months, A.P.M. had begun drinking cow’s milk and seasonal allergies followed
shortly thereafter. Id. Ms. Barnhill recommended many nutritional supplements. Id. A.P.M. was
also seen at that time by Lucas Ramirez, a nurse practitioner, who diagnosed A.P.M. with
unspecified metabolism disorder, immune mechanism disorder, nutritional deficiency, and
encephalopathy after T.M. & R.R.M reported that he had experienced developmental regression a
month after receipt of the MMR vaccine (or at approximately 16 months). Pet’rs’ Ex. 18, part 1 at
37-42. Again, however – the medical records at this point temporally contain no treater opinion
agreeing with T.M. & R.R.M that A.P.M.’s developmental problems related to any vaccination he
had received.

Four months later, in February 2008 (at which time A.P.M. was nearly three years old),
T.M. & R.R.M brought A.P.M. to see Dr. Michael Reiff, a developmental pediatrician, and Dr.
Robin Rumsey, a pediatric neurologist, at the Autism Spectrum Disorders Clinic at the University
of Utah. Pet’rs’ Ex. 1 at 55-72. Based on several tests administered, A.P.M. (who was now nearly
three years old) was determined to have the overall development level equivalent to a 19 to 20
month-old child. Id. These treaters recommended that T.M. & R.R.M have A.P.M. undergo genetic
testing, particularly fragile x testing, and referred Petitioners to Dr. Khalid Khan, a pediatric
gastroenterologist, at the University of Minnesota. Id. But such testing found “no numerical or
structural chromosomal abnormality” and also did not find the “fragile x chromosome.” Pet’rs’
Ex. 13 at 1-16.5

5
At most, genetic testing performed at the University of Minnesota identified a copy number loss within 14q32.33
(Pet’rs’ Ex. 15) – but T.M. shares that same loss without any similar or identifiable symptoms. Pet’rs’ Ex. 18, part 1
at 28-29.

6
 It was not until 2010, however – almost four years after the July 2006 vaccinations – that
any treater formally suggested that A.P.M.’s developmental problems were vaccine-related.6 On
February 17, 2010, A.P.M. first saw Dr. Richard Frye, a child neurologist, at the University of
Texas. Pet’rs’ Ex. 16 at 52. In his contemporaneous notes from the visit, Dr. Frye stated that
A.P.M. had “high functioning autism [with] an abnormal EEG7 and staring episodes,” and
recommended further EEG studies and additional testing. In particular (and as discussed in more
detail below), Dr. Frye was interested in evaluating whether A.P.M.’s autism might be linked to
the amount of folate his brain was receiving.

At Dr. Frye’s direction, A.P.M. underwent testing for the presence of folate receptor
blocking and binding autoantibodies in October 2010 at the State University of New York
Downstate Medical Center in Brooklyn, New York. Pet’rs’ Ex. 16 at 38-39. The testing results
(notably, performed four years after the relevant vaccinations) revealed that A.P.M. had a folate
transporter blocking autoantibody titer of 1.19 pmoles/ml. Id. at 38. Based upon a range dependent
on levels found for “normal population, women with neural tube defect and children with [cerebral
folate deficiency] syndrome,” the measured amount fell on the “high” end of the range, because
the titer exceeded 1.0 pmoles/ml (with a “medium” range specified as .6 – 1.0). Id. Notably,
however, a patient summary chart prepared for A.P.M. by Dr. Frye’s office in 2014 characterized
the same titer value (based on the same October 2010 testing) as merely falling in the “medium”
range (consistent with the medium range if the 1.19 value was rounded down). Pet’rs’ Ex. 64 at
40.

Dr. Frye reviewed the results with Petitioners in December 2010. He expressed the opinion
that the blocking autoantibodies were in the high range, and therefore possibly indicative of a
shortage (deficiency) of the B-vitamin folate (also called vitamin B9) in the brain – amounting to
a cerebral folate deficiency.8 Pet’rs’ Ex. 16 at 35-36. However, Dr. Frye misstated in his written
6
During this time, A.P.M. continued being seen by Thoughtful House (now known as the Johnson Center) on a regular
basis. See generally, Pet’rs’ Ex. 18, part 1. On August 2, 2010, Dr. Jepson wrote a letter exempting A.P.M. from any
future immunizations. Pet’rs’ Ex. 39 at 5; Pet’rs’ Ex. 34 at 9; Pet’rs’ Ex. 18, part 1 at 13.
7
An EEG is an electroencephalogram. Dorland’s at 594.
8
Cerebral folate deficiency is a neurological syndrome associated with low levels of 5-methyltetrahydrofolate
(“MTHF”), the active folate metabolite, as measured in cerebral spinal fluid samples and in contrast to normal levels
in blood serum. Tr. at 117-20 (citing Pet’rs’ Ex. 50, Ref 1 (Vincent T. Ramaekers, et al., Autoantibodies to Folate
Receptors in the Cerebral Folate Deficiency Syndrome, 352(19) N. Engl. J. Med 1985 (May 12, 2005) (“Ramaekers
I”)). The MTHF transported across the blood-brain and blood-cerebral spinal fluid barriers is mediated primarily by
membrane-associated folate receptors. Ramaekers I at 1985. It has been hypothesized that impairments in folate
transport across the blood-cerebral spinal fluid barrier is caused by circulating autoantibodies that prevent folate from
binding to certain folate receptors. Id. at 1986. Insufficient levels of folate within the central nervous system have
been linked to neuropsychiatric disorders, with the first clinical manifestations of cerebral folate deficiency reported
as having appeared after the age of four to six months. Id. at 1990-91.
7
record the titer value as 1.9, rather than the actual result of 1.19 (an amount significantly lower).
Id. at 35. He also acknowledged that A.P.M.’s presentation did not precisely fit the usual clinical
indicia of cerebral folate deficiency. Thus, he noted that children with a definitive cerebral folate
deficiency diagnosis (who would similarly have high levels of the blocking autoantibodies)
presented with striking, degenerative neurological features that A.P.M. had not experienced. Id.
(“children with the severe disorder usually are blind very early in life”).

In light of the findings, Dr. Frye concluded that “it is very possible that [A.P.M.] has a mild
form” of a cerebral folate deficiency. Pet’rs’ Ex. 16 at 35. To confirm the proposition, Dr. Frye
scheduled a lumbar puncture in order to measure A.P.M.’s folate level in his cerebral spinal fluid
(“CSF”)9 (a more direct indication of the presence of a cerebral folate deficiency). Pet’rs’ Ex. 16
at 35.

A spine lumbar puncture and a brain MRI were thereafter performed on A.P.M. on March
30, 2011. Pet’rs’ Ex. 64 at 40; Pet’rs’ Ex. 16 at 10, 47-50. The MRI results were deemed normal.
Id. at 47-50. Details of the lumbar puncture procedure, however, require explication, given the
extent to which (as discussed below) the parties dispute the procedure’s adequacy. The notes from
the date of testing state as follows:

An interspinous lumbar puncture was carried out under fluoroscopic
guidance with a 25 gauge short spinal needle at the level of L3-4
under sterile conditions. A total amount of 10 cc of CSF was withdrawn.
CSF was initially slightly blood-tinged but cleared.

3.5 cc of CSF was distributed in appropriate amounts into the required
containers and delivered to the neurology lab. The remaining 6.5 cc
of CSF were submitted to the general lab for routine analysis. Opening
pressure measured 24 cm water. No complication was noted.

***

Impression: Technically successful fluoroscopically guided lumbar puncture.

9
Cerebrospinal fluid (“CSF”) is a “clear, colourless liquid that fills and surrounds the brain and the spinal cord and
provides a mechanical barrier against shock” and “transports metabolic waste products, antibodies, chemicals, and
pathological products of disease away from the brain and spinal-tissue into the blood stream.” Encyclopedia
Britannica Online, Encyclopedia Britannica Inc. (2016), available at
https://www.britannica.com/science/cerebrospinal-fluid (last accessed Aug. 5, 2016). Examination of the CSF through
a lumbar puncture (or spinal tap) can be used to diagnose a number of diseases. Id.

8
Id. at 10-11 (emphasis added). Among other things, the lumbar puncture measured the amount of
5-methyltetrahydrofolate (“MTHF”), or active folate metabolite, in the CSF at the time as 53
nmols/L, an amount characterized as “within our reference range” of 40-128 nmols/L, and
therefore normal. Pet’rs’ Ex. 16 at 22. In a September 2011 note recording a discussion held with
T.M. & R.R.M about the results of the CSF testing, Dr. Frye termed the folate levels measured as
“low normal.” Id. at 3.10

More tests were performed on A.P.M. to determine the extent to which he might be
suffering from some kind of metabolic disorder. Thus, later in 2011, Dr. Frye conducted additional
blood work that revealed an increased level of pyruvate in A.P.M.’s CSF. Pet’rs’ Ex. 16 at 3. Dr.
Frye noted, however, that he was “not sure what to make of the isolated increased CSF pyruvate
as all of the other mitochondrial markers were negative.” Id. In addition, organic acid testing
conducted in May 6, 2012, was “not consistent with a known disorder of amino acid metabolism.”
Pet’rs’ Ex. 27, part 2 at 18-28. A.P.M. also had hair and stool analyses in May 2012, both of which
were normal. Pet’rs’ Ex. 27, part 1 at 5-20.

On February 14, 2014, T.M. & R.R.M returned to see Dr. Frye, now at the Arkansas
Children’s Hospital, for formal consideration of whether A.P.M. had experienced a developmental
encephalopathy, or could be diagnosed with a cerebral folate deficiency or some mitochondrial
disorder that may have played a role in his developmental problems. Pet’rs’ Ex. 46 at 1-3; Pet’rs’
Ex. 64 at 39-40, 60-63. Dr. Frye at that time repeated the assertion that A.P.M. had a cerebral folate
deficiency based on purported “below normal levels of folate in his cerebral spinal fluid,” but did
not elaborate on the existence of any measurements taken after the 2011 lumbar puncture (which,
as noted above, showed folate amounts in the low normal range). Pet’rs’ Ex. 46 at 1. A.P.M. was
still seeing Dr. Frye on a regular basis as of May 2015. See generally Pet’rs’ Ex. 64.

II. PROCEDURAL HISTORY

T.M. & R.R.M filed this action on April 17, 2008, as a short-form autism petition to be
included in the Omnibus Autism Proceeding (“OAP”).11 Pet. (ECF No. 1). Thereafter, Respondent
10
With the passage of time (and unbound by the aforementioned March 2011 CFS results – which from the record
appears to be the sole instance A.P.M.’s CSF was tested) Dr. Frye greatly expanded his characterization of this reading.
Thus, in a February 2014 note from a subsequent visit to his clinic by T.M. & R.R.M, Dr. Frye states that A.P.M. had
been “diagnosed with cerebral folate deficiency with frank below normal levels of folate in his cerebral spinal fluid.”
Pet’rs’ Ex. 46 at 1.
11
This case was initially among the more than 5,400 cases initially filed under short form petition in the OAP, where
thousands of petitioners’ claims that certain vaccines caused autism were joined for purposes of efficient resolution.
A “Petitioners’ Steering Committee” was formed by many attorneys who represent Vaccine Program petitioners, with
about 180 attorneys participating. This group chose “test” cases to represent the entire docket, with the understanding
that the outcomes in these cases would be applied to cases with similar facts alleging similar theories.
9
filed her Rule 4(c) Report and identified certain deficiencies in the record. On June 22, 2008,
Petitioners, in compliance with the initial order of the first special master assigned to the case (ECF
No. 4), filed a Statement Regarding Onset. ECF No. 9. Respondent agreed that this case was timely
filed and appropriate for inclusion in the OAP given A.P.M.’s ASD diagnosis. ECF No. 10.

After the conclusion of the OAP test cases in 2010, Petitioners opted to continue pursuit of
their claim. To that end, T.M. & R.R.M filed an amended petition on May 14, 2012, alleging that
A.P.M’s receipt of the MMR and/or the DTaP-Hib vaccines in July 2006 had caused his regression.
ECF No. 24 at 4. A status conference was held on June 29, 2012, and the special master ordered
Petitioners to file their medical records by July 30, 2012, and also to file a status report on or before
August 13, 2012, advising the Court as to their efforts in locating an expert. ECF No. 27.

Petitioners complied and filed medical records on July 30, 2012 (ECF No. 28), but missed
the deadline to update the Court on their attempts to obtain an expert. As a result, the special master
issued an order to show cause as to why the case should not be dismissed by September 4, 2012.
ECF No. 29. On the date of that deadline, Petitioners filed a response, explaining that their failure
to comply was the result of a clerical error. ECF No. 30 at 3. But they also indicated that they were
having difficulty obtaining expert support for their theory that a cerebral folate deficiency had
caused A.P.M.’s developmental disorder and were considering alternative causal theories. Id. at 3,
5.

The Petitioners’ Steering Committee chose six test cases to present two different theories regarding autism causation.
The first theory alleged that the measles portion of the measles, mumps, rubella (“MMR”) vaccine precipitated autism,
or, in the alternative, that MMR plus thimerosal-containing vaccines caused autism, while the second theory alleged
that the mercury contained in thimerosal-containing vaccines could affect an infant’s brain, leading to autism.

The first theory was rejected in three test case decisions, all of which were subsequently affirmed. See generally
Cedillo v. Sec’y of Health & Human Servs., No. 98-916V, 2009 WL 331968 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), mot.
for review den’d, 89 Fed. Cl. 158 (2009), aff’d, 617 F.3d 1328 (Fed. Cir. 2010); Hazlehurst v. Sec’y of Health &
Human Servs., No. 03-654V, 2009 WL 332306 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), mot. for review den’d, 88 Fed.
Cl. 473 (2009), aff’d, 605 F.3d 1343 (Fed. Cir. 2010); Snyder v. Sec’y of Health & Human Servs., No. 01-162V, 2009
WL 332044 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), mot. for rev. den’d, 88 Fed. Cl. 706 (2009).

The second theory was similarly rejected. Dwyer v. Sec’y of Health & Human Servs., No. 03-1202V, 2010 WL
892250 (Fed. Cl. Spec. Mstr. Mar. 12, 2010); King v. Sec’y of Health & Human Servs., No. 03-584V, 2010 WL 892296
(Fed. Cl. Spec. Mstr. Mar. 12, 2010); Mead v. Sec’y of Health & Human Servs., No. 03-215V, 2010 WL 892248 (Fed.
Cl. Spec. Mstr. Mar. 12, 2010).

Ultimately a total of eleven lengthy decisions by special masters, the judges of the U.S. Court of Federal Claims, and
the panels of the U.S. Court of Appeals for the Federal Circuit, unanimously rejected petitioners’ claims. These
decisions found no persuasive evidence that the MMR vaccine or thimerosal-containing vaccines caused autism. The
OAP proceedings concluded in 2010.

10
 In response, the special master ordered Petitioners to file an amended petition by
September 13, 2012. ECF No. 31. Again, Petitioners requested an unopposed extension (ECF No.
32), which the special master granted. ECF No. 33. Petitioners filed their second amended petition
on October 4, 2012, alleging that Petitioners would be proceeding on the basis of a
challenge/rechallenge theory.12 ECF No. 34. In the ensuing months, Petitioners struggled to
complete the filing of medical records, requesting several extensions of time to do so but not
completing the task until August 2013. ECF No. 60. By February 24, 2014 (one of several extended
deadlines Petitioners were provided), T.M. & R.R.M requested an additional month to file their
expert report or “take other appropriate action” as “[i]t is not clear at this juncture whether or not
[P]etitioners will be able to produce an expert report supporting the Second Amended Petition.”
ECF No. 65 at 1. After several more extensions of time, however, Petitioners finally filed their
expert report from Dr. Yuval Shafrir on August 25, 2014. ECF No. 74.13

In September 2014, the case was reassigned to me. ECF Nos. 76, 77. Following a status
conference held on November 6, 2014, I ordered the Parties to submit a Joint Status Report
proposing available hearing dates and extended Respondent’s deadline for an expert report until
January 30, 2015. ECF No. 78. A two-day entitlement hearing was set for July 28-29, 2015, in
Washington, DC, and a pre-hearing schedule was set.

On January 28, 2015, Respondent requested a few extra days to submit her expert report,
(ECF No. 81), and ultimately did file one from Dr. Max Wiznitzer, along with his curriculum vitae
and a single medical article, on February 2, 2015. ECF No. 82. Petitioners and Respondent then
filed their pre-hearing submissions on April 16, 2015, and May 15, 2015, respectively. ECF Nos.
83, 84. On June 11, 2015, Petitioners filed a supplemental expert report from Dr. Shafrir along
with several additional pieces of medical literature. ECF Nos. 85-88.14

Petitioners and Respondent both filed their witness lists on June 15, 2015. ECF Nos. 94

12
As noted in Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1322 (Fed. Cir. 2006), “[a] rechallenge
event occurs when a patient who had an adverse reaction to a vaccine suffers worsened symptoms after an additional
injection of the vaccine.”
13
In the early spring of 2014, Petitioners expected to advance a theory that A.P.M. suffered from a mitochondrial
disorder that, in conjunction with his vaccinations, caused his developmental regression. Mar. 26, 2014, Motion for
Extension of Time (ECF No. 67) at 2-3. They offered two pieces of scientific literature in support of the theory. See
Pet’rs’ Exs. 46 and 48. However, the Petitioners subsequently backed away from this theory. May 27, 2014, Motion
for Extension of Time (ECF No. 70) at 1 (“[t]he retained expert further advises counsel that his opinion is not
predicated on a formal diagnosis of mitochondrial disease”). At hearing, mitochondrial disease was not discussed
(except in passing), and Petitioners’ theory does not propose that A.P.M. had such a metabolic disorder.
14
Dr. Shafrir’s updated curriculum vitae, along with annotations of the formerly filed exhibits and a corrected version
of a typographical error in his supplemental report, were all filed on June 15, 2015. ECF Nos. 89-93.

11
and 96. Petitioners also filed several more exhibits – as well as a third amended petition, which
entirely disposed of the challenge/rechallenge theory set forth in their second amended petition,
asserting instead that the vaccines administered to A.P.M. caused a cerebral folate deficiency,
which in turn precipitated developmental regression, developmental delay, apraxia of speech, and
multiple physiological symptoms. ECF No. 97. They also filed more medical records and their
response to Respondent’s pre-hearing memorandum (ECF Nos. 98-101), and then even more
medical literature. ECF Nos. 103 and 105.

The entitlement hearing took place as scheduled on July 28-29, 2015, and I thereafter set
the schedule for the parties’ post-trial briefings. On August 19, 2015, Respondent filed additional
medical literature she had identified at the entitlement hearing. ECF No. 107. After two extensions
of time, Petitioners filed their post-hearing brief along with even more medical literature on
November 10 and 11, 2015. ECF Nos. 114 and 115 (“Post-Trial Brief”). Respondent asked for
similar extensions, filing her post-hearing brief on January 11, 2016. ECF No. 124. 15 Petitioners
followed with an additional supplemental report by Dr. Shafrir on the protein homology issue on
February 3, 2016 (ECF No. 128), and then filed their response to Respondent’s post-hearing
memorandum on February 10, 2016. ECF No. 129 (“Reply”).

III. TESTIMONY PRESENTED AT HEARING16

A. T.M.

T.M., A.P.M.’s mother, was the only fact witness testifying at the hearing. See generally
Tr. at 4-87. She provided a narrative about A.P.M.’s development, with particular emphasis on the
differences she observed in his behavior after the 15-month vaccinations.

T.M. testified that she witnessed A.P.M. experience varied reactions to the vaccines he
had received. Thus, after receiving some initial childhood vaccinations on June 14, 2005, and
August 16, 2005, respectively, A.P.M. was “ill and irritable” and “showed signs and symptoms of
severe pain and discomfort.” Pet’rs’ Ex. 63 at 2. He had a fever and was screaming, and was
thereafter inconsolable for weeks despite T.M.’s efforts to comfort him. Id.; Tr. at 11-13. His
reaction to his six-month vaccinations, however, was less notable, characterized only by a fever

15
On December 21, 2015, a stipulation for an award of interim attorney’s fees was filed (ECF No. 117), and that same
day I issued a decision granting an award of fees based on the stipulated sums. ECF No. 120. Judgment for the interim
award entered on December 23, 2015. ECF No. 122.
16
Besides the records previously discussed, the witness testimony, and medical and scientific literature offered in this
case, Petitioners also filed a lengthy compilation of photographs intended to display A.P.M.’s condition at various
points in his life, and thereby illustrate their arguments about the course of his regression. See generally Pet’rs’ Ex.
65 (ECF No. 100). The photos were not discussed at hearing, however, and (having reviewed them), I do not find that
they aid Petitioners in meeting their evidentiary burden in this action.
12
and rash. Tr. at 14. A.P.M. otherwise continued to meet his developmental milestones during this
time period. Id. He was using approximations of 20 to 30 words, “although many of his words
were garbled and difficult to understand.” Pet’rs’ Ex. 67 at 2; Tr. at 18, 33. He also played well
with other children and was “happy.” Pet’rs’ Ex. 67 at 2. T.M. testified that he was “nothing
different than my daughter.” Tr. at 7.

A.P.M.’s reactions to the DTaP and MMR vaccines administered in July 2006, however,
were in her view qualitatively different. Within three or four weeks following his receipt of the
MMR and DTaP-Hib vaccines on July 14, 2006, she testified, A.P.M. became “socially withdrawn
and fearful.” Pet’rs’ Ex. 67 at 2; Tr. at 19-20. He lost interest in toys, stopped using many of the
words he had used previously, and was less interactive. Id. at 3; Tr. at 22-23. T.M. characterized
the change as “[n]ight and day, completely,” although she also expressed the view that the
regression was also “gradual” in nature. Tr. at 25, 32. A.P.M. also began engaging in repetitive
routines in September 2006, such as pressing his face against the liquid-crystal-display (“LCD”)
television. Id. at 24-25. A.P.M.’s gastrointestinal issues intensified greatly during this period.
Pet’rs’ Ex. 67 at 3. Overall, it seemed to T.M. as if A.P.M. “kind of started to disappear.” Tr. at
28.

T.M. conceded that the record does not document her concerns about A.P.M.’s
developmental problems before his 18-month visit with Dr. Kooima in October 2006 – three
months after the vaccinations in question – and that this record actually stated that (as of that time)
A.P.M. was healthy and developing normally. Tr. at 34-35, 71, 74. She attributed this in part to
the fact that she and her husband had disagreed whether A.P.M.’s developmental problems were
significant enough to warrant professional attention. Id. at 27-28. She also asserted that she had
attempted to call Dr. Kooima’s office concerning A.P.M.’s initial reactions to his 15-month
vaccines “multiple times.” Id. at 71-72. Only at A.P.M.’s two-year well-child visit, however, did
the records reflect T.M.’s report to a treater about her concern that A.P.M. had an ASD, leading
Dr. Kooima to concur and provide T.M. & R.R.M with developmental assessment specialist
referrals. Id. at 35-36.

T.M. was asked some questions about A.P.M.’s alleged cerebral folate deficiency and
efforts to treat it. She noted that for several years, and at Dr. Frye’s recommendation, A.P.M. had
been receiving some form of leucovorin,17 which contains “super-high doses of folinic acid” and
therefore could help alleviate his purported folate deficiency. Tr. at 48-50, 60-62. Dr. Frye
recommended this course of action in reaction to A.P.M.’s high levels of folate receptor blocking
autoantibodies as measured in 2010 by the SUNY Downstate Center. Id. at 52-54. She also

17
Leucovorin is in a class of medications called folic acid analogs. Dorland’s at 1026. It is a metabolically active form
of folic acid that has been used in cancer therapy to protect normal cells against methotrexate – called also citrovorum
factor, folinic acid. Id.
13
admitted that up to the date of the 18-month well-child visit, she had “exclusively” nursed A.P.M.,
but around that time started him on cow’s milk. Tr. at 72-73. Not long after bovine milk was
introduced into A.P.M.’s diet, however, he broke out in eczema. Id. at 73. She therefore
hypothesized that A.P.M. had a lactose intolerance. Id. at 83-84. As a result, in July 2007, and with
the added urging of certain treaters, T.M. & R.R.M put A.P.M. on a dairy-free diet, which in her
opinion had lessened his aggression. Id. at 47-48; 83.

Currently, T.M. stated, A.P.M. is “doing phenomenal” and is a “very, very high-
functioning” child despite continuing to have developmental issues. Tr. at 46, 59. Even though he
does not engage in back-and-forth dialogue much, he now has some conversational language. Id.
Indeed, his improvement is such that some people do not even realize A.P.M. has been diagnosed
with autism. Id. at 59.

B. Petitioners’ Expert – Dr. Shafrir

Dr. Yuval Shafrir is a child neurologist who graduated from the Sackler School of Medicine
at Tel Aviv University in 1982. Tr. at 88; Pet’rs’ Ex. 62 at 1. He thereafter did residencies in
pediatrics at Kaplan University and the Bellinson Medical Center in Israel. Pet’rs’ Ex. 62 at 1. Dr.
Shafrir went on to do residencies in pediatrics at North Shore University Hospital in New York,
and in pediatric neurology at the Washington University Medical Center in Missouri. Id. at 1-2;
Tr. at 88. From 1992 to 2000, Dr. Shafrir worked at a number of different U.S. hospitals. Tr. at 88.
Currently, he practices pediatric neurology in private practice affiliated with Sinai Hospital in
Baltimore. Id. at 91. He is licensed to practice medicine in Maryland, and has board certifications
in child neurology, although he has not renewed his board certification in pediatrics. Id. at 88. He
has worked and taught across the country in pediatrics and neurology and presently does so at the
University of Maryland School of Medicine. Pet’rs’ Ex. 62 at 3-4. He has also written extensively
on issues of pediatric neurology. Id. at 4-6; Tr. at 89-90.

Dr. Shafrir described himself as an “epileptologist by training” and general pediatric
neurologist. Tr. at 91. He testified as an expert in pediatric neurology. Id. at 94. He claims to have
experience treating individuals suffering from immune system-mediated conditions as well. Id. He
is not, however, an expert in immunology, metabolic conditions, or the specific topic of cerebral
folate deficiency. Id. at 228 (admitting that this was the first case in which Dr. Shafrir had even
considered the subject, although he “read about the syndrome and . . . knew about it”). He is also
not one of A.P.M.’s treating physicians and has never examined A.P.M. himself. Id. at 94-95. Over
the course of his career, he has seen approximately 1,500 ASD patients. Id. at 91, 104. But he does
not have an academic background in studying or researching ASDs. See generally Pet’rs’ Ex. 62.

Dr. Shafrir primarily opined that A.P.M. developed autistic regression as a result of what
he termed “an autoimmune anti-folate receptor antibody syndrome,” precipitated by receipt of the
14
DTaP vaccine. Tr. at 95. He distinguished this from cerebral folate deficiency, acknowledging that
A.P.M.’s presentation was not consistent with “the current clinical picture of cerebral folate
deficiency.” Id. at 201. Dr. Shafrir thus disputed Dr. Frye’s assertions (as set forth in the medical
record) that a cerebral folate deficiency diagnosis was appropriate, since the levels of folate
measured in A.P.M.’s CSF were not below normal (although Petitioners nevertheless assert that
the “low normal” measurements had clinical significance). Id. at 204-07.

The core of Dr. Shafrir’s opinion arose from the results of the October 2010 testing
performed on A.P.M. that revealed high levels of the folate receptor blocking autoantibodies. Tr.
at 113. Even though the testing results alone are not equivalent to a formal diagnosis that A.P.M.
had a true cerebral folate deficiency, high blocking autoantibody levels had been shown to have
significance to the condition. See generally Pet’rs’ Ex. 50, Ref 1 (Vincent T. Ramaekers, et al.,
Autoantibodies to Folate Receptors in the Cerebral Folate Deficiency Syndrome, 352(19) N. Engl.
J. Med 1985 (May 12, 2005) (“Ramaekers I”)).

As Dr. Shafrir testified, the authors of Ramaekers I examined serum specimens taken from
28 children already diagnosed with a cerebral folate deficiency (due to the presence of severe
neurologic symptoms akin to those already mentioned, such as “marked irritability, slow head
growth, psychomotor retardation, cerebellar ataxia, pyramidal tract sings in the legs, dyskinesias .
. . , and in some cases, seizures”). Tr. at 118-27, Ramaekers I at 1985. That study determined that
the subjects also had high levels of the folate receptor blocking autoantibodies – suggesting that
the cerebral folate deficiency was the “consequence” of impairment of the folate transport process
caused by the presence of the blocking autoantibodies. Ramaekers I at 1990. Ramaekers I did not,
however, propose how the blocking autoantibodies themselves came to be, other than to speculate
that (a) they were produced in the first four to six months of a child’s life, and (b) they might have
been “induced by soluble folate-binding proteins in human or bovine milk or result from
sensitization by unknown antigens with similar epitopes.”18 Id. at 1991 (emphasis added).

Dr. Shafrir opined that the “unknown antigens” were derived from the pertussis component
of the DTaP vaccine. Tr. at 163-64.19 The antibodies subsequently produced attacked A.P.M.’s
folate receptor molecule. Tr. at 113, 176. The blocking, Dr. Shafrir asserted, led to a milder,

18
An epitope is also known as an antigenic determinant – which is part of an antigen that is recognized by the immune
system and capable of stimulating an immune response. Dorland’s at 502, 637.
19
At trial, Petitioners abandoned a prior element of their claim: that the MMR vaccine played a role in A.P.M.’s
regression. Tr. at 443, 457; Post-Trial Brief at 19 n.5. They did so because, as Dr. Shafrir admitted, he could not
identify any homology between the peptide sequences of any MMR vaccine components and the sequences comprising
the folate receptors to which the vaccine antigens would be presented and initiate the autoimmune production of self-
attacking antibodies. Tr. at 443-44, 474.

15
cerebral folate deficiency-like syndrome for A.P.M. that may not have had the hallmarks of the
more severe form of the disease, but nevertheless manifested as autism. Id. at 183-84.

To explain how the DTaP vaccine actually caused the production of the blocking
autoantibodies, Dr. Shafrir proposed the mechanism of molecular mimicry. He thus discussed the
concept of homology – “identical sequences of amino acids of two different proteins.” Tr. at 142,
157, 161-65, 173, 220-25 (citing Pet’rs’ Ex. 53, Ref. 6; Pet’rs’ Ex. 53, Ref. 7 (G. Lucchese, et al.,
Peptidology: Short Amino Acid Modules in Cell Biology and Immunology, 33 Amino Acids 703
(2007) (“Lucchese I”))); Pet’rs’ Ex. 53, Ref. 8 (G. Lucchese, et al., The Peptide Network between
Tetanus Toxin and Human Proteins Associated with Epilepsy, 2014 Epilepsy Research and
Treatment, available at http://dx.doi.org/10.1155/2014/236309 (“Lucchese II”))).20 Peptide
similarity can cause the production of antibodies that attack the self due to the body’s inability to
distinguish the between self and a foreign antigen. Id. at 159, 170 (citing Pet’rs’ Ex. 53, Ref. 5 (G.
Poland, et al., Vaccinomics, Adversomics, and the Immune Response Network Theory:
Individualized Vaccinology in the 21st Century, 25(2) Semin. Immunol. 89 (Apr. 2013))). Dr.
Shafrir proposed that a five-peptide sequence in the pertussis component of the DTaP vaccine had
sufficient homology with proteins in the cerebral folate receptors to initiate an autoimmune
process, attempting to demonstrate the claimed homology based upon a number of articles
discussing protein chain sequences. Tr. at 165.

Dr. Shafrir admitted that (unlike with milk) there is no proven or studied homology
between the folate receptor and the components of any vaccines – nor could he establish the larger
concept that a vaccine could cause the production of the blocking autoantibodies by any
mechanism. Pet’rs’ Ex. 50 at 31-32. He therefore relied on instances in which other vaccines have
been deemed causally related to autoimmune disorders. Tr. at 155-56 (citing Pet’rs’ Ex. 53, Ref.
10 (Nancy Agmon-Levin, Vaccines and Autoimmunity, 5 Nat. Rev. Rheumatol. 648 (2009)
(“Agmon-Levin”))). Agmon-Levin, a review article, broadly considers the propensity of different
vaccines to produce autoimmune illnesses, and in the course of its overview discusses a variety of
mechanisms by which the illness can occur, such as molecular mimicry. Tr. at 157-58; Agmon-
Levin at 650, Box 2. Because, Dr. Shafrir opined, the anti-folic acid receptor antibody syndrome
that A.P.M. had was autoimmune in origin, it too could be vaccine-caused. Tr. at 161.

20
A significant amount of time at hearing was devoted by both experts to contesting the issue of homology. Petitioners
offered numerous exhibits to support their claim that homology exists. See, e.g., Pet’rs’ Ex. 53, Ref. 6; Lucchese I;
Lucchese II; Pet’rs’ Ex. 53, Ref. 9; Pet’rs’ Ex. 73 (Rodrigo Villarino Romero, et al., Filamentous Hemagglutinin of
Bordetella Pertussis: a Key Adhesin with Immunomodulatory Properties? 9(12) FUTURE MICROBIOL. 1339 (2014)).
Indeed, Petitioners even submitted an additional expert report from Dr. Shafrir post-hearing, attempting to refute Dr.
Wiznitzer’s claim that there was insufficient homology between pertussis components and the folate receptors. Pet’rs’
Ex. 74. This is despite the fact that neither expert is an immunologist, and therefore neither has the professional
expertise to opine on such issues (beyond their general medical training and personal familiarity with molecular
biology).

16
 Next, Dr. Shafrir discussed the scientific support linking the presence of cerebral folate
receptor blocking autoantibodies with developmental regression or autism. The mere fact that
A.P.M. possessed a high level of the blocking autoantibodies, and the fact that he was also
diagnosed as autistic, was in his view important, given that a significant portion of the children
studied in Ramaekers I also were autistic (although they also unquestionably suffered from
cerebral folate deficiency based on symptomatology not possessed by A.P.M.). Tr. at 119 (citing
Ramaekers I at 1989). But Dr. Shafrir also stressed the strong correlation between cerebral folate
deficiency and autistic syndrome that he claimed was documented in several relevant studies. Tr.
at 201-02, 218-19. For example, in a second Ramaekers article also offered in support of the
purported autism-cerebral folate deficiency link (Pet’rs’ Ex. 50, Ref. 3 (V.T. Ramaekers, et al.,
Folate Receptor Autoimmunity and Cerebral Folate Deficiency in Low-Functioning Autism with
Neurological Deficits, 38 Neuropediatrics 276 (2007) (“Ramaekers II”))), 25 children suffering
from infantile-onset cerebral folate deficiency (and thus in possession of the same kind of severe
symptoms not characterizing A.P.M.’s condition) were studied, with 23 possessing low CSF folate
levels and 19 of that subgroup also having the higher levels of autoantibodies (suggesting a
connection between the autoantibodies and low folate levels in the CSF). Ramaekers II at 280-81.

Another article echoed the findings in Ramaekers II. Pet’rs’ Ex. 50, Ref. 2 (Paolo Moretti,
et al., Brief Report: Autistic Symptoms, Developmental Regression, Mental Retardation, Epilepsy,
and Dyskinesias in CNS Folate Deficiency, 38 J. Autism Dev. Disord. 1170 (2008) (“Moretti”)).
The Moretti authors conducted assessments of seven children who had been diagnosed with a
cerebral folate deficiency and determined that a “subset” of those manifesting developmental
regression also had folate level abnormalities. Moretti at 1170. The studied sample, however, was
not only facially small, but included four children who had “demonstrated neurological
abnormalities in the neonatal period,” and two whose neurologic impairments were so severe that
they could not be assessed at all. Id. at 1171. The article observed an overlap between ASD
symptoms and cerebral folate deficiency symptoms in five of the studied subjects and speculated
that the blocking autoantibodies may have played a role in the manifestation of ASD symptoms,
but that “their causative role remains to be determined.” Id. at 1176.

Dr. Shafrir also cited R.E. Frye, et al., Cerebral Folate Receptor Autoantibodies in Autism
Spectrum Disorder, 18 Molecular Psychiatry 369 (2013) (“Frye”).21 The Frye article purports to
demonstrate a correlation between the level of receptor-blocking autoantibodies and lower levels
of MTHF in the CSF in children who had not been diagnosed with a cerebral folate deficiency. Tr.
at 137 (citing Frye at 6, Figure 2). The study specifically tested for the presence of blocking
autoantibodies in 93 patients diagnosed with an ASD (a large subset of whom were patients of Dr.

21
One of the Frye authors is Dr. Richard Frye – the same treater who first proposed that A.P.M. suffered from a
cerebral folate deficiency. Tr. at 124.
17
Frye like A.P.M.). Frye at 372; Tr. at 135-36. Within the tested group, 56 patients were “positive”
for the blocking autoantibodies – meaning they possessed them, although the majority of that
subgroup possessed low levels of the antibodies at best. Frye at 372-73.

An alternative avenue of support Dr. Shafrir proposed for Petitioners’ causation theory was
the purportedly beneficial effects of treatments A.P.M. received after testing revealed the elevated
folate receptor antibodies. According to Dr. Shafrir, the success of A.P.M.’s treatment with drugs
(like leucovorin) containing folinic acid (along with the elimination of milk from his diet)
corroborated his opinion that A.P.M. had a cerebral folate deficiency-like syndrome, by showing
that reduction of the blocking effect of the autoantibodies was possible. Tr. at 109-10, 132, 139,
183, 202-03. He referenced studies showing that taking oral folinic acid supplements could rectify
low CSF MTHF and lead to partial or complete clinical recovery. Id. at 122-26 (citing Ramaekers
I). For example, Frye discussed the ameliorative effects of treating such children with leucovorin,
although the article’s authors admit that proof of the treatment’s efficacy was anecdotally obtained
from parent interviews rather than determined objectively. Frye at 371, 378 (“[t]his study was not
a clinical trial”).22

A significant deficiency in Dr. Shafrir’s theory was the fact that – as he admitted – other
than the elevated blocking antibody measurements, the medical records did not support the
conclusion that A.P.M. had a cerebral folate deficiency of any kind. Thus, A.P.M. possessed none
of the more severe symptoms of the subjects in Ramaekers I – something Dr. Shafrir conceded,
and that even Dr. Frye before him had admitted. Tr. at 189; Pet’rs’ Ex. 16 at 35. Indeed, Dr. Shafrir
himself would not accept Dr. Frye’s diagnosis that A.P.M. suffered from a cerebral folate
deficiency, preferring instead to characterize it as an inadequately-studied “syndrome” – milder
than a true cerebral folate deficiency, but still capable of producing developmental regression. Tr.
at 103, 161 (“it hasn’t been delineated yet”), 189-90, 204-05, 229 (citing Ramaekers I).

Dr. Shafrir similarly admitted that A.P.M.’s measured MTHF levels (as determined in his
2011 lumbar puncture) were within normal ranges. Tr. at 203-04. But he argued that the measured
folate levels were more precisely characterized as “low normal” that (because the nature of cerebral
folate deficiency was still not well understood) were nevertheless pathologic. Id. at 132. He also
questioned the extent to which the CSF testing was reliable, noting that the medical records from

22
Less than one week before the hearing, Petitioners filed additional literature suggesting that children who had
experienced regression as part of their autism showed improvement after treatment with corticosteroids, thus
attempting to further bulwark their contention that developmental regression can be the result of an autoimmune illness
(since treatment focusing on suppressing the immune process is beneficial). Pet’rs’ Ex. 70 (Frank H. Duffy, et al.,
Corticosteroid Therapy in Regressive Autism: A Retrospective Study of Effects on the Frequency Modulated Auditory
Evoked Response (FMAER), Language, and Behavior, 14(70) BMC Neurol. 1471-2377 (2014)); Pet’rs’ Ex. 71
(Sailaja Golla & John A. Sweeney, Corticosteroid Therapy in Regressive Autism: Preliminary Findings from a
Retrospective Study, 12(79) BMC Med. 1741-7015 (2014)).

18
the lumbar puncture indicated that the tested CSF specimen was blood-tinged, thereby raising the
possibility that the results were untrustworthy. Id. at 133, 205-06. Red blood cells, he reasoned,
contain folic acid, and so the presence of red blood cells in the measured sample would alter the
accuracy of the reading and artificially raise the reported level of MTHF. Id. at 449-52.

More broadly, Dr. Shafrir offered nothing, whether based on his own experience or a
particular study, demonstrating or suggesting a link between any vaccine and the development of
a cerebral folate deficiency, let alone the milder syndrome he was proposing as part of his opinion.
He thus admitted that he was aware of no studies involving or suggesting that any vaccine may
play a role in the production of the folate receptor blocking autoantibodies. Pet’rs’ Ex. 50 at 32.
At best, he proposed that since other vaccines have been shown to be associated with the
development of other neurologic injuries caused by autoimmune processes, the same is possible
here. Tr. at 147-48; Pet’rs’ Ex. 53, Ref. 2 (M. Partinen, Increased Incidence and Clinical Picture
of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland,
7(3) PLoS ONE (Mar. 2012) (“Partinen”)).

Partinen, for example, studied the widespread occurrence of narcolepsy after Finnish
children received a particular formulation of influenza (“flu”) vaccine. Partinen at 6. Dr. Shafrir
proposed that Partinen demonstrated that a vaccine could cause a neurologic autoimmune-
mediated disease, as well as the fact that the autoimmune process would occur in a progressive
fashion akin to what A.P.M. allegedly experienced. Tr. at 147-48. He acknowledged, however, the
many ways in which the Partinen study was inapposite, since (a) it involved a vaccine substantially
different than the kind of flu vaccines administered elsewhere, including an adjuvant that was
suspected to have played a role in the reaction, (b) genetic susceptibility to narcolepsy (perhaps
even unique to Finland) had been proposed as an alternative causative factor, and (c) most
importantly, Partinen did not even identify autoimmunity as the illness’s mechanism. Id. at 152-
55.

Dr. Shafrir’s testimony also touched upon the impact of bovine milk consumption on the
generation of the blocking autoantibodies. Dr. Shafrir admitted in his testimony that milk proteins
had “up to 90 percent homology” with the folate receptors. Tr. at 185. This was consistent with
Petitioners’ literature. Ramaekers I at 1991. Indeed, another study, co-authored by Ramaekers and
also submitted in support of Petitioners’ causation theory, directly considers the relationship
between milk and generation of the folate receptor-blocking autoantibodies. See generally Pet’rs’
Ex. 50, Ref. 6 (V.T. Ramaekers, et al., A Milk-Free Diet Downregulates Folate Receptor
Autoimmunity in Cerebral Folate Deficiency Syndrome, 50 Developmental Medicine & Child
Neurology 346 (2008) (“Ramaekers III”)). Ramaekers III found that re-introduction of milk to
diets of children who previously had a cerebral folate deficiency caused their folate receptor
blocking autoantibody titer to increase significantly. Dr. Shafrir thus maintained (consistent with
19
T.M.’s testimony) that elimination of milk from A.P.M.’s diet had the opposite effect, helping him
to increase folate uptake (by reducing the production of autoantibodies). Tr. at 109-10, 139.

Even while testifying that milk played a defined role in the production of the blocking
autoantibodies, however, Dr. Shafrir vigorously contested the notion that the blocking
autoantibodies detected in A.P.M. in 2010 might have been the product of antigens contained in
bovine milk (which T.M. admitted introducing to A.P.M.’s diet not long before he was 18 months
old (id. at 72-73)), asserting that “if this was the cause [of A.P.M.’s autism] . . . then the entire
children population in the world should be autistic,” given widespread milk consumption. Id. at
110, 186. He further opined that it could not have happened in A.P.M.’s case in any event, because
A.P.M. was exposed to some form of milk from birth (although this argument ignored the fact that
A.P.M. had received bovine milk long before he was tested for the blocking autoantibodies in
2010). Id. at 185, 215-16.

Dr. Shafrir proposed that the timeframe between A.P.M.’s receipt of the DTaP vaccine and
development of regressive/ASD-like symptoms (within three months of the vaccine’s
administration, or by the time A.P.M. was 18 months old) was medically acceptable. Tr. at 184;
Pet’rs’ Ex. 53 at 2; Pet’rs’ Ex. 50 at 32. However, he acknowledged that the existing medical
records did not permit him to propose precisely what that timeframe would be, or to cite instances
from the medical record reflecting the course of the process. Tr. at 194. He averred that onset of
A.P.M.’s developmental regression was even more difficult to pinpoint in this case because it was
a “gradual process,” without evidence of a sudden change in A.P.M.’s behavior (despite T.M.’s
testimony that she did observe a dramatic change in the weeks immediately after the July 2006
vaccination). Id. at 102. He could conclude only that regression likely began before A.P.M. was
18 months old, given that T.M. had suggested that A.P.M. began to evince symptoms of
developmental regression slightly before the 18-month well-child visit, and it was therefore
reasonable to conclude she had observed such symptoms before records from that visit suggest.
Id. at 194, 197-98.

Dr. Shafrir offered little beyond general medical literature directly supporting his
arguments about the timeframe in which the autoimmune process leading to the production of the
folate receptor-blocking autoantibodies would be expected to occur. See, e.g., Agmon-Levin at
649. He instead relied on evidence involving other vaccines and other diseases to support the more
general relationship between vaccines and autoimmunity and the timing of the autoimmune
process. Thus, to counter Dr. Wiznitzer’s claim that three to four months post-vaccination was too
long for an autoimmune condition to develop, Dr. Shafrir pointed to an example in the Vaccine
Table, which allows claims to proceed based on a timeframe of 42 days (or approximately a month
and a half) for autoimmune conditions such as chronic arthritis after receipt of the MMR vaccine.
Tr. at 146 (citing Pet’rs’ Ex. 50, Ref. 5). He also pointed again to Partinen, which found a time
20
delay of several months between immunization and the subsequent narcolepsy. Id. at 143-45.23 In
light of such literature, he proposed that the latency period could be days, or even years, before
onset manifested. Id. at 145.

C. Respondent’s Expert – Dr. Wiznitzer

Dr. Wiznitzer graduated from the honors program in medical education at Northwestern
University, where he received a bachelor’s of science in medicine in 1975 and then his medical
degree in 1977. Tr. at 236. He completed a three-year internship and residency in pediatrics at
Cincinnati Children’s Hospital, followed by a one-year fellowship in child development and
developmental disorders at the Cincinnati Center for Developmental Disorders. Id. He also
completed a three-year child neurology fellowship at the University of Pennsylvania and
Children’s Hospital of Philadelphia, followed by a two-year National Institute of Health fellowship
in disorders of higher cortical function in children at the Albert Einstein College of Medicine in
the Bronx, New York (which involved working with children with autism spectrum disorders). Id.
Dr. Wiznitzer currently works at Rainbow Babies and Children’s Hospital in Cleveland, Ohio. Id.
at 235. Dr. Wiznitzer also serves as a journal reviewer and on two editorial boards (the Lancet
Neurology and the Journal of Child Neurology). Id. at 245-46. Dr. Wiznitzer holds board
certifications in pediatrics, neurology (with special qualification in child neurology), and
neurodevelopmental disabilities. Id. at 237-40.

Dr. Wiznitzer has an active clinical practice, and he estimates that more than a quarter of
the patients he sees weekly are individuals with autism (many of whom receive that diagnosis from
him). Tr. at 238.24 He also has ASD-related research and teaching experience. Id. at 239-40. When
Dr. Wiznitzer started his current job at Rainbow Babies and Children’s Hospital in 1986, he
immediately got involved in autism research and has issued approximately 60 publications. Id. at
241. Additionally, Dr. Wiznitzer is on the Autism Subcommittee of the American Academy of
Pediatrics and the American Academy of Neurology, both of which are working on new guidelines

23
Dr. Shafrir also referenced these papers in support of an alternative causative mechanism – that the adjuvants
contained in vaccines to stimulate their immunologic properties could play a role in the development of autoimmune
diseases. Tr. at 152-53. However, he only brushed on the topic briefly, and adjuvant stimulation is not a central
component of Petitioners’ theory in this case. I note as well that theories relying on adjuvants to explain an adverse
vaccine reaction have often been rejected by other special masters as unpersuasive in any event. See, e.g., D'Angiolini
v. Sec'y of Health & Human Servs., No. 99-578V, 2014 WL 1678145, at *57 (Fed. Cl. Spec. Mstr. Mar. 27, 2014),
mot. for review denied, 122 Fed. Cl. 86 (2015), aff'd, No. 2015-5141, 2016 WL 1426294 (Fed. Cir. Apr. 12, 2016)
(expert opinion that an adjuvant present in a vaccine could lead to an adverse reaction did not have sufficient scientific
support to be a reliable basis for compensation in the Vaccine Program); see also Snyder, 2009 WL 332044 (thimerosal
component of vaccines not shown to cause or contribute to development of autism).
24
When he is in Cleveland, Dr. Wiznitzer normally sees patients at least seven half-days a week, and he also sees in-
patients, on average, about two months out of the year. Tr. at 307, 309-10.

21
for the diagnosis and management of autism. Id. at 239-40. And he is also involved in teaching
related to autism both at the medical center, as well as in the Cleveland area and nationally. Id. at
240.

Dr. Wiznitzer did not dispute that A.P.M. has an ASD,25 but disagreed that the vaccines
A.P.M. received on July 14, 2006, precipitated his development of autism. Tr. at 248-29, 265. In
reaching this conclusion, Dr. Wiznitzer rejected Petitioners’ assertion that A.P.M. has a cerebral
folate deficiency, or that the anti-folate antibodies measured in A.P.M. caused his autism. Id. He
also proposed that in fact it was the introduction of cow’s milk in A.P.M.’s diet that was the more
likely cause for his elevated levels of autoantibodies. Id. 26

Dr. Wiznitzer questioned Dr. Frye’s diagnosis of cerebral folate deficiency (as well as Dr.
Shafrir’s concurrent diagnosis that A.P.M. had some milder syndrome characterized primarily by
the elevated blocking autoantibodies). First, he noted that A.P.M. was found to have normal levels
of MTHF in his CSF, as Dr. Frye (as well as Dr. Shafrir) recognized. Tr. at 283, 288. Dr. Wiznitzer
acknowledged the results may have been somewhat on the lower end of normal, but stressed that
this had, in his opinion, no significance from a medical standpoint. Id. at 288, 438-39.

Second, Dr. Wiznitzer stressed that A.P.M.’s medical history did not reflect the typical
clinical presentation of a child with cerebral folate deficiency, or any other neurodegenerative
disorder for that matter. Tr. at 282, 287. Thus, A.P.M. had never experienced deceleration of head
growth, poor vision, seizures, or other immediate intellectual impairment. Id. at 282-83, 360-61.

25
The term ASD encompasses a group of complex neurodevelopmental disorders characterized by “self-absorption,
impairment in social interaction and communication, and a restricted range of activities and interests.” Dorland’s 180;
see also Autism Spectrum Disorder Fact Sheet, NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND
STROKES, Oct. 7, 2015, available at http://www.ninds.nih.gov/disorders/autism/detail_autism htm (last visited July
11, 2016); see also Resp’t’s Ex. C (Chris P. Johnson, et al., Identification and Evaluation of Children with Autism
Spectrum Disorders, 120 Pediatrics 1183-1215 (2007) (noting that “ASDs are neurodevelopmental conditions with
strong genetic underpinnings,” and indicating that “[i]n addition to being a spectrum disorder, autism has a wide
variability with respect to the presence and intensity of symptoms”)). Children diagnosed with ASD are often reported
by their parents to have displayed developmental or behavioral problems around 18 months of age, if not by the age
of two, and a significant minority of children with ASD experience regression/loss of skills, including language or
vocabulary. Lehner v. Sec’y of Health & Human Servs., No. 08-554V, 2015 WL 5443461, at *34-35 (Fed. Cl. Spec.
Mstr. July 22, 2015) (discussing the diagnostic criteria and characteristics of ASDs). The parties largely did not contest
the general scientific and medical understanding of ASDs.
26
Although my decision includes review and discussion of Dr. Wiznitzer’s primary testimonial points, I note that he
has no more personal or professional expertise on the subjects of cerebral folate deficiency, immunology, or molecular
biology that Dr. Shafrir, and therefore his opinions on medical and scientific topics ranging from the content of the
DTaP vaccine and its protein sequences to the causes of the development of folate receptor blocking autoantibodies
are subject to the same weighting concerns that I apply to Dr. Shafrir’s testimony. Of course, because the Petitioners
carry the initial burden of proof, and therefore must offer the proper expert to opine on the matters most relevant to
their causation theory, the reliability of Dr. Shafrir’s testimony was of primary importance.

22
Instead, Dr. Wiznitzer maintained that A.P.M.’s ASD development was consistent with one of the
several ASD trajectories: autism with regression of skills manifesting during the second year of
life. Id. at 260-66 (citing Resp’t’s Ex. D). Dr. Wiznitzer characterized such a temporal trajectory
as common, with this type of clinical presentation occurring in approximately 10 to 15 percent of
children diagnosed with ASD. Id. at 262. Dr. Wiznitzer concluded that A.P.M.’s autistic regression
is of unknown etiology. Id. at 407-08.

A significant portion of Dr. Wiznitzer’s testimony was devoted to rebutting Dr. Shafrir’s
assertions that the CSF testing results that indicated A.P.M. had “low normal” levels of folate were
unreliable due to blood in the sample. Dr. Wiznitzer maintained that records from the procedure
report pertaining to the CSF testing revealed that several CSF vials were collected, and that the
first, purportedly bloody specimen would not have been the tested sample (out of the total amount
collected). Tr. at 283-84, 367-71; see also Pet’rs’ Ex. 16 at 10-11. He further maintained, drawing
upon his experience in ordering similar tests and then reviewing the results, that a lab would not
have run the MTHF level test on a visibly blood-tinged sample. Id. at 437-39.27 He acknowledged,
however, that the recorded test results did in one place characterize the red blood cell count as
“high,” but pointed out the notes from when the sample was drawn suggested any contaminated
amount later cleared; he also proposed, based on his personal experience, that lab technicians
would “spin [red blood cells] out” of a sample before testing (meaning subject the sample to a
centrifuge to separate out serum portions to be tested). Id. at 371-74.

Dr. Wiznitzer also addressed Petitioners’ arguments about the significance of A.P.M.’s
elevated folate receptor-blocking autoantibodies. Although he did not dispute the accuracy of the
testing results, Dr. Wiznitzer characterized them as no more than an “interesting finding” having
little clinical importance – especially since they stood as the only lab results that even came close
to suggesting A.P.M. had any kind of cerebral folate deficiency. Tr. at 301-02, 348. And even if
A.P.M. was assumed to suffer from some lesser-understood syndrome evidenced by the presence
of the folate receptor blocking autoantibodies, Dr. Wiznitzer denied that the DTaP vaccine could
have caused the production of those antibodies, due to insufficient homology between the proteins
in the vaccines and the folic acid receptor. Id. at 268. In that regard, he challenged whether a
pentapeptide sequence – a five amino acid chain – was similar enough to a folate receptor protein
chain to initiate the process needed to produce the blocking autoantibodies. Id. Instead, he
proposed that a chain of at least 15 to 20 amino acids was necessary. Id. at 270-73 (citing Resp’t’s
Exs. E and F), 303-09. Dr. Wiznitzer also offered evidence that Dr. Shafrir had referenced incorrect
strains of components of the MMR and DTaP vaccines in arguing that either could potentially
cause an autoimmune process via molecular mimicry. Id. at 307-310; 327-35. (As noted above, as

27
Respondent filed several articles post-hearing supporting Dr. Wiznitzer’s characterization of the cerebral spinal
fluid testing procedures. Resp’t’s Exs. M-O.

23
a result of these arguments, Dr. Shafrir at hearing admitted that he could not establish homology
for the MMR vaccine, and Petitioners dropped the MMR vaccine from their claim). Tr. at 443-44,
474; see also Post-Trial Brief at 19 n.5.

Dr. Wiznitzer characterized the scientifically-demonstrated homology between milk and
proteins in the folate receptors (as also reflected in Petitioners’ literature and expert testimony) as
the “800-pound gorilla in the room,” and therefore a more likely cause of A.P.M.’s heightened
blocking autoantibody levels. Tr. at 272; 313; see also Ramaekers III. To that end, Dr. Wiznitzer
presented evidence that there is 90 percent homology between the relevant peptide sequences in
milk and the folate receptors in the brain – and thus molecular mimicry as the mechanism for the
production of the blocking autoantibodies was far more plausible than what Dr. Shafrir proposed
occurred with merely a five-protein homologous sequence. Id. at 315-16. Moreover, A.P.M. had
previously been exposed to vaccines earlier in life with no similar alleged reaction, but had not
been exposed to cow’s milk prior to 18 months (around the time when A.P.M.’s language loss was
first observed), further suggesting that milk had more likely generated the autoantibodies than the
DTaP vaccine. Id. at 317.

Finally, Dr. Wiznitzer addressed the temporal relationship between receipt of the DTaP
vaccine and onset of A.P.M’s developmental symptoms. He argued that there was insufficient
temporal proximity to link the vaccines received in July 2006, when A.P.M. was 15 months old,
to the first description of regression at A.P.M.’s two year visit in April 2007, when “loss of
language” was clearly described. Tr. at 279 (citing Pet’rs’ Ex. 1 at 7). At best, three to four months
passed between the vaccination and the earliest possible onset of regression in 2006 – too long in
Dr. Wiznitzer’s opinion for an autoimmune process to manifest. Id. at 280-81.

IV. APPLICABLE LEGAL STANDARDS

A. Petitioner’s Overall Burden in Vaccine Program Cases

To receive compensation in the Vaccine Program, a petitioner must prove either: (1) that
he suffered a “Table Injury” – i.e., an injury falling within the Vaccine Injury Table –
corresponding to one of the vaccinations in question within a statutorily prescribed period of time
or, in the alternative, (2) that his illnesses were actually caused by a vaccine (a “Non-Table
Injury”). See Sections 13(a)(1)(A), 11(c)(1), and 14(a), as amended by 42 C.F.R. § 100.3; §
11(c)(1)(C)(ii)(I); see also Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed.
Cir. 2010); Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006).28
28
Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding
authority. Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998). By contrast, Federal Circuit rulings
concerning legal issues are binding on special masters. Guillory v. Sec’y of Health & Human Servs., 59 Fed. Cl. 121,
24
In this case, Petitioners do not assert a Table claim.

For both Table and Non-Table claims, Vaccine Program petitioners bear a “preponderance
of the evidence” burden of proof. Section 13(1)(a). That is, a petitioner must offer evidence that
leads the “trier of fact to believe that the existence of a fact is more probable than its nonexistence
before [he] may find in favor of the party who has the burden to persuade the judge of the fact’s
existence.” Moberly, 592 F.3d at 1322 n.2; see also Snowbank Enter. v. United States, 6 Cl. Ct.
476, 486 (1984) (mere conjecture or speculation is insufficient under a preponderance standard).
Proof of medical certainty is not required. Bunting v. Sec’y of Health & Human Servs., 931 F.2d
867, 873 (Fed. Cir. 1991). In particular, a petitioner must demonstrate that the vaccine was “not
only [the] but-for cause of the injury but also a substantial factor in bringing about the injury.”
Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344,
1352-53 (Fed. Cir. 1999)); Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed.
Cir. 2006). A petitioner may not receive a Vaccine Program award based solely on his assertions;
rather, the petition must be supported by either medical records or by the opinion of a competent
physician. Section 13(a)(1).

In attempting to establish entitlement to a Vaccine Program award of compensation for a
Non-Table claim, a petitioner must satisfy all three of the elements established by the Federal
Circuit in Althen: “(1) a medical theory causally connecting the vaccination and the injury; (2) a
logical sequence of cause and effect showing that the vaccination was the reason for the injury;
and (3) a showing of a proximate temporal relationship between vaccination and injury.” Althen,
418 F.3d at 1278.

Each of the Althen prongs requires a different showing. Under Althen prong one, petitioners
must provide a “reputable medical theory,” demonstrating that the vaccine received can cause the
type of injury alleged. Pafford, 451 F.3d at 1355-56 (citations omitted). To satisfy this prong, a
petitioner’s theory must be based on a “sound and reliable medical or scientific explanation.”
Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such a theory
must only be “legally probable, not medically or scientifically certain.” Id. at 549.

Petitioners may satisfy the first Althen prong without resort to medical literature,
epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical
theory. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1378-79 (Fed. Cir. 2009) (citing
Capizzano, 440 F.3d at 1325-26). Special masters, despite their expertise, are not empowered by
statute to conclusively resolve what are essentially thorny scientific and medical questions, and
thus scientific evidence offered to establish Althen prong one is viewed “not through the lens of

124 (2003), aff’d, 104 F. App’x 712 (Fed. Cir. 2004); see also Spooner v. Sec’y of Health & Human Servs., No. 13-
159V, 2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).

25
the laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant evidence
standard.” Id. at 1380. Accordingly, special masters must take care not to increase the burden
placed on petitioners in offering a scientific theory linking vaccine to injury. Contreras v. Sec’y of
Health & Human Servs., 121 Fed. Cl. 230, 245 (2015) (“[p]lausibility . . . in many cases may be
enough to satisfy Althen prong one” (emphasis in original)), appeal docketed, No. 2015-5097 (Fed.
Cir. June 19, 2015). But this does not negate or reduce a petitioner’s ultimate burden to establish
his overall entitlement to damages by preponderant evidence. W.C. v. Sec’y of Health & Human
Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013) (citations omitted).29

The second Althen prong requires proof of a logical sequence of cause and effect, usually
supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Andreu,
569 F.3d at 1375-77; Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Human Servs., 956
F.2d 1144, 1148 (Fed. Cir. 1992). In establishing that a vaccine “did cause” injury, the opinions
and views of the injured party’s treating physicians are entitled to some weight. Andreu, 569 F.3d
at 1367; Capizzano, 440 F.3d at 1326 (“medical records and medical opinion testimony are favored
in vaccine cases, as treating physicians are likely to be in the best position to determine whether a
‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury’”)
(quoting Althen, 418 F.3d at 1280). Medical records are generally viewed as particularly
trustworthy evidence, since they are created contemporaneously with the treatment of the patient.
Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).

However, medical records and/or statements of a treating physician’s views do not per se
bind the special master to adopt the conclusions of such an individual, even if they must be
considered and carefully evaluated. Section 13(b)(1) (providing that “[a]ny such diagnosis,
conclusion, judgment, test result, report, or summary shall not be binding on the special master or
court”); Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (“there is
nothing . . . that mandates that the testimony of a treating physician is sacrosanct – that it must be
accepted in its entirety and cannot be rebutted”). As with expert testimony offered to establish a
theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the
reasonableness of their suppositions or bases. The views of treating physicians should also be
weighed against other, contrary evidence also present in the record – including conflicting opinions
among such individuals. Hibbard v. Sec’y of Health & Human Servs., 100 Fed. Cl. 742, 749 (2011)
(not arbitrary or capricious for special master to weigh competing treating physicians’ conclusions

29
There is ample contrary authority for the more straightforward proposition that the first Althen prong, like the overall
test itself, simply applies a preponderance standard when evaluating if a reliable and plausible causal theory has been
established. Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1350 (Fed. Cir. 2010). For purposes of
the present analysis, I am stressing those cases focusing on the plausibility of the causal theory proposed, as opposed
to whether preponderant evidence supports it, in order to avoid imposing on Petitioners a greater evidentiary burden
than the law requires. This does not, however, change the fact that the theory’s plausibility is properly analyzed by
subjecting its components to the Daubert tests for scientific reliability. Terran v. Sec’y of Health & Human Servs.,
195 F.3d 1302, 1316 (Fed. Cir. 1999).
26
against each other), aff'd, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y of Dep't of Health &
Human Servs., 100 Fed. Cl. 119, 136 (2011), aff'd, 463 F. App'x 932 (Fed. Cir. 2012); Veryzer v.
Sec’y of Health & Human Servs., No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr.
Apr. 29, 2011), mot. for review den’d, 100 Fed. Cl. 344, 356 (2011), aff’d without opinion, 475
Fed. App’x 765 (Fed. Cir. 2012).

The third Althen prong requires establishing a “proximate temporal relationship” between
the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to the
phrase “medically-acceptable temporal relationship.” Id. A petitioner must offer “preponderant
proof that the onset of symptoms occurred within a timeframe which, given the medical
understanding of the disorder’s etiology, it is medically acceptable to infer causation.” Bazan v.
Sec'y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for what
is a medically acceptable timeframe must also coincide with the theory of how the relevant vaccine
can cause an injury (Althen prong one’s requirement). Id. at 1352; Shapiro v. Sec’y of Health &
Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand, 105 Fed. Cl. 353 (2012),
aff’d mem., 2013 WL 1896173 (Fed. Cir. 2013); Koehn v. Sec'y of Health & Human Servs., No.
11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review den’d (Fed. Cl.
Dec. 3, 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014).

B. Law Governing Analysis of Fact Testimony

The process for making determinations in Vaccine Program cases regarding factual issues
begins with consideration of the medical records. Section 11(c)(2). The special master is required
to consider “all [] relevant medical and scientific evidence contained in the record,” including “any
diagnosis, conclusion, medical judgment, or autopsy or coroner’s report which is contained in the
record regarding the nature, causation, and aggravation of the petitioner’s illness, disability, injury,
condition, or death,” as well as “the results of any diagnostic or evaluative test which are contained
in the record and the summaries and conclusions.” Section 13(b)(1)(A). The special master is then
required to weigh the evidence presented, including contemporaneous medical records and
testimony. See Burns v. Sec’y of Health & Human Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (it is
within the special master’s discretion to determine whether to afford greater weight to
contemporaneous medical records than to other evidence, such as oral testimony surrounding the
events in question that was given at a later date, provided that such a determination is evidenced
by a rational determination).

Medical records that are created contemporaneously with the events they describe are
presumed to be accurate and “complete” (i.e., presenting all relevant information on a patient’s
health problems). Cucuras, 993 F.2d at 1528; Doe/70 v. Sec’y of Health & Human Servs., 95 Fed.
Cl. 598, 608 (2010) (“[g]iven the inconsistencies between petitioner’s testimony and his
contemporaneous medical records, the special master’s decision to rely on petitioner’s medical
27
records was rational and consistent with applicable law”), aff’d, Rickett v. Sec’y of Health &
Human Servs., 468 F. App’x 952 (Fed. Cir. 2011) (non-precedential opinion). This presumption is
based on the linked propositions that (i) sick people visit medical professionals; (ii) sick people
honestly report their health problems to those professionals; and (iii) medical professionals record
what they are told or observe when examining their patients in as accurate a manner as possible,
so that they are aware of enough relevant facts to make appropriate treatment decisions. Sanchez
v. Sec’y of Health & Human Servs., No. 11-685V, 2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr.
Apr. 10, 2013); Cucuras v. Sec'y of Health & Human Servs., 26 Cl. Ct. 537, 543 (1992), aff'd, 993
F.2d 1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would fail to accurately
report the onset of their daughter’s symptoms. It is equally unlikely that pediatric neurologists,
who are trained in taking medical histories concerning the onset of neurologically significant
symptoms, would consistently but erroneously report the onset of seizures a week after they in fact
occurred”).

Accordingly, if the medical records are clear, consistent, and complete, then they should
be afforded substantial weight. Lowrie v. Sec’y of Health & Human Servs., No. 03-1585V, 2005
WL 6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed, contemporaneously medical
records are generally found to be deserving of greater evidentiary weight than oral testimony –
especially where such testimony conflicts with the record evidence. Cucuras, 993 F.2d at 1528;
see also Murphy v. Sec’y of Health & Human Servs., 23 Cl. Ct. 726, 733 (1991), aff'd, 968 F.2d
1226 (Fed. Cir.), cert. den’d, Murphy v. Sullivan, 506 U.S. 974 (1992) (citing United States v.
United States Gypsum Co., 333 U.S. 364, 396 (1947) (“[i]t has generally been held that oral
testimony which is in conflict with contemporaneous documents is entitled to little evidentiary
weight.”)).

However, there are situations in which compelling oral testimony may be more persuasive
than written records, such as where records are deemed to be incomplete or inaccurate. Campbell
v. Sec’y of Health & Human Servs., 69 Fed. Cl. 775, 779 (2006) (“like any norm based upon
common sense and experience, this rule should not be treated as an absolute and must yield where
the factual predicates for its application are weak or lacking”); Lowrie, 2005 WL 6117475, at *19
(“[w]ritten records which are, themselves, inconsistent, should be accorded less deference than
those which are internally consistent”) (quoting Murphy v. Sec’y of Health & Human Servs., 23
Cl. Ct. 726, 733 (1991), aff'd per curiam, 968 F.2d 1226 (Fed. Cir. 1992)). Ultimately, a
determination regarding a witness’s credibility is needed when determining the weight that such
testimony should be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec’y of Health & Human
Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

When witness testimony is offered to overcome the presumption of accuracy afforded to
contemporaneous medical records, such testimony must be “consistent, clear, cogent, and
compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec’y of Health & Human
28
Servs., No. 90-2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)). In
determining the accuracy and completeness of medical records, the Court of Federal Claims has
listed four possible explanations for inconsistencies between contemporaneously created medical
records and later testimony: (1) a person’s failure to recount to the medical professional everything
that happened during the relevant time period; (2) the medical professional’s failure to document
everything reported to her or him; (3) a person’s faulty recollection of the events when presenting
testimony; or (4) a person’s purposeful recounting of symptoms that did not exist. La Londe v.
Sec’y Health & Human Servs., 110 Fed. Cl. 184, 203-04 (2013), aff’d, 746 F.3d 1334 (Fed. Cir.
2014). In making a determination regarding whether to afford greater weight to contemporaneous
medical records or other evidence, such as testimony at hearing, there must be evidence that this
decision was the result of a rational determination. Burns, 3 F.3d at 417.

C. Analysis of Expert Testimony

Establishing a sound and reliable medical theory often requires a petitioner to present
expert testimony in support of his claim. Lampe v. Sec’y of Health & Human Servs., 219 F.3d
1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is usually evaluated according to
the factors for analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509
U.S. 579, 594-96 (1993). See Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328, 1339
(Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir.
1999)). “The Daubert factors for analyzing the reliability of testimony are: (1) whether a theory or
technique can be (and has been) tested; (2) whether the theory or technique has been subjected to
peer review and publication; (3) whether there is a known or potential rate of error and whether
there are standards for controlling the error; and (4) whether the theory or technique enjoys general
acceptance within a relevant scientific community.” Terran, 195 F.3d at 1316 n.2 (citing Daubert,
509 U.S. at 592-95).

The Daubert factors play a slightly different role in Vaccine Program cases than they do
when applied in other federal judicial fora (such as the district courts). Daubert factors are usually
employed by judges (in the performance of their evidentiary gatekeeper roles) to exclude evidence
that is unreliable and/or could confuse a jury. In Vaccine Program cases, by contrast, these factors
are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health
& Human Servs., 94 Fed. Cl. 53, 66-67 (2010) (“uniquely in this Circuit, the Daubert factors have
been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of
expert testimony already admitted”). The flexible use of the Daubert factors to evaluate the
persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g., Snyder, 88
Fed. Cl. at 742-45. In this matter (as in numerous other Vaccine Program cases), Daubert has not
been employed at the threshold, to determine what evidence should be admitted, but instead to
determine whether expert testimony offered is reliable and/or persuasive.

29
 Respondent frequently offers one or more experts of her own in order to rebut a petitioner’s
case. Where both sides offer expert testimony, a special master’s decision may be “based on the
credibility of the experts and the relative persuasiveness of their competing theories.”
Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing
Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert’s conclusion
“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too
great an analytical gap between the data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743
(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 146 (1997)); see also Isaac v. Sec’y of Health & Human
Servs., No. 08-601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot. for
review den’d, 108 Fed. Cl. 743 (2013), aff’d, 540 Fed. App’x 999 (Fed. Cir. 2013) (citing Cedillo,
617 F.3d at 1339). Weighing the relative persuasiveness of competing expert testimony, based on
a particular expert’s credibility, is part of the overall reliability analysis to which special masters
must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at 1325-26
(“[a]ssessments as to the reliability of expert testimony often turn on credibility determinations”);
see also Porter v. Sec’y of Health & Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this
court has unambiguously explained that special masters are expected to consider the credibility of
expert witnesses in evaluating petitions for compensation under the Vaccine Act”).

In determining whether a particular expert’s testimony was reliable or credible, I may
consider whether the expert offers an opinion that exceeds his training or competence. Walton v.
Sec’y of Health & Human Servs., No. 04-503V, 2007 WL 1467307, at *17-18 (Fed. Cl. Spec. Mstr.
Apr. 30, 2007) (otolaryngologist not well suited to testify about disciplines other than her own
specialty). While (in keeping with the liberality with which evidence offered in Vaccine Program
cases is treated) I heard and have considered all of the testimony of the experts offered at the
entitlement hearing, I may properly evaluate, and give appropriate weight to, whether certain
testimony is beyond a particular expert’s purview. See, e.g., King v. Sec’y of Health & Human
Servs., No. 03-584V, 2010 WL 892296, at *78-79 (Fed. Cl. Spec. Mstr. Mar. 12, 2010)
(petitioner’s expert far less qualified to offer opinion on general causation issues pertaining to
autism than specific issues pertaining to the petitioner’s actual medical history, given the nature of
the expert’s qualifications). An opinion does not obtain legitimacy in the Program simply because
it comes out of the mouth of a medical doctor – especially if that opinion concerns matters well
outside the doctor’s expertise.

D. Consideration of Medical Literature

Both parties filed medical and scientific literature in this case, including many articles
(such as those discussing molecular mimicry and protein sequences in vaccines) that do not factor
into the outcome of this decision. While I have reviewed all of the medical literature submitted in
this case, I only discuss those articles that are most relevant to my determination and/or are central
to Petitioners’ case – just as I have not exhaustively discussed every individual medical record
30
filed. Moriarty v. Sec’y of Health & Human Servs., No. 2015-5072, 2016 WL 1358616, at *5 (Fed.
Cir. Apr. 6, 2016) (“[w]e generally presume that a special master considered the relevant record
evidence even though he does not explicitly reference such evidence in his decision”) (citation
omitted); see also Paterek v. v. Sec’y of Health & Human Servs., 527 F. App'x 875, 884 (Fed. Cir.
2013) (“[f]inding certain information not relevant does not lead to — and likely undermines —
the conclusion that it was not considered”).30

V. ANALYSIS

A. Petitioners Did Not Establish that A.P.M. Suffered from Any Form of
Cerebral Folate Deficiency

Putting aside the allegedly causative role the DTaP vaccine played in A.P.M.’s regression,
Petitioners’ entire causation theory hinges upon acceptance of either Dr. Frye’s diagnosis that
A.P.M. suffered from a cerebral folate deficiency, or Dr. Shafrir’s alternative proposal that A.P.M.
suffered from some less-studied “syndrome” characterized by heightened levels of folate receptor
blocking autoantibodies. Respondent squarely contests that A.P.M. had anything close to a
cerebral folate deficiency. It therefore makes sense to consider at the outset whether Petitioners
have successfully established in this case that A.P.M. suffered from any form of cerebral folate
deficiency before evaluating whether the Athen test prongs have been satisfied. Broekelschen, 618
F.3d at 1346 (when an injury or diagnosis is disputed, and “the proposed injuries differ
significantly in their pathology,” the special master may “first find which of [the] diagnoses was
best supported by the evidence presented in the record before applying the Althen test so that the

30
In certain instances, Petitioners have emphasized, in their post-hearing filings, findings contained in literature either
not offered as part of their main case, or buried within another document, and thus not highlighted for my attention as
significant, contrary to the Pre-Hearing Order in this action. See Order, dated Dec. 18, 2014 (ECF No. 80) at 2 (setting
deadline for submission of medical literature, directing parties to highlight significant portions thereof, and warning
parties that “[a]bsent compelling circumstances, any exhibits not previously filed, nor timely filed and served by the
date specified above, will not be admitted at the hearing”).

Thus, Exhibit 72 (filed November 5, 2015) is a 102-page compendium of materials pulled from the website of an
entity that apparently tests folate receptor blocking autoantibodies (offered in response to the question of whether the
blocking antibody testing could be replicated, since here A.P.M. was only tested a single time). Hidden within that
compendium is yet another Ramaekers-authored article – V.T. Ramaekers, et al., Folinic Acid Treatment for
Schizophrenia Associated With Folate Receptor Autoantibodies, Mol. Genet. Metab. (2014),
http://dx.doi.org/10.1016/j.ymgme.2014.10.002 (“Ramaekers IV”). Petitioners in their post-hearing briefing now
address this article at length, suggesting that a “low normal” folate level measured in CSF can still be significant for
purposes of determining if an individual suffers from a cerebral folate deficiency. Post-Hearing Brief at 24-26. I
acknowledge that the point was referenced by Dr. Shafrir in his testimony (and in response to Dr. Wiznitzer’s
testimony about whether the blocking autoantibody testing conducted for A.P.M. could have been repeated (Tr. at
289)), and I have given it consideration in my decision. Nevertheless, it constitutes a piece of evidence that should
have been identified before the hearing, since all parties understood that the significance of A.P.M.’s tested MTHF
levels was disputed. I find the casual disregard with which Petitioners treated my Order on literature filed in this case
to be inappropriate, and admonish counsel in the future to be more exacting in identifying literature his clients will
rely on in advance of hearing.
31
special master could subsequently determine causation relative to the injury”).

The parties do not dispute for the most part what constitutes a cerebral folate deficiency.
Ramaekers I defines it as “any neuropsychiatric condition associated with low levels of [MTHF],
the active folate metabolite in the [CSF],” in comparison with normal folate levels measured in
blood serum. Ramaekers I at 1985; see also Ramaekers III at 346. The form of the condition with
the most bearing on Petitioners’ claim is infant-onset cerebral folate deficiency, a neurologic
syndrome that commonly develops within four to six months after birth. Ramaekers I at 1985. This
is because much of the literature offered by Petitioners for the core of their theory that a cerebral
folate deficiency could result in autism involved children who were diagnosed with infant-onset
cerebral folate deficiency. See Ramaekers I at 1985, 1987; Ramaekers II at 277; Ramaekers III at
346.

Infant-onset cerebral folate deficiency is characterized by “marked irritability, slow head
growth, psychomotor retardation, cerebellar ataxia, . . . dyskinesias . . . ,” and can in some cases
(usually after the child is three years old) result in optic atrophy and blindness. Ramaekers I at
1985. Some children already diagnosed with this kind of infant-onset cerebral folate deficiency
(and the severe symptoms outlines above) have also been found to display autistic symptoms as
well, although no clear relationship has been drawn between children suffering from idiopathic
autism and folate deficiency. Ramaekers III at 346; Moretti at 1175 (“these patients with CFD
clearly differ in their neurological presentations and complexity from those with autism alone”).
It is evident from both the literature filed in this case, as well as the testing benchmarks used to
evaluate the significance of MTHF levels, that infant-onset cerebral folate deficiency offers the
proper paradigm for reference in this case. See, e.g., Pet’rs’ Ex. 16 at 38.

There is also scientific support for the effect that blocking autoantibodies can have on the
process of delivering folic acid to the brain (the relevant focus of analysis for present purposes).
As Dr. Wiznitzer explained, the folate receptor acts as a “parking space” that transports folic acid
from the blood to the central nervous system. Tr. at 287-88. Among other places in the body, these
receptors are found on the surface of “epithelial cells on the choroid plexus”31 – a network of blood
vessels in the brain’s ventricles that produces CSF. Ramaekers I at 1985; Tr. at 166. High levels
of folate receptor-blocking autoantibodies can impede the transportation of folic acid into the
central nervous system – evidenced by below-normal levels of MTHF levels in the CSF, in
comparison to the amounts in the blood serum. Tr. at 287-88; Ramaekers I at 1985-86. This lack
of folic acid in the central nervous system causes the symptoms associated with the infant-onset
form of cerebral folate deficiency discussed in Petitioners’ literature. Tr. at 287-88.

31
The choroid plexus is the part of the brain that makes cerebrospinal fluid. Dorland’s at 1463.
32
 Despite the above, the evidence does not support Dr. Frye’s cerebral folate deficiency
diagnosis. A.P.M.’s MTHF levels were unquestionably within a normal range. Pet’rs’ Ex. 16 at
22. In addition, and as Dr. Frye himself admitted, other than autism A.P.M. displayed none of the
symptoms that would otherwise characterize infant-onset cerebral folate deficiency. Id. Even Dr.
Shafrir could not accept Dr. Frye’s diagnosis – a telling admission for a testifying expert. Tr. at
204 (“I just think we should reserve the term ‘CFD’ to the original description of the syndrome . .
. and if we stick to it, [A.P.M.] did not have CFD. He just has autism”). Certainly I am not bound
to accept Dr. Frye’s diagnosis merely because he was one of A.P.M.’s treaters – especially in light
of more persuasive contrary evidence. Snyder, 88 Fed. Cl. at 746 n.67. At bottom, Petitioners
placed inordinate weight on the very fact that A.P.M. had a developmental problem as proof of its
purported cause (cerebral folate deficiency) (Tr. at 96, 100, 103-105), even though this component
for the diagnosis stood alone, without evidence of any of the other clinical criteria relevant to a
cerebral folate deficiency diagnosis.

Petitioners’ arguments to the contrary were unpersuasive. For example, Petitioners
attempted to cast doubt on the reliability of A.P.M.’s CSF tests, asserting that the sample tested
was contaminated by red blood cells that resulted in a false-normal reading. Yet the medical
records filed in the case strongly suggest that multiple samples of A.P.M.’s CSF were taken at one
time, thereby making it likely that the CSF folate measurements were not thrown off by a single
poor sample. Pet’rs’ Ex. 16 at 10-11. Those records further note that the lab technicians themselves
were aware of the problem with the purportedly tainted sample (Pet’rs’ Ex. 16 at 10 (“CSF was
initially slightly blood-tinged but cleared”) (emphasis added)), allowing the reasonable inference
that had the sample truly been contaminated, it would not have been tested. And the procedure was
deemed successful when the sample was drawn, further bulwarking the test’s reliability. Pet’rs’
Ex. 6 at 11. Dr. Wiznitzer also convincingly testified (based upon his own clinical experience with
lumbar puncture procedures and bulwarked by documentary evidence) that a lab would not test a
contaminated sample, or would separate the constituent elements in the CSF before testing. Tr. at
439. The weight of the evidence supports the conclusion that A.P.M.’s CSF folate test results are
reliable.

Petitioners also argued (amplified in their post-hearing filings) that “a finding of low
normal folate levels in the [CSF] of patients does not operate to exclude or vitiate the diagnosis of
cerebral folate deficiency, especially when other factors are present.” Post-Hearing Brief at 26
(citing V.T. Ramaekers, et al., Folinic Acid Treatment for Schizophrenia Associated With Folate
Receptor Autoantibodies, Mol. Genet. Metab. (2014),
http://dx.doi.org/10.1016/j.ymgme.2014.10.002 (“Ramaekers IV”)). But Dr. Shafrir failed to
reliably or persuasively explain why a low normal reading could still be significant, especially
since he personally lacked the expertise to interpret the significance of a lower normal result. His
other testimony disputing Dr. Frye’s conclusion (which simply accepts the CSF test results as
33
accurate and does not qualify the meaning of a low normal result) that A.P.M. even had a cerebral
folate deficiency, given the lack of other corroborative evidence, also undermines his “low normal”
argument.

Ramaekers IV itself does not aid Petitioners’ argument. Ramaekers IV involved testing
for CSF folate levels and the presence of the folate receptor blocking autoantibodies in 18 patients,
all of whom were older than A.P.M. and all of whom were diagnosed with schizophrenia – a
condition not comparable to A.P.M.’s ASD beyond its general neurologic underpinnings.
Ramaekers IV; Pet’rs’ Ex. 72 at 96-98. Putting aside that such factors immediately highlight the
danger of overstating the article’s relevance herein, the larger problem is that Ramaekers IV did
not focus at all on the significance of a low normal folate reading in the CSF. Instead, Ramaekers
IV concerned itself (in part) with the relationship that the blocking autoantibodies have to the
levels of folate measured in the CSF, as fluctuating levels of the antibodies can change how much
folate is transported to the brain over time (and subsequently reflected in CSF testing). Even on
that topic, the article was somewhat inconclusive. Ramaekers IV (Pet’rs’ Ex. 72 at 100 (“our data
do not suggest a close correlation between the titer of FRα antibodies and CSF MTHF values at
the time of the spinal tap, [but] it may well be that CSF MTHF concentrations reflect the
cumulative result of blocked MTHF transfer taking place during the days or weeks prior to the
spinal tap”)). Here, other than the “low normal” folate levels, there is no evidence of fluctuation
of blocking autoantibodies, and Petitioners did not otherwise establish what A.P.M.’s levels were
at the time of his vaccinations (which occurred four years before the autoantibody testing).
Petitioners are thus left with a normal folate reading, which rebuts their claim that A.P.M. suffered
from a cerebral folate deficiency.

Petitioners’ fallback argument – that the elevated levels of blocking autoantibodies as
determined in 2010 suggest that A.P.M. suffered from some milder, less-understood form of
cerebral folate deficiency – fares no better. As a threshold matter, Dr. Shafrir’s affirmation of the
existence of such a clinically-significant syndrome is unsupported by any filed medical or
scientific literature. No evidence was offered showing that a child who did not suffer from an
infant-onset kind of cerebral folate deficiency, like A.P.M., might nevertheless experience
developmental regression simply because the child displayed heightened levels of the blocking
autoantibodies, without any other indicia of a cerebral folate deficiency beyond autism. Instead,
the filed literature all involved patients with a clear, agreed-upon cerebral folate deficiency
diagnosis, established by evidence of clinical factors lacking for A.P.M.

Ramaekers I, for example – the piece of literature most cited in this action – involved a
study of 28 children much younger than A.P.M. at the time of vaccination, none of whom were
shown to have been vaccinated first, but all of whom were diagnosed with infant-onset cerebral
folate deficiency, based on obvious clinical criteria which they had displayed in the months after
34
birth – unlike A.P.M., who had no such symptoms even at 18 months of age, when his language
loss is alleged to have begun. Ramaekers I at 1986-87. Thus, although Ramaekers I did determine
that the studied children possessed heightened levels of the blocking autoantibody, and proposed
that the presence of those autoantibodies might have significance, its studied sample would not
have included A.P.M., as Dr. Shafrir readily admitted. Tr. at 212. As a result, any association
Ramaekers I drew between possession of a heightened level of the autoantibodies and development
of cerebral folate deficiency cannot be reasonably applied to A.P.M.

The other literature was similarly unsupportive of Dr. Shafrir’s proposal of the existence
of a blocking autoantibodies syndrome. In each instance, the studied patients found to possess
heightened levels of the antibodies were unquestionably suffering from infant-onset cerebral folate
deficiency, presenting with a number of symptoms far more severe than what A.P.M. experienced.
The only article that comes close to evaluating the matter from the other end of the spectrum (the
impact of the presence of the autoantibodies and their relationship to autism) is Frye, which at best
(and based, by the authors’ own admission, on a biased sample32) finds some association between
children with an ASD and the presence of the autoantibodies, without considering the
autoantibodies’ causal role, or even what produced them in the first place. Frye at 378.

Arguments that A.P.M.’s allegedly successful folinic acid treatments established indirectly
that he likely suffered from some form of cerebral folate deficiency were similarly unpersuasive.
Post-Trial Brief at 30-31. The claims of A.P.M.’s improvement as a result of the treatments were
largely anecdotal, coming mostly from T.M. & R.R.M themselves, or were mainly linked to the
elimination of milk from his diet. Tr. at 139-40. Respondent, by contrast, pointed to record
evidence (in particular, language and communication assessments by trained developmental
professionals performed on A.P.M. in 2011) that suggested no dramatic improvements of the kind
claimed by Petitioners. Tr. at 295-97 (citing Resp’t’s Ex. A at 110 (Dr. Wiznitzer’s expert report,
in which he opines that the rapid improvements T.M. reported A.P.M. having experienced after
beginning to take folinic acid are contradicted by notations in the contemporaneous medical
records)). The Petitioners otherwise could offer no additional autoantibody testing results to
quantify the level of autoantibodies after A.P.M.’s treatments or corroborate their purported
ameliorative effects. And (as discussed below), it is just as likely (to the extent the autoantibodies
were in fact causing A.P.M.’s developmental problems) that the milk reduction was the reason for
their diminishment. Thus, the purported benefits of these treatments are too subjective, and their
results too uncertain, to constitute reliable proof that A.P.M. in fact suffered from a cerebral folate
deficiency, especially given the strong evidence (such as normal folate levels and lack of severe

32
The children tested for the presence of the autoantibodies in Frye were, like A.P.M., being treated by doctors like
Dr. Frye who were actively exploring the relationship between cerebral folate deficiency and autism, and were even
tested at the same SUNY Downstate lab that tested A.P.M. Frye at 370. Frye’s authors thus admitted that the test was
potentially subject to “referral bias.” Frye at 378.
35
symptoms) going the other direction.

Beyond all of the above, the determination (treated by Petitioners as unassailable) that
A.P.M.’s blocking autoantibody levels were “very high” (Post-Trial Brief at 8-9) is itself an
unreliable basis for Petitioners’ theory. A single test – performed in October 2010, more than four
years after the July 2006 DTaP vaccination – is the sole evidence offered for this conclusion, but
its temporal remoteness from the date of vaccination is enough to call into question the implication
of its findings. In effect, Petitioners are proposing that an autoimmune process initiated in 2006
was sufficiently robust and persistent to be measurable in a clinically significant manner four years
later. Yet, at the same time (and in their effort to defend the meaningful nature of the “low normal”
MTHF measurements from A.P.M.’s lumbar puncture), Petitioners also argue that folate levels
fluctuate as autoantibody levels change. Post-Trial Brief at 24-26; Tr. at 458-60 (“the important
thing, they showed dramatic fluctuation in the level of the antibodies”). If so, then how can a 2010
test ever reveal what autoantibody levels were four years before, and whether the levels were at
that time sufficiently high to be pathologic? Moreover, the autoantibody test results were just
outside the moderate range, rather than facially high in the manner emphasized by Petitioners. To
the extent the results were later characterized as alarmingly high by Dr. Frye, the record clearly
establishes that he did so in error (confusing a 1.19 titer level for 1.9) (compare Pet’rs’ Ex. 16 at
38 with Pet’rs’ Ex. 16 at 35).33

B. Petitioners Did Not Adequately Rebut Evidence
That Bovine Milk Can Promote Blocking Autoantibodies

Petitioners sought to bulwark their argument about the role the blocking autoantibodies
played in A.P.M.’s developmental regression with assertions about the effectiveness of treatments
intended to reduce the antibodies, such as medicines containing folinic acid, or diet alterations to
eliminate bovine milk. But in so doing, they highlighted Respondent’s arguments that bovine milk
could also have contributed to A.P.M.’s elevated blocking antibody titer levels.

The single piece of medical literature most relied upon by Petitioners in this case,
Ramaekers I, clearly acknowledges a relationship between bovine milk and the production of the
blocking autoantibodies. Ramaekers I at 1991. Ramaekers III goes on to explicitly evaluate that
relationship, exploring the impact of the reduction of bovine milk consumption on the antibody
levels. Ramaekers III at 346 (“[i]n the CFD syndrome, the clinical manifestations typically occur
after the switch to bovine milk”). It was also undisputed that the homology between certain bovine

33
In addition, although Dr. Frye did not testify at trial, there are other discrepancies in his characterization of testing
results (such as his later inflation of the “low normal” folate levels reflected in A.P.M.’s CSF testing as actually
“below” normal) that lead me to question the overall reliability of some of the conclusions he reached. Pet’rs’ Ex. 14
at 3; Pet’rs’ Ex. 46 at 1. The fact that he was literally one of A.P.M.’s “treaters” (albeit four years after the vaccination
in question) is reasonably weighed against medical record evidence undercutting his assertions.
36
milk proteins and the folate receptor protein sequences is high – far more so than what Petitioners
argued was sufficient for the molecular mimicry process to work under their theory. Tr. at 185,
314-16. Because Petitioners rely on a five-peptide sequence to argue molecular mimicry was
sufficient to cause an autoimmune reaction to the DTaP vaccine, they cannot credibly dispute that
even greater homology between milk proteins and the folate receptors would not have at least the
same effect.

In addition, the facts of this case are not inconsistent with the proposition that bovine milk
might have contributed to A.P.M.’s receptor-blocking autoantibody levels. T.M.’s testimony
established that she began feeding A.P.M. with bovine milk within months after he received the
DTaP vaccine in 2006. Tr. at 72-73. Removing milk from A.P.M.’s diet purportedly resulted in
improvement in his development and related behavior. Id. at 470-48, 109. And the four-year lag
between when A.P.M.’s autism is alleged to have begun and the date of the autoantibody testing
further allows for the possibility that milk consumption in the intervening time period had
something to do with A.P.M.’s autoantibody levels.

In response to such persuasive evidence, Dr. Shafrir simply offered sweeping denials. He
argued that if bovine milk did in fact play a role in the blocking autoantibody production, A.P.M.
should have had problems long before his regression symptoms actually manifested (since he was
breast-fed from birth) (Tr. at 185-86), or more globally that all children fed bovine milk should be
autistic. Id. at 110; Reply at 11. But such arguments only highlight the weakness of Petitioners’
theory, which invests heavily in the concept that the presence of high levels of autoantibodies for
A.P.M. is significant. If Petitioners’ argument that the DTaP vaccine could possibly cause an
increase in the production of the autoantibodies sufficient to trigger a developmental regression is
accepted, then how can more scientifically-reliable evidence – evidence cited by Petitioners
themselves – that milk plausibly causes the production of those autoantibodies be rejected as
preposterous?34

To be sure – I am not determining in this case that Respondent has established bovine milk
as an alternative cause of A.P.M.’s elevated blocking autoantibody levels, as measured in October
2010. The evidence does not permit that conclusion, nor have I found that Petitioners carried their
prima facie case sufficiently to shift the burden to Respondent. Gerhardt v. Sec'y of Health &

34
Petitioners’ shrugging off the science linking bovine milk to the blocking autoantibodies is also contrary to the very
legal standards applicable herein. It is well-recognized in the Vaccine Program that, “in a field bereft of complete and
direct proof of how vaccines affect the human body” (Althen, 418 F.3d at 1280), claimants seek to prove something
that is inherently uncommon – an adverse reaction to a vaccine sufficient to cause significant injury – and for this
reason, petitioners are allowed to rely on circumstantial evidence, not required to submit epidemiologic proof of a
vaccine’s capacity for harm, etc. Yet in this case, Petitioners attempt to turn that presumption on its head, arguing that
an otherwise scientifically-reliable explanation for the role of bovine milk in the production of the blocking
autoantibodies must be rejected because its purported effects (autism) are insufficiently common.

37
Human Servs., No. 9-180V, 2014 WL 4712690, at *8 (Fed. Cl. Spec. Mstr. Aug. 29, 2014) (once
a petitioner has satisfied the three prongs of Althen, “the burden shifts to the Respondent to
demonstrate by preponderant evidence that the petitioner's injury is ‘due to factors unrelated to the
administration of the vaccine’”). But it is well-recognized that Respondent may offer evidence, or
point to existing evidence in the record, that contradicts or weakens a petitioner’s evidence, and in
so doing demonstrate that the petitioner cannot meet her overall burden, without the burden of
proof ever shifting. Stone v. Sec’y of Health & Human Servs., 676 F.3d 1373, 1379 (Fed. Cir.
2012) (“[o]ur decisions support the commonsense proposition that evidence of other possible
sources of injury can be relevant not only to the ‘factors unrelated’ defense, but also to whether a
prima facie showing has been made that the vaccine was a substantial factor in causing the injury
in question”); La Londe v. Sec’y of Health & Human Servs., 110 Fed. Cl. 184, 198 (2013)
(“[r]egardless of whether the burden ever shifts to the respondent, the special master may consider
the evidence presented by the respondent” when determining if petitioner’s initial burden has been
met), aff’d, 736 F.3d 1334 (Fed. Cir. 2014). Respondent has done so here, but Petitioners have
failed to persuasively address that showing.

C. Petitioners Have not Satisfied the Althen Prongs

Petitioners’ case heavily relied upon the finding that A.P.M. suffered from cerebral folate
deficiency or some milder variant, so my contrary conclusions are fatal to their claim. Yet review
of the three Althen prongs for establishing Non-Table causation reveals that Petitioners also would
not be able to prevail on their claim due to other evidentiary failures.

1. Petitioners did not Establish a Reliable and Plausible Causation Theory

Highly relevant to my analysis is Dr. Shafrir’s lack of expertise on the topics most relevant
to Petitioners’ causation theory. Dr. Shafrir has competence to testify on a variety of neurological
conditions, including autism itself, and to draw upon his experience in proposing possible causes
for a child’s developmental regression based on the case’s record. But by his own admission, he
has no personal experience in studying or diagnosing cerebral folate deficiencies, or how the
conditions might relate to autism, and thus his testimony largely tracked the scientific or medical
literature offered by Petitioners and was otherwise speculative. Tr. at 228. This greatly diminished
the evidentiary value of the opinions he offered in this action and the resulting weight I gave
them.35 Murfam Farms, LLC ex rel. Murphy v. United States, No. 06-245T, 2008 WL 4725468, at

35
Notably, this case is not the first time Dr. Shafrir has provided expert testimony in support of the claim that a child’s
autism was vaccine-caused, based on the concept that the vaccine precipitated an autoimmune condition. Never,
however, has he been found to be persuasive in so doing, and his expertise on the subject has repeatedly been called
into question. See, e.g., R.V. & E.V., parents & natural guardians of L.V., a minor v. Sec’y of Health & Human Servs.,
No. 08-504V, 2016 WL 3882519 (Fed. Cl. Spec. Mstr. Feb. 19, 2016), mot. for review den’d, 127 Fed. Cl. 136 (2016),
appeal docketed, No. 16-2400 (Fed. Cir. July 29, 2016); R.K. on behalf of A.K. v. Sec’y of Health & Human Servs.,
38
*1 (Fed. Cl. Sept. 19, 2008) (“[u]nder Daubert . . . , reliable expert testimony is grounded in the
methods and procedures of scientific, technical, or specialized knowledge in the expert’s
discipline, and is not merely subjective belief or unsupported speculation”).

Beyond such expert issues, however, the substance of Petitioners’ medical theory was itself
unreliable on several levels. Overall, T.M. & R.R.M proposed that a child could develop some
form of cerebral folate deficiency after receiving the DTaP vaccine and that the deficiency in turn
would produce autistic regression. At least one link in their theory’s chain – the relationship
between folate levels in the CSF and the presence of blocking autoantibodies – was supported by
reasonable medical literature, as demonstrated by the Ramaekers series of articles, although these
studies largely involved children with symptoms far more closely associated with the condition
than anything A.P.M. displayed, limiting the overall weight associated by establishing the
existence of this relationship.

From there, however, Petitioners’ theory weakens considerably. In particular, Petitioners
lacked reliable and persuasive medical or scientific literature demonstrating a link between the
DTaP vaccine and the production of the blocking autoantibodies. Instead, Petitioners relied on
studies involving other vaccines and other illnesses, for the circumstantial proposition that because
vaccines can be linked to autoimmune conditions, the same occurred here. But the support offered
for the proposition was too attenuated, involving different vaccines, different illnesses, or different
circumstances. Partinen, for example, not only involved a different vaccine and injury
(narcolepsy), but also occurred in circumstances (admitted by Dr. Shafrir) where the vaccine’s
adjuvant was more likely than not the cause of the injury, or some genetic susceptibility specific
to the study subjects. Partinen at 7-8; Tr. at 141-45. Articles such as Agmon-Levin were simply
too broad in focus to constitute persuasive support for the theory offered in this case; simply
because other vaccines have been linked to autoimmune conditions does not mean the same can
be concluded to have occurred in this case.

The same deficiencies characterize the scientific support offered by Petitioners to suggest
a relationship between autism and cerebral folate deficiency. Articles like Moretti were
insufficiently powered to constitute reliable support for this part of the theory, given the seven-
subject sample size – not to mention the fact that a majority of the studied children displayed
symptoms produced by infant-onset cerebral folate deficiency that the parties agree were never
experienced by A.P.M. Moretti at 1171, 1176. The Frye article suffered from sample bias (given
that so many of the tested children were already receiving treatment from Dr. Frye himself as well

No. 03-0632V, 2015 WL 10936124 (Fed. Cl. Spec. Mstr. Sept, 28, 2015), mot. for review den’d, 125 Fed. Cl. 57
(2016), appeal docketed, No. 16-1609 (Fed. Cir. Feb. 23, 2016); see also Wright v. Sec'y of Health & Human Servs.,
No. 12-423V, 2015 WL 6665600, at *2 (Fed. Cl. Spec. Mstr. Sept. 21, 2015) (characterizing causation opinion offered
by Dr. Shafrir that child had experienced autoimmune encephalitis resulting in regression as “highly speculative,
unsupported, and completely unpersuasive”).
39
as like-minded treaters), and lacked a reasonable control group to gauge autoantibody levels in
children that did not suffer from an ASD. Frye at 371, 378. To the extent Petitioners relied upon
Frye because its reporting of the allegedly successful results of folinic acid treatment also suggests
(from a different angle) a relationship between autism and folate deficiency, the evidence of such
positive results was subjective, derived entirely from parental reports, and therefore insufficiently
reliable from a scientific standpoint.

The topic of molecular mimicry well illustrates the nature of Petitioners’ failure to carry
their overall causation theory burden. Proof of a mechanism by which a vaccine causes illness is
not necessary to establish a plausible scientific theory under the first Althen prong. Andreu, 569
F.3d at 1378-79; Knudsen, 35 F.3d at 551. Petitioners nevertheless devoted a great deal of hearing
time to presenting evidence intended to prove homology between components of the DTaP and
MMR vaccines and human proteins in the folate receptor cites. Tr. at 166-69; Post-Trial Brief at
19-24.36 In so doing, however, they relied on the testimony of an expert who not only lacked direct
experience on the topic, but who made a mistake about homology involving one of the relevant
vaccines (the MMR) that was significant enough to cause Petitioners to abandon the MMR vaccine
entirely at trial as a basis for their claim. Post-Trial Brief at 19 n.5.

Petitioners’ contradictory position on bovine milk’s role in the generation of the blocking
autoantibodies is glaring as well. Petitioners ask for a finding that a five-protein sequence common
to pertussis and the folate receptor sites was sufficiently homologous to initiate an autoimmune
process, while questioning evidence suggesting bovine milk’s role in the generation of those same
autoantibodies, based on an even greater demonstrated homology between protein sequences in
bovine milk and the folate receptors in the body. See generally Ramaekers III. And at the same
time, Petitioners also highlighted the allegedly salutary impact of removing milk from A.P.M.’s
diet.

In defending their causation theory, Petitioners shield themselves behind the more lenient
evidentiary standards in the Program (specifically in relation to Althen prong one) that, they
correctly state, do not require scientific certainty. Post-Trial Brief at 20, 32 (citing Althen, 418 F.3d
at 1280). Here, however, the evidence offered by Petitioners is notably weak in important respects,
failing to link those components of the theory that have somewhat more reliability or narrower
points. It was the failure of certain integral components of the theory that compel the determination

36
In their defense, Petitioners explained that they invested efforts in establishing the mechanism underlying their
theory in order to burnish the theory’s reliability overall. Post-Trial Brief at 20. Such efforts were misplaced, however
– for even if I accepted that sufficient homology existed for an autoimmune reaction to have theoretically occurred, I
would still find that the theory was unreliable for other reasons, given (a) a lack of evidence linking any vaccine to
production of the blocking autoantibodies, and (b) a lack of persuasive evidence linking the presence of the
autoantibodies (without other symptoms of cerebral folate deficiency) to the development of an ASD.

40
that the theory overall lacks plausibility and/or is unreliable from a scientific standpoint.

My conclusions herein do not occur in a vacuum, but are properly informed by the
similarities between Petitioners’ theory in this case and those of the many claimants who have
gone before. Since the resolution of the OAP cases, there have been numerous petitions attempting
to establish that a variety of vaccines cause autism or an ASD. See, e.g., Hardy v. Sec’y of Health
& Human Servs., No. 08-108V, 2015 WL 7732603, at *4-5 (Fed. Cl. Spec. Mstr. Nov. 3, 2015)
(petitioners failed to demonstrate that DTaP vaccine caused or significantly aggravated underlying
mitochondrial disease resulting in ASD); Miller v. Sec’y of Health & Human Servs., No. 02-235V,
2015 WL 5456093 (Fed. Cl. Spec. Mstr. Aug. 18, 2015) (petitioners failed to demonstrate that
several childhood vaccines caused encephalopathy or aggravated underlying mitochondrial
disease/dysfunction); Lehner, 2015 WL 5443461 (petitioners failed to demonstrate that flu vaccine
resulted in autoimmune encephalitis). As Special Master Hastings noted in the recent Hardy
decision, however, to date every post-OAP Non-Table claim seeking compensation for autism
injuries purportedly related to a vaccine that has been tried has failed. Hardy, 2015 WL 7732603,
at *4-5 (referencing eleven autism claims unsuccessfully tried (including Miller and Lehner), plus
six that were rejected (over the petitioners’ objections) without trial). In particular, theories that a
vaccine provoked an autoimmune reaction resulting in developmental problems have also failed
repeatedly. See, e.g., R.V. & E.V., parents & natural guardians of L.V., a minor v. Sec’y of Health
& Human Servs., No. 08-504V, 2016 WL 3882519 (Fed. Cl. Spec. Mstr. Feb. 19, 2016), mot. for
review den’d., 127 Fed. Cl. 136 (2016), appeal docketed, No. 16-2400 (Fed. Cir. July 29, 2016);
R.K. on behalf of A.K. v. Sec’y of Health & Human Servs., No. 03-0632V, 2015 WL 10936124
(Fed. Cl. Spec. Mstr. Sept, 28, 2015), mot. for review den’d, 125 Fed. Cl. 57 (2016), appeal
docketed, No. 16-1609 (Fed. Cir. Feb. 23, 2016). This case is no different.

2. The DTaP Vaccine Did Not Cause A.P.M.’s Regression.

The medical records suggest other weaknesses in Petitioners’ proof that support my
conclusion that they have not shown by a preponderance that the DTaP vaccine caused A.P.M.’s
developmental symptoms and ASD.

In particular, the record does not establish that A.P.M. experienced a reaction to the
vaccine sufficient to suggest he was undergoing an autoimmune process. All Petitioners could
point to were his initial regression symptoms – but they occurred (at the earliest) three months
from the July 2006 vaccination, with little to no prior temporal hints that A.P.M. was experiencing
any reaction to the DTaP vaccine. Thus, even if I credit T.M.’s assertions (corroborated somewhat
by records establishing phone calls) that she contacted A.P.M.’s pediatrician to report a post-
vaccination reaction she witnessed within the weeks immediately after the vaccination, the record
is devoid of evidence that A.P.M.’s symptoms were more than a transient reaction to the vaccines
41
he received, rather than the start of some progressive autoimmune process sufficient to create the
blocking autoantibodies. Indeed, those autoantibodies were not measured until four years after
vaccination, and Petitioners provided no persuasive evidence explaining why such testing could
reliably predict what the autoantibody levels would have been when A.P.M. was 15-months old.
The overall record more persuasively suggests that any loss of skills A.P.M. experienced was
consistent with idiopathic autism, as proposed by Dr. Wiznitzer. Tr. at 265-66, 349.37

The post-vaccination months are especially telling in this respect, for they suggest A.P.M.’s
regression may have begun even later than that alleged by Petitioners. There is complete medical
record “radio silence” between the July 2006 date of A.P.M.’s DTaP vaccination and the next well-
child visit in October of that year – an absence of any suggestion that the vaccine was causing a
significant physiologic change in A.P.M. In addition, the record from that October visit alludes
only tangentially to a speech problem (in comparison to the subsequent record from April 2007).
Compare Pet’rs’ Ex. 21 at 32 (October 18, 2006, visit where listed as “very healthy”) with Pet’rs’
Ex. 1 at 7, 36 (April 14, 2007, visit documenting concerns regarding A.P.M.’s development
resulting in a referral to a specialist). Indeed, the bulk of the record evidence revealing T.M. &
R.R.M’ dawning awareness of A.P.M.’s regression was generated some time after the 18-month
visit, suggesting an even longer period of time had passed – but with no demonstrable reaction that
could serve as a persuasive link between the vaccination and the regression itself. This is too long
a period (especially given the lack of a persuasive theory) to find that any reaction to the DTaP
vaccine was causally-related.

37
For purposes of comparison, it is instructive to consider the facts of two of the only cases where the petitioners have
successfully established entitlement based on the argument that a vaccine reaction precipitated ASD-like symptoms.
While both cases involve Table claims (and therefore where causation was not at issue), they still provide some
example of the kind of evidence of severity that would be present if a child were in fact experiencing a reaction
sufficient to produce a developmental regression.

In Poling v. Sec’y of Health & Human Servs., No. 021466V, 2011 WL 678559 at *1 (Fed. Cl. Spec. Mstr. Jan. 28,
2011), for example, the child in question (who was later diagnosed with a mitochondrial disease) had received several
vaccinations (including MMR), and then within 48 hours developed a high fever that became low-grade over the next
several days, along with inconsolable crying, sleeplessness, and significant, noticeable motor problems that worsened
over the next several days. See R.V. & E.V., parents & natural guardians of L.V., a minor v. Sec’y of Health & Human
Servs., No. 08-504V, 2016 WL 3882519 at *36 (Fed. Cl. Feb. 19, 2016), review denied, decision aff'd sub nom. R.V.
v. Sec'y of Health & Human Servs., 127 Fed. Cl. 136 (2016). More recently, in Wright v. Sec'y of Health & Human
Servs., No. 12-423V, 2015 WL 6665600 (Fed. Cl. Spec. Mstr. Sept. 21, 2015) a child was proven, by a meticulous
factual showing, to have received Pentacel (a multi-virus vaccine), and then, on the drive home from the pediatric visit
at which the vaccination was administered, experienced a brief seizure, followed by a week in which he displayed a
decreased level of consciousness and lethargy, during which the child’s parents made many unsuccessful efforts to
convince his pediatric treaters of the severity of his condition. Wright, 2015 WL 6665600, at *12-16.

42
 3. Petitioners did not Establish a Medically Reasonable Timeframe

Petitioners appear to have conceded to some degree that they cannot propose either a
precise timeframe in which the autoimmune process leading to the production of blocking
autoantibodies should take place, or a timeframe in which the process in this case occurred. Thus,
Dr. Shafrir’s own expert report stated that the timeframe is “simply not known” (Pet’rs’ Ex. 53 at
2), and he reiterated that admission at trial. Tr. at 182-84.

Petitioners’ post-trial brief nevertheless asserts that this third Althen prong was met, but
relies on conclusory reasoning for this point. Thus, they argue that because A.P.M. displayed initial
symptoms of a developmental regression around three months after vaccination, it logically took
that long for the process to work. Post-Trial Brief at 37-38; Reply at 2-5. As already noted,
however, Petitioners were unable to offer a reliable, plausible causation theory supporting their
claim – including how long the process of production of the blocking autoantibodies would be
expected to take. They also did not offer any literature that would shed light on how long it would
actually take to inhibit folate transport to the brain38 sufficient to cause the developmental
regression seen with A.P.M.

At most, Petitioners offered articles such as Agmon-Levin, which makes the sweeping
statement that “the latency period between vaccination and autoimmunity ranges from days to
years” (Agmon-Levin at 648) – an all-inclusive timeframe that is entirely too broad to satisfy this
Althen prong. Pafford v. Sec’y of Health and Human Servs., 451 F.3d 1352, 1358 (Fed. Cir. 2006)
(“[w]ithout some evidence of temporal linkage, the vaccination might receive blame for events
that occur weeks, months, or years outside of the time in which scientific or epidemiological
evidence would expect an onset of harm”). Or they relied on the fact that there exist Table claims
permitting petitioners to establish entitlement based on evidence of autoimmune processes
occurring in shorter time periods (Tr. at 146) – even though the fact that such claims are actionable
cannot stand as proof in a Non-Table claim of what is “medically acceptable” under these
circumstances.

Program petitioners cannot satisfy the third Althen prong by reflexively arguing that the
actual span of time (reflected in the medical record) between vaccination and onset of illness
automatically establishes a “medically acceptable” timeframe. Koehn v. Sec'y of Health & Human
Servs., 773 F.3d 1239, 1244 (Fed. Cir. 2014) (characterizing expert opinion that the “time for
developing sufficient antibodies for immunity after receiving a vaccine is always consistent with

38
Dr. Shafrir admitted at hearing that not all folate receptors are located in the brain or are necessary for folate transport
(which he termed “redundancy”), and therefore the loss in function of many receptors would have no causal
relationship to the developmental symptoms at issue in this case. Tr. at 145.

43
injury from the vaccine” as “a proposition that, without any evidentiary support, we simply cannot
accept”). But that is plainly the Petitioners’ position in this case.

CONCLUSION

After review of the record in this case and having heard T.M.’s testimony, I can easily
conclude that T.M. & R.R.M are loving parents and have done all they can to care for A.P.M. and
treat his autism. I also have no reason to doubt their sincerity in pursuing this claim. But the factual
record simply does not support their contention that the DTaP-Hib vaccine had any connection to
A.P.M.’s developmental regression and ASD diagnosis, nor have the Petitioners established that
the vaccine could result in that kind of regression in the manner proposed by their theory, given
its heavy reliance of establishing that A.P.M. suffered from a mild form of cerebral folate
deficiency. There is no more than a temporal relationship between vaccination and regression –
not nearly enough to satisfy the Act’s otherwise-lenient preponderance evidentiary standard. This
is not a close case. Petitioners have not established entitlement to a damages award.39

IT IS SO ORDERED.
/s/ Brian H. Corcoran
Brian H. Corcoran
Special Master

39
Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by filing a joint notice renouncing their
right to seek review.
44