Vernacchio v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 08-504V
(To be published)

*****************************
*
R.V. and E.V., parents and natural guardians of * Special Master Corcoran
L.V., a minor, *
* Filed: February 19, 2016
Petitioners, *
* Entitlement Decision; Influenza
v. * (“Flu”) vaccine; Autism Spectrum
* Disorder (“ASD”); Mitochondrial
SECRETARY OF HEALTH AND * Disease; Autoimmune
HUMAN SERVICES, * Encephalopathy Following Fever
* or Vaccine.
*
Respondent. *
*
*****************************

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 July 11, 2008, R.V. and E.V. filed a petition on behalf of their minor child, L.V. seeking
compensation under the National Vaccine Injury Compensation Program (the “Vaccine
Program”).2 The Vs sought to establish that the influenza (“flu”) vaccine that L.V. received on
December 8, 2006, when he was 21 months old, caused an encephalopathy, and/or aggravated
L.V.’s alleged underlying mitochondrial disorder, resulting in L.V.’s physiological symptoms and

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) [hereinafter “Vaccine Act” or “the
Act”]. Individual section references hereafter will be to § 300aa of the Act.
subsequent developmental regression.

An entitlement hearing was held on April 13-14, 2015, and in the following months 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 BACKGROUND3

A. Birth and Early Medical History.

L.V. was born at term by caesarean section on March 15, 2005, at Abington Memorial
Hospital in Abington, Pennsylvania, presenting with no abnormalities. Pet’rs’ Ex. 1 at 7, 15-16.
L.V. passed his hearing screening on March 16, 2005, and was routinely discharged on March 19,
2005. Pet’rs’ Ex. 2 at 4-5, 7. Throughout the first weeks of L.V.’s life, he had red and swollen eyes
with yellow drainage. Pet’rs’ Ex. 3 at 5. He was ultimately diagnosed with acute nasolacrimal
stenosis,4 and then subsequently diagnosed with gastro-esophageal reflux 5 during his first well-
child appointment on March 31, 2005. Id. at 5, 25.

At L.V.’s second well-child appointment on May 12, 2005, he was determined to be
developing appropriately for his age, and received: (a) Diphtheria, Tetanus, and acellular Pertussis
(“DTaP”) vaccine; (b) haemophilus influenza type B (“Hib”) vaccine; (c) inactivated polio vaccine
(“IPV”); and (d) pneumococcal conjugate vaccine (“PCV”). Pet’rs’ Ex. 3 at 113-14. A month later,
L.V. was diagnosed with onychia.6 Id. at 37-41.

On July 22, 2005, L.V. had his third well-child visit, at which time his pediatrician, Dr.
Sharon Corcoran, evaluated him as developing appropriately for his age. Pet’rs’ Ex. 3 at 50-51.
3
The medical records in this case are particularly voluminous, and include many records pertaining to efforts to treat
L.V.’s autism (and possible causes of it) post-vaccination that only bear tangentially on the issues to be resolved in
this entitlement proceeding. Although I have reviewed the entire record, I do not discuss all such medical records in
detail, but instead focus on what both sides have identified as the most significant records relevant to the causation
issues presented herein.
4
Acute nasolacrimal stenosis is the short term narrowing of the tear duct. Dorland’s Illustrated Medical Dictionary
(32d ed. 2012) at 24, 1233, 1769 [hereinafter Dorland’s]. See also Nasolacrimal Duct Obstruction, AMERICAN
ASSOCIATION FOR PEDIATRIC OPHTHALMOLOGY AND STRABISMUS (July 2014),
http://www.aapos.org/terms/conditions/72.
5
Gastro-esophageal reflux is defined as the “reflux of the stomach and duodenal contents into the esophagus, which
sometimes occurs normally, particularly in the distended stomach” after meals, or “as a chronic pathological condition
that leads to the conditions known as gastroesophageal reflux disease and reflux esophagitis.” Dorland’s at 1616
(emphasis in original).
6
Onychia refers to the “inflammation of the matrix of the nail resulting in shedding of the nail.” Dorland’s at 1321.

2
L.V. again received the DTaP, Hib, IPV, and PCV vaccines. Id. at 113, 114. On August 15, 2005,
L.V. developed cold symptoms including a cough, as well as a possible toe infection. Id. at 54, 56,
59. L.V. was prescribed augmentin7 for his toe infection and his parents subsequently reported that
he experienced vomiting and an upset stomach. Id. at 61, 63.

On September 16, 2005, L.V. had his fourth well-child visit, and once again Dr. Corcoran
evaluated L.V. as developing appropriately for his age. Pet’rs’ Ex. 3 at 66. At this time L.V.
received the DTaP, IPV, and PCV vaccines, after which he developed a localized rash. Id. at 69,
113, 114. Months later, on December 16, 2005, L.V. was again evaluated by Dr. Corcoran as
developing appropriately for his age. Id. at 77.

As L.V. approached his first birthday, there remained no obvious signs of developmental
problems. In February of 2006, L.V. was taken to the pediatrician because he was experiencing
diarrhea, and was diagnosed with gastroenteritis.8 Pet’rs’ Ex. 3 at 93. On March 16, 2006, Dr.
Corcoran determined that L.V. was still developing appropriately for his age, and at that time he
received the hepatitis B; measles, mumps, and rubella (“MMR”); and varicella vaccines. Id. at 96,
98, 114. In March of 2006, L.V. was diagnosed with both peanut butter and blueberry allergies.
Id. at 100, 102, 110. On July 10, 2006, L.V. was again evaluated as overall developing
appropriately for his age and received the DTaP and PCV vaccines. Id. at 112, 194. L.V. was taken
back to Dr. Corcoran’s office on August 7, 2006, where he was diagnosed with “other acute
sinusitis” and prescribed amoxicillin.9 Pet’rs’ Ex. 3 at 115, 117. In September of 2006, the Vs
called Dr. Corcoran to report that L.V. was experiencing diarrhea, and Dr. Corcoran prescribed
home management. Id. at 119.

On September 8, 2006, L.V. visited the pediatrician for a 17-18 month well-child
appointment. At this visit, L.V. was assessed as having normal growth and development (including
motor skills such as use of a cup and spoon), and received the hepatitis A vaccine. Pet’rs’ Ex. 3 at
123-24, 194. Later that same month, the Vs also brought L.V. to Allergy and Asthma Specialists,
P.C. in Flourtown, Pennsylvania, because L.V. had developed a large hive after eating blueberry
yogurt and pancakes. Pet’rs’ Ex. 7 at 39-40.

7
Augmentin is “the trademark for combination preparations of amoxicillin and clavulanate potassium.” Dorland’s at
179.
8
Gastroenteritis refers to the “inflammation of the lining of the stomach and intestines.” Dorland’s at 764.
9
Amoxicillin is a “semisynthetic derivative of ampicillin effective against a broad spectrum of gram-positive and
gram-negative bacteria.” Dorland’s at 65.

3
 B. Flu Vaccine Administration and Subsequent Developmental Regression.

L.V. received the first dose of flu vaccine on November 8, 2006 (at approximately 20
months of age), and the second on December 8, 2006 (at approximately 21 months of age).10 Pet’rs’
Ex. 3 at 125, 128-29. Records from these two pediatric visits say nothing about developmental
problems, and there are no records from the intervening period between visits.

Three days after L.V. received the second flu vaccine dose, on December 11, 2006, Mrs.
V phoned the pediatrician’s office to report that L.V. was experiencing serious constipation “for a
while,” and had not had a bowel movement since December 9th. Pet’rs’ Ex. 3 at 132. She reported
no other problems, however. An office appointment was set for December 13, 2006. Id.

At the December 13th visit, Mrs. V again identified only constipation as the reason for the
appointment. Pet’rs’ Ex. 3 at 134-35. Thus, the medical records explicitly state that L.V. had not
been “going regularly for 1-2 months” despite alteration of his diet. Id. In addition to the
constipation, L.V. also now presented with left otitis media,11 although the records do not state
that he had a fever, and in fact state he displayed no acute distress. Id. at 135. Significantly, for the
first time the pediatric records reflect a concern with “speech delay,” although no details are given
as to the source of this concern. Id. L.V. was prescribed miralax for constipation and amoxicillin
for the ear infection, with the recommendation that any pain/fever that later resulted be treated
with an over-the-counter medication such as Tylenol or Motrin. Id. Mrs. V was instructed to return
to the pediatrician if symptoms did not improve in three days. Id. The speech delay was to be
evaluated through a hearing screen once the ear infection resolved, but the record also notes that
Mrs. V was supplied with a phone number for early intervention services in Montgomery County,
Pennsylvania. Id. at 135, 137.

Over a week passed without any further contact with L.V.’s pediatrician. Then, on
December 22, 2006, Mrs. V called Dr. Corcoran’s office to report that L.V. (who had been on
antibiotics to treat the ear infection for nine days) had now developed a fever of 102 degrees (which
later that same day rose to 104 degrees). Pet’rs’ Ex. 3 at 138-40. L.V.’s treaters prescribed

10
The flu vaccine is an “inactivated trivalent virus vaccine, containing two influenza A virus strains and one influenza
B virus strain, usually prepared from virus subunits.” Dorland’s at 2016. “The composition of the vaccine is changed
each year in response to antigenic shifts and changes in prevalence of influenza virus strains.” Id. L.V. received the
trivalent influenza vaccination, including one type B and two type A strains. Am. Pet. at 1 (ECF No. 27); see also
2006-2007 Influenza (Flu) Season, CENTERS FOR DISEASE CONTROL AND PREVENTION (July 8, 2009),
http://www.cdc.gov/flu/pastseasons/0607season.htm.
11
Acute suppurative otitis media refers to a short course inflammation of the ear with a discharge of pus. Dorland’s
at 24, 1351.

4
augmentin and recommended an in-office visit if L.V.’s symptoms did not improve in the next few
days. Id. at 138.

L.V.’s follow-up pediatric visit occurred on December 26, 2006. Pet’rs’ Ex. 3 at 142-47.
At this point, the Vs reported to L.V.’s treaters that he was suffering from rashes on his face,
shoulders, back, and diaper area that had first become evident on December 23rd, along with a
cough and runny nose. Id. at 144. The records make no mention, however, of an ongoing fever
(beyond reference to the fever that the Vs reported on December 22nd), and indicate that L.V.
displayed no particular distress. Dr. Corcoran diagnosed L.V. as suffering from an augmentin
allergy (based upon the circumstantial link between the time that medication was started and the
rash development), and he was prescribed omnicef as a substitute for augmentin. Id. at 142, 144.

Before their first visit to the pediatrician in 2007, the Vs obtained an initial early
intervention assessment from Montgomery County’s provider on January 17, 2007, after
requesting it on January 10th. See generally Pet’rs’ Ex. 13 at 1-11 and Ex. 30 at 475. The written
report generated from this initial assessment (based on observation of L.V. along with parental
reports) placed L.V. at eleven months for cognitive development, ten months for communication
development, six months for social development, and sixteen months for fine motor/physical
development. Pet’rs’ Ex. 13 at 5-6. The report contains references to L.V. having lost language or
expressive abilities, but notes that “he lost these abilities around 18 months.” Id. at 8. In addition,
other developmental problems (such as not responding to his name, or making eye contact) are
noted as uncommon occurrences, rather than behaviors that abruptly ceased or regressed. See, e.g.,
Id. at 5 (L.V. “did not respond to his name today. Parents report that he will respond to his name
20% of the time (at best)”).

L.V.’s next pediatric visit was on January 18, 2007. Pet’rs’ Ex. 3 at 148-49. Although L.V.
returned to Dr. Corcoran in part for a follow-up visit regarding his ear infection, the Vs also made
it clear that they wished to discuss “developmental issues.” Id. at 149. Specifically, the medical
records from that visit note the Vs’ statements that L.V. had “lost some of his language and does
not make a lot of eye contact.” Id. at 149. The January 18th records do not indicate when the lost
language began or was first observed – nor do they make any reference to the flu vaccine or L.V.’s
subsequent ear infection, brief fever, or rash as having any role in such developmental matters.
However, these records substantiate that the Vs had already initiated the process for obtaining an
early intervention assessment, as noted above. Id. at 149.

Dr. James Coplan, M.D., of Neurodevelopmental Pediatrics of the Main Line, P.C. in
Rosemont, Pennsylvania thereafter (upon referral by Dr. Corcoran) performed another early
evaluation assessment, completing his write-up of the assessment on January 23, 2007. See
generally Pet’rs’ Ex. 5 at 3-7. The assessment was based on both a physical examination and a
medical and personal history provided by the Vs (including the January 17th early assessment
5
report). Dr. Coplan’s conclusions were discouraging: he diagnosed L.V. with autism or autism
spectrum disorder (“ASD”).12 Id. at 4, 6. Consistent with the prior assessment performed by
Montgomery County, Dr. Coplan noted regressive developmental issues, as well as developmental
plateaus or behaviors that had not properly manifested. L.V.’s use and acquisition of words is said
to have “faded and disappeared” around 18-20 months (id. at 4), but L.V. never “reliably” said
“mama” or “dada” at all (a ten-month developmental milestone), while other behaviors (such as
fine motor skills in self-feeding) that should have begun earlier were only recently manifesting
(such as scoop-feeding with a spoon, which the Vs identified to Dr. Coplan as having begun only
“within the past week or two”). Id. at 1, 3-4.13 L.V. was scored at 40 on the Childhood Autism
Rating Scale14 (with 30 being the cutoff for autism). Id. at 6.

Dr. Coplan’s assessment included some discussion of the course of L.V.’s developmental
problems. He thus noted that the developmental and skills “deterioration” in a child’s second year,
as evidenced by L.V.’s history, occurs in 20 percent of autistic children. Pet’rs’ Ex. 5 at 6.
However, Dr. Coplan also proposed that despite the “striking history of developmental
deterioration” at 18 months provided by the Vs’ personal recollections, it was not entirely clear
that L.V. was truly regressing developmentally, given other information provided by the Vs about
L.V.’s earlier developmental abnormalities (such as his failure to “acquire appropriate use of
‘mama’ and ‘dada’). Id. at 6. Dr. Coplan also indicated that it was unlikely the immunizations that
L.V. had received played any role in his development of autism (and this record does not contain
any statement from the Vs linking L.V.’s alleged regression and his receipt of the flu vaccine in
November and December of 2006). Id. at 6.

The Vs later obtained a child development evaluation from Dr. Hillary Kruger, M.D., at
Children’s Hospital of Philadelphia (“CHOP”). See generally Pet’rs’ Ex. 6. In her initial pediatric
evaluation, dated May 21, 2007, Dr. Kruger concurred with the autism diagnosis proposed earlier
that year by Dr. Coplan. Id. at 5. Her written report also references previous records from 2007 in
which the Vs had stated to treaters that they noticed L.V.’s regression when he was 18 to 19 months
old. Id. at 1.

12
Section IV(A) of this decision contains a discussion of ASDs generally.
13
As discussed below, however, Petitioners contest the accuracy of Dr. Coplan’s assessment that L.V.’s spoon usage
was delayed, pointing to a contrary, earlier pediatric record suggesting normal development. See Pet’rs’ Ex. 3 at 122.
14
The Childhood Autism Rating Scale “helps to identify children with autism and determines symptom severity
through quantifiable ratings based on direct observation.” Childhood Autism Rate Scale, Second Edition (CARS-2),
WPS, http://www.wpspublish.com/store/p/2696/childhood-autism-rating-scale-second-edition-cars-2 (last visited
Feb. 3, 2016).
6
 C. Dating the Onset of L.V.’s Regression.

In this action, Petitioners have alleged that L.V. experienced a dramatic developmental
regression after he received the second flu vaccine. However, as the medical records
contemporaneous with L.V.’s alleged regression consistently reveal, the Vs repeatedly reported to
doctors that L.V.’s regression began no later than when he was 18 to 19 months old.

As noted above, the contemporaneous records from January of 2007 (when Dr. Coplan
evaluated L.V. at 22 months of age) reveal that the Vs informed treaters such as Drs. Coplan and
Kruger that L.V.’s developmental problems and/or regression had been evident to them since L.V.
was 18 months old, or around September of 2006. Pet’rs’ Ex. 5 at 3. This reported onset is repeated
numerous other times in the subsequent medical record. Thus, Mrs. V informed Dr. James A.
Neubrander in September of 2007 (when L.V. was almost two and a half years old) that at 19
months she noticed L.V. had lost the few words he had, lost social interest, and appeared
withdrawn and irritable, and at around 20 months, L.V. lost eye contact, began constantly jumping,
became increasingly irritable, and began making only a few sounds with vibrations. Pet’rs’ Ex. 8
at 4. Dr. Bryan Jepson’s 2008 notes corroborate the same timeframe, reporting that according to
the Vs “[t]here was a regression from normal development around age 12 months in hindsight:
more noticeable around 18 months” including “arm flapping, loss of contact, less socially
interactive, [and] loss of his few words.” Pet’rs’ Ex. 10 at 5.

There are many other similar examples from the medical record. See, e.g., Pet’rs’ Ex. 7 at
29-30 (January 31, 2007 visit to CHOP for genetic testing); Pet’rs’ Ex. 10 at 78 (April 15, 2007
visit at Thoughtful House with Dr. Jepson); Pet’rs’ Ex. 6 at 1 (May 21, 2007 visit with Dr. Kruger);
Pet’rs’ Ex. 9 at 6 (June 14, 2007 visit with Dr. Krigsman); Pet’rs’ Ex. 8 at 3 (September 27, 2007
visit with Dr. Neubrander); Pet’rs’ Ex. 8 at 32 (September 29, 2007 visit with Dr. Neubrander).

D. The Vs’ Attempts to Explain L.V.’s ASD.

After L.V.’s initial ASD diagnosis in January of 2007, the Vs (whom the record
underscores were extremely dutiful in caring for their son) explored possible explanations for
L.V.’s autism, as well as treatments that would be effective under the circumstances. Eventually
they became very interested in determining whether L.V.’s purported post-vaccine regression had
something to do with an underlying disorder involving dysfunction (if not disease) in his
mitochondria and their efficiency in producing energy.

To that end, the Vs consulted with a variety of autism specialists, some of whom were
themselves exploring the links between autism and mitochondrial diseases. In May of 2007, L.V.
saw Dr. Corcoran and Dr. Hilary Kruger, a developmental pediatrician, both at CHOP, who
determined after genetic testing and evaluation that L.V. had no clinically significant genetic

7
abnormalities15 and had normal weight gain and growth. Pet’rs’ Ex. 6 at 1-5; Pet’rs’ Ex. 7 at 36-
37.16 L.V.’s ASD diagnosis was at that time confirmed as well. Id.

The Petitioners next brought L.V. to Texas specifically in search of a Defeat Autism Now
(“DAN”)17 doctor, and found Dr. Arthur Krigsman at Thoughtful House, in Austin, Texas. Tr. at
92. The Thoughtful House is associated with the DAN movement. Pet’rs’ Ex. 9 at 1. Dr. Krigsman
referred L.V. for an endoscopy and colonoscopy, which were performed by Mount Sinai on June
14, 2007. Id. His results showed mild lymphonodular hyperplasia. Id. L.V. was also diagnosed
with duodenal ulcers, gastritis, and suspected esophagitis. Id. at 2. L.V. also saw Dr. Jepson (a
member of Thoughtful House) for the first time on June 19, 2007. Pet’rs’ Ex. 10 at 7. Dr. Jepson
continued treating L.V. through the end of 2008, prescribing various medications and supplements
and at-home behavioral intervention therapy to treat L.V.’s autism. Id. at 1.

At the recommendation of Dr. Krigsman and other Thoughtful House practitioners, the Vs
traveled to New Jersey to bring L.V. to see Dr. Neubrander, another noted DAN doctor, who L.V.
first saw on September 29, 2007. Pet’rs’ Ex. 8 at 1-3. Following a physical exam performed that
same day, Dr. Neubrander confirmed L.V.’s autism diagnosis, and also diagnosed him with
“gastroenteritis associated with autistic spectrum disorders” and nutritional deficits. Id. at 36-37.18

The Vs eventually obtained treatment from Dr. Richard Frye, beginning in August of 2008,
who at the time was a physician at the Child and Adolescent Neurology Clinic at the University of
Texas Health Science Center in Houston, Texas. Pet’rs’ Ex. 8 at 2. Petitioners learned of Dr. Frye
from Dr. Krigsman, and it was Dr. Frye who first proposed to them that L.V. might have some

15
L.V. was found to have a duplication of 1q44, which he appears to have inherited from his father, but the lab
interpretation noted that this may represent a normal population variant. Pet’rs’ Ex. 7 at 1.
16
During this time, the Vs continued seeking assessments of L.V. to better his daily life. In April of 2007, the Vs took
L.V. for an occupational therapy assessment after which he received ongoing occupational therapy through at least
July of 2007, when the records stop. See generally, Pet’rs’ Ex. 15. They also brought L.V. for an applied behavior
analysis/verbal behavior evaluation in May of 2007. See generally Pet’rs’ Ex. 16. In July of 2007, L.V. had a
communication evaluation. See generally Pet’rs’ Ex. 17. Finally, in November of 2007, L.V. underwent a Behavior
Language Assessment. See generally Pet’rs’ Ex. 18, 19.
17
DAN is composed of doctors and medical professionals who believe, among other things, that autism can 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).
18
The Vs later brought L.V. back to Pennsylvania and saw Dr. Coplan again in the winter of 2008. Dr. Coplan
maintained his diagnosis of autism with unclear underlying cause; he also recommended some additional metabolic
testing, but noted that testing performed for methylene tetrahydrofolate reductase did not indicate any abnormality.
Pet’rs’ Ex. 5 at 11-13.

8
kind of mitochondrial disease that had played a role in his ASD. Tr. at 93-94. The Vs traveled back
to Texas in order to obtain Dr. Frye’s services.

Dr. Frye performed testing to evaluate whether in fact L.V. displayed any of the clinical
indicia necessary for a mitochondrial disease diagnosis. At L.V.’s first visit with Dr. Frye on
August 1, 2008, extensive blood work was performed. Pet’rs’ Ex. 11 at 3. Then, on December 3,
2008, Dr. Frye had Quest Diagnostics, Inc. perform an amino acid analysis and a comprehensive
metabolic panel, intended to clarify what type of mitochondrial disorder L.V. had, if any. Id. at 17-
22.

Initial test results did not suggest the existence of a specific or inherited metabolic defect,
and returned an essentially normal acylcarnitine profile.19 Pet’rs’ Ex. 11 at 2, 6, 18, 20. But the
same lab results also showed elevated lactate (with values of 18 and 23 on a normal range of 4-16)
(Pet’rs’ Ex. 21 at 29), urinary tricarboxylic acid20 excretion (indicated by high levels of ammonia,
of which L.V. had a value of 83 when normal is equal to or below 47) (id. at 12), and the presence
of ethylmalonic aciduria. Id. at 13. 21

In 2009, L.V. underwent additional testing at Dr. Frye’s direction, through the
Mitochondrial Diagnostic Laboratory of the Medical Genetics Laboratories of the Baylor College
of Medicine (“BCM”) in Houston, Texas. See generally Pet’rs’ Ex. 34. There, specialists
performed a MitoMet oligo aCGH analysis22 that came back negative, showing no abnormalities.
Pet’rs’ Ex. 34 at 4. A year later, on September 9, 2010, the Urinary Creatine and Guanidinoacetate
results from BCM, Biochemical Genetics Lab suggested the possibility of a creatine transporter
deficiency,23 but further clinical correlation was needed. Pet’rs’ Ex. 26 at 37. Shortly thereafter,

19
Acylcarnitine profile analysis “is performed for the biochemical screening of disorders of fatty acid oxidation and
organic acid metabolism.” P. Rinaldo, et al., Acylcarnitine profile analysis, 10 GENETICS IN MEDICINE 151 (2008),
http://www nature.com/gim/journal/v10/n2/full/gim200822a.html (last visited Feb. 11, 2016).
20
The Krebs Cycle, or the tricarboxylic acid cycle, is “the final common pathway for the oxidation to CO2 of fuel
molecules, most of which enter the cycle as acetyl coenzyme A.” The cycle occurs “in the mitochondria and generates
ATP by providing electrons to the electron transport chain.” Dorland’s at 454.
21
Ethylmalonic aciduria is a genetically heterogeneous disorder due to deficiencies in the electron transport system,
characterized by the accumulation and excretion of acids normally oxidized by mitochondria. Dorland’s at 652, 791.
The presence of high ethylmalonic acid is a biomarker for mitochondrial disease and/or dysfunction. Tr. at 449-50;
560-62.
22
The MitoMet oligo aCGH analysis is used to detect some genetic deletions or duplications involved in mitochondrial
and metabolic related diseases. Medical Genetics Test: MitoMet®Plus aCGH Analysis, BAYLOR MIRACA GENETICS
LABORATORIES, https://www.bcm.edu/research/medical-genetics-labs/test_detail.cfm?testcode=2000 (last visited
Feb. 11, 2016).
23
Creatine transport deficiency is a genetic syndrome caused by mutations in the SLC6A8 gene on the X chromosome.
Pet’rs’ Ex. 26 at 6.

9
on September 16, 2010, a Magnetic Resonance Spectroscopy (“MRS”)24 test produced results
indicating that L.V.’s major metabolites were normal for his age, and there was evidence of a
normal creatine peak25 as well. Id. at 40. Not long thereafter, on October 14, 2010, the
Mitochondrial Diagnostic Lab at BCM preformed a creatine transporter 1 sequencing test that
detected no known deleterious mutations in the CRTR.26 Pet’rs’ Ex. 34 at 8.

During the time of this testing under Dr. Frye’s direction, the Vs brought L.V. back to
CHOP. Pet’rs’ Ex. 36 at 18. Metabolic studies of L.V. performed on August 12, 2010, “were
essentially normal and were not suggestive of metabolic or mitochondrial dysfunction.” Id.; Pet’rs’
Ex. 26, Part 2 at 1-9. During their September 2, 2010, visit, the doctors confirmed that
interpretation. Pet’rs’ Ex. 36 at 18.

By the fall of 2010, the Vs sought the opinion of another specialist with views similar to
Dr. Frye’s regarding the possible metabolic causes of autism, Dr. Richard Kelley at the Kennedy
Krieger Institute in Baltimore, Maryland. Dr. Frye had recommended in August of 2010 that
Petitioners speak with Dr. Kelley (Pet’rs’ Ex. 33 at 30), and (in written communication introducing
the Vs to him) set forth the opinion that L.V. had a “mitochondrial complex deficiency.” Pet’rs’
Ex. 26 at 4. Dr. Kelley and his assistants subsequently reviewed L.V.’s lab work. Id. at 32-33.
After review of the relevant results and L.V.’s history, however, Dr. Kelley expressed the belief
that there were “no metabolic abnormalities,” and thus nothing consistent with mitochondrial
dysfunction (although he acknowledged that L.V.’s condition could be consistent with an
encephalitis). Id.

Despite such inconclusive results, the Vs nevertheless pursued further attempts to identify
the source of L.V.’s ASD. To that end, on January 21, 2011, L.V. underwent a muscle biopsy,
performed to measure lactic acid27 levels (with the tested sample taken from L.V.’s right lateral

24
MRS is “a noninvasive diagnostic test for measuring biochemical changes in the brain, especially the presence of
tumor.” Magnetic Resonance (MR) Spectroscopy, Mar. 2010, MAYFIELD BRAIN & SPINE,
http://www mayfieldclinic.com/PE-MRspectroscopy.htm (last visited Feb. 11, 2016). “Spectroscopy is a series of tests
that are added to the MRI scan of your brain or spine to measure the chemical metabolism of a suspected tumor.” Id.
25
Creatine is “an amino acid formed by methylation of guanidinoacetic acid, found in vertebrate tissues, particularly
in muscle.” Dorland’s at 429.
26
The CRTR “is in a sodium chloride dependent transporter 1 that belongs to the solute carrier family 6 member 8
(SLC6A8).” Pet’rs’ Ex. 34 at 8. “In patients with CRTR deficiency, the urinary creatine excretion relative to the
creatinine excretion is elevated, and the creatine/creatinine ratio can be used as a first biochemical diagnostic marker
for CRTR deficiency.” Id.
27
Lactic acid is “a metabolic intermediate involved in many biochemical processes; it is the end product of glycolysis,
which provides energy aerobically in the heart for energy production or can be converted back to glucose.” Dorland’s
at 997. While elevated lactic acid in the blood is not specific for a diagnosis of mitochondrial disease (Tr. at 133-34),
it has previously been used as a measurement of autism in children. Dorland’s at 571.

10
thigh muscle), at BCM. Pet’rs’ Ex. 23 at 3. The results showed: “[f]iber type 1 predominance,
moderate” and “[m]ildly increased oxidative enzyme reaction (COX), and increased mitochondria
by electron microscopy.” Id. Nevertheless, L.V.’s muscle biopsy was interpreted by the performing
neuropathologist to show “no specific pathologic findings,” and he recommended further enzyme
tests aimed at analyzing the functioning of the electron transport chain [“ETC”]28 in L.V.’s
mitochondria, or additional attempts to measure mitochondrial DNA. Pet’rs’ Ex. 33 at 121.

Such additional testing was performed at Dr. Frye’s direction in late January of 2011, but
detected no deficiencies in L.V.’s mitochondrial ETC enzymes. Pet’rs’ Ex. 23 at 1-3. However,
the mitochondrial DNA content analysis performed at BCM on February 7, 2011, showed that
L.V.’s muscle contains approximately 189% of the mean value of the age and tissue-matched
controls, suggesting a compensatory amplification of mitochondrial DNA due to some other kind
of mitochondrial dysfunction. Pet’rs’ Ex. 34 at 16. A follow-up ETC test performed at BCM on
February 22, 2011, once again did not detect any deficiencies. Id. at 9.

In spite of such generally inconclusive data, on August 4, 2011, Dr. Frye diagnosed L.V.
(who was at that time six years old) with a mitochondrial disorder. Pet’rs’ Ex. 72, Part 2 at 25-26.
He did so by applying criteria set forth in an article written by Morava, entitled Mitochondrial
Disease Criteria, Diagnostic Applications in Children (the “Morava criteria”). Pet’rs’ Ex. 41, Ref.
25 at 31 (E. Morava, et al., Mitochondrial disease criteria: Diagnostic applications in children,
67 NEUROLOGY 1823 (Nov. 2006) [hereinafter Morava]). As discussed in greater detail below,
Morava set forth diagnostic guidelines for evaluating whether a child suffers from some kind of
mitochondrial disease, through application of a point system for various symptoms or test results
observed in the diagnosed patient. Pet’rs’ Ex. 24 at 1; Tr. at 120-21, 442-44.

In a “to whom it may concern” letter dated February 29, 2012, Dr. Frye identified the
specific grounds for his conclusion that L.V. suffered from a “definite” mitochondrial disease
(based on application of the Morava criteria). See generally Pet’rs’ Ex. 24 at 1-3. In his opinion,
L.V. exhibited three clinical signs consistent with a mitochondrial disorder, including: (i) exercise
intolerance, (ii) history of regression in skills, and (iii) gastrointestinal abnormalities. Id. at 1. Dr.
Frye then listed three metabolic indicators (based on previous bloodwork) he found significant,
including: (i) elevated lactate,29 (ii) urinary tricarboxylic acid excretion, and (iii) ethylmalonic
aciduria. Id. Dr. Frye also noted that L.V. had abnormal mitochondrial morphology30 as viewed

28
An electron transport chain is embedded within the inner mitochondrial membrane, and makes the same chemical
reduction of oxygen to water. Tr. at 428. “The oxidation of the carbon to carbon dioxide regenerate ATP as opposed
to an explosive force” and then the ATP is used by the cell to function, including muscle contraction, allowing the
eyes to see, the heart to beat, the ears to hear, etc. Id. at 428-29.
29
Lactate is the anionic form of lactic acid. Dorland’s at 997.
30
Mitochondrial morphology refers to the form and structure of the mitochondria. Dorland’s at 1169, 1181.
11
via electron microscopy (“EM”).31 Id. These factors were enough to score a “9” in Dr. Frye’s
application of the Morava criteria, resulting in the conclusion that L.V. definitely had a
mitochondrial disease. Dr. Frye also suggested, without elaboration, that the ETC test results and
muscle biopsy results supported his conclusion, while admitting at the same time that the genetic
evidence supporting his diagnosis was lacking. Id.

II. PROCEDURAL HISTORY

As stated above, the Vs filed this petition in 2008. On May 6, 2009, Respondent filed a
statement expressing no objection to the jurisdiction and appropriateness of Petitioners proceeding
within the Omnibus Autism Proceeding (“OAP”).32 However, after the relevant test cases in the
OAP were litigated, and their causation theories rejected, the Vs elected to remain in the Vaccine
Program, filing an amended petition on April 9, 2012, that explained how their revised theory of
vaccine causation differed from the decided test cases. ECF No. 27.

31
Electron microscopy involves the use of a microscope “in which an electron beam, instead of light, forms an image
for viewing, allowing much greater magnification and resolution.” Dorland’s at 1162.
32
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.

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), aff’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.

12
 After filing a statement of completion on September 25, 2012, Petitioners offered the expert
report of Dr. Frances Kendall on August 20, 2013. ECF No. 64. On February 19, 2014, Respondent
filed a Rule 4(c) Report, contending that the record failed to establish by preponderant evidence
the causal connection between the flu vaccine and L.V.’s subsequent conditions, and disputing the
reliability of Petitioners’ medical theory. ECF No. 71. In response, Respondent filed an expert
report from Dr. Bruce Cohen. ECF No. 72. The Vs then elected to file a supplemental expert report
from Dr. Yuval Shafrir on December 30, 2014. ECF No. 95. With records gathering and the filing
of relevant evidence and expert reports complete, a two-day entitlement hearing was set for April
of 2015. (Petitioners later moved to file out of time a second supplemental expert report from Dr.
Shafrir on March 17, 2015 (ECF No. 129), and I permitted them to do so.)

On January 4, 2015, Petitioners filed a second amended petition that presented facts and
allegations relevant to Petitioners’ claim for compensation.33 ECF No. 105. The next day,
Petitioners filed: (i) their Prehearing Submissions (ECF No. 111); and (ii) a motion to compel
Respondent’s admission of Petitioners’ medical theory, alleging that Respondent had conceded
Petitioners’ theory in the case Poling v. Sec’y of Health & Human Servs., No. 02-1466v, 2008 WL
1883059 (Fed. Cl. Spec. Mstr. Apr. 10, 2008) through Respondent’s Rule 4(c) Report in that case.
ECF No. 112. After considering each side’s arguments, I denied Petitioners’ Motion for Judicial
Estoppel in my March 6, 2015, Order. ECF No. 124.34 In the meantime, Respondent filed her
prehearing submissions on February 24, 2015. ECF No. 119. Petitioners then filed their prehearing
submissions reply on March 9, 2015. ECF No. 127.

On April 13-14, 2015, a two-day entitlement hearing was held. During the hearing, I heard
testimony from Mrs. V; Petitioners’ experts Drs. Kendall and Shafrir; and Respondent’s expert
Dr. Cohen. After requesting two extensions of time (ECF Nos. 147 and 152) both of which I
granted, Petitioners filed their post-hearing brief on July 13, 2015. ECF No. 155. In response,
Respondent then filed her post-hearing brief on September 14, 2015. ECF No. 157. Petitioners
replied to Respondent’s argument on October 14, 2015.

III. TESTIMONY PRESENTED AT HEARING

A. Mrs. V

E.V., L.V.’s mother, was the only non-expert witness who testified at the entitlement
hearing. See generally Tr. at 7-103. Her testimony provided some context about L.V.’s overall
development – and also sought to rebut the notion, reflected in the medical records, that the Vs

33
On July 6, 2015, the Parties filed a stipulation for interim fees and costs (ECF No. 148), and I entered a decision
awarding the stipulated amount on July 7, 2015. ECF No. 150.
34
Petitioners filed a Motion for Reconsideration of that Order on April 4, 2015 (ECF No. 137) which I subsequently
denied by Order dated April 10, 2015. ECF No. 148.
13
were aware of signs of L.V.’s regression before he received the flu vaccines in November and
December 2006. In order to do so, she frequently attempted to diminish the weight to be given
statements in the medical record reporting earlier onset.

Thus, Mrs. V repeatedly stressed that the first time she or her husband had observed
developmental issues with L.V. was in mid-December of 2006, after he received the second dose
of flu vaccine. Compare Tr. at 29, 36, 40 with Tr. at 56, 58. Some photographs of L.V. were offered
to bulwark her assertions that L.V.’s pre-vaccination development was completely normal. Id. at
54-74.35 Yet she also admitted that she had witnessed some “subtle issues” pertaining to L.V.’s
development a month to two months before the second flu vaccine was administered. Id. at 54, 88.

More significantly, Mrs. V was unable to deny the many instances from the
contemporaneous medical records in 2007 in which she and/or her husband reported to treaters
evaluating L.V.’s autism that L.V. first displayed such symptoms by the time he was 18 months
old. For example, on cross-examination, Respondent pointed out that the excel sheet prepared by
Mrs. V documenting L.V.’s issues and presented to Dr. Neubrander at L.V.’s September 29, 2007,
visit reported that at 19 months L.V. “lost a few words he had, lost social interest, seemed
withdrawn, irritable.” Tr. at 87-88; Pet’rs’ Ex. 8 at 4. This is in apparent contradiction to Mrs. V’s
testimony (nearly nine years after the events in question) and her affidavit (prepared nearly three
years after the vaccination), both of which maintain that L.V.’s regression manifested no sooner
than 21 months, or after his receipt of the flu vaccine in December 2006. Compare Tr. at 29, 36,
40 with Tr. at 56, 58. Mrs. V had also prepared a narrative for Dr. Krigsman for L.V.’s June 2007,
visit, which is similarly inconsistent with her testimony and affidavit. Id. at 90; Pet’rs’ Ex 9 at 6
(reporting that L.V. “did always seem to be more difficult than other children” and that he “began
flapping his arms as early as 12 to 18 months”).

To the extent Mrs. V admitted that she had made such statements about the actual onset of
L.V.’s ASD-related symptoms, she attempted to downplay their significance, suggesting that she
and her husband had not considered L.V.’s earlier symptoms to be alarming enough to merit a
medical response. Tr. at 63. This line of reasoning – that L.V.’s “real” regression began only after
the second flu vaccine administration, and that any earlier signs of developmental problems were
too inconclusive to meaningfully relate to the later, agreed-upon developmental difficulties L.V.
experienced – was a general theme that Petitioners and their experts came back to during the

35
The Vs provided an array of photographs, and three videos, in an attempt to demonstrate visually that L.V. had
experienced a significant change in behavior and affect following his receipt of the second dose of flu vaccine in
December of 2006. See generally Pet’rs’ Ex. 43-65, 74-79. Neither of Petitioners’ experts commented on this evidence
at length. While these photographs do show L.V. demonstrating a variety of emotions and engaging in multiple social
interactions, and generally support the conclusion that L.V. has been well-loved and cared for, I do not find this
evidence probative in establishing the onset of L.V.’s purported regression. I could not draw useful conclusions or
inferences about L.V.’s capacity or developmental state at the time each photograph was taken simply by looking at
them, and testimony Mrs. V offered to explain them did not increase their evidentiary value.
14
hearing multiple times. See, e.g., id. at 86, 93, 152, 179-80.

B. Petitioners’ Experts36

1. Dr. Frances Kendall

Dr. Kendall offered an expert report and testimony at the entitlement hearing in support of
Petitioners’ theory that L.V. likely had an underlying, preexisting mitochondrial disease that was
exacerbated by receipt of the flu vaccine, thereby precipitating L.V.’s autism.

Dr. Kendall graduated from UMDNJ-New Jersey Medical School in 1987 after which she
completed her residency in pediatrics at Thomas Jefferson University Hospital in Philadelphia,
Pennsylvania. Pet’rs’ Ex. 42 at 1; Tr. at 106. From 1990 to 1993 she completed two fellowships in
genetics and metabolism at Children’s Hospital and Harvard Medical School and Tufts University
and is licensed by the American Board of Medical Genetics. Pet’rs’ Ex. 42 at 1; Tr. at 106. She
has worked and taught across the country in genetics and metabolism, including as Director of the
Mitochondrial Disorders Program at the Children’s Hospital of Boston, and written extensively,
including her own reports and reviews of others, on issues of mitochondrial energy production and
the errors of metabolism. Pet’rs’ Ex. 42 at 6-8; Tr. at 106, 108-09. She is presently board-certified
in biochemical genetics, and was previously board-certified in pediatrics. Tr. at 111. Dr. Kendall
currently treats patients from all over the world “for evaluation of and management of
mitochondrial disease” and estimates that since 2009 she has seen about a thousand patients, most
of whom she continues to treat. Id. at 105.

Dr. Kendall’s expertise thus lies in the specific field of mitochondrial disorders. Tr. at 104.
She did not, however, claim expertise in autism or in immunology. Id. at 233-34. In preparing her
expert opinion, Dr. Kendall reviewed the contemporaneous pediatric records, including L.V.’s
various evaluations discussed above, although she admitted that certain records relevant to Dr.
Frye’s analysis of L.V. were not provided to her at the time of her report’s preparation in July of

36
Petitioners’ two experts offered in total 71 individual articles or pieces of medical literature (in addition to the 101
articles also filed by Petitioners but not directly relied upon by their experts). Although I have reviewed all such
submitted evidence, I do not herein discuss, or include a summarization of, each individual article offered in this case.
La Londe v. Sec'y of Health & Human Servs., 110 Fed. Cl. 184, 209 (2013), aff’d, 746 F.3d 1334 (Fed. Cir. 2014) (on
appeal, it is presumed that special master reviewed all literature submitted in support of vaccine claim); Hennessey v.
Sec’y of Health & Human Servs., 91 Fed. Cl. 126, 137 (2010) (special master not obligated to discuss individually
each of over 200 medical or scientific journal articles filed in an action, and the failure to do so did not lead to the
conclusion that they were ignored). In most cases, discussion of a series of related articles (such as the literature
submitted by Dr. Shafrir to support Petitioners’ contention that components of the flu vaccine could have homology
with epitopes in the brain, or epitopes associated with autoimmune reaction) are not extensively reviewed herein since
my decision does not turn on an understanding or parsing of these articles. Indeed – my decision largely turns on my
factual findings about L.V.’s condition and the onset of his developmental problems.

15
2013. Id. at 130, 214. Nor did Dr. Kendall ever specifically examine or evaluate L.V.; her opinion
relied solely on test results performed by other treaters. Id. at 231.

Dr. Kendall characterized the diagnosis of mitochondrial disease as an “imperfect science”
(tr. at 198), stating that it is “not an easy process, and it’s not clean” (id. at 114), given limitations
in the available tools to evaluate it, along with a general lack of a medical/scientific consensus as
to the proper diagnostic criteria. Id. at 117, 119. Ultimately she embraced the Morava criteria
applied by Dr. Frye in his diagnosis of L.V. Pet’rs’ Ex. 10. She admitted, however, that there is
actually no accepted set of criteria (based on scientific consensus) that can be used in diagnosing
mitochondrial disease. Tr. at 119. In most cases, a definitive diagnosis of mitochondrial disease
requires a muscle biopsy or confirmation by molecular testing aimed at looking for a possible
genetic cause. Id. at 116-18, 146; Pet’rs’ Ex. 41 at 9.

Dr. Kendall also acknowledged the evolving nature of the criteria (and specific tests)
applied when attempting to diagnose a mitochondrial disease. Thus, Dr. Kendall noted that when
the science for detecting mitochondrial diseases was less advanced, muscle biopsy tests were the
“gold standard” diagnostic tool (Tr. at 241), but that more recently such tests were applied only to
confirm a mitochondrial disease diagnosis (id. at 118), and that she herself rarely performs them.
Id. at 119. She maintained that now there are many diagnostic tools available to test for
mitochondrial disease more useful than the muscle biopsy. Id. at 118-19.

Based upon her review of the results of the many tests performed on L.V., along with his
medical history, Dr. Kendall provided her opinion that the mitochondrial disease/dysfunction
diagnosis for L.V., as first proposed by Dr. Frye and based upon his application of the Morava
criteria, had evidentiary support. Tr. at 131-32. She acknowledged, however, that she did not
accept the Morava number assigned to L.V. by Dr. Frye (nine points); rather, she would reclassify
the total as six or seven,37 meaning that (under Morava) the proper diagnosis for L.V. was only
“probable” mitochondrial disorder38 rather than definitive (a diagnostic classification that she
indicated she would rarely accept, given the impossibility of confirming the diagnosis precisely).
Id. at 144, 149-50; Pet’rs’ Ex 10. To be more definitive in her diagnosis, Dr. Kendall stated that
she would require either some kind of advanced genetic testing, to look for mutations that would
directly impact mitochondrial function, or evidence that the patient’s particular symptoms matched
one of the more well-understood, and severe, forms of mitochondrial disease (such as Leigh
disease). Id. at 200, 243 (discussing that genetic testing performed on L.V. was negative for
mitochondrial disease).

37
Dr. Kendall vacillated between denoting six or seven points on the Morava scale to L.V., although either score is
sufficient to fall under its “probable” classification. Tr. at 143, 149-50.
38
See Section IV(B) below for a discussion of Morava’s points system.

16
 Dr. Kendall agreed with Dr. Frye’s analysis that L.V. was properly assigned three Morava
“points” for clinical signs and symptoms. Thus, she found worthy of a Morava point the exercise
intolerance that L.V. was reported to have displayed, pointing to his limited eye movement as
evidence thereof. Tr. at 148. Yet, as Dr. Kendall acknowledged, there was little record evidence
supporting this conclusion – going so far as to admit that her embrace of Dr. Frye’s scoring for
this Morava factor was wholly dependent on what the Vs had reported to treaters about L.V. rather
than objective evidence, and that she herself did not believe based on her own review of those
records that L.V. in fact had ever displayed any such weakness. Id. at 193-94, 245. She admitted
the same with respect to L.V.’s purported low muscle tone (hypotonia), another factor relevant to
the application of the Morava criteria (and indeed acknowledged that there were contrary reports
in the medical records undermining the conclusion that L.V. displayed low muscle tone). Id. at
148, 194.

Dr. Kendall otherwise accepted the two additional points assigned by Dr. Frye in this
category, based on L.V.’s alleged autistic regression (evidence of a CNS-related symptom)39 and
purported ongoing gastrointestinal tract illness (proof that L.V.’s disease was multi-systemic). 40
Tr. at 148. She also agreed with Dr. Frye’s view of the significance of L.V.’s abnormal
mitochondria morphology as seen via electron microscopy (a diagnostic factor worth two points
on the Morava scale). Pet’rs’ Ex. 41 at 7; Tr. at 197. Certain histological tests measuring
mitochondrial proliferation also revealed a higher than normal mtDNA count. Tr. at 141-42. Dr.
Kendall acknowledged that this particular diagnostic factor was not as closely correlated with
mitochondrial dysfunction in children as a high nuclear DNA count (id. at 243), but insisted that
it was a reasonable factor to be considered, and that the results in question were (taken together
with the morphology observations) worthy of consideration. Id. at 198-99. Ultimately, she
admitted that L.V.’s overall muscle biopsy results (pertinent to the “morphology” category) did
not display any enzymatic abnormalities of his muscle tissue (tr. at 143), although she still
maintained that the results suggested some form of mitochondrial dysfunction. Id. at 197-98.

Dr. Kendall did not, however, accept every aspect of Dr. Frye’s application of the testing
results under Morava. In particular, she substantively disagreed with Dr. Frye’s point calculation
with respect to the results of the enzymatic and metabolic tests. Thus, Dr. Frye gave L.V. the four

39
Dr. Kendall acknowledged that the Morava criteria’s inclusion of autism-like symptoms as evidence of an
underlying mitochondrial disorder highlighted a circularity in the logic of Petitioners’ causation theory offered in this
case. Tr. 236-37. As Dr. Kendall admitted, individuals could be properly diagnosed with an ASD and not also have
mitochondrial disease. Id. at 237. Yet here, the very same ASD symptoms being pointed to as evidence of the impact
of the relevant vaccine were also being cited as evidence of the underlying condition that caused those symptoms. In
effect, L.V.’s illness was proof of its cause.
40
Dr. Kendall displayed some ambivalence, however, as to whether L.V.’s reported constipation was a factor
suggesting the presence of a mitochondrial disorder, or merely reflective of the autistic regression that purportedly
occurred in reaction to the vaccination. Tr. at 173-74.

17
point maximum under the Morava diagnostic framework for test results showing elevated lactate
(two points), urinary tricarbon acid excretion (one point), and ethylmalonic aciduria (two points).
Pet’rs’ Ex. 24 at 1. Dr. Kendall, however, questioned the weight given by Dr. Frye to the elevated
lactate finding because “it’s not a true elevation from a biochemical mitochondrial perspective”
and “we don’t have any concurrent data to show whether it was a collection artifact.” Tr. at 140.
She therefore indicated that she disagreed with awarding a Morava point for the lactate results
because concurrent tests of other enzyme levels (alanine to lysine ratios) did not corroborate them.
Id. at 149. But she agreed with Dr. Frye that L.V. had high tricarboxylic acid excretion (tr. at 149),
as well as high ethylmalonic acid levels, which (as corroborated by the fatty oxidation studies done
on skin fibroblasts) were in her opinion suggestive of mitochondrial disease. Id. at 138-39. Thus
she would have granted only two or three points for the test results relevant to this biomarker
category.

More broadly, Dr. Kendall admitted (consistent with the manner in which she applied the
Morava criteria) that any mitochondrial disease L.V. suffered from was on the mild end of the
spectrum, and did not approach the severity of something like Leigh disease41 (given, for example,
the normal MRI readings obtained for L.V. (tr. at 202)) or other more easily diagnosed phenotypes.
Thus, although she argued that mitochondrial diseases were “extremely variable” in their manner
of development, the most obvious forms were progressive – but that she was not aware of any
record evidence suggesting that L.V. had experienced a truly dramatic, downward progression in
his symptoms post-vaccination. Id. at 188-90.

Dr. Kendall also acknowledged that her opinions about Dr. Frye’s diagnosis arose from her
own expertise and familiarity with the Morava criteria, and that she therefore did not particularly
rely on much of the independent literature filed by the Petitioners in support of their claim, noting
that some of it was not pertinent to L.V.’s circumstances.42 Tr. at 207. However, she did in her

41
Leigh disease is a subacute necrotizing encephalomyelopathy which is a type of “encephalopathy of unclear clinical
and pathological criteria, causing neuropathologic damage like that of the Wernicke-Korsakoff syndrome. It occurs in
two forms: the infantile form is caused by mitochondrial energy metabolism protein mutations and pyruvate
carboxylase complex mutations and is characterized by degeneration of gray matter with necrosis and capillary
proliferation in the brainstem; hypotonia, seizures, and dementia; anorexia and vomiting; slow or arrested
development; and ocular and respiratory disorders, with death usually before age 3. The adult form usually first
manifests as bilateral optic atrophy with central scotoma and colorblindness, followed by quiescent period of up to 30
years and then late symptoms such as ataxia, spastic paresis, clonic jerks, grand mal seizures, psychic lability, and
mild dementia.” Dorland’s at 614.
42
Thus, Dr. Kendall discussed one piece of literature that Petitioners highlighted as significant (Pet’rs’ Ex. 41, Ref.
27 (J. Shoffner, et al., Fever Plus Mitochondrial Disease Could Be Risk Factors for Autistic Regression, 25(4) J. OF
CHILD NEUROLOGY 429 (Jun. 2009) [hereinafter “Shoffner”]), because it suggested a relationship between fever and
subsequent regression. Dr. Kendall, however, agreed that Shoffner involved a study of individuals who plainly had
measurably high fevers lasting over a period of three to seven days – circumstances wholly distinguishable from the
facts of this case. Tr. at 210-11.

18
testimony reference literature discussing the Poling case as supportive of the theory that young
children with dysfunctional cellular metabolism may be prone to autistic regression if they
simultaneously experience infections and immunizations (both “stressors” that could exacerbate
an underlying mitochondrial disorder). Pet’rs’ Ex. 41, Ref. 26 (J. Poling, et al., Developmental
Regression and Mitochondrial Dysfunction in a Child with Autism, 21(2) J CHILD NEUROL 170-72
(2006); Tr. at 106, 136, 153, 155-56. While admitting that Poling was a single case rather than a
verifiable, reproducible scientific study, she nevertheless placed great trust in what it revealed. Id.
at 208-09, 212.

Based upon all of the above, Dr. Kendall proposed that Petitioners could meet all three of
the prongs necessary to establish causation in a non-Table case under Althen v. Sec’y of Health &
Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005). First, Dr. Kendall offered the theory that the
flu vaccine could sufficiently exacerbate an underlying mitochondrial disorder, synergistically
reacting with an intercurrent infection,43 to produce an autistic regression. Specifically, she opined
that “the constellation of stressors” experienced by L.V. after receiving two flu vaccines plus his
ear infection (tr. at 211) “had a synergistic effect on him that led to worsening of his – or
aggravation of his underlying [mitochondrial] disorder or problem.” Id. at 164-65.

To support this proposition, Dr. Kendall relied on literature discussing that vaccines can
act as stressors for sufferers of mitochondrial diseases (tr. at 153-60), although she admitted that
only isolated cases, or incidents involving well-understood and particularly severe forms of
mitochondrial diseases such as Leigh disease, supported this element of her theory. Id. at 174. She
also pointed to a paper filed by Petitioners but not relied upon in her report, indicating that “the
influenza virus can, via a specific mitochondrial component . . . cause a cascade of events leading
to apoptosis, which is a kind of programmed cell death.” Id. at 162 (citing Pet’rs’ Ex. 101 (A. Tran,
et al., Influenza Virus Induces Apoptosis via BAD-Mediated Mitochondrial Dysregulation, 87(2)
J. OF VIROLOGY 1049 (Jan. 2013)) [hereinafter “Tran”]). She then said that such a study made it
more likely or plausible that the flu vaccine could cause an injury in a person with mitochondrial
disease. Tr. at 163. Given the understanding that an infection can itself precipitate a regression or
decompensation (id. at 155-56), she testified, the introduction of flu vaccine could similarly place
stress on a patient with a preexisting mitochondrial disease. Id. at 165-66.

Second, Dr. Kendall testified that in fact the medical record confirmed that L.V. had been
affected by the flu vaccine as she proposed. But she was generally unable to reference evidence
from that record in support of this assertion. Tr. at 178-79, 184-86. At best, Dr. Kendall vaguely
cited to reports of L.V.’s loss of words or irritability, but could not recall much else. Id. at 170-72.

43
Notably, on this aspect of her testimony Dr. Kendall diverted somewhat from her original expert report, which
suggested that the flu vaccine alone had produced L.V.’s regression, rather than in concert with his ear infection.
Compare Tr. 231-32 with Pet’rs’ Ex. 42 at 11.

19
She also admitted that the speech delay as reported by the Vs on December 13, 2006, was not itself
strong proof of a dramatic, vaccine-induced regression caused by an underlying mitochondrial
disease (id. at 180), and that L.V.’s constipation and related problems were ongoing, having been
present prior to his receipt of the flu vaccine. Id. She further agreed that ASD features,
development delays, developmental regression, and constipation are symptoms that are often seen
independent of a mitochondrial disorder. Id. at 196-97. Indeed, Dr. Kendall admitted on cross-
examination that, given the paucity of evidence suggesting an immediate, post-vaccination
regression, her overall theory would be undermined if it were determined that L.V.’s
developmental regression began before he received the flu vaccine. Id. at 184-86.44 However,
because it was her opinion that whatever mitochondrial dysfunction L.V. had was mild in form, it
would not be likely (in her opinion) that his regression would be as evident as in cases where a
child unquestionably was experiencing one of the more severe forms of the disease, such as
mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (“MELAS”).45 Id. at
196-97.

Finally, Dr. Kendall asserted that the timeframe from the December 8, 2006, administration
of the second dose of flu vaccine to L.V.’s alleged developmental regression was medically
acceptable. Under Dr. Kendall’s proposed theory, onset of regression would occur in seven to ten
days – a length of time she derived from a single piece of literature involving a retrospective study
of individuals suffering from mitochondrial disease, some of whom experienced developmental
regression as is alleged to have occurred with L.V. Tr. at 166-69; Pet’rs’ Ex. 84 at 6 (J. Edmonds,
et al., The Otolaryngological Manifestations of Mitochondrial Disease and the Risk of
Neurodegeneration with Infection, 128 ARCH. OTOLARYNGOL. HEADNECK SURG. 355 (Apr. 2002)
[hereinafter, “Edmonds”] (setting forth that in most patients the neurologic event occurred three
to seven days after onset of infection)). Approximately one week after L.V.’s second flu
vaccination, there was “some question about some neurological changes or problems or certainly
by his parents’ report of changes in his irritability.” Tr. at 169-70. Although Dr. Kendall admitted
that irritability was not particularly strong evidence of an encephalopathy, when viewed in context

44
Dr. Kendall also made some attempt to address the fact that Petitioners’ theory required L.V. to have suffered from
a mitochondrial disease prior to his receipt of the flu vaccine. Thus, she indicated that it was not surprising to her that
L.V. might have begun to display some symptoms of autism before he received the flu vaccine, since a child suffering
from some form of a preexisting mitochondrial disease would experience ASD-like symptoms regardless of the role
a vaccine played in those symptoms’ exacerbation. Tr. at 136.
45
MELAS is a condition that “affects many of the body’s systems, particularly the brain and nervous system and
muscles.” Symptoms include “muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and
seizures.” Mitochondrial Encephalomyopathy, lactic acidosis, and stroke-like episodes, GENETICS HOME REFERENCE,
(Dec. 2013), http://ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-
episodes (last visited Feb. 11, 2016).

20
with L.V.’s purported subsequent skill loss, in her opinion it was proof of the existence of a
“regressive encephalopathy” that was “certainly temporally related.” Id. at 170-172, 176.

2. Dr. Yuval Shafrir

Dr. Shafrir is a child neurologist who graduated from the Sackler School of Medicine at
the Tel Aviv University in 1982. He thereafter did residencies in pediatrics at Kaplan University
and the Bellinson Medical Center in Israel. Tr. at 252-53; Pet’rs’ Ex. 81 at 2. 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. Tr. at 254; Pet’rs’ Ex. 81 at
2. From 1992 to 2000, Dr. Shafrir worked at a number of different U.S. hospitals, but currently
practices pediatric neurology in private practice affiliated with Sinai Hospital in Baltimore,
Maryland. Tr. at 252. 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 252,
322, 334. 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. 81 at 4. He has also written
extensively on issues of pediatric neurology. Id. at 4-8.

Dr. Shafrir testified as an expert in pediatric neurology. Tr. at 252. He is not an expert in
immunology or mitochondrial disease, however. Id. at 268, 321, 361-62, 380. He is also not one
of L.V.’s treating physicians, and has never examined L.V. himself. Id. at 404. Dr. Shafrir sees
approximately 300 patients per month. Tr. at 252-54, 402. Mostly, he treats headaches and
seizures, but twenty percent of his practice is developmental in nature, and approximately ten
percent of his patients have an ASD diagnosis. Id. at 252-54, 402. But he does not have clinical
experience studying ASDs, nor does he possess specific research experience or training in that
specialty. See generally Pet’rs’ Ex. 81.46

Dr. Shafrir offered brief testimonial support for Dr. Kendall’s theory that L.V.’s autism
was related to his alleged preexisting mitochondrial disease. Tr. at 267-68, 317-18; Pet’rs’ Ex. 193
at 3. The vast majority of his testimony, however, related to his own, alternative causation theory,
which was somewhat confusing and extremely wide-ranging. Dr. Shafrir’s opinion began with a
distinction he drew between autism that proceeds on a natural course and the “regressive autism”

46
Dr. Shafrir was passionate in defending his opinions at hearing – but some of that passion was lacking in scientific
grounding. Thus, Dr. Shafrir acknowledged his belief that today, autism is present in the United States and the world
more generally at epidemic levels that cannot be explained by genetic factors (“genetics cannot occur in epidemics”
Tr. at 295; see also Id. at 257, 259, 330-31, 403. He did not, however, offer reliable evidence suggesting that the
scientific community of ASD experts shares his opinion, let alone that his opinion about an “autism epidemic” is
scientifically well-founded. He similarly denied the possibility that the rise in ASD diagnoses could be explained by
the fact that medical practitioners have become better at spotting and diagnosing the relevant behaviors and/or
symptoms, claiming that “any preschool teacher” can make the diagnosis. Pet’rs’ Ex. 80 at 31.

21
he believes L.V. experienced. Tr. at 336. Indeed, he disputed the concept of a “natural course of
autism” that would typically include a developmental regression. Id. at 329. Rather, according to
Dr. Shafrir, sudden autistic regression is more likely caused by an encephalopathy. Id. at 251. He
thus maintained that regressive autism – which in his view accounts for approximately thirty
percent of all ASD patients, and is in some cases treatable (due to its causes) – was a form of
autism, although he admitted that it does not constitute a separate clinical phenotype that is
formally recognized medically. Id. at 336-37.

In Dr. Shafrir’s opinion, L.V. experienced an “acute autistic regression following his
second influenza immunization” (tr. at 264) at 20 months (id. at 338) which “can be best explained
as an autoimmune process.” Id. at 264-65, 274. He based this view on post-vaccination evidence,
which he argued revealed “all the components” of autistic regression. Id. at 280. His opinion was
also based on scientific articles and literature that he maintained drew a connection between the
administration of the flu vaccine and L.V.’s allegedly abrupt subsequent regressive incident.

First, Dr. Shafrir testified that the flu vaccination has been demonstrated to be a cause of
autoimmune encephalopathy. Tr. at 284; Pet’rs’ Ex. 80 at 28. As proof, he mentioned several
pieces of literature associating vaccines (and particularly the flu vaccine) with antibody-mediated
autoimmune encephalitis. Tr. at 284 (citing Pet’rs’ Ex. 80, Ref. 10 (J. Dalmau, Clinical experience
and laboratory investigations in patients with anti-NMDAR encephalitis, 10 LANCET NEUROL 63
(Jan. 2011) [hereinafter “Dalmau”]); Pet’rs’ Ex. 80, Ref. 11 (T. Hung, et al., Anti-N-methyl-D-
Aspartate Receptor Encephalitis, 52 PEDIATRICS & NEUROLOGY 361 (Jan. 2011)); Pet’rs’ Ex. 80,
Ref. 12 (M. Kubota and Y. Takahasi, Steroid-Responsive Chronic Cerebellitis with Positive
Glutamate Receptors δ2 Antibody, 23(2) J. OF CHILD NEUROLOGY 228 (Feb. 2008)); and Pet’rs’
Ex. 80, Ref. 13 (J. Takanashi, et al., Late Delirious Behavior with 2009 H1N1 Influenza: Mild
Autoimmune-Mediated Encephalitis? 129 PEDIATRICS 1068 (2012)). He maintained that scientific
studies have plainly observed a tendency in individuals to develop autoantibodies following receipt
of the flu vaccine. Pet’rs’ Ex. 80 at 30 (citing Pet’rs’ Ex. 80, Ref. 31 (N. Toplak, et al., Autoimmune
response following annual influenza vaccination in 92 apparently healthy adults, 8
AUTOIMMUNITY REVIEWS 134 (2008)). Such autoantibodies, in turn, attack human brain tissues,
resulting in an encephalopathic incident. Tr. at 208 (citing Pet’rs’ Ex. 41, Ref. 26 (E. Hsiao, et al.,
Modeling an autism risk factor in mice leads to permanent immune dysregulation, PROC. OF THE
NAT’L ACAD. OF SCI. www.pnas.org/cgi/doi/10.1073/pnas.1202556109)47; Tr. at 301; Pet’rs’ Ex.
80, Ref. 19 (D. Obregon, et al., Potential Autoepitope within the Extracellular Region of

47
“Developmental Regression and Mitochondrial Dysfunction in a Child with Autism” is a case abstract of one child
who experienced severe regression following a vaccination. Petitioners have attempted on numerous occasions to
equate L.V.’s situation with that of the child in Poling. See, e.g., Motion to Compel Respondent’s Admission of the
Medical Theory, Jan. 5, 2015 (ECF No. 112). However, Poling was a severe example of a Table Injury following
vaccination, unlike the non-Table claim here.

22
Contactin-Associated Protein-like 2 in Mice, 4(1) BRITISH J. OF MED. & MED. RES. 416 (2014)
[hereinafter “Obregon”]))48; Tr. at 297 (citing Pet’rs’ Ex. 80, Ref. 14 (R. Dhamija, et al., Neuronal
Voltage-Gated Potassium Channel Complex Autoimmunity in Children, 44 PEDIATR NEUROL 44
(2011) [hereinafter “Dhamija”])49). Thus, Dr. Shafrir maintained that the flu vaccine could in
theory produce an autoimmune reaction through the creation of antibodies and/or active T-cells
which cross-react with certain proteins in the brain. Tr. at 361 (citing Pet’rs’ Ex. 80 at 31). This
“more likely than not” causes “widespread disruption of the brain function, resulting in autism.”
Tr. at 294, 296, 331.

For additional support, Dr. Shafrir referenced literature highlighting instances in which
vaccines have been associated with negative neurologic conditions. Tr. at 287-89; Pet’rs’ Ex 80,
Ref. 5 (K. Lapphra, et al., Adverse Neurologic Reactions After Both Doses of Pandemic H1N1
Influenza Vaccine With Optic Neuritis and Deymyelination, 30(1) THE PED. INFECTIOUS DISEASE
J. 84 (Jan. 2011) [hereinafter, “Lapphra”]). Lapphra describes a case study showing the occurrence
of neurologic changes in a two-year-old Filipino boy shortly after receiving the H1N1 flu virus
vaccine. Id. at 18-19. The child was diagnosed with acute disseminated encephalomyelitis
(“ADEM”)50; his initial symptoms had spontaneously resolved after the first dose of vaccine, but
worsened after the second. Id. at 19. The Lapphra authors claimed the displayed progression in
symptom development strongly suggested that the flu vaccine was a causative factor for the child’s
illness, arguing that the sequence of events was consistent with the production of greater amounts
of myelin-attacking antibodies after each vaccination. Id. Here, by contrast, L.V.’s regression has
never been attributed to ADEM, nor was he ever diagnosed with that or any other similar
demyelinating disease. In addition, the H1N151 flu vaccine at issue in Lapphra is not precisely
analogous to the vaccine L.V. received herein, further limiting the relevance of this case study to
L.V.’s circumstances. Tr. at 363-66.

48
Dr. Shafrir referenced Obregon numerous times throughout his testimony. Even though the study solely evaluated
how human viral and bacterial wild pathogens can trigger the creation of antibodies that attack certain brain proteins,
resulting in an encephalopathy, Dr. Shafrir suggested that a similar homology existed between components of the flu
vaccine and those same proteins, and thus the same result was possible. Tr. at 405-06.
49
Dr. Shafrir referenced Dhamija as evidence that influenza vaccinations cause an autoimmune attack on the brain
that produced autistic regression. Tr. at 297. This article, however, mentions only a single example of such an
association (Pet’rs’ Ex. 80, Ref 14 at 2) and concludes that larger case studies are necessary. Id. at 7.
50
ADEM is an acute or subacute inflammation involving both the brain and spinal cord characterized by perivascular
lymphocyte and mononuclear cell infiltration and demyelination. “[I]t occurs most often after an acute viral
infection…but may occur without a recognizable antecedent. It is believed to be a manifestation of an autoimmune
attack on the myelin of the central nervous system. Symptoms include fever, headache, and vomiting; sometimes
tremor seizures, and paralysis; and lethargy progressing to coma that can be fatal.” Dorland’s at 613.
51
As Dr. Shafrir admitted on cross, strains of the H1N1 virus were not added to the seasonal flu vaccine until 2010 –
four years after L.V. received the flu vaccine. Tr. at 366.

23
 Dr. Shafrir next opined that autoimmune encephalitis (as well as immune dysfunction more
generally) is a recognized cause of regressive autism. Tr. at 285; Pet’rs’ Ex. 80 at 30-31. As
exemplifying a portion of the “accumulating evidence” that an autoimmune process can start in
the brain and precipitate autism, he pointed to a series of case studies: one of which occurred in a
child with Voltage-Gated Potassium Channel [“VGKC”]52 antibodies (Dhamija), and two others
where the patients had measurably heightened levels of anti-NMDA-receptor53 antibodies, which
have been linked to a specific kind of encephalitis.54 See Pet’rs’ Ex. 80, Ref. 15 (O. Scott, et al.,
Anti-N-Methyl-d-Aspartate (NMDA) Receptor Encephalitis: An Unusual Cause of Autistic
Regression in a Toddler, J. OF CHILD NEUROLOGY 1 (2013)), and Ref. 16 (C. Creten, et al., Late
onset autism and anti-NMDA-receptor encephalitis, 378 LANCET 98 (2011)). He also referenced
an article that speculates about the possible relationship between autoimmune synaptic encephalitis
and autism. Tr. at 376-77 (citing Pet’rs’ Ex. 80, ref. 18, M. Kayser, et al., The Emerging Link
Between Autoimmune Disorders and Neuropsychiatric Disease, 23(1) NEUROPSYCHIATRIC CLIN.
NEUROSCI. 90 (Winter 2011) [hereinafter “Kayser”]); see also Pet’rs’ Ex. 80 at 29.

However, Dr. Shafrir acknowledged limitations to the portion of his theory connecting the
flu vaccine to autoimmune-mediated encephalopathies. On cross-examination, Dr. Shafrir
admitted that the literature he cited (and in particular, Dalmau) observed no more than an
association between the flu vaccine and encephalopathy, and thus did not support the conclusion
that the flu vaccine was itself causative of any form of encephalopathy. Tr. at 366-67, 370. He also
conceded that, because there is no evidence that L.V. has anti-NMDA encephalitis, anti-NMDA
antibodies, or anti-VGKC encephalitis or antibodies, studies focusing on such narrow forms of
autoimmune illnesses were largely inapposite. Id. Indeed, as Dr. Shafrir admitted, L.V. displayed
no objective evidence of an autoimmune reaction in his brain, and no MRI findings that would be
associated with an autoimmune encephalopathy. Id. at 362-63, 369, 508. Dr. Shafrir nevertheless
stressed there were individual case studies where regression associated with an encephalopathic
event had occurred, and that such regressions could be treated. Id. at 373-75.

52
As noted in Dhamija, voltage-gated potassium channels are proteins in neurons in the central and peripheral nervous
systems that play a role in membrane repolarization, axonal conduction, and synaptic transmission. Dhamija at 275.
53
NMDA stands for “N-methyl-d-Aspartate.” NMDA is a “neurotransmitter similar to glutamate, found in the central
nervous system; a synthetic preparation is used experimentally to study the excitatory mechanisms of glutamate
transmitters.” Dorland's at 1152.
54
Anti-NMDA receptor encephalitis is a clinical disorder, mostly in adolescents, that presents with a sudden onset of
altered mental status, with and without seizures, behavior change, often fever, and ovarian or testicular tumors. Tr.
515-16.

24
 To explain the biologic mechanism by which the flu vaccine could precipitate an
autoimmune encephalopathy as Petitioners alleged to have happened with L.V., Dr. Shafrir
proposed molecular mimicry through homology of epitopes.55 Tr. at 267; Pet’rs’ Ex. 80 at 29-30
(citing Obregon). In a typical immune response, he explained, cells produce antibodies in reaction
to the viral or bacterial invader. Tr. at 301, 405. However, due to similarities (the “mimicry”) in
the structure of the amino acid sequences in the healthy tissue and the virus, the antibodies
produced mistakenly attack healthy tissue (as well as the virus they were intended to attack), thus
triggering an autoimmune reaction. Id. at 405. The same process could occur with vaccination; as
evidence, Dr. Shafrir offered specific literature that demonstrated homology between components
of the flu vaccine and brain tissues. Id. at 298-99. In particular, Dr. Shafrir discussed the homology
between the amino acid sequence in the CSPR-2 protein56 found in the brain and the hemagglutinin
protein of influenza A virus, which he maintained have been found by reputable studies to be
sufficiently similar to cross-react and thereby create the necessary autoantibodies to attack self,
and which he purported is a component of the flu vaccine.57 Id.

In further support of his proposed molecular mimicry mechanism (and also as evidence of
the pathogenic potential of the flu vaccine), Dr. Shafrir cited a Finnish study involving narcolepsy
among children after receipt of the H1N1 Pandemrix flu vaccine, along with other literature
addressing the same event. See, e.g.,Tr. at 291; Pet’rs’ Ex. 80 at 31 (citing Pet’rs’ Ex. 80, Ref. 33
(A. Kӓll, The Pandemrix – narcolepsy tragedy: how it started and what we know today, 102
FOUNDATION ACTA PAEDIATRICA 2 (2013)); Pet’rs’ Ex. 80, Ref. 34 (M. Partinen, Narcolepsy as
an autoimmune disease: the role of H1N1 infection and vaccination, 13 LANCET NEUROL 600
(2014));, Pet’rs’ Ex. 80, Ref. 35 (M. Partinen, et al., Does autoreactivity have a role in
narcolepsy?, 13 LANCET NEUROL 1072 (Nov. 2014)); and Pet’rs’ Ex. 80, Ref. 36 (A. Singh, et al.,
Genetic association, seasonal infections and autoimmune basis of narcolepsy, 43 J. AUTOIMMUN.
26 (Jun. 2013)). However, Dr. Shafrir admitted that the formulation of the Pandemrix vaccine was
not equivalent to what L.V. received (and indeed is not even administered in the U.S. (tr. at 365)),

55
As Dr. Shafrir explained, “epitope” is a term in immunology to describe a short segment of an amino acid that can
produce an immune reaction to an antigen. Tr. at 267. He argued that the best example of how molecular mimicry
worked in L.V.’s case was provided by the studies that show a relationship between the H1N1 vaccination and
narcolepsy. Id. at 291.
56
Dr. Shafrir explained that CSPR-2 protein is one of the two major proteins (the other being Lg-1) that are targets
for an autoimmune attack. Tr. at 301. Antibodies against this particular protein could, according to Dr. Shafrir,
precipitate symptoms related to autism. Id. at 302.
57
Dr. Shafrir specifically testified that the influenza-a and influenza-b components were both present in the flu vaccine
L.V. received, but it was the homology between hemagluttinin protein in the influenza-a virus and the CSPR-2 protein
in the brain that caused the autoimmune reaction. Tr. at 300-02. Although L.V.’s brain had never been tested for these
proteins, Dr. Shafrir maintained that this component of his theory still had plausibility. Id. at 302-03.

25
although he nevertheless maintained that, because both versions had some of the same protein
sequence components, the study still had relevance to his theory. Id. at 366.

Dr. Shafrir also maintained that an individual like L.V. could be especially sensitive to
stimulation by the flu vaccine given other aspects of his overall health. Tr. at 318, 380-81; Pet’rs’
Ex. 190 (G. Morris, et al., The Many Roads to Mitochondrial Dysfunction in Neuroimmune and
Neuropsychiatric Disorders, 13 BIOMED CENTRAL 68 (2015)). Thus, Dr. Shafrir asserted that L.V.
was immunosensitive (tr. at 285-86), having obvious abnormalities in his immune system, as
evidenced by his multiple, severe allergies, high erythrocyte sedimentation rate, documented IgA
deficiency, and inflammatory bowel disease diagnosis. Id. at 285-86, 296; Pet’rs’ Ex. 80 at 27. He
emphasized that patients who are susceptible to immune abnormalities are more likely to suffer
autoimmune reactions. Tr. at 323 (citing Pet’rs’ Ex. 187 (Y. Takahashi, et al., Vaccination and
infection as causative factors in Japanese patients with Rasmussen syndrome: Molecular mimicry
and HLA class I 13(2-4) CLINICAL & DEVELOPMENTAL IMMUNOLOGY 381 (Jun.-Dec. 2006))).
Individuals with allergies are also more likely to be autistic. Id. However, he admitted that he could
cite no objective evidence from the record of L.V.’s purported immune-sensitivity, and that (once
again) existing MRI findings did not support this aspect of his theory. Tr. at 362-63.58

Based upon the above, Dr. Shafrir offered an interpretation of L.V.’s medical history aimed
at demonstrating that the regression L.V. experienced appeared suddenly, after L.V.’s second flu
vaccination. He maintained that the medical record showed that L.V. was developing normally
until December 8th, with a sudden and severe regression thereafter, beginning within a week (or
around the time of the December 13th pediatric visit). Tr. at 268-69, 339. Yet Dr. Shafrir admitted
that he lacked data from the medical record that substantiated this assertion, beyond some mention
of constipation and the ear infection L.V. was experiencing at the time. Id. at 342-44. He could
point to little else in the record (beyond the Vs’ recollections) that L.V. ever experienced anything
medically dramatic, in this period or thereafter.

Dr. Shafrir also attempted to grapple with contrary evidence in the record suggesting that
L.V.’s ASD symptoms were evident before he received even the first flu vaccine. Thus, he
admitted that L.V.’s medical records were “all over the place,” in identifying the onset of his
alleged regression and/or ASD symptoms. Tr. at 328, 409. However, he posited that the Vs became
“very concerned” about L.V.’s development only at 21 months, downplaying the significance of
pre-vaccination evidence of developmental problems they may have observed (and reported to
treaters as having occurred at 18 and 19 months – before receipt of the first dose of the flu vaccine).

58
At best, Dr. Shafrir proposed that L.V. likely possessed a genetic defect inherited from his parents (as evidenced by
a gene “deletion that was found in [L.V.’s] father” (tr. at 296)), offering additional literature to support the conclusion
that autistic children with demonstrated allergies more likely also suffer from immune system abnormalities. Id.

26
Id. at 277-78, 347, 387. Thus, Dr. Shafrir proposed that the Vs likely mistook normal childhood
behaviors, such as flapping (which the medical records show was observed at 12 months), as the
first signs of autism. Id. at 277-78, 347-58.

Dr. Shafrir similarly attempted to rebut the many instances in the medical record, beginning
in January 2007, where the Vs directly informed a treater (such as Dr. Coplan) that L.V.’s
developmental regression had been evident at 18 months of age rather than 21 months. Tr. at 347.
To do so, he persistently relied on a pediatric well-child visit record from September 2006, which
reported that L.V. was, at that time, a “normal child,” as well as Mrs. V’s testimony. Id. at 281.
Dr. Shafrir characterized all subsequent, contrary medical records that referenced an earlier start
to L.V.’s autism symptoms as “profoundly wrong.” Id. at 348. But Dr. Shafrir was generally
unsuccessful in his efforts to explain why such records were untrustworthy.59 He otherwise
categorically dismissed the many contemporaneous statements about L.V.’s onset of symptoms as
instances in which the Vs simply repeated a “story” about L.V.’s onset by rote. Id. at 324-25, 350-
51, 356.60

Ultimately, Dr. Shafrir opined that the flu vaccine was the “only obvious cause” of L.V.’s
regression. Tr. at 283; Pet’rs’ Ex. 80 at 31. In so determining, he rejected the possibility of some
underlying genetic or other environmental explanation. Tr. at 294, 296. Indeed, Dr. Shafrir went
so far as to reject genetic causes of autism in general, stating that “genetics cannot occur in
epidemics.” Id. at 295.61

In an attempt to support Petitioners’ overall burden of demonstrating a medically
acceptable timeframe between vaccination and onset of L.V.’s autistic regression, Dr. Shafrir

59
For example, Dr. Shafrir questioned a statement set forth in Dr. Coplan’s January 23, 2007, record regarding L.V.’s
purported delay in use of a spoon and/or cup to feed, pointing out that a contemporaneous record from a 12-month
visit suggested that L.V. had by that time already mastered spoon-feeding (thus not only calling into question the
accuracy of Dr. Coplan’s record but also suggesting the degree of L.V.’s post-vaccination regression). Tr. at 397-400.
As discussed below, however, even if this part of Dr. Coplan’s evaluation is inconsistent with an earlier record (a
conclusion I do not adopt given other records), I do not find that it is meaningfully so, such that I would find Dr.
Coplan’s January 2007 written evaluation overall untrustworthy in the manner urged by Petitioners.
60
Thus, Dr. Shafrir was cross-examined about several specific such instances in the medical record from 2007 and
into 2008, where the Vs were reported to have specified an earlier onset of L.V.’s ASD regression and/or symptoms.
In every case, Dr. Shafrir disputed the record’s accuracy. See, e.g., Tr. at 347, 350, 351, 353 (disputing references to
regression beginning at 18 months in the Early Intervention evaluation (Pet’rs’ Ex. 13 at 8); the Vs’ report to Dr.
Coplan (Pet’rs’ Ex. 5 at 3); reports to Dr. Brian Jepson at the Thoughtful House in Austin, Texas (Pet’rs’ Ex. 10 at
78); Dr. Hillary Kruger’s records in May of 2007 (Pet’rs’ Ex. 6 at 1); Dr. Arthur Krigsman’s records in June of 2007
(Pet’rs’ Ex. 9 at 6); and Dr. James Neubrander’s chart in September of 2007 (Pet’rs’ Ex. 8 at 3)).
61
Dr. Shafrir later, however, admitted that the interaction of environmental factors with a genetic predisposition is, in
his view, the most likely cause of autism in the majority of cases. Tr. at 404.

27
argued that there was evidentiary support from the medical record for the conclusion that a reaction
occurred within five days. Tr. at 278, 280, 289-90. He based this argument in part on the fact that
L.V. had already received the first dose of the flu vaccine in November, which he claimed played
“an obvious role” because “[p]rimary immune reaction cannot occur in five days.” Id. at 292-93.
He thus differentiated these circumstances from the typical conception of “symptomatic
rechallenge,”62 instead asserting that this was an instance of what he termed “immunological
rechallenge.” Id. at 305-06. Immunological memory from the first vaccination facilitated the
molecular mimicry and the production of antibodies which acted against parts of the brain, causing
autism. Id. at 285. In further support of the reasonableness of the time period from vaccine to
injury, Dr. Shafrir noted that neurological loss can occur within a couple of days and usually within
a week to ten days. Id. at 169. In this regard, he compared L.V.’s regression to the development of
narcolepsy and/or Guillain-Barré syndrome both of which can manifest within 72 hours of a trigger
event. Id. at 289-91.

Again, however, Dr. Shafrir had difficulty identifying record support for this aspect of his
opinion. He thus admitted that he could point to very little record evidence actually establishing
the profound regression he posited that L.V. had experienced in December, beyond statements
contained in Dr. Coplan’s assessment about behavioral and developmental changes that the Vs had
observed in L.V. – records he simultaneously attacks as inaccurate or inconsistent with the Vs’
view of L.V.’s history. Tr. at 343. At most, he referenced evidence of L.V.’s constipation around
the time immediately after the December 8th vaccination. Id. at 344-46.

C. Respondent’s Expert – Dr. Bruce Cohen

Respondent’s expert, Bruce Cohen, M.D., offered testimony mostly responding to
Petitioners’ theory that L.V. suffered from a mitochondrial disease or disorder of some kind that
related to his alleged post-vaccine developmental regression.
Dr. Cohen graduated from Albert Einstein College of Medicine of Yeshiva University in
1982 (after completing his undergraduate degree at Washington University in St. Louis). Resp’t’s
Ex. B at 2. Dr. Cohen went on to complete a pediatric residency at Children’s Hospital of
Philadelphia, followed by a Pediatric Neurology Residency at the Neurological Institute of New
York and Babies Hospital of Columbia Presbyterian Medical Center and a Pediatric Neuro-
Oncology Fellowship at the Children’s Hospital of Philadelphia. Id. Dr. Cohen is board-certified
in Neurology, with Special Competence in Child Neurology, and was previously board-certified
in Pediatrics. Id. at 3.

62
According to Dr. Shafrir, the typical concept of rechallenge is a symptomatic rechallenge, where an individual has
a reaction to a medicine or a vaccination, and then has a similar or worse reaction after the second exposure to the
medicine or vaccine. Tr. at 305-06.

28
 Dr. Cohen is currently the Director of Neurology at the Children’s Hospital Medical Center
of Akron and a Professor of Pediatrics at Northeast Ohio Medical University, where he teaches
general pediatric neurology to medical students, residents, and fellows. Resp’t’s Ex. B at 3; Tr. at
414. He has also taught courses specifically on mitochondrial disease in symposia. Resp’t’s Ex. B
at 5-6. He is a reviewer for several journals and on the editorial board for the Mitochondrion and
the Pediatric Neurology Journal. Id. at 4. And he serves on various review committees – seven in
total – including the Neurofibromatosis Consortium. Id. Dr. Cohen has written extensively on
issues of mitochondrial diseases, authoring or co-authoring nearly 100 peer-reviewed articles. See
generally, id. Dr. Cohen has served in many different capacities for The United Mitochondrial
Disease Foundation since 1999 and served on many different committees regarding mitochondrial
disease. Id. at 4-5.

Dr. Cohen has particular expertise in studying and treating mitochondrial diseases. He has
been assisting with or treating patients with mitochondrial disorders or suspected mitochondrial
disorders since 1994. Tr. at 415. As a child neurologist, Dr. Cohen sees adults and children with
mitochondrial diseases and brain tumors. Id. at 412. Although Dr. Cohen does not diagnose ASDs,
some of his patients have autism as well as suspected mitochondrial diseases. Id. at 417. He
routinely diagnoses mitochondrial diseases or dysfunction in his patients, estimating that he has
seen several thousand patients in which the disease was suspected, or actually diagnosed, since
1994. Id. at 416. Of the nearly 100 peer-reviewed articles he has published, approximately a fourth
of them are readily discernible as dealing primarily with issues of mitochondrial dysfunction. See
generally, Resp’t’s Ex. B.

Relying on his experience treating patients with mitochondrial diseases, Dr. Cohen
formulated his opinion after reviewing L.V.’s medical records and the expert reports and journal
articles filed, along with Petitioners’ expert reports. Resp’t’s Ex. A at 4; Tr. at 423. Based on this
review, Dr. Cohen opined that there is no credible evidence that L.V. has a mitochondrial illness,
or that any vaccination L.V. received in any way contributed to his autism or other medical
conditions. Resp’t’s Ex. A at 4.

Dr. Cohen began by providing an overview of mitochondria, and the function they play in
the generation of energy necessary for the human body. Tr. at 424. He explained that mitochondria
exist in all mammalian cells, except for mature red blood cells. Id. at 425. Mitochondria are one
micron in length, or one-forty-thousandth of an inch, and have an outer membrane and an inner
mitochondrial membrane. Id. The mitochondria generate energy, or adenosine triphosphate
(“ATP”),63 which is held in covalent bonds, and some metallic molecules within the mitochondria
conduct the electricity via the ETC. Id at 428. The ETC is found within the inner mitochondrial

63
Adenosine triphosphate is a nucleotide involved in energy metabolism, which occurs in all cells and is used to store
energy. Dorland’s at 30.
29
membrane and allows for the regeneration of ATP, which can then be used by the cells throughout
the human body to cause muscle contractions, allow the ears to hear, or even cause the heart to
beat. Id. at 429. This process also creates heat and free radicals that can damage the cell or serve
“healthful purposes” within the body. Id.

Because not all mitochondrial diseases are the same, not every patient displays the same
symptoms, though there are some classic phenotypes. Tr. at 430. Mitochondrial diseases were
described as early as 1930, and since that time the diagnostic criteria used to discern if an individual
suffers from such a disease have been refined. Id. at 429-30. The development of genetic testing,
however, has increased the surety of the diagnosis, lessening the reliance on muscle biopsies or
enzymology,64 which were in the past the best ways to confirm a suspected mitochondrial disease.
Id. at 430, 432, 462.

Dr. Cohen discussed the differences between primary and secondary mitochondrial
disease. Tr. at 434. Primary mitochondrial disease refers to those diseases that have a “known,
verified genetic cause that is linked to the clinical phenotype of the patient” and “primarily affect
the mitochondrial structure.” Id. Although primary mitochondrial dysfunction can be most directly
diagnosed by genetic testing, it can still be properly diagnosed even in the absence of such testing
if the patient’s symptoms match a known phenotype, such as Leigh disease. Id. at 435-36.
Secondary mitochondrial disease usually involves a problem external to the mitochondria that
indirectly produces metabolic dysfunction, such as a genetic defect that causes iron not to be
processed properly, with the excess iron harming the mitochondria. Id. at 435-36, 595. Dr. Cohen
also discussed mitochondrial dysfunction, which he defined as a “global, generic term” referring
to when the mitochondria work imperfectly or are overloaded, but not necessarily as the result of
disease. Id. at 435-36. Such mitochondrial dysfunction can occur in otherwise benign, everyday
contexts (i.e. eating a high-fat meal). Id. at 436.

To diagnose a mitochondrial disease, Dr. Cohen proposed, a physician should begin with
a patient’s medical history, including a physical exam and family history. Tr. at 432. If the patient
fits a known mitochondrial disease phenotype, then the physician should conduct tests of the blood,
urine, and cerebral spinal fluid for indication of the mitochondrial process. Id. at 433. While some
biochemical markers on their own may suggest dysfunction, Dr. Cohen proposed that review of
biomarker test results should be considered collectively rather than in isolation. Id. at 461, 477.
The physician should also do a functional organ test, depending on which organ(s) the physician
suspects the mitochondrial disease may be affecting. Id. Other factors indicative of an ongoing

64
Enzymology is “the study of enzymes and enzymatic action.” Dorland’s at 629.

30
disease process are evidence of too few mitochondria or (in the case of adults) too few mtDNA.
Id. at 460.

A muscle biopsy with electron or light microscopy testing can also be performed to confirm
the presence of a mitochondrial disease. Tr. at 452. Through electron microscopy, a piece of
muscle is processed and then magnified 25 to 40,000 times. Id. at 456. In light microscopy, by
contrast, a pathologist takes a piece of muscle, slices it into thin sections for staining with different
stains, sometimes at different pH levels, and then looks at it under an ordinary microscope to make
a diagnosis. Id. at 452-53. As science has evolved, however, the emphasis placed on the importance
or meaning of certain tests used to diagnose mitochondrial disease has changed, Dr. Cohen
indicated. Thus, because over the past several years genetic testing capable of reliably confirming
a mitochondrial disease has become more widely available, the significance of muscle biopsies
and other tests have greatly diminished. Id. at 434.

One recent piece of literature Dr. Cohen co-authored and emphasized as particularly useful
in understanding what factors are most suggestive of the existence of a mitochondrial disease is R.
Haas, et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians, 120
PEDIATRICS 1326 (2007), filed as Ct. Ex. 1. ECF No. 133.65 Dr. Cohen noted that Haas
differentiates between “red flag” indicia of the presence of mitochondrial disease versus what the
article terms ‘nonspecific” criteria. Id. at l; Tr. at 431-32, 470-72. In effect, the nonspecific criteria
are far less persuasive evidence of the presence of mitochondrial disease than the red flag indicia
because they are not exclusively or predominantly associated with mitochondrial disease. Tr. at
446.

Dr. Cohen provided examples of the ways in which certain nonspecific criteria (that in the
past might have been given more weight in making a mitochondrial disease diagnosis) were not
particularly useful in signifying the presence of the disease. Thus, Dr. Cohen noted that the
gastrointestinal dysfunction commonly experienced by individuals with an ASD was not
commensurate with the far more severe kind of gastrointestinal symptoms those with classic
phenotypes of mitochondrial diseases experienced. Tr. at 441-44. Similarly, the level of brain
injury suffered in autism was not nearly as progressively debilitating and monophasic as that
experienced by someone diagnosed with Leigh disease (whose brain injuries and other symptoms
would in most cases result in death – not the outcome inevitably experienced by those diagnosed
with an ASD). Id. at 434, 439.

Dr. Cohen also expressed the overarching opinion that the scientific community rejects the
concept (based on present science) of a link between ASDs and mitochondrial disease (even

65
While I filed the Haas article as a Court Exhibit, Dr. Cohen also referenced the article extensively in his testimony.
See, e.g., Tr. at 431.

31
though in rare circumstances developmental regression is seen with certain mitochondrial
diseases). Tr. at 437. He recalled that when he began studying mitochondrial disease, it was widely
theorized that autism might be related, given similarities in how suddenly the symptoms could
develop, and/or how they seemed to involve similar energy deficiencies. Id. However, as
understanding of mitochondrial diseases expanded, in his view medical science was slowly
reaching the conclusion that there was no such relationship, given how few of those diagnosed
with autism also presented with known symptoms of a mitochondrial disease, and the lack of other
links. Id. at 438.

Turning to the record herein, Dr. Cohen explained why he differed with Drs. Kendall’s and
Frye’s mitochondrial disease diagnosis. Tr. 455-56. In Dr. Cohen’s view, L.V. merited a score of
zero on the Morava scale, given the minimal morphologic data, and lack of persuasive enzymology
test results. Resp’t’s Ex. A at 12. Rather, Dr. Cohen asserted that L.V.’s medical history and
clinical phenotype reflected autism without a known etiology. Tr. at 440.

In so doing, Dr. Cohen provided his own understanding of the value of the Morava criteria,
especially in light of subsequent scientific thinking on the diagnosis of mitochondrial disease. Tr.
at 462-63. He pointed out Dr. Kendall’s concurrence that Morava had limited application as the
most up-to-date criteria (in particular given the availability today of genetic testing), and that the
community of mitochondrial disease-oriented specialists were generally “walking away” from its
use. Id. at 463-64, 551, 567. He reiterated the general point that Morava gives too much weight to
nonspecific symptoms (for example, “exercise intolerance”). Id. at 445-46. He also stressed,
however, that even current clinical diagnostic criteria for evaluating whether a mitochondrial
disease was present could not be applied precisely in most cases, and could accordingly result in
certain test results being interpreted as abnormal when they did not in fact suggest the presence of
disease. Id. at 464-65.

Dr. Cohen examined Dr. Frye’s specific application of the Morava criteria in detail. Tr. at
440-41, 444. At the outset, Dr. Cohen observed that L.V.’s clinical presenting features (primarily
autistic symptoms and developmental regression) were not congruent with the severe disease
phenotypes displayed by children in the study used to develop the Morava criteria (such as MELAS
or Leigh disease). Id. at 465-66, 603. Dr. Cohen therefore suggested that (although he did not take
issue with Dr. Frye’s decision to consider the possibility that L.V. had a mitochondrial disease),
the diagnostic utility of the Morava criteria in this context should have been viewed with some
skepticism.

Turning to the specific Morava criteria tallies, Dr. Cohen opined that the point given by
both Drs. Kendall and Frye for exercise intolerance was inappropriate. Exercise intolerance seen
in relation to a mitochondrial disease is typically a product of “myopathy, muscle disease, or nerve

32
neuropathy, nerve disease, or cardiomyopathy.”66 Tr. at 445. Here, however, L.V.’s medical
history not only was far more vague in depicting L.V.’s purported intolerance, but it was also a far
cry from the kind of byproduct symptom commonly seen with true mitochondrial disease. Id. at
445-46.

Dr. Cohen also challenged the point denoted by Dr. Frye for L.V.’s ASD. Tr. at 469. In Dr.
Cohen’s interpretation, L.V’s developmental regression was more reflective of idiopathic autism
than a mitochondrial disease. Id. at 471-72. In patients with mitochondrial diseases, Dr. Cohen
testified, problems in brain function are clearly demonstrated through evidence of brain atrophy,
lesions in the brain, and/or lactate peaks on their MRI scans, and can result in dementia and other
severe, progressive declines in function that are measurable. Id. at 575. That kind of drastic loss of
cognitive skills associated with mitochondrial diseases is readily distinguishable from the loss of
cognitive skills in autism, or the loss demonstrated by L.V.’s history, which Dr. Cohen argued
discounted scoring it under Morava’s point system. Id.

Dr. Cohen further testified that L.V. should receive a score of zero under the Morava
criteria for his purported gastrointestinal symptoms. L.V.’s constipation was mild enough to be
relieved by miralax, and therefore did not rise to the level of severity commonly associated with
mitochondrial diseases. Tr. at 444; Resp’t’s Ex. A at 12. Dr. Cohen elaborated that the
gastrointestinal disturbances common to ASD look markedly different from those experienced by
patients with classic mitochondrial phenotypes. Tr. at 438-39. Patients with definite mitochondrial
diseases, like MELAS, experience total, severe obstruction that may require exploratory surgery
to find the blockage. Id. at 442. In contrast, ASD patient constipation is much less severe. Id. at
443.

With respect to the results of various lab tests performed on L.V., Dr. Cohen maintained
that even though some of the results revealed abnormalities that might merit some consideration
under the Morava criteria, they were either uncorroborated by other confirmatory tests or simply
overwhelmed by the weight of far more persuasive evidence that in fact L.V. did not have a
mitochondrial disease. Tr. at 477.

Thus, Dr. Cohen expressed the view that the results of L.V.’s laboratory tests were also not
worthy of any Morava points. Tr. at 446. With respect to the lactic acid measurements, Dr. Cohen
stressed that such testing is routinely prone to false elevation because “struggling” can raise the
lactic acid (and struggling is far more likely when a biopsy is obtained from a child). Id. at 447.
Here, Dr. Cohen proposed that the results showing elevated lactate levels were questionable for
that very reason. Resp’t’s Ex. A at 13. Furthermore, Dr. Cohen noted that L.V.’s amino acid testing

66
Dr. Cohen describes these, moreover, as “objective disorders” that would be readily evident to a treater. Tr. at 445.

33
and the alanine-to-lysine ratio67 results – tests well-understood as corroborating an elevated lactate
result – were both normal, and therefore undermined the elevated lactate findings. Tr. at 448-49.

As for the abnormal ethylmalonic acid and tricarboxylic acid/Krebs cycle intermediates
test results, Dr. Cohen did not consider the results to be sufficiently high, or sufficiently confirmed
by additional testing, therefore suggesting only that further in-depth evaluation was required to
determine if there was in fact mitochondrial dysfunction. Tr. at 450, 559-60. In addition, the
acylglycine test results (used to help confirm the meaningfulness of abnormal ethylmalonic acid
and kreb cycle intermediates results) were normal, further diminishing the value of some of these
abnormal biomarker test results. Id. at 450.

The last category – mitochondrial morphology – also received a score of zero from Dr.
Cohen. Resp’t’s Ex. A at 10, 12. While Dr. Cohen agreed that abnormal morphology – specifically
the presence of increased mitochondria with some swelling (Resp’t’s Ex. A at 7) – was seen on
L.V.’s electron microscopy, there were “no light microscopy correlates.” Id. at 13. According to
Dr. Cohen, there are “well-established immunohistochemical features” that should have been seen
on “light microscopy,” such as ragged red fibers and COX-negative fibers, none of which were
found in L.V.’s muscle biopsy. Id. Otherwise, the finding that L.V.’s electron miscroscopy results
showed swollen mitochondria was more consistent with a lab error than disease, and would
therefore “be a stretch” to award a point under Morava. Id. at 11; Tr. at. 451-56. If the swelling
was in fact indicative of a mitochondrial disease, the patient would also display disruption in the
interim crystalline structure. Tr. at 457. Moreover, the amount of cytochrome oxidase enzyme68
(102 percent), citrate synthase69 (107 percent), and succinate dehydrogenase70 (116 percent)
present were within normal range, and thus not elevated enough to be of concern. Id. at 459.

Dr. Cohen took issue with two of the pieces of literature offered in support of Dr. Kendall’s
report. He dismissed her reference to the Poling article (a case report involving vaccines other than
the flu vaccine) as insufficient to draw an association between vaccinations and the development
of mitochondrial disorders in children with autism. Tr. at 476-77. He similarly dismissed the

67
Alanine is a “nonessential amino acid, 2-aminopropanoic acid, occurring in proteins; high levels also occur free in
plasma.” Dorland’s at 43. Lysine is an essential amino acid and is “necessary for optimal growth in infants and for
maintenance of nitrogen equilibrium in human adults.” Dorland’s at 1089.
68
Cytochrome oxidase is “an enzyme complex of the inner mitochondrial membrane that catalyzes the transfer of
electrons from cytochrome c to oxygen, oxidizing the former and reducing the latter in the final step of the electron
transport chain by which oxygen is used for fuel combustion.” Dorland’s at 465.
69
Citrate Synthase is “an enzyme of the transferase class that catalyzes the condensation of oxaloacetate and the acetyl
group of acetyl coenzyme A to form citrate and coenzyme A.” Dorland’s at 366.
70
Succinate dehydrogenase is “an enzyme of the oxidoreductase class that catalyzes the oxidation of succinate to
fumarate, using a variety of hydrogen acceptors.” Dorland’s at 1795.

34
Shoffner article as having little bearing herein. Even if L.V. had a mitochondrial dysfunction, there
is, in Dr. Cohen’s opinion, no known association between the flu vaccine and aggravation of a
mitochondrial disease. Id. at 479-80.

Finally, Dr. Cohen addressed some components of Dr. Shafrir’s theory that L.V.’s
regression was the result of an autoimmune encephalopathy. He disputed that L.V. had
experienced a regressive form of autism caused by an autoimmune encephalopathy induced by the
first vaccination and magnified by the second vaccination, observing that the record suggested that
L.V.’s problems actually began prior to his first flu vaccination. Tr. at 482-83. Dr. Cohen also
challenged the conclusion that L.V. had experienced any traumatic brain injury along the lines of
an encephalopathy, noting that MRI scans of children with autoimmune encephalopathy will often
show particular abnormalities absent in this case. Thus, testing of brains in cases of anti-NMDA
receptor antibody autoimmune encephalopathies will often show disease in the temporal lobes or
other parts of the brain. Id. at 508-09. But, as conceded by Dr. Shafrir, L.V.’s MRI showed no
similar abnormalities. Id. at 363. Moreover, none of L.V.’s treaters performed the kinds of tests
that Dr. Cohen would expect would be performed if anti-NMDA receptor encephalitis had been
suspected (such as a spinal tap, an imaging study like a CT scan or an MRI scan, or an EEG), nor
was immunoglobulin therapy71 effective for L.V. Id. at 363, 510-13. L.V.’s change in
developmental status was far more gradual and mild overall than indicated by the timeline of
regression supported by Petitioners, and therefore not reflective of a dramatic autoimmune
reaction. Id. at 511, 514.

IV. SUMMARY OF RELEVANT MEDICAL CONCEPTS

Prior to analyzing Petitioners’ claims, it would be beneficial to briefly consider the two
medical conditions most relevant to this case (along with relevant case law dealing with both in
the Vaccine Program): ASDs and mitochondrial disorders. The summary below is derived from
materials filed by both parties in this case, as well as discussions of the conditions set forth in the
decisions of other special masters or the Court of Federal Claims.

A. Autism Spectrum Disorder

Autism or 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 at 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.html (last visited Feb. 11,

71
Immunoglobulin therapy is often used to treat NMDA receptor antibody autoimmune encephalopathy. Tr. at 513.

35
2016). 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).72

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, based on causations theories highly
similar to those asserted in the present action. 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 claim73 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)).

B. Mitochondrial Disease and Diagnostic Criteria

Mitochondrial disease is (as put by Dr. Kendall) a “heterogeneous group of disorders that
affect the body’s ability to ultimately metabolize energy through a series of complicated reactions

72
In this case, other than some occasional disagreement about the diagnostic value of the term “regressive autism,”
the parties did not dispute L.V.’s ASD diagnosis, and therefore offered no medical literature directly defining the term.
I reference Lehner (which does cite to several exhibits offered therein) and its discussion of ASD’s characteristics
only for the broad purpose of framing this topic.
73
In a single instance, petitioners (the parents of a vaccinated child) successfully established a Table injury – an
encephalopathy – after vaccination that resulted in autistic-like developmental regression. See, e.g., Wright v. Sec’y of
Health & Human Servs., No. 12-423V, 2015 WL 6665600 (Fed. Cl. Spec. Mstr. Sept. 21, 2015). In Wright, the
petitioners met the Table criteria for an “acute encephalopathy” following vaccination by establishing by preponderant
evidence that the vaccinated child experienced a seizure followed by loss of consciousness shortly after receipt of
pertussis-containing vaccine; the severe reaction lasted for more than 24 hours, with resulting demonstrable significant
changes in behavior. But the special master responsible for that decision (former Chief Special Master Vowell)
explicitly noted in her decision that petitioners would not have been able to establish entitlement under their non-
Table claim, because their expert presented a causation opinion that she found “absurd and biologically impossible.”
Wright, 2015 WL 6665600, at *2. Petitioners in this case rely on the same expert, Dr. Shafrir.

36
inside the mitochondria.” Tr. at 112-13. Mitochondrial disease can manifest with a multitude of
symptoms, including autism or autistic features and gastrointestinal symptoms, both of which L.V.
experienced. Id. at 113, 173. Classic phenotypes of mitochondrial disease are “usually progressive
and multisystemic” (Haas at 1327) and progressively severe, especially in the case of infants and
young children. Id. at 1329-30. But (as all experts testifying in this case agreed), it can be difficult
to diagnose mitochondrial disease given the variety of possible symptoms and the lack of a reliable
and agreed-upon diagnostic biomarker. Id. at 1327; Tr. at 114, 431-32. Thus, based upon up-to-
date medical and scientific thinking on the topic, the clearest diagnostic evidence that an individual
in fact has a mitochondrial disease is provided by genetic testing. Haas at 1327; Tr. at 433-44.

There are differences between a mitochondrial “disease,” “disorder,” and “dysfunction.”
As Dr. Kendall put it, “mitochondrial disease is a situation in which either you have definitive
information that clearly states that this person has a mitochondrial disease based on laboratory and
other factors,” while mitochondrial dysfunction is the proper term when there is not a clear
diagnosis. Tr. at 115. Dr. Cohen largely echoed this distinction, albeit by reframing the distinction
as between primary and secondary mitochondrial disease (which, as Haas defines it, is the result
not of a genetic mutation directly affecting the functioning of the electron transport chain, but
instead reflects impairment of the oxidative phosphorylation process by an “unrelated genetic or
environmental cause.”) Haas at 1330; Tr. at 435-36 (characterizing the phrase “mitochondrial
dysfunction” as “a very global generic term”). Ultimately, Dr. Kendall used the terms
“mitochondrial disease” and “mitochondrial disorder” somewhat interchangeably, while stressing
that the existence of a secondary mitochondrial disease, less severe than more classic phenotypes
such as Leigh disease, was nevertheless in her opinion sufficient to make the introduction of a
vaccine problematic. Tr. at 235.

The Petitioners’ argument that L.V. suffered from some form of mitochondrial disease
relies on a specific set of diagnostic criteria applicable to children first set forth in 2006 and
referred to in this decision as the “Morava” criteria. See generally Pet’rs’ Ex. 41, Ref. 25. It is
uncontested that Dr. Frye’s and Dr. Kendall’s diagnoses of L.V. rely on application of the Morava
criteria. Tr. at 120. Dr. Cohen also applied these criteria in reviewing Petitioners’ arguments
(although he questioned whether they have become obsolescent in light of scientific progress in
understanding mitochondrial disease).

The Morava criteria include three broad categories – clinical signs and symptoms,
metabolic/imaging studies, and morphology – and then, within each category, assign points to
certain defined symptoms or test results as set forth on a table contained in the article in which the
criteria were first proposed. Morava at 1824. Thus, one of the subcategories under the “clinical
signs and symptoms” heading is “CNS presentation,” which in turn sets forth ten different possible
symptoms, such as seizures, developmental delay, or cortical blindness, each of which is worth a
point under the proposed Morava system, with a “cap” of two points possible for this category. Id.
37
Similarly, the metabolic/imaging studies category sets forth eleven possible test results that could
merit awarding points (such as evidence of ethylmalonic aciduria or elevated lactate). Id.

Once points have been assigned, they are totaled and then compared to a range to determine
the likelihood that the patient has a mitochondrial disease. A score of one means that disease is
unlikely; two to four points merit a determination of “possible” mitochondrial disease; five to
seven points suggest mitochondrial disease is “probable”; and eight points or more result in the
determination that mitochondrial disease is definitely present. Morava at 1824 (Table). By the
Morava criteria’s own parameters, some symptoms are given slightly less weight than others, with
certain muscle biopsy morphology results given up to four points. Id. Indeed, as the Morava
authors acknowledged at the time of the article’s writing, some of the criteria’s utility lay in making
the very determination as to whether a muscle biopsy should be performed. Id. at 1823 (“[t]he
method could also be applied in children with a suspected mitochondrial disorder prior to
performing a muscle biopsy”).

Importantly, however, in the ten years that have passed since the publication of Morava,
there has been refinement of the diagnostic tools used to make the difficult determination of
whether an individual in fact suffers from a mitochondrial disease. Haas anticipated this progress,74
drawing a line between “red-flag” evidence of mitochondrial disease (Haas at 1327 (Table 1)) and
“nonspecific” findings that “do not indicate a mitochondrial problem per se, although their
presence should prompt concern.” Id. at 1328 (Table 2). Haas also stresses that genetic testing is
the most telling clinical factor, along with the “limited utility” of measuring lactate and/or pyruvate
via a muscle biopsy (id. at 1329) – a test that had only a few years previously been (Dr. Kendall
agreed) the “gold standard” for making the diagnosis. Tr. at 118. Although both mitochondrial
disease experts applied the facts to Morava, they largely agreed that the best approach to
diagnosing the disease is broader and less rigid than Morava’s framework. Tr. at 143, 240 (Dr.
Kendall stating that she uses the Morava criteria – albeit “loosely”); Id. at 463 (Dr. Cohen agreeing
with Dr. Kendall in the imprecise application of Morava).

It has become more common for Vaccine Program petitioners to assert that a particular
vaccine caused, or exacerbated, a child’s preexisting, often-unidentified metabolic disorder, such
as a mitochondrial disease, and that the disease was affected by the vaccine in such a way as to
precipitate the child’s autism or ASD-like symptoms. However, to date the vast majority of

74
As previously noted, I filed Haas as a Court Exhibit. Haas has previously been discussed in other cases in which a
petitioner sought to establish a causal relationship between a child’s receipt of a vaccine and her subsequent ASD, due
to a preexisting mitochondrial disease. See, e.g., Padmanabhan v. Sec'y of Health & Human Servs., No. 11-141V,
2015 WL 1736345, at *18 (Fed. Cl. Spec. Mstr. Mar. 26, 2015), mot. for review den’d, No. 11-141V (Fed. Cl. Aug.
6, 2015), aff’d, ___ F.3d ___, 2016 WL 463085 (Fed. Cir. 2016) (applying Haas (also filed as a court exhibit) in case
in which petitioners alleged that child’s preexisting mitochondrial disease was aggravated by vaccines, resulting in
ASD).

38
petitioners have failed in establishing any of the Althen elements in support of this kind of theory,
regardless of the vaccine at issue. See, e.g., Hardy, 2015 WL 7732603; R.K. v. Sec’y of Health &
Human Servs, slip. op. (Fed. Cl. Spec. Mstr. Sept. 28, 2015), mot. for review den’d, ___ Fed. Cl.
__ (Dec. 18, 2015); Padmanabhan v. Sec'y of Health & Human Servs., No. 11-141V, 2015 WL
1736345 (Fed. Cl. Spec. Mstr. Mar. 26, 2015), mot. for review den’d, No. 11-141V (Fed. Cl. Aug.
6, 2015), aff’d, ___ F.3d ___, 2016 WL 463085 (Fed. Cir. 2016) (petitioners failed to demonstrate
plausible causation theory in support of claim that child’s preexisting mitochondrial disease was
significantly aggravated by vaccines).

The only exception to the above is Paluck v. Sec’y of Health & Human Servs., 786 F.3d
1373 (Fed. Cir. 2015). There, the Federal Circuit affirmed a Court of Federal Claims’
determination that a special master erred in denying compensation to petitioners claiming (in a
non-Table case) that the MMR, varicella, and pneumococcal vaccines significantly aggravated
their child’s mitochondrial disease, resulting in severe neurodegeneration. However, that case is
facially distinguishable – not only because it involved different vaccines and a more obvious
immediate reaction75 to them (that, significantly, was classified as “neurodegenerative,” rather
than as an ASD), but more importantly because the child’s mitochondrial disease was not a
contested fact (as is the case here). The result in Paluck thus cannot be reasonably understood to
predict the theory’s likely acceptance in future decisions, but instead was the product of its own
unique set of facts. See, e.g., Hardy, 2015 WL 7732603, at *35 (Fed. Cl. Spec. Mstr. Nov. 3, 2015)
(“in no case presented to me . . . has there been presented any persuasive evidence that even in a
child with an actual mitochondrial disorder, vaccines can cause or aggravate that child's ASD”).76

75
The vaccinated child (a one-year old) in Paluck had experienced a persistently high fever in the two to seven days
immediately after receiving the vaccines, and was soon thereafter diagnosed with possible neurologic problems
confirmed by MRI results, among other things. Paluck, 786 F.3d at 1376. Also likely relevant to the causation theory
offered in Paluck was the fact that the Paluck petitioners relied on Dr. Frye himself as their testifying expert – unlike
here, where Dr. Frye’s diagnosis is only indirectly referenced (and not wholly accepted by Dr. Kendall either).
76
Petitioners have suggested that the Federal Circuit’s finding that Respondent “conceded” the causation theory
offered in Paluck bulwarks the theory’s reliability in this case. Petitioners’ Post-Trial Brief (ECF No. 155) at 65-66.
But it is a well-worn axiom in Vaccine Program cases that the results in one case do not dictate the results in another.
Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998). A corollary principle is that Respondent’s
concession based on the facts of a particular case similarly does not bind Respondent in a different case.
Padmanabhan, 2015 WL 1736345, at *42 n.115 (“a concession by respondent in one case does not constitute a
concession in another, as science and medicine are not immutable, and evidence filed in one case may not be filed in
another case. For example, a concession that the measles vaccine can cause an encephalopathy occurring within five
to fifteen days of a vaccination is not a concession that it can do so at times shorter or longer”) (citing Shyface v. Sec’y
of Health & Human Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)). In this case Respondent unequivocally does not
concede the theory’s reliability or plausibility. Respondent’s Post-Trial Brief (ECF No. 157) at 21 n.8; Tr. at 477-78,
480, 482.

Moreover, Petitioners exaggerate the extent to which Respondent actually conceded the Paluck causation theory.
Although Respondent’s expert in Paluck admitted, during the initial hearing and while under cross-examination, that
the theory had plausibility, Respondent never formally agreed that Petitioner had established this particular Althen
39
V. 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).77
No Table claim is asserted in this case, nor do I find the facts would support one.

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

prong. In addition (as observed by the special master presiding over the case, after it was remanded to him the first
time), Respondent effectively dropped the issue entirely (perhaps discouraged from further litigating it after the Court
of Federal Claims’ first remand, in which the Court strongly indicated its view that the evidence presented was
sufficient to satisfy the “can cause” first Althen prong). Paluck v. Sec’y of Health & Human Servs., No. 07-889V, 2013
WL 2453747, at *42 (Fed. Cl. Spec. Mstr. May 10, 2013), mot. for review granted, 113 Fed. Cl. 210 (2013), aff’d,
786 F.3d 1373 (Fed. Cir. 2015) (Paluck special master noting that even though Respondent had not made an “outright
concession” of petitioners’ theory, she “did not present any substantive argument regarding prong one of Althen in
any of her post-remand briefs”). Although an unrebutted evidentiary showing, and/or admission by a witness, may
constitute a “concession” within that single case for purposes of determining whether a petitioner has met his “can
cause” causation burden, such an occurrence cannot be expanded to mean that the Respondent has accepted the
scientific or medical plausibility of the same theory applied to different fact patterns.
77
Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding
authority. Hanlon, 40 Fed. Cl. at 630. 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, 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).

40
13(a)(1).

In attempting to establish entitlement to a Vaccine Program award of compensation, 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,
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.” Knudsen, 35 F.3d 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
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)). But this does not negate or reduce a
petitioner’s ultimate burden to establish his 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).

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).
41
 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
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).

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).

In this matter, besides arguing that the flu vaccine caused L.V.’s autism and/or autistic
regression, Petitioners also offer a parallel theory that the flu vaccine significantly aggravated a
preexisting condition in L.V. – his purported mitochondrial disease. Where a petitioner so alleges,
the Althen test is expanded, as a petitioner has additional evidentiary burdens to satisfy. See
generally Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl. 135, 144 (2009). In Loving, the
Court of Federal Claims combined the Althen test with the test from Whitecotton v. Sec’y of Health
& Human Servs., 81 F.3d 1099, 1107 (Fed.Cir.1996), which related to on-Table significant
aggravation cases. The resultant “significant aggravation” test has six components, which are:

(1) the person's condition prior to administration of the vaccine, (2) the person’s current
42
 condition (or the condition following the vaccination if that is also pertinent), (3) whether
the person’s current condition constitutes a ‘significant aggravation’ of the person's
condition prior to vaccination, (4) a medical theory causally connecting such a significantly
worsened condition to the vaccination, (5) a logical sequence of cause and effect showing
that the vaccination was the reason for the significant aggravation, and (6) a showing of a
proximate temporal relationship between the vaccination and the significant aggravation.

Loving, 86 Fed. Cl. at 144; see also W.C. v. Sec’y of Health & Human Servs., 704 F.3d 1352, 1357
(Fed. Cir. 2013) (holding that “the Loving case provides the correct framework for evaluating off-
table significant aggravation claims”). In effect, the last three prongs of the Loving test correspond
to the three Althen prongs.

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
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.
43
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
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.
44
Sec’y Health & Human Servs., 110 Fed. Cl. 184, 203-04 (2013), aff’d, 2014 WL 1258137 (Fed.
Cir. Mar. 28, 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 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.

Respondent frequently offers one or more experts of her own in order to rebut 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
45
(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 is offering an opinion that exceeds the expert’s 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). The mere fact that a person dons a “white lab coat,” so to speak, and
then offers an expert opinion does not imbue that opinion with automatic legitimacy.

VI. ANALYSIS

Both of the Petitioners’ causation theories depend on evidentiary fact-findings in their
favor – either that L.V. had a specific, preexisting mitochondrial disorder, or that he experienced
an autoimmune encephalopathy that in turn produced a dramatic, post-vaccination regression. It is
logical to first determine if the evidence supports either requested finding before considering if the
Althen prongs can be 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 special master could subsequently determine causation
relative to the injury”).

46
 A. L.V. Did Not Have a Mitochondrial Disease or Mitochondrial Dysfunction.

Neither expert accepted Dr. Frye’s diagnosis that L.V. had a “definite” mitochondrial
disease under the Morava criteria, so the primary fact issue posed at trial was whether the evidence
established a “probable” disease. Resolving this issue required weighing the testimony of Dr.
Kendall78 against that of Dr. Cohen, and evaluating their competing interpretations of the various
test results relevant to the disputed diagnosis. Although Dr. Cohen has more overall experience in
the specialty of mitochondrial disease,79 both experts were qualified to opine on the topic, and I
found both comprehensible in their testimony and willing to concede reasonable points.

Dr. Cohen’s opinion, however, in light of the relevant facts gleaned from the medical
records as well as its logic, was the more persuasive of the two. In particular (and although Dr.
Cohen did directly grapple with Petitioners’ argument that L.V.’s test results and other symptoms
met the Morava criteria for diagnosis), his underlying point – that the Morava criteria have been
supplanted by more precise diagnostic guidelines, and are therefore not a reliable basis for
assessing whether a child has a mitochondrial disease – had considerable force and was unrebutted
by Petitioners.

As Dr. Cohen established, Morava’s point system, despite its seeming structure, is
imprecise, giving too much weight to nonspecific findings, such as exercise intolerance or
gastrointestinal problems, and equating them with “red flag” evidence that is closely linked with
well-recognized phenotypes of mitochondrial diseases. Petitioners have thus relied on an outdated
diagnostic toolset, since current science and medical knowledge (which has made more definitive
tests like genetic testing possible) has cast doubt on the significance of certain criteria previously
considered important. Thus, even if the Morava criteria were correctly applied under the
circumstances to reach the tentative conclusion that L.V. had some mitochondrial disease (subject
to a muscle biopsy – one of the possible uses for the criteria, as the article itself indicates (Morava
at 1823)), it is evident today that overreliance upon it is inadvisable.

I therefore do not accept Petitioners’ assertions that the determination that L.V. had a
mitochondrial disease is simply a matter of deciding if Morava’s point system is satisfied by the
evidence. Rather, I find persuasive Dr. Cohen’s testimony that, based on the more up-to-date

78
Dr. Kendall adequately explained Petitioners’ mitochondrial disease-related causation theory. I therefore do not
address Dr. Shafrir’s brief parallel statements about mitochondrial disease and its relevance to this case (although I
also note that he plainly lacked sufficient professional expertise in the field to reliably comment on it).
79
Dr. Cohen has the edge over Dr. Kendall in experience studying mitochondrial disease, diagnosing it in patients,
and treating it. Indeed, he was an author of Haas, a piece of literature that was especially persuasive in evaluating
advances in diagnosing mitochondrial disease. I therefore give more weight to his conclusions simply (although not
exclusively) on this basis.

47
diagnostic guidelines that differentiate nonspecific symptoms80 from “red flag” symptoms, the
overall weight of the evidence – which takes into account L.V.’s history and test results – does not
support the conclusion that L.V. had such a disease of any kind. L.V.’s medical history is devoid
of the kind of clear symptoms associated with the most severe phenotypes of mitochondrial disease
like MELAS or Leigh disease, and the results of his testing that would most persuasively confirm
the existence of a mitochondrial disease, like a muscle biopsy or genetic test, were negative for the
disease. The biomarker test results were largely inconclusive, with some pointing to a possible
problem and some not, thus indicating that positive results are worthy of less weight than the
Petitioners urge. Applying up-to-date clinical criteria, Petitioners did not establish by a
preponderance that L.V. had a mitochondrial disease.

Regardless of the above, even if I simply apply the Morava criteria mechanically to the
various test results and other factors in light of it (but based on each expert’s interpretation of those
results), I still conclude that the evidence does not preponderate in L.V.’s favor. It is undisputed
by both testifying experts that neither genetic testing nor L.V.’s lactate levels were supportive of
a mitochondrial disease. See, e.g., tr. at 140. Dr. Cohen also persuasively testified to the diminished
value of the nonspecific criteria for which Dr. Frye awarded Morava points, such as L.V.’s ongoing
constipation, since they did not amount to the kind of more telling, serious indicia that would
suggest to most treaters that an individual actually had a mitochondrial disease. Id. at 566-67
(“[c]onstipation is common in autism. The constipation doesn’t rise to the level that we see it in
mitochondrial disease”). And Dr. Kendall admitted that other nonspecific findings, such as
exercise intolerance, that were the basis for Morava points had little support in the medical record.
Id. at 193-94, 245.

The remaining Morava points awarded by Dr. Kendall are based on a mix of biochemical
marker and morphology test results. But, as Dr. Cohen established, those findings were either not
supportive of the diagnosis, inconclusive in light of subsequent tests (or a failure to repeat an
abnormal finding), or could reasonably be interpreted as normal. Dr. Cohen was steadfast in
denying the significance of the morphology findings (as observed in the microscopy evaluations
of L.V.’s muscle tissue samples), such as the increased mtDNA (which is not associated with
pediatric mitochondrial disease in any event) or swollen mitochondria. Tr. at 555-58. He
acknowledged that some other biomarker tests (the urinary tricarboxylic acid and ethymalonic

80
Dr. Cohen’s point about the diminished value of many of the nonspecific factors relied upon by Drs. Frye and
Kendall herein, in light of the shift in thinking about the most accurate clinical tests for diagnosing a mitochondrial
disease, has particular resonance in the context of deciding a Vaccine Program claim. Morava posits that evidence of
developmental delay is itself worthy of a “point” in evaluating the presence of a mitochondrial disease – yet in the
context of a Vaccine Program claim, it is highly circular and conclusory to argue that the existence of the claimed
illness that a vaccine is alleged to have caused is also proof of causation. Although Morava may have some scientific
value, this is a legal proceeding, and it is thus reasonable in this context to view skeptically a diagnostic toolset that
imbues such nonspecific evidence with significance.

48
aciduria findings) produced elevated results, but convincingly testified that they were
insufficiently high to warrant any additional points. Id. at 559, 563.81

Drs. Frye’s and Kendall’s reliance on L.V.’s ASD and related regression as worthy of a
Morava point is especially troubling given the undisputed medical record. Dr. Kendall readily
acknowledged that L.V. does not have a primary mitochondrial disease, given the lack of severity
of other symptoms. Tr. at 237-38. She also struggled to point to evidence from the same record of
any dramatic signs of regression post-vaccination, and could identify little to nothing from L.V.’s
earlier medical history that evidenced the condition pre-vaccination. Id. at 246-49. And yet, as Dr.
Cohen noted, it is only the most severe phenotypes of mitochondrial disease that are associated
with the kind of sudden and dramatic decompensations that would establish the existence of the
disease. L.V.’s mitochondrial disease was, by contrast, (and as Dr. Kendall admitted), mild – but
that cannot be squared with the concept that it nevertheless produced a dramatic change in L.V.

In concluding as I do, I am not attempting to diagnose L.V. myself (an act well outside the
purview of my function herein). Rather, I am weighing the sufficiency of the evidence presented
from a legal standpoint – and finding that such evidence does not make it “more likely than not”
that L.V. suffered from a mitochondrial disease of any kind. I have given consideration to the
treatment evidence from Dr. Frye upon which the Petitioners rely. But as noted above, a treater’s
opinion need not be accepted at face value, but is subject to weighing against the other evidence
in the case. Snyder, 88 Fed. Cl. at 746 n.67. Dr. Frye’s conclusions (which were arrived at four to
five years ago, and well after the vaccination event in question) are undermined not merely by Dr.
Cohen’s more persuasive interpretation of the relevant test results, but also by the fact that none
of L.V.’s immediate treaters (who were present contemporaneously when L.V.’s developmental
regression is alleged to have occurred, and therefore better positioned to observe his symptoms)
ever opined that L.V. suffered from a mitochondrial disease or dysfunction, whether before or after
he received the flu vaccine. Indeed, Dr. Kelley (to whom the Vs were referred by Dr. Frye)
reviewed many of those same test results upon which Dr. Frye based his diagnosis, but offered the
conclusion that L.V. likely did not have a mitochondrial disease. Pet’rs’ Ex. 26 at 32-33; Tr. at
202-04.

B. L.V. Did Not Experience a Post-Vaccination Encephalopathy.

Petitioners offered a second causation theory in this case: that L.V.’s receipt of the flu
vaccine precipitated an encephalopathy that resulted in the regression and other ASD symptoms

81
Even if I credited these test results and agreed with Drs. Kendall and Frye that they merited any Morava points, I
would conclude only that the tally of points is three, which under Morava results in the determination of a “possible”
mitochondrial disorder. Morava at 1824 (Table). Given the total lack of other, more telling indicia corroborating the
diagnosis (genetic testing, lactate levels, or symptoms associated with known disease phenotypes), and conflicting
treatment evidence (as evidenced by the conflicting diagnosis of Dr. Kelley), I would still be unable to conclude that
such a showing establishes by preponderant evidence that L.V. had a mitochondrial disease.
49
he experienced. As discussed below (in the section on the Althen prongs), there are strong reasons
to find this theory wanting. But independent of the theory’s scientific plausibility, the facts from
the medical records do not support the conclusion that L.V. did experience the encephalopathy
necessary under this theory.

The medical records from December 2006 and January 2007 are directly relevant to this
part of the Petitioners’ case. They plainly demonstrate that on December 13, 2016 – five days after
L.V.’s receipt of the second dose of flu vaccine – Mrs. V brought L.V. back to the pediatrician,
primarily to treat his ongoing constipation. No mention was made of the second vaccination, let
alone any of the kind of symptoms that might be expected if L.V. was suffering a reaction to it (in
particular, fever). Pet’rs’ Ex. 3 at 134-35. The records from this visit also set forth the fact that he
was at that time apparently suffering from an ear infection, but do not note any fever associated
with it. Id.

Significantly, the December 13th records contain the first obvious reference to any
developmental problems (specifically, speech delay), but provide no detail about whether they had
just recently been observed (as opposed to something noticed before). Pet’rs’ Ex. 3 at 135. But
speech delay is not itself congruent with the severe regressive occurrence alleged in this case –
especially given the absence of evidence of any other kind of medically-concerning reaction to the
vaccine received less than a week earlier, such as a high fever. And the probative value of the
timing of this reported speech delay is further diminished by later, particularly persuasive
contemporaneous evidence (beginning in January 2007) that the Vs repeatedly told treaters that
they had observed the start of L.V.’s developmental plateau or regression before he was 22 months
old. See, e.g., Pet’rs’ Ex. 13 at 8 and Ex. 5 at 4.

The next most significant contemporaneous records relevant to the encephalopathy-related
assertions are from December 22 and 26, 2006. These detail treatment of L.V.’s ongoing ear
infection, and establish that (several days after the start of the infection) he did eventually develop
a fever over 100 degrees, going as high as 104 degrees. Pet’rs’ Ex. 3 at 138-40. However, the fever
does not appear to have been persistent, and by December 26, 2006, the records merely note a rash,
suggesting that in the ensuing period the fever had resolved. Id. at 144. Certainly the records do
not reflect L.V.’s hospitalization in this period, or any other truly catastrophic reaction requiring
emergency intervention; rather, they establish the Vs’ diligence in attending to L.V.’s care over
the holidays by reporting his fever and other ear infection symptoms to their primary care
pediatrician. And there are no further records of L.V. seeing the pediatrician until several weeks
later, in January – by which time the Vs had already begun the process of having L.V.
professionally evaluated for his developmental problems. Such evidence does not support the
contention that L.V. experienced an encephalopathy.

For purposes of comparison, it is instructive to consider the facts of the Poling and Wright
50
cases, where petitioners successfully established (or settled) Table claim82 encephalopathies
resulting in ASD symptoms. In the Poling case, for example – a matter that the Petitioners have
repeatedly argued is highly relevant – the child in question (who was later diagnosed with
mitochondrial disease) had received several vaccinations (not including the flu vaccine), 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. Pet’rs’ Ex. 41, ref. 26 at 170. In Wright, the petitioners’ child received
Pentacel (a multi-virus vaccine)83, 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 noticeable decreased level of consciousness and lethargy, during which the child’s
parents made many unsuccessful efforts to convince the relevant pediatric treaters of the severity
of his condition. Wright, 2015 WL 6665600, at *12-16. Although both cases are distinguishable
for many reasons, together they demonstrate the extreme factual circumstances reflecting an
encephalopathy – in contrast to the evidence here.

Petitioners have offered little else to prove that an encephalopathy in fact occurred. An
encephalopathy can often be corroborated after the fact, through an MRI, direct evidence of
inflammation, or testing demonstrating the presence of certain antibodies associated with
autoimmune reactions affecting the brain – but as both of Petitioners’ experts admitted, there is no
such evidence in this case. Tr. at 201-02, 362-64. And no treaters who saw L.V. at the relevant
time opined otherwise. The overall factual record (as Dr. Cohen proposed, based on his review of
L.V.’s treatment history and in light of his experience as a pediatric neurologist) does not support
the conclusion that L.V. experienced any encephalopathy of the sort that would prompt the
dramatic regression alleged by Petitioners. Id. at 508-14.

C. Petitioners Have Not Satisfied the Althen Prongs.

Petitioners’ claim depends upon my finding that L.V. either had a mitochondrial disease or
experienced a post-vaccination encephalopathic regression, so my contrary factual conclusions are
fatal to their case. Yet review of the three Althen prongs for establishing a non-Table causation
case reveals that Petitioners could not otherwise prevail on their claim due to evidentiary failures
independent of my fact-findings set forth above.84
82
This case does not involve a Table claim, but Wright and Poling provide the only comparable instances in which a
petitioner has established the kind of encephalopathy that produced the sort of neurologic and/or developmental
changes that Petitioners alleged herein occurred to L.V.
83
Pentacel is the trade name for a vaccine that consists of combined DTaP, inactivated polio virus, and Haemophilus
influenza type B vaccines. Dorland’s at 1406.
84
Because I have determined that Petitioners have not established by preponderant evidence that L.V. suffered from
any form of mitochondrial disease, L.V. also cannot be said to have suffered from a preexisting condition subject to
aggravation, and therefore I do not review the first three prongs of the Loving test. See, e.g., Bushnell v. Sec’y of Health
51
 1. The Flu Vaccine did not Cause L.V.’s Regression (Althen Prong Two)

The greatest deficiency in the Petitioners’ case is that they have not established by
preponderant evidence that the flu vaccine did in fact cause L.V.’s regression – whether directly
(by precipitating an encephalopathy that then resulted in a dramatic developmental regression) or
indirectly (by impacting L.V.’s preexisting mitochondrial disease, which in turn precipitated the
purported regression). Rather, the overall record suggests that any loss of skills or language L.V.
suffered likely began before his receipt of the second flu vaccine. The records otherwise do not
reveal a dramatic drop-off in skills after the December 8th vaccination, let alone an
encephalopathic incident of sufficient magnitude to produce regression.

I find especially probative the numerous occasions on which the Vs reported to ASD
specialist treaters that they were aware of L.V.’s problems at 16-18 months, well before he received
even the first flu vaccine. The presumption of the accuracy of statements contained in
contemporaneous medical records is based on the reasonable belief that individuals attempt to tell
treaters as much of the truth about an illness as they can, in the expectation that doing so increases
the likelihood of effective treatment. Capizzano, 440 F.3d at 1326; Sanchez, 2013 WL 1880825,
at *2. It is proper to give such records more weight than subsequent testimony attempting to rebut
the statements that is otherwise not sufficiently compelling. Cucuras, 993 F.2d at 1528; Sanchez,
2013 WL 1880825, at *3.

Admittedly, L.V.’s pediatric records before November 2006 say little about developmental
problems, as the Petitioners stress. Petitioners have also identified occasional inconsistencies
between those records and subsequent autism/developmental evaluation records.85 But there are

& Human Servs., No. 02-1648V, 2015 WL 4099824, at *19 n.22 (Fed. Cl. Spec. Mstr. June 12, 2015) (no need to
apply Loving factors to claim that child’s autism was significantly aggravated by preexisting mitochondrial disorder
where petitioners could not demonstrate any vaccine involvement in child’s condition).

Petitioners’ significant aggravation theory would, however, still founder on the third Loving prong even had they
established that L.V. suffered from the milder form of mitochondrial disease proposed by Dr. Kendall. The Petitioners
and their experts offered little reliable or persuasive evidence that L.V.’s post-vaccine developmental and behavioral
changes were more severe than what a similarly-situated child would experience without vaccination. Indeed – the
Petitioners point to L.V.’s ASD symptoms (under Morava) as evidence of his mitochondrial disease, based upon
Morava’s assumption that developmental problems are associated with mitochondrial dysfunction (even in the absence
of vaccination). But if so, this renders it difficult to determine whether L.V. was really worse off post-vaccination than
he would have been otherwise, and Petitioners’ conclusory argument that this was nevertheless the case is inadequate
to establish preponderant proof of this third Loving factor. See Broussard-Pacot v. Sec’y of Health & Human Servs.,
No. 09-107V, 2012 WL 5357478, at *19 (Fed. Cl. Spec. Mstr. Sept. 4, 2012) (petitioners’ claim of significant
aggravation of preexisting seizure disorder was inadequately “developed or substantiated,” because it lacked medical
support that child’s development would have been different but for the vaccines).
85
During the entitlement hearing, the Petitioners devoted some effort to suggesting that statements of the Vs from
2007 and later about the onset of L.V.’s regression should be ignored because they were contained in untrustworthy
52
sufficient documented instances in which the Petitioners made post-vaccination contemporaneous
statements about the timing of L.V.’s developmental regression to find that the evidence
preponderates against the fact-finding urged by Petitioners. Indeed – Mrs. V admitted to having
had concerns about L.V.’s development prior to his receipt of the flu vaccine (a fact Dr. Shafrir
also admitted), and thus her testimony was inconsistent in supporting Petitioners’ overall claim
that the records setting forth the pre-vaccination onset were not credible.

In addition, as discussed above, the evidence pertaining directly to L.V.’s post-vaccination
health and developmental condition similarly does not suggest that he experienced an immediate,
dramatic change that was vaccine-related, even if some of his developmental problems became
more evident after December 8th. The weight of the evidence does not support the conclusion that
the second dose of the flu vaccine caused L.V. to react in the manner that the literature suggests a
person experiencing an immune-mediated encephalopathic event would, and that could in turn
precipitate developmental regression. No evidence was offered to suggest that the flu vaccine was
causally related to L.V.’s ear infection, or that the infection was not the source of the fever he
subsequently experienced. L.V.’s most immediate post-vaccination illness was constipation
(something he had suffered from previously), followed by an ear infection that did not result in
fever until almost two weeks after the second flu vaccine dose, and which was successfully treated
without hospitalization. The medical records do not corroborate Petitioners’ allegations that L.V.
experienced an autoimmune reaction from the flu vaccine – as Petitioners’ experts admitted. Tr. at
362 (Dr. Shafrir admitting on cross-examination as to the absence of “objective evidence in the
record of an immune reaction in L.V.’s brain to the flu vaccine”).

medical records, which were either poor examples of record-keeping, reflected incompetency on the part of the
medical professional responsible for creating them, or were contradicted by other documents. Thus, for example, they
took particular issue with the statement in Dr. Coplan’s January 23, 2007 written assessment that L.V. had only
recently begun scoop-feeding (“typically a 12-month milestone,” as Dr. Coplan put it (Pet’rs’ Ex. 5 at 3)), observing
that a September 8, 2006, pediatric record (when L.V. was 18 months old) not only stated that L.V. was
“developmentally appropriate” at the time, but also that he “uses spoon and cup.” Pet’rs’ Ex. 3 at 122-23; Tr. at 539-
41. Although I agree the earlier record is inconsistent, I do not find that inconsistency a sufficient basis to discredit
Dr. Coplan’s entire record (given the number of other subsequent records in which the Vs placed onset before
vaccination). It is also reasonable to expect that a pediatric well-child visit would less likely include a careful
evaluation of a child’s development unless the parents raised the issue (and in fact, when the Vs did raise such issues,
they are reflected in such pediatric records), or something obvious occurred during the visit.

There is other evidence, moreover, suggesting that Dr. Coplan’s January 2007 assessment about L.V.’s self-feeding
capabilities was closer to the truth than the September 2006 pediatric record. Thus, in the January 17, 2007, early
intervention assessment performed by Montgomery County (before the Vs informed Dr. Corcoran of their intent to
seek early intervention for L.V. and were referred to Dr. Coplan), in the section entitled “Adaptive Development,”
which asks for a statement on the assessed child’s “self-help skills such as feeding,” the treater (Dr. Beth Appelbaum)
recorded the Vs’ statement to her that L.V. “will bring a spoonful of food to his mouth once Mom has scooped the
food.” Pet’rs’ Ex. 13 at 7 (emphasis added). This statement (which permits the inference that L.V.’s feeding skills
were in fact developmentally behind) is consistent with Dr. Coplan’s similar statement.

53
 This is far from a case in which a sudden, dramatic developmental regression is evident –
or where a vaccine has a demonstrable, severe physiological effect on an individual which in turn
could theoretically be connected to the subsequent regression into an ASD. Instead, the facts are
consistent with a more typical ASD presentation – when, over time, parents become aware that a
variety of smaller developmental missteps, setbacks, or plateaus in their child’s development have
significance.

2. Petitioners did not Establish Reliable Causation Theories (Althen Prong
86
One)

Neither theory proposed by Petitioners was sufficiently grounded in relevant science to
constitute a reliable theory in satisfaction of the first Althen prong.

a. Mitochondrial Disease Theory - The primary causation theory
offered in the case was that a child suffering from a preexisting mitochondrial disease could
experience a reaction to the flu vaccine sufficient to produce autism. But the expert responsible for
presenting the theory, Dr. Kendall, is not an immunologist. In fact, she was notably circumspect
in articulating the components of the theory involving the flu vaccine’s “but for” capabilities,
preferring instead to emphasize her opinion that the record supported L.V.’s diagnosis of
mitochondrial disease. Otherwise, beyond her conclusory suggestion that a vaccine could cause
sufficient oxidative stress to an individual with a mitochondrial disease to precipitate a regression,
she offered little reliable evidence – whether from her own experience or research, or a laboratory
test or case study cited in her report – establishing that the flu vaccine could be so associated with
causing developmental regression in children who also suffer from a mitochondrial disease. Tr. at
212-13, 162-63.87

Instead, Dr. Kendall’s testimony on the flu vaccine’s causation role primarily relied on case
studies (one of which was merely a description of the facts from Poling) that are limited in
probative value since they describe only unrepresentative outlier instances that ultimately assume,
without direct study or evidence, that vaccination could precipitate a chain of events resulting in

86
I reject Petitioners’ oft-repeated argument in this case that Respondent has waived objecting to their causation theory
that vaccines can exacerbate preexisting mitochondrial disorders resulting in autism. As I ruled previously in this
matter, the fact that Respondent settled the Poling case has no preclusive effect herein, mainly because Poling involved
a Table claim that was not adjudicated to a reasoned decision. See ECF No. 124. Former Chief Special Master Vowell
ruled similarly in the recent case of R.K., and the Court of Federal Claims upheld that aspect of her decision (in
addition to her bases for denying compensation). R.K., ___ Fed. Cl. __, at 18 (Dec. 18, 2015). Because R.K. is subject
to a broad redaction challenge (in which the case’s index number has been requested redacted), and because the
decision is not yet published, my reference to it is vague by necessity.
87
In addition, Dr. Kendall would not affirmatively state it was “more likely than not” that the flu vaccine had anything
to do with L.V.’s condition if in fact his developmental problems preceded the time of vaccination. Tr. at 185-86.

54
regression. The Shoffner article, for example, involved a retrospective chart review of 28
individuals diagnosed with both mitochondrial disease and an ASD. Nearly a third of the studied
individuals (17 of 28) experienced developmental regression, and nearly 71 percent of that subset
regressed after fever (although the fevers’ extent and duration were unknown, as the study relied
wholly on parental reports of fever rather than clinically-confirmed data, making that variable
unreliable scientifically). But as noted above, the applicability of a study involving high fever as
the immediate proximate factor in causing regression is greatly diminished in a case in which
evidence of a similarly prolonged, medically-concerning fever is lacking. Nor did Dr. Kendall link
Shoffner’s findings to additional literature suggesting any vaccine’s propensity to cause the kind
of fever necessary to precipitate the decompensation observed in Shoffner. Indeed – the article’s
authors explicitly recognized that their study found no relationship between vaccination and the
observed regression. Shoffner at 432 (“the vaccines did not appear related to the neurologic
regression”). Such literature may suggest to a scientist an avenue for further study but does not
substantiate Petitioners’ causation theory.

Thus, Dr. Kendall generally failed to provide reliable evidence plausibly linking the flu
vaccine to regression in individuals with mitochondrial diseases. Petitioners offered no other
testimony from a qualified immunologist on the topic (the kind of expert best suited to opining on
the biologic capabilities or functioning of a vaccine generally).88

Petitioners attempted to fill this evidentiary hole with literature – voluminous amounts,
much of which was only glancingly referenced during the hearing. See generally Pet’rs’ Exs. 101-
05 and 113-16; Tr. at 153-68. Dr. Kendall was asked at certain points in her testimony to comment

88
Petitioners attempted to suggest that Dr. Cohen had in the past admitted that vaccines might have some precipitating
effect on children with mitochondrial disease, primarily by cross-examining him about an article from 2008 that he
co-authored (with nine other specialists), J.R. Weissman, et al., Mitochondrial Disease in Autism Spectrum Disorder
Patients: a Cohort Analysis, 3(11) PLOS ONE 1-6 (2008) [hereinafter, Weissman]; Tr. at 584-90. Weissman is a
retrospective review of the medical histories of 25 ASD-diagnosed patients who also had identifiable mitochondrial
disease or dysfunction, and argues that “defective mitochondrial oxidative phosphorylation is an additional pathogenic
basis for a subset of individuals with autism.” Weissman at 5. Dr. Cohen acknowledged his role in the paper’s writing,
but testified that before its publication, he tried unsuccessfully to have his name removed as an author. Tr. at 586. He
also disputed the accuracy of certain statements it contains, including one proposing that the stress caused by a vaccine
reaction might be comparable to that of the “diseases which are known precipitants of mitochondrial regression.”
Weissman at 4; Tr. at 588. I do not find that Dr. Cohen’s prior scientific interest in the possibility of a relationship
between a vaccine and regression in individuals with confirmed mitochondrial disease undermines his present
testimony that he no longer believes such a relationship exists.

These purportedly inconsistent views of Dr. Cohen (to the extent they are considered his actual views, rather than
statements in an article he now claims to have disavowed at time of publication) must also be considered in light of
his other, unrebutted testimony that earlier in his study of mitochondrial diseases, he had considered the possibility of
a relationship between autism and such diseases, but later rejected the connection. Tr. at 438-39. This, plus the fact
that Weissman was written approximately eight years ago, greatly diminishes the significance of Petitioners’
suggestion that Dr. Cohen has conceded that a vaccine could have any causal role in precipitating regression or other
ASD-like behavioral or developmental problems in children with mitochondrial diseases.

55
on some of this additional literature. However, in some cases, she was unfamiliar with the cited
article (tr. at 164), whereas in other cases she did nothing more than repeat the article’s findings
and then attempt to relate them to her opinion, rather than demonstrate how her opinion actually
arose from or relied upon their findings.89

Such literature formed a patchwork theory, attempting to analogize disparate circumstances
to the present. At best, some of the medical/scientific evidence offered in this case suggests that
children suffering from the most severe phenotypes of mitochondrial disease (e.g., Leigh disease
or MELAS) might experience a dramatic regression in development, as one facet of a progressively
worsening condition that could result in death, but without any relationship to vaccination. Tr. at
601-04. L.V.’s condition, by contrast, while surely lamentable, is unquestionably not characterized
by that degree of severity, as Dr. Kendall acknowledged. Id. at 237. There was also evidence
offered suggesting that many individuals with ASDs also experience mitochondrial diseases or
lesser dysfunction. In contrast, Dr. Cohen forcefully testified that the notion that there is a possible
pathogenic relationship between autism and mitochondrial disease has (at least to date) not been
sufficiently substantiated by science (and which he personally doubts based on his own
experience). Id. at 437-39. At bottom, Petitioners failed to offer a reliable theory that such
individuals would ever experience a dramatic developmental regression of the kind alleged to have
happened to L.V. as a result of the flu vaccine’s effects on the body.

89
Such articles, moreover, were not especially helpful or pertinent, and reflected the same “connect the dots” approach
(linking literature that only facially relates to the causation theories presented in this case, while omitting crucial
evidence required for the theory’s overall validity) that was so characteristic of Dr. Shafrir’s testimony. Thus, for
example, Dr. Kendall was asked about Tran. Tr. at 162. Tran involves an in vitro study of the live flu virus (rather
than vaccine) and its capacity to induce apoptosis (cell death) in the process of the virus’s replication through
“dysregulation of the mitochondrial outer membrane permeabilization and the subsequent release of apoptogenic
factors.” Tran at 1050. Tran has nothing to do with mitochondrial disease or dysfunction per se or a vaccine’s capacity
to trigger a reaction in an individual suffering from such a disease, however, as its authors explicitly state (“[o]ur study
presents evidence to further emphasize the importance of understanding the intricate relationship apoptosis has in
promoting influenza virus propagation”). Id. at 1059-60.

In the same vein, the Petitioners briefly questioned Dr. Kendall about another article (Pet’rs’ Ex. 114, N. Klein, et
al., 12 Evaluation of Immunization Rates and Safety Among Children with Inborn Errors of Metabolism, PEDIATRICS
1139-46 (2011) [hereinafter, Klein]) ostensibly supporting the proposition that “stressors” could precipitate illness in
children suffering from mitochondrial diseases. Tr. at 159-60. Klein presented a retrospective epidemiologic study of
a population of immunized children, including a small percentage known to have inborn errors of metabolism (“IEM”).
But the article merely concluded that although “the most vulnerable” children demonstrated increased hospitalization
rates two weeks after vaccination, “vaccinating children with IEMs with routinely recommended vaccines does not
seem to put them at increased risk of adverse effects.” Klein at 1146. Citing such an article as support for the notion
that the flu vaccine in this case could have plausibly harmed a child in L.V.’s circumstances (because it is always
possible even if the vaccine in most cases is not contraindicated for children with metabolic disorders, such as a
mitochondrial disease) is no more helpful to the Petitioners’ case than citing the broadly true, but (from an evidentiary
standpoint) irrelevant, fact that the Vaccine Program itself often awards compensation to injured parties even though
the relevant vaccine is safe for the vast majority of individuals.

56
 b. Autoimmune Encephalopathy Theory - Petitioners’ second
causation theory – that the flu vaccine can precipitate an autoimmune encephalopathy resulting in
regression – is similarly weak.90 Admittedly, isolated subcomponents of Dr. Shafrir’s theory have
found acceptance in other Vaccine Program cases, such as the concept of molecular mimicry as
the proposed mechanism by which an autoimmune process can occur.91 But the same cannot be
said for his causation theory as a whole. Rather, primary links in the theory chain were missing or
proved unreliable, given the disconnect between the theoretical proposition and the evidence
offered to support it. As another special master noted in considering the Althen prong one analysis,
“[t]he weight to be given an expert’s opinion is based in part on the size of the gap between the
science and the opinion proffered.” Isaac, 2012 WL 3609993, at *17 (citing Cedillo, 617 F.3d at
1339). That gap is far too wide here.

Petitioners could not offer direct evidentiary support establishing the flu vaccine’s capacity
to function as alleged, in this or other analogous circumstances. Instead, they sought to prove their
theory with even more attenuated circumstantial evidence, pointing to studies involving the impact

90
Dr. Shafrir also posited that L.V.’s purported “immune abnormalities” played a role in his purported reaction to the
second flu vaccine dose (tr. at 286-88), but the argument was based on supposition about L.V.’s condition that was
not verified by evidence or the overall record, consisting instead of selectively-identified facts (such as L.V.’s
allergies). Id. at 286. He also proposed Lapphra – a case study involving a single occurrence and a different illness
entirely (ADEM) – as suggesting the fact that a second dose of a vaccine could precipitate a neurologic condition, but
its fit to the present circumstances was lacking. He later somewhat contradicted this point by admitting that he lacked
the evidence, such as genetic proof, for a genetic component to L.V.’s purported “susceptibility” to vaccines. Id. at
296.
91
Although Vaccine Program petitioners are not required to establish a precise biologic mechanism by which a vaccine
would have the physiologic effect it is alleged to have, Petitioners herein proposed that the flu vaccine could produce
an autoimmune reaction as the starting point of an encephalopathy via molecular mimicry, supporting the contention
with seven articles discussing the homologies observed between components of the flu vaccine or virus and different
human tissue protein sequences. Tr. at 285, 297-302, 405-06. Molecular mimicry has been found (albeit when applied
to different illnesses and diseases) to be a plausible component of a causation theory, as the concept has reliable and
reasonable scientific support. See, e.g., Tompkins v. Sec’y of Health & Human Servs., No. 10-261V, 2013 WL
3498652, at *22 (Fed. Cl. Spec. Mstr. June 21, 2013) (in the specific context of establishing causation of Guillain-
Barré syndrome occurring after vaccination, “[t]he molecular mimicry theory is the one most widely accepted for the
agents most frequently accepted as causal”), mot. for review den’d, 117 Fed. Cl. 713 (2014).

In acknowledging the above, however, I do not mean to suggest that molecular mimicry is always viewed as a
plausible theory in every case. The acceptance of a theory in a single case, or even when commonly invoked to a
specific kind of injury, does not mean that the theory can always be offered in rote fashion in other cases and deemed
to satisfy the first Althen prong. Hennessey v. Sec'y of Health & Human Servs., 91 Fed. Cl. 126, 134-35 (2010)
(expert’s overly broad application of the molecular mimicry theory made it meaningless). For example, an expert
unqualified to opine on the topic of molecular mimicry might well be unsuccessful in persuasively offering it as a part
of a causation theory. In this regard, I note that Dr. Shafrir lacks the scientific background and experience necessary
to persuasively explain molecular mimicry generally, and therefore also is not qualified to apply it specifically to the
flu vaccine formulation in question.

57
of different vaccines, or different formulations of the flu vaccine not used in the U.S., such as
Pandemrix. Tr. at 288-92, 363-71, 373-81. They also invoked studies and literature involving
brain-centered injuries (as the brain is the likely locus of where a neurologic change resulting in
regression would occur) resulting from autoimmune diseases that L.V. unquestionably did not
have, such as anti-NMDA encephalitis or other neurodegenerative conditions. Such conditions,
more often than not, had been induced by wild virus infections (which were not established by the
Petitioners to be comparable in impact to a vaccine simply because they contain the same viral
protein chains). Petitioners otherwise invoked individual case studies (Poling, for example, or the
incident discussed in Lapphra) that are facially distinguishable and otherwise not particularly
reliable evidence.

As noted above, Vaccine Program petitioners are not required to prove their causation
theories to a degree of scientific certainty, nor must they offer a particular kind of evidence (such
as epidemiologic studies). But that does not relieve Petitioners of the obligation to offer proof of
their theory that corresponds to facts of their claim. Moberly, 592 F.3d 1315, 1322 (Fed. Cir. 2010)
(a petitioner must “provide a reputable medical or scientific explanation that pertains specifically
to the petitioner's case” (emphasis added)). Petitioners here have instead offered a strung-together
chain of a few individual patient case reports (which “are not, in general, strong evidence of
causation” (Raymo v. Sec’y of Health & Human Servs., No. 11-0654V, 2014 WL 1092274, at *21
(Fed. Cl. Spec. Mstr. Feb. 24, 2014)), along with scientific or medical articles that themselves do
not stand for the principle for which they are cited or are factually inapposite. Similarly, their
autoimmune encephalopathy theory makes analogies to different illnesses or vaccines, but without
literature or scientific support for the validity of those analogies.

A qualified expert could conceivably tie together such diffuse scientific and medical
literature through the force and persuasiveness of his testimony and explanations. Dr. Shafrir is
not that expert. He is not an immunologist, does not specialize in the study of autoimmune diseases
let alone degenerative encephalopathies precipitated by autoimmunity, is not notably experienced
in treating autoimmune-mediated illness, and has no background studying the effect of vaccines
on individuals (other than the experience he may have gained either treating patients who he
believes were so affected, or through his participation as an expert witness in other Program cases).
His broad, multidisciplinary testimony required him to step well outside the bounds of his actual
expertise. Although I have nevertheless considered his testimony carefully, it is reasonable to
afford it significantly less weight under such circumstances. Daubert v. Merrell Dow Pharm., Inc.,
43 F.3d 1311, 1317 (9th Cir. 1995) (“[o]ne very significant fact to consider is whether the experts
are proposing to testify about matters growing naturally and directly out of research they have
conducted independent of the litigation, or whether they have developed their opinions expressly
for purposes of testifying”).

My reaction to the overall ineffective and unpersuasive nature of this second causation
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theory should also be placed in context of other Vaccine Program cases in which the same theory
was advanced. Dr. Shafrir has asserted a similar causation theory in other cases involving claims
about vaccines and autism. See, e.g., Lehner, 2015 WL 5443461. In fact, he relied on much of the
same literature in Lehner as he does in the present case, particularly in discussing molecular
mimicry and anti-NMDA encephalitis, and its relationship to developmental or neurologic
regression. Id. at *47-48. Former Chief Special Master Vowell concluded in Lehner, however, that
“[t]his evidence fails to demonstrate that Dr. Shafrir’s theory has sufficient indicia of reliability to
be persuasive,” and therefore “Dr. Shafrir’s opinions are wishful thinking premised on unverified
and unsupported assumptions.” Id. at *45-47. Based upon my review of the record, and having
heard Dr. Shafrir testify in this case, I concur with such statements entirely.

3. Petitioners Did Not Establish a Medically Reasonable Timeframe.

As noted above, the facts support the conclusion that L.V.’s developmental problems were
more likely than not evident before he received the second flu vaccine, given the numerous
instances in which the Vs so told various ASD specialists. It is reasonable to infer that the Vs
would not have repeatedly done so in error. Cucuras, 26 Cl. Ct. at 543. In addition, the Petitioners
and their experts have acknowledged that the Vs perceived developmental problems in L.V. earlier
than December 8th, and their efforts at hearing to distinguish between pre- and post-vaccination
problems as qualitatively different were not successful. There is also little to no evidence of any
identifiable reaction to the second flu dose, or evidence that it synergistically reacted with L.V.’s
ear infection. Finally Petitioners’ experts did not offer persuasive causation theories, thus dooming
their ability to place onset within the context of those theories.92

CONCLUSION

I have great sympathy for the Vs and the suffering they have experienced in their loving
care of L.V., and I do not question their sincerity in proceeding with this claim. But the factual
record does not support their contention that L.V. suffered from a mitochondrial disease or

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Dr. Kendall was for her part able to cite only one piece of literature, Edmonds, suggesting what the timeframe would
be (3-7 days) for the flu vaccine to theoretically have had the alleged effect on an individual with a preexisting
mitochondrial disease. Tr. at 166. That piece of literature has been found to be reliable in other circumstances (most
notably the Paluck case). Paluck v. Sec’y of Health & Human Servs., 104 Fed. Cl. 457, 481-82 (2012). But the “fit”
of medical or scientific evidence offered in support of a theoretical component of a theory to the facts of an action is
relevant in weighing its probative value. Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 591-92 (1993).
Edmonds (like many other articles cited in this matter) involved the result of infection by wild-type viruses rather than
vaccination (which cannot be presumed to have the same effect biologically). Tr. at 167 (citing Edmonds at 360).
Petitioners did not otherwise establish (beyond their experts’ ipse dixit) that the flu vaccine would have the same
effect, or in the same amount of time.

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experienced an autoimmune encephalopathy, that the flu vaccine had a causal connection to L.V.’s
developmental regression and subsequent ASD diagnosis, or that the vaccine could produce the
kind of regression or ASD symptoms L.V. experienced. The desire to find some explanation for
L.V.’s condition is understandable – but the arguments presented herein purporting to provide that
explanation are not enough to meet the standards for an entitlement award in the Vaccine Program.

I therefore DENY an entitlement award in this case. I instruct the Clerk of Court to enter
judgment dismissing the case unless a motion for review is filed.93

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

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