VICP Registry Case Source Bundle
Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_18-vv-00440
Package ID: USCOURTS-cofc-1_18-vv-00440
Petitioner: A.V.
Filed: 2018-03-23
Decided: 2024-03-25
Vaccine: DTaP
Vaccination date: 2015-04-20
Condition: seizure disorder
Outcome: denied
Award amount USD: 

AI-assisted case summary:
Angelica and Marius Vinesar filed a petition on behalf of their daughter, A.V., alleging that the DTaP vaccine administered on April 20, 2015, caused her to develop a seizure disorder, specifically Dravet syndrome. A.V. received her third dose of the DTaP vaccine at six months old. Within hours, she experienced a prolonged febrile seizure, leading to hospitalization. Over the next few years, A.V. continued to have seizures, and she was eventually diagnosed with Dravet syndrome, a condition linked to a pathogenic variant in her SCN1A gene. The Vinesars argued that the vaccine triggered her initial seizure, causing brain injury and accelerating the onset and severity of her seizure disorder. They presented expert opinions from Dr. Marcel Kinsbourne, Dr. Mark McNulty, and Dr. Richard Boles suggesting a link between vaccines and Dravet syndrome, particularly in children with SCN1A mutations. The Secretary of Health and Human Services contended, through expert Dr. Gerald Raymond, that A.V.'s SCN1A gene mutation was the sole cause of her Dravet syndrome and that the vaccine did not cause or aggravate her condition. Special Master Christian J. Moran denied entitlement, finding that the Vinesars failed to establish a reliable medical theory linking the DTaP vaccine to the development or aggravation of A.V.'s seizure disorder, and that the evidence did not show a logical sequence of cause and effect. The Special Master also found that the Secretary proved by a preponderance of the evidence that the genetic mutation was the sole cause. This decision was reviewed by Chief Judge Elaine D. Kaplan of the Court of Federal Claims, who affirmed the Special Master's findings, concluding that the evidence supported the denial of compensation. The court found no reversible error in the Special Master's factual determinations regarding the lack of a proven causal link between the vaccine and A.V.'s seizure disorder, nor in the finding that the genetic mutation was the sole cause. The petition was denied.

Theory of causation field:
Petitioners alleged that the DTaP vaccine administered on April 20, 2015, caused A.V. to develop Dravet syndrome. Their theory was that the vaccine triggered her initial febrile seizure, which caused brain injury and accelerated the onset and severity of her seizure disorder. Petitioners' experts, Drs. Kinsbourne, McNulty, and Boles, opined that the DTaP vaccine could cause or aggravate seizure disorders, particularly in children with SCN1A mutations, and that environmental factors like vaccines could trigger the disorder's onset and worsen its severity. The Special Master, Christian J. Moran, found that Petitioners failed to establish a reliable medical theory for causation or aggravation and did not show a logical sequence of cause and effect. He also found that the Secretary, through expert Dr. Raymond, proved by a preponderance of the evidence that A.V.'s SCN1A gene mutation was the sole cause of her seizure disorder. The Court of Federal Claims affirmed, finding the Special Master's conclusions neither arbitrary, capricious, nor contrary to law. The petition was denied.

Public staged source text:

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DOCUMENT 1: USCOURTS-cofc-1_18-vv-00440-1
Date issued/filed: 2023-08-23
Pages: 76
Docket text: PUBLIC DECISION (Originally filed: 7/28/2023) regarding 136 DECISION of Special Master, Signed by Special Master Christian J. Moran. (dksc) Service on parties made.
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Case 1:18-vv-00440-EDK Document 140 Filed 08/23/23 Page 1 of 76
In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
* * * * * * * * * * * * * * * * * * * * * *
ANGELICA VINESAR and *
MARIUS VINESAR as best friends *
of their daughter, *
A.V., * No. 18-440V
* Special Master Christian J. Moran
Petitioners, *
* Filed: July 28, 2023
v. *
*
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
* * * * * * * * * * * * * * * * * * * * * *
John F. McHugh, New York, NY, for petitioners;
Julia M. Collison, United States Dep’t of Justice, Washington, DC, for respondent.
DECISION DENYING ENTITLEMENT TO COMPENSATION1
Mr. and Ms. Vinesar allege that various vaccinations caused their daughter
(A.V.) to suffer a seizure disorder. Pet., filed March 23, 2018. The parties have
developed evidence, particularly opinions from experts on this topic as well as the
issue as to whether a genetic variant in A.V.’s SCN1A gene caused the seizure
1 Because this Decision contains a reasoned explanation for the action taken in this case,
it must be made publicly accessible and will be posted on the United States Court of Federal
Claims’ website, and/or at https://www.govinfo.gov/app/collection/uscourts/national/cofc, in
accordance with the E-Government Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal
Management and Promotion of Electronic Government Services). This means the Decision will
be available to anyone with access to the internet. In accordance with Vaccine Rule 18(b), the
parties have 14 days to identify and move to redact medical or other information, the disclosure
of which would constitute an unwarranted invasion of privacy. Any changes will appear in the
document posted on the website.

Case 1:18-vv-00440-EDK Document 140 Filed 08/23/23 Page 2 of 76
disorder independently. The parties also submitted briefs and participated in an
oral argument.
The evidence is similar to the evidence in other cases in which special
masters have found that an SCN1A mutation solely caused a child’s seizures. The
outcomes and findings of facts, as extensively discussed below, have been affirmed
by the Court of Federal Claims and the Federal Circuit. Although the Vinesars
argue that a 2020 opinion from the Federal Circuit has altered the legal landscape,
the Vinesars’s argument fails to account for other precedents from the Federal
Circuit. Due to the prominence of the Vinesars’s legal arguments, the series of
cases that provide a background to SCN1A litigation are set forth in Section I as an
introduction.
The outcomes of those cases, however, do not preclude the Vinesars from
receiving compensation if the evidence differed. Thus, the evidence regarding the
events in their child’s life are detailed in Section II. Those events are the
foundations for the Vinesars’s claim that typical childhood vaccinations harmed
their daughter, and the procedural history is briefly outlined in Section III. The
standards for adjudication are presented in Section IV.
The analysis is found in two parts. Section V considers whether a
vaccination caused A.V.’s seizure disorder. Section VI addresses whether the
genetic mutation by itself caused A.V.’s seizure disorder. As explained in Section
VII, a hearing is not required to resolve these questions in part because numerous
other cases have considered very similar issues.
I. Precedents Involving Children with Genetic Variants
Within the last thirteen years, the Federal Circuit has reviewed eight
decisions by special masters in cases in which a child with a genetic variant
received a vaccine and developed problems.2 Many of the decisions from special
masters are lengthy, reflecting the complexity of the issues. Thus, the special
masters’ decisions are summarized extensively below. The special masters’
decisions are the foundations for actions taken by the Federal Circuit, which
constitute binding precedent. The Federal Circuit’s rulings must be read in
context. See Bristol-Myers Squibb Co. v. Teva Pharmaceuticals USA, Inc., 769
F.3d 1339, 1353 n.1 (Fed. Cir. 2014) (Taranto, J., dissenting from denial of a
petition for rehearing en banc) (“It is a well-recognized principle, and one essential
2 An appendix is provided for cases with a lengthy history.
2

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to our system of precedent, that statements in opinions must be read in context,
considering their role in the decision and the facts of the case”).
A. Stone/Hammitt
Although Stone and Hammitt were consolidated at the Federal Circuit, the
chief special master separately adjudicated them initially. Thus, they are
summarized one at a time.
1. Stone
The daughter of Jennifer and Gary Stone, Amelia, received a dose of the
diphtheria-tetanus-acellular pertussis (“DTaP”) vaccine as part of her four-month
well-child pediatric appointment. Stone v. Sec’y of Health & Hum. Servs., No. 04-
1041V, 2010 WL 1848220, at *2 (Fed. Cl. Spec. Mstr. Apr. 15, 2010), mot. for
rev. granted, 95 Fed. Cl. 233 (2010). The day after her vaccination, Amelia
experienced two seizures, each of which lasted about thirty minutes. Id. at *2.
After being hospitalized, Amelia was found to have returned to her usual state of
health and an MRI did not identify any abnormalities. Id.
Following approximately two years of periodic seizures, a pediatric
neurologist diagnosed Amelia as suffering from Dravet syndrome. Id. at *3. More
than one year later, a genetic test revealed that Amelia possessed a de novo
mutation in her SCN1A gene. Id.
Mr. and Ms. Stone alleged that the DTaP vaccine caused Amelia to develop
Dravet syndrome. Id. at *1. To assist with their claim, Mr. and Ms. Stone retained
Dr. Marcel Kinsbourne. The essence of Dr. Kinsbourne’s opinion was that “the
pertussis vaccination caused the fever; that the fever caused a prolonged seizure
classifiable as complex febrile, and indeed status epilepticus. That seizure caused
harm to the children, and that harm was reflected in a lowering of level of seizure
propensity, thus facilitating future seizures.” Id. at *10 (citing Tr. 2 at 443).
To address the genetic issues, the Secretary retained Dr. Gerald Raymond.
To start, Dr. Raymond recognized that “a vaccination can cause a fever; a fever can
trigger a seizure, including a complex febrile seizure; and a complex febrile seizure
can cause brain damage.” Id. at *11. However, “Dr. Raymond opined that
Amelia’s vaccinations neither caused nor exacerbated her [Dravet syndrome], but
rather a mutation in her SCN1A gene is solely responsible for her [Dravet
syndrome].” Id. at *13. Dr. Raymond pointed to the following factors as
significant to his opinion that the SCN1A gene caused Amelia’s condition:
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Amelia’s mutation arose de novo;
the mutation at issue results in a non-conservative
amino acid change with the new amino acid having very
different physical properties from what is found at that
location in non-affected individuals;
the mutation affects the pore of a sodium channel,
a functionally important region;
the mutation occurs in an area that is well
conserved across species, signaling significant
ramifications when altered;
there are reports evidencing similar or comparable
mutations resulting in [Dravet syndrome]; and
there is an absence of the mutation in the normal
population.
Id. at *41.
The chief special master resolved the case in a decision, which exceeded
thirty pages, noting that Stone’s significance in the Vaccine Program is a rare
example of a case in which the Secretary was contending that a factor unrelated to
a vaccine (the SCN1A gene) caused the vaccinee’s condition. Id. at *12-13.
Commensurate with the case’s importance, the chief special master described
genes, protein synthesis, and the SCN1A gene specifically. Id. at *13-15.
Ultimately, the chief special master found that the Secretary had
“demonstrated by a preponderance of the evidence that Amelia’s SCN1A gene
mutation was more likely than not the ‘but for’ and ‘substantial factor’ that caused
her . . . Dravet Syndrome.” Id. at *42. The chief special master provided several
reasons for this finding including the disparity in the credentials between Dr.
Kinsbourne, who “has no past or present experience or credentials in the field of
genetics,” and Dr. Raymond, who “provided a complete and thorough review of
the underlying genetics in this matter and then applied the medical principles and
his clinical experience as a geneticist and pediatric neurologist to the facts of this
case.” Id. at *40.
The chief special master also extensively reviewed the factors that Dr.
Raymond considered in concluding that the SCN1A gene caused Amelia’s Dravet
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syndrome. Id. at *20-38 (see factors listed supra). In short, the decision found
those factors to be an appropriate way for clinical geneticists to counsel their
patients. The decision emphasized that no evidence showed that the initial seizure
harmed Amelia. Accordingly, Mr. and Ms. Stone were denied compensation.
Mr. and Ms. Stone sought review of the April 15, 2010 decision. A judge
from the Court of Federal Claims held that the chief special master “failed to apply
the correct legal standard to respondent’s evidence of a factor unrelated to the
vaccine.” Stone v. Sec’y of Health & Hum. Servs., 95 Fed. Cl. 233, 238 (2010)
(noting that “[i]n order to enter judgment for respondent, the special master would
have to have found that the SCN1A gene mutation was the ‘sole cause’ or
‘principally responsible’ for Amelia's SMEI”). The judge, thus, remanded the
case.
Upon remand, the chief special master found “beyond any doubt that
respondent proved by a preponderance of the evidence that Amelia’s SCN1A gene
mutation was the sole cause and was principally responsible for her [Dravet
syndrome].” 2011 WL 836992, at *3 (Fed. Cl. Spec. Mstr. Jan. 20, 2011).
Mr. and Ms. Stone sought a second review by a judge of the Court of
Federal Claims. This time, the judge denied the motion for review. 99 Fed. Cl.
187 (2011). Specifically, the judge ruled that a specific genotype-phenotype study
was not required for Dr. Raymond to predict the outcome of the SCN1A mutation
in Amelia. Id. at 190. The judge acknowledged Dr. Raymond’s position as the
only expert in genetics to testify. Id. at 190-91. The judge also found that the
chief special master was not arbitrary in rejecting Dr. Kinsbourne’s opinion that
the vaccine-induced fever lowered Amelia’s seizure threshold. Id. at 191. Finally,
the judge found that the evidence supported the chief special master’s finding that
Amelia did not suffer any lasting brain damage from her two initial seizures. Id. at
191-92. Accordingly, the Court entered a judgment against Mr. and Mrs. Stone.
Id. at 193.
2. Hammitt
Around the same time the chief special master was resolving Stone, the chief
special master also was considering a similar case that Scott Hammitt brought on
behalf of his daughter, Rachel.3 No. 07-170V, 2010 WL 3735705 (Fed. Cl. Spec.
Mstr. Aug. 31, 2010). Rachel received her second dose of the DTaP vaccine when
3 After the remands from the Court of Federal Claims, the chief special master conducted
a consolidated hearing to receive testimony from the experts.
5

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she was four months old. That evening, Rachel experienced a seizure lasting
approximately forty-five minutes for which she was given Valium. Id. at *2. A
CT scan was normal and by the next day, Rachel was “playful and cheerful.” Id.
Rachel had a second seizure about one month later and the CT scan was
again within normal limits. However, an EEG showed “focal epilepsy.” Id.
Rachel experienced more seizures, and her development was recognized as delayed
when she was 14 months old. Id.
A genetic test revealed that Rachel had a de novo mutation in her SCN1A
gene. Id. at *3. She was diagnosed with severe myoclonic epilepsy of infancy
(“SMEI”), which is also known as Dravet syndrome. Id. at *10.
Like Mr. and Ms. Stone, Mr. Hammitt retained Dr. Kinsbourne to explain
how the vaccine harmed his daughter. Dr. Kinsbourne opined “that Rachel was
predisposed to suffer seizures due to her SCN1A genetic mutation. However, Dr.
Kinsbourne further opined that Rachel’s DTaP vaccination was a substantial
contributing cause of her seizure disorder in addition to her genetic
predisposition.” Id. at *10 (internal citations omitted).
The Secretary again predominantly relied upon an opinion from Dr.
Raymond. Dr. Raymond maintained that “a mutation in [Rachel’s] SCN1A gene is
solely responsible for her [Dravet syndrome].” Id. at *16.
The analysis from the chief special master is essentially the same as the
analysis in Stone. Id. at *23-45. As such, he found that Mr. Hammitt was not
entitled to compensation. Id. at *47.
Mr. Hammitt filed a motion for review, and, although the opinion is not
reported, the court remanded the case. On remand, the chief special master again
found that “respondent proved by a preponderance of the evidence that the genetic
mutation was the sole cause, principally [responsible] for Rachel’s [Dravet
syndrome].” No. 07-170V, 2011 WL 1135878, at *10 (Fed. Cl. Spec. Mstr. Mar.
4, 2011). As in Stone, a second motion for review was denied. 98 Fed. Cl. 719
(2011).
3. Federal Circuit Opinion in Stone/Hammitt
The foregoing decisions and opinions were the basis of the Federal Circuit’s
opinion in the consolidated appeals brought by Mr. and Ms. Stone as well as Mr.
Hammitt. The Federal Circuit summarized the events in Amelia’s medical history
and Rachel’s medical history as set forth above. Stone v. Sec’y Health & Hum. &
6

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Servs., 676 F.3d 1373,1375-76 (Fed. Cir. 2012). The Federal Circuit explained
that the special master had found that Amelia’s and Rachel’s seizure disorders
were “triggered by the SCN1A gene mutation alone, and the initial febrile seizures
did not result in any brain injury that caused, triggered, or rendered either child
more susceptible to developing [Dravet syndrome].” Id. at 1382.
The Federal Circuit determined that a special master could consider
evidence of a potentially causative factor other than the vaccination in determining
whether petitioners had met their burden to present a prima facie case. In the
words of the Federal Circuit, “in some cases a sensible assessment of causation
cannot be made while ignoring the elephant in the room—the presence of
compelling evidence of a different cause for the injury in question.” Id. at 1380.
In these cases, the “special master concluded that the DTaP vaccine played no role
whatsoever in either child’s [Dravet syndrome].” Id. at 1381.
The Federal Circuit also rejected the appellants’ challenge to this factual
finding due to the deferential standard of review. The Federal Circuit stated the
special master could reject Dr. Kinsbourne’s opinion because of his lack of recent
experience in the fields of pediatric neurology and genetics. Id. at 1382. The
Federal Circuit stated that the evidence supported a finding that Dr. Raymond is an
expert in neurology and genetics, who was “extremely well qualified” to testify
about Amelia’s unusual SCN1A mutation. Id. In stating that the special master
could accept Dr. Raymond’s reasoning, the Federal Circuit pointed to the seven
factors that Dr. Raymond considered. Id. at 1383. The Federal Circuit rejected the
appellants’ argument that the special master should have found that “a child’s
clinical condition cannot be predicted based on the [child’s] SCN1A gene
mutation.” Id.
Separately, the Federal Circuit also addressed the special master’s finding
that the children did not suffer brain damage from their initial seizures. The
Federal Circuit stated that the special master “merely sought evidence of the
existence of brain damage—a key component of Dr. Kinsbourne’s theory—and Dr.
Kinsbourne was unable to provide any.” Id. at 1385. This was because, in part,
the clinical records showed no brain damage. Therefore, the Federal Circuit
affirmed the judgments that denied compensation. Id. at 1386.
The petitioners-appellants sought a rehearing en banc. However, the full
court denied this petition with one judge dissenting.
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B. Deribeaux
Gus Deribeaux and Kimberly Burshiem alleged that a DTaP vaccine caused
their daughter, Madison, to suffer a seizure disorder. Deribeaux v. Sec’y of Health
& Hum. Servs., No. 05-306V, 2011 WL 6935504, at *1 (Fed. Cl. Spec. Mstr. Dec.
9, 2011). Initially, a special master found that they were entitled to compensation.
Id. (citing Deribeaux v. Sec’y of Health & Hum. Servs., No. 05-306V, 2007 WL
4623461 (Fed. Cl. Spec. Mstr. Dec. 17, 2007). However, during the process for
determining the amount of compensation, medical records were produced that
showed Madison suffered from a genetic mutation “known to cause” Dravet’s
syndrome. Id. Thus, the parties developed evidence as to whether “the Secretary
had rebutted Petitioners’ prima facie case by showing that Madison’s disorder was
caused by an unrelated factor.” Id. at *3.
Madison received the DTaP vaccine when she was seven months old in
2002. Id. The next day, she suffered a seizure and was taken to the emergency
room. Id. The parties’ experts agreed that this seizure was in the context of a
fever. Id. at *3 n.9. While in the hospital a few days later, an EEG and MRI were
normal. Id. at *3.
Madison continued to have seizures periodically and by the age of one year,
her development stopped. Id. at *6. When Madison was four years old at the end
of 2005, a genetic test showed that she had a mutation in her SCN1A gene. Id. at
*7. This mutation arose de novo. According to the company performing the test,
Athena Diagnostics, “approximately 90% of amino acid variants associated with
the more severe phenotypes of SMEI or SMEB arise de novo, while the inherited
variations are associated with milder disorders.” Id. Madison’s specific mutation
had not previously been reported. Thus, Athena Diagnostics report stated: “it is
not possible to conclude with any reasonable degree of clinical certainty at this
time whether or not this variant is associated with the phenotype in question.’” Id.
(citing Pet’r’s Exhibit 15 at 9).
In the proceedings before the special master to determine whether the
Secretary had met his burden of establishing that the genetic mutation caused
Madison’s Dravet syndrome, the Secretary relied primarily upon Dr. Raymond.
2011 WL 6935504 at *23. The Secretary “conceded that vaccination likely
triggered Madison’s first, prolonged seizure.” Id. at *1. “The Secretary’s theory
was that Madison experienced a fever following vaccination and that the fever
caused her initial, prolonged seizure. The Secretary maintained that the course of
Madison’s disorder was not altered or aggravated by her initial seizure, however,
and that the disabilities caused by her genetic mutation would have been the same
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with or without the vaccine-induced seizure.” Id.; accord id. at *23-26
(summarizing Dr. Raymond’s testimony).
In contrast, Mr. Deribeaux and Ms. Burshiem relied upon an opinion from a
neurologist, Carlo Tornatore. Dr. Tornatore was not board-certified in genetics or
pediatrics. Id. at *9. Their theory was the “vaccination not only caused Madison’s
initial seizure but also triggered an immune deficiency that led to . . . further
neurological damage. Petitioners propounded several related theories of vaccine
causation and/or aggravation, including that vaccination could precipitate a first
seizure at a time when the victim was particularly vulnerable to neurological
injury.” Id. at *1; accord id. at *27-30 (summarizing Dr. Tornatore’s testimony).
The special master denied entitlement in a decision exceeding forty pages.
The thrust of the reason for the denial was set forth in the decision’s introduction:
[P]reponderant evidence demonstrated that Madison’s
genetic abnormality caused both her susceptibility to a
post-vaccine seizure and, more importantly, her
numerous subsequent seizures and other neurological
problems. There is an association between Madison’s
initial febrile seizure and her vaccination, to be sure—the
Secretary did not deny it—but no causative relationship
was established between vaccination and the neurological
problems that are known to occur in individuals with
[Dravet syndrome].
Id. at *2.
As part of its background, the decision described Dravet syndrome. 2011
WL 6935504, at *8-9. The decision also summarized an extensive amount of
literature. Id. at *12-22.
The finding that the genetic mutation was the cause of Madison’s Dravet
syndrome was organization around the three factors used to evaluate whether a
vaccine is the cause-in-fact of a condition. Id. at *33-44. Under this test’s first
prong, the special master found that mutations in an SCN1A gene can cause Dravet
syndrome. The special master explained:
As evidenced by the extensive literature summarized
above, both the fact of the causal association between
de novo SCN1A mutation and [Dravet syndrome], as
well as the underlying biological basis for this
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association, have been studied extensively. The medical
research is well documented in the record and establishes
that mutation of the SCN1A gene, without any other
factor, genetic or environmental, can cause the symptoms
characterized as [Dravet syndrome].
Id. at *34.
For the second prong, the special master found that the evidence showed a
logical sequence of cause and effect that the mutation caused Madison’s Dravet
syndrome. The special master emphasized that the mutation arose de novo,
credited Dr. Raymond’s testimony that the mutation would impair the structure /
function of the resulting protein and noted Madison’s treating doctors attributed
Madison’s neurological problems to the genetic mutation. Id. at *35-36.
In this context, the special master extensively discussed and rejected
challenges to this finding. For example, the special master found that the initial
seizure did not damage Madison’s brain. In making this finding, the special master
credited Dr. Raymond’s opinion over Dr. Tornatore’s opinion because, in part, Dr.
Raymond is a pediatric neurologist. Id. at *36-39. The special master also
declined to credit an assertion that Madison had a “lower seizure threshold” that
allowed the vaccine to trigger a seizure that would not have happened. Id. at *39-
40. The special master elaborated on the structural deformity due to the gene:
Petitioners in vaccine cases often advance the theory that
individuals with unspecified genetic characteristics have
a lower seizure threshold and that vaccination pushes
them over the edge, resulting in a first seizure followed
by further, ultimately devastating convulsions. Such an
allegation might constitute a viable theory of causation if
all one knew about such cases was that a child had a
seizure following vaccination. But much more has been
revealed by medical science in cases like Madison’s.
Individuals with [Dravet syndrome] have serious
channelopathies that interfere with normal neuronal
activity. Susceptibility to febrile seizures is only one
aspect of their disorder. An initial febrile seizure is
followed by more seizures of all types, with and without
fever. Ataxia and developmental delay occur because of
pervasive brain dysfunction. This is a known syndrome,
not an isolated case of a vaccination followed by
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seizures. In light of what is known, one cannot say that
Madison’s neurological condition was caused by
vaccination, even if her initial seizure was triggered by
the vaccination. It is not Madison’s seizure that caused
her condition, but her condition that caused the seizure.
[Dravet syndrome] would have taken its tragic toll on
Madison’s health whether or not she was vaccinated on
March 28, 2002.
2011 WL 6935504, at *40. As part of this finding, the special master relied upon
Dr. Raymond’s testimony that “vital structures in Madison’s brain cells were not
‘built’ properly because one of the building blocks (an amino acid) was effectively
missing, due to the missense mutation. . . . As a result, the structure of Madison’s
brain cells was permanently flawed.” Id. at *41.
On the third and final prong of the causation-in-fact test, the special master
found that “Madison’s initial seizure occurred at the time of life when such an
event typically would occur in a child with [Dravet syndrome].” Id. at *43. Thus,
the special master concluded: “Respondent submitted more than preponderant
evidence that an alternative factor, Madison’s genetic mutation, was the sole
substantial cause of her neurological condition.” Id. at *44. While the special
master in Deribeaux denied compensation, the special master commented upon
how genetics might (and might not) play a role in future cases:
[This case’s finding that a mutation caused Madison’s
Dravet syndrome] is not to say that medical science has
all the answers to questions about [Dravet syndrome],
vaccinations, and/or genetics. Genetic causation does not
necessarily exclude the possibility that environmental
factors may play a role in the way genes are expressed,
even changing the outcome for an individual. Much
more research will be needed to explore these possible
interactions . . . . The possibilities for variation in
individuals with [Dravet syndrome], and their cause, are
complex and have yet to be explored. . . . But “definitive”
proof, to borrow Dr. Tornatore’s term, is not required to
prove that genetic causation is more likely than not.
Proof of an unrelated factor does not, under the Vaccine
Act, require absolute certainty.
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Id. at *32 (internal citations omitted). In a different part of the decision, the special
master stated:
There was no medical evidence that would support the
contention that the mutation must be identical to one
previously identified in order to produce the
characteristics known to result from the type of mutation
in question. Nor is it logical to require proof of an
identical mutation in order to establish a chain of cause
and effect between the mutation and the disorder.
Id. at *42.
Mr. Deribeaux and Ms. Burshiem challenged this decision by filing a motion
for review. Preliminarily, the Court of Federal Claims rejected their argument that
the special master should have elevated the Secretary’s burden of proof.
Deribeaux v. Sec’y of Health & Hum. Servs., 105 Fed. Cl. 583, 588-91 (2012).
As to the special master’s finding of facts, the Court ruled the special master
was not arbitrary in crediting Dr. Raymond’s testimony over Dr. Tornatore’s
testimony. Id. at 591-94. The Court ruled that the special master was not arbitrary
in finding that “Madison’s genetic mutation was a sole substantial cause of her
condition despite the fact that the vaccine triggered her initial seizure.” Id. at 594.
The Court also rejected petitioners’ argument that “they should prevail because it
cannot be said with absolute certainty that Madison, by reason of her genetic
mutation, would have experienced the same symptoms even if she had not been
vaccinated,” because the special master “was not required to find that a conclusive
one-to-one relationship existed between Madison’s illness and her genetic
mutation.” Id. at 596. Accordingly, the Court entered judgment against
petitioners.
The petitioners appealed to the Federal Circuit. In its opinion, the Federal
Circuit set forth Madison’s basic medical history and the case’s procedural history.
Deribeaux v. Sec’y of Health & Hum. Servs., 717 F.3d 1363, 1364-66 (Fed. Cir.
2013). The Federal Circuit disagreed with the appellants’ contention that the
special master evaluated the Secretary’s claim under a standard that was too low:
“The special master correctly identified that the Secretary’s burden was to show a
sequence of cause and effect that is logical and legally probable, although
causation by the unrelated factor need not be established to a medical or scientific
certainty.” Id. at 1368.
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As to the evidence on which the special master relied to credit the
Secretary’s argument that the SCN1A mutation caused Madison’s Dravet
syndrome, the Federal Circuit found “no basis to disturb her factual findings as
arbitrary or capricious in view of both the record before us and the highly
deferential standard of review under which we must conduct such an evaluation.”
Id. at 1369. Thus, the Federal Circuit affirmed the judgment. Id.
C. Snyder / Harris
While the Snyder and Harris cases were consolidated at the Federal Circuit,
they were treated together while in the Court of Federal Claims, including the
Office of Special Masters. Because the analysis was the same in both cases, only
one case (Snyder) is summarized.
Jed and Lilia Snyder alleged that a DTaP vaccine given to their son, N.S., in
2005 caused him to suffer a worse form of Dravets syndrome. Snyder v. Sec’y of
Health & Hum. Servs., No. 07-59V, 2011 WL 3022544, at *1 (Fed. Cl. Spec. Mstr.
May 27, 2011). He received a dose of the DTaP vaccine when he was four months
and experienced a seizure in the morning of the next day. Id. at *2. After a second
seizure, which occurred about one month later, an EEG was normal. Id. About
one year later, genetic tests showed that N.S. had a mutation in his SCN1A gene
“that is diagnostic for [Dravet] syndrome.” Id. at *3.
In Snyder, the (undersigned) special master set forth some basic information
about how genes encode proteins and how mutations in genes may (or may not)
affect the functioning of the anticipated protein. Id., at *4, 13. For the sodium
channel, a proper flowing of sodium ions allows neurons to fire properly but
defects in the sodium channel impair the flow of electrical impulses, causing a
seizure. Id.
Mr. and Ms. Snyder presented the opinion of Dr. Kinsbourne. He opined
that an “SCN1A mutation is ‘not a sufficient cause in itself.’” 2011 WL 3022544,
at *6 (quoting Dr. Kinsbourne’s report). He also maintained that the DTaP vaccine
can harm neurological development. Id.
The Secretary relied upon opinions from Dr. Raymond and a pediatric
neurologist, Max Wiznitzer. While Dr. Wiznitzer generally supported Dr.
Raymond’s opinion that the DTaP vaccine did not harm N.S., Dr. Raymond
discussed the genetic aspects more extensively. Dr. Raymond stated that the
mutation in N.S.’s “SCN1A gene . . . ‘is the sole cause of his epilepsy condition.’”
Id. at *7 (quoting Dr. Raymond’s report).
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The special master’s decision contained two sections of analysis (sections IV
and V). In section IV, the special master found that the evidence showing the
SCN1A gene was the sole cause of N.S.’s Dravet syndrome. The special master
credited the opinion of Dr. Raymond in part because Dr. Raymond “is the most
qualified expert to express an opinion. Dr. Raymond treats patients with genetic-
based neurological disorders as part of his professional practice of medicine.” Id.
at *14. In reaching his conclusion that the SCN1A mutation was the sole cause of
N.S.’s Dravet syndrome, Dr. Raymond reviewed four factors: “(a) the type of
mutation, (b) the location of the mutation, (c) what the mutation did, that is, what
amino acids were substituted, and (d) the existence of precedent cases reported in
the literature.” Id. (internal citations omitted). The special master found these
factors supported Dr. Raymond’s opinion. Id. at *15-16.
The special master also considered, but found unpersuasive, challenges to
Dr. Raymond’s opinion. The special master summarized literature that Mr. and
Ms. Snyder had submitted but found that the literature did not persuasively support
their position. Id. at *17-21. The special master rejected the opinion from Dr.
Kinsbourne because he “essentially stopped practicing pediatric neurology in
1981.” Id. at *21. In this context, the special master cited another special master’s
decision from 2000 in which that special master stated that she “really cannot rely
on Dr. Kinsbourne who has had no clinical experience in ten years and does not
treat [tuberous sclerosis] or any patients.” Id. (citing Flanagan v. Sec’y of Health
& Hum. Servs., No. 90-1126V, 2000 WL 1207256, at *13 (Fed. Cl. Spec. Mstr.
Aug. 4, 2000), mot. for rev. denied, 48 Fed. Cl. 169, 173-74 (2000), aff’d sub
nom., Turner v. Sec’y of Health & Hum. Servs., 268 F.3d 1334, 1338-39 (Fed. Cir.
2001)).
In summary, the special master found “N.S.’s mutation arose de novo and
occurred in a conserved region of the gene, specifically a portion that codes for the
pore of the sodium channel. These undisputed characteristics about N.S.’s gene
meant, according to Dr. Raymond, that ‘[t]he alteration in his gene is the cause of
his SMEI.’” 2011 WL 3022544, at *25 (citation omitted).
Section IV of the decision also discussed whether DTaP can cause a seizure
disorder via two mechanisms. Id. at *25-34. One mechanism was that the
acellular pertussis vaccine affects the central nervous system because, in theory, a
residual portion of the pertussis vaccine is not toxoided, crosses the blood-brain
barrier, and injures neurons. Id. at *27. The special master declined to evaluate
this evidence because of “shortcomings in the parties’ presentation.” Id. at *30. A
second mechanism was that the DTaP vaccine caused a fever, and a fever caused
the seizure. Id. The special master rejected this mechanism because mice models
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for Dravet syndrome indicated that genetically defective mice experienced seizures
regardless of whether they were heated. Id. at *31-33 (citing John C. Oakley et al.,
Temperature-and Age-Dependent Seizures in a Mouse Model of Severe Myoclonic
Epilepsy in Infancy; Frank W. Yu et al., Reduced Sodium Current in GAGAergic
Interneurons in a Mouse Model of Severe Myoclonic Epilepsy in Infancy).4
Further, Dr. Kinsbourne did not show that the initial seizure harmed N.S. Id. at
*34.
The lack of damage from N.S.’s first seizure was the foundation for the
finding in section V that Mr. and Ms. Snyder failed to establish that any injury
lasted more than six months. Id. at *34-36. In this context, Dr. Kinsbourne was
unable to say how N.S. would have been but for the vaccine. In contrast, Dr.
Raymond was persuasive in explaining the vaccine did not affect his development.
Consequently, the special master denied entitlement.
Mr. and Ms. Snyder sought review of the special master’s decision denying
them compensation. A judge from the Court of Federal Claims ruled that Mr. and
Ms. Snyder had established that N.S.’s “[s]yndrome was Caused-In-Fact by the
DTaP Vaccine.” Snyder v. Sec’y of Health & Hum. Servs., 102 Fed. Cl. 305, 321
(2011). The Court indicated that the special master erroneously required Mr. and
Ms. Snyder to present “scientific certainty,” rather than “simple preponderance of
evidence.” Id. at 322. As support for the proposition that a DTaP vaccine can
cause seizures, the Court cited the warning label for the DTaP vaccine that advises
“despite detoxification, sufficient pertussis toxin may be present to trigger fever
and seizures.” Id.
The Court also ruled that the “Special Master Erred in Finding That The
Government Demonstrated Alternative Causation.” Id. at 323. The Court stated:
“There is no evidence in this record, scientific or otherwise, that establishes that a
child with a SCN1A mutation, necessarily will develop SMEI [severe myoclonic
epilepsy of infancy] or another seizure disorder.” Id. Later, the Court explained:
“although there is a relationship between SCN1A gene mutations and SMEI, a one-
to-one relationship has not been established, nor has it been determined that
exposing a patient with a SCN1A mutation to acellular pertussis will have no
adverse consequences.” Id. at 324. The Court also viewed the value of Dr.
Kinsbourne’s opinion as in equipoise with the value of the opinions from Dr.
Raymond and Dr. Wiznitzer. Thus, the government failed to meet its burden of
proof. Id. at 325 (citing Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543,
4 Complete bibliographic information for the medical articles is found in the appendix.
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550-51 (Fed. Cir. 1994). The Court, accordingly, reversed the decision of the
special master, found that Mr. and Ms. Snyder were entitled to compensation, and
remanded the case to determine compensation. Id. at 326.
After the (undersigned) special master determined the compensation to
which Mr. and Ms. Snyder were entitled and a judgment was issued, the Secretary
appealed the judgment to the Federal Circuit. The Federal Circuit reversed the
judgment awarding compensation and reinstated the special master’s decision.
Snyder v. Sec’y of Health & Hum. Servs., 553 Fed. App’x 994 (Fed. Cir. 2014)
(citing Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373, 1379 (Fed. Cir.
2012)). The Federal Circuit determined that the special master did not err in
considering the record as a whole and finding that the Secretary met his burden to
establish “the gene mutations were the sole cause of the seizure disorders.” Id. at
1000.
With respect to the special master’s factual findings, the Federal Circuit
noted that Dr. Raymond and Dr. Wiznitzer were more qualified than Dr.
Kinsbourne due to their differences in experience. The Federal Circuit did “not
discern error in this conclusion.” Id. at 1002. The Federal Circuit disagreed with
the view of the Court of Federal Claims that the evidentiary value of the opinions
from the experts was in equipoise. Instead, according to the Federal Circuit, the
special master “made particular findings, supported by the record, in favor of the
Secretary.” Id. at 1003. Thus, the Federal Circuit reversed the determination of
the Court of Federal Claims and reinstated the decision finding “the SCN1A gene
mutation was, more likely than not, the sole cause of Petitioners’ seizure
disorders.” Id. at 1004.
D. Other SCN1A Cases
As collected in Oliver v. Sec’y of Health & Hum. Servs., No. 10-394V, 2017
WL 747846, at *1 n.3, in numerous cases, special masters have not credited the
claim that a childhood vaccination caused a seizure disorder when the child had a
mutation in the SCN1A gene.5 As indicated in the parentheticals, in some cases
petitioners voluntarily dismissed their petitions and the decisions in those cases are
5 Oliver lists Sucher v. Sec’y of Health & Hum. Servs., 07–58V, 2010 WL 1370627 (Fed.
Cl. Spec. Mstr. Mar. 15, 2010), as among the cases in which special masters did not award
compensation. However, Oliver’s cite to Sucher is mistaken because the special master found
that the petitioners were awarded compensation. 2010 WL 1370627, at *45. Sucher’s value is
nevertheless limited because the child in Sucher was not found to have a genetic mutation,
although Dr. Kinsbourne assumed she had one.
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relatively short (two or three pages). In other cases, the parties fully litigated the
case, leading to much longer decisions by special masters. Some, but not all, of
those determinations were the subject of a motion for review. When a motion for
review was filed, the decision denying compensation was found not arbitrary.
A list of those cases, presented in chronological order starting with the
earliest, includes:
No.6 Name and Citation Appellate Review
4 Craner v. Sec’y of Health & Hum. Servs., 10–
475V, 2011 WL 6401290 (Fed. Cl. Spec. Mstr.
Oct. 27, 2011) (decision granting petitioners’
motion to dismiss their petition after the
SCN1A mutation was discovered)
5 Barnette v. Sec’y of Health & Hum. Servs., mot. for rev. den’d, 110
06–868V, 2012 WL 5285414 (Fed. Cl. Spec. Fed. Cl. 34 (2013)
Mstr. Sept. 26, 2012)
6 Schniegenberg v. Sec’y of Health & Hum.
Servs., 13–347V, 2014 WL 4674382 (Fed. Cl.
Spec. Mstr. Apr. 29, 2014) (decision
dismissing case after petitioners failed to
present any evidence after the SCN1A
mutation was brought forward in litigation)
7 McHerron v. Sec’y of Health & Hum. Servs.,
07-753V, 2014 WL 3360324 (Fed. Cl. Spec.
Mstr. June 18, 2014) (decision granting
petitioners’ motion to dismiss their petition
after testing revealed their child had an
SCN1A mutation)
8 Mathis v. Sec’y of Health & Hum. Servs., 09-
467V, 2014 WL 3955650 (Fed. Cl. Spec. Mstr.
July 24, 2014) (decision granting petitioner’s
motion to dismiss her petition after testing
revealed her child had an SCN1A mutation)
6 The numbering begins with “four” to account for the three cases (Stone, Deribeaux, and
Snyder) that were already discussed. Because Stone was consolidated with Hammitt and
because Snyder was consolidated with Harris, the list could have started with “six.”
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9 Waters v. Sec’y of Health & Hum. Servs., 15–
320V, 2015 WL 3898079 (Fed. Cl. Spec. Mstr.
June 4, 2015)
10 Santini et al. v. Sec’y of Health & Hum. mot. for rev. den’d, 122
Servs., 06–725V, 2014 WL 7891507 (Fed. Cl. Fed. Cl. 102 (2015)
Spec. Mstr. Dec. 15, 2014)
11 Barclay ex rel. Ramirez v. Sec’y of Health & mot. for rev. den’d, 122
Hum. Servs., 07–605V, 2014 WL 7891493 Fed. Cl. 189 (2015)
(Fed. Cl. Spec. Mstr. Dec. 15, 2014)
12 Faoro v. Sec’y of Health & Hum. Servs., 10– mot. for rev. den’d, 128
704V, 2016 WL 675491 (Fed. Cl. Spec. Mstr. Fed. Cl. 61 (2016)
Jan. 29, 2016)
Other than their consistency in outcome, these cases carry less precedential
weight. None of them reached the Federal Circuit.
E. Oliver
The fourth SCN1A case to reach the Federal Circuit was initiated by Laura
and Eddie Oliver on behalf of their son, E.O. They alleged that various vaccines,
including the DTaP vaccine given to E.O. in 2009, caused him to develop a fever
and febrile seizures. Oliver v. Sec’y of Health & Hum. Servs., No. 10-394V, 2017
WL 747846, at *1 (Fed. Cl. Spec. Mstr. Feb. 1, 2017).
E.O. had a mutation in his SCN1A gene. Id. at *1, *6. E.O. received his
vaccinations as part of a six-month well-child exam. Id. at *4. He experienced his
first seizure, which was febrile, the same day. Id. at *4, *17 n.47. After about one
year in which his seizures increased in frequency, a genetic test showed that he had
a mutation in his SCN1A gene that neither parent carried. Id. at *6. The report
from Athena Diagnostics, Inc. characterized the mutation as of “unknown
significance.” Id. at *7 n.10. However, a database from China reported a child
with an identical mutation who also had Dravet syndrome. Id. at *7, *18.
Mr. and Ms. Oliver advanced their claim by retaining a pediatric neurologist,
Yuval Shafrir. Id. at *10. His theory, in essence, was “the SCN1A mutation made
E.O. susceptible to developing Dravet syndrome, that a gene-environmental
interaction is at play, and that the vaccinations trigger that interaction.” Id. at *1.
The Secretary responded with reports from Dr. Raymond, as well as one
report from a neurologist specializing in pediatric epilepsy, Rajesh Sachdeo. Id. at
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*11. Their view was that “E.O.’s mutation is the sole cause of his Dravet
syndrome and his resulting neurological condition.” Id. at *1.
In discussing how a DTaP vaccine can cause Dravet syndrome, Dr. Shafrir
acknowledged that “the SCN1A mutation is a necessary cause of Dravet syndrome,
but he opine[d] that the mutation alone is not sufficient to cause the disease.” Id. at
*12. Dr. Shafrir proposed two mechanisms to bring forth Dravet syndrome in a
vulnerable person: either “second hit” or an immune-mediated reaction (molecular
mimicry). Id. at *12-13.
However, Dr. Raymond disagreed and offered a threefold response:
First, the existing medical studies and literature have
established that a significant alteration in the SCN1A
gene alone is sufficient to cause Dravet syndrome . . . .
Second, animal models have demonstrated significant
abnormalities of SCN1A mutation that “mirror the
human condition,” and in these studies the animals
spontaneously developed seizures without any triggers . .
. . Third, the McIntosh et al. and Berkovic et al. studies
show that the occurrence of febrile seizures following
vaccinations does not change the clinical course or
outcome of Dravet syndrome.
Id. at *15 (internal citations omitted).
The special master found that Mr. and Ms. Oliver had failed to meet their
burden of proof. The special master explained:
[T]he existing medical literature has established that
vaccination does not affect the clinical course or
prognosis of Dravet syndrome. The animal models, as
presented by Dr. Raymond, provide strong evidence that
Dravet syndrome will develop in children with the
SCNIA mutation, whether or not they receive
vaccinations.
2017 WL 747846, at *16.
In addition to finding Mr. and Ms. Oliver’s proof lacking for Althen prong
one, the special master determined that they had not established Althen prong two.
Id. at *16-21. For Althen prong three, the special master found that the onset of
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seizures within twenty-four hours of vaccination was not sufficient for finding that
the vaccination caused the Dravet syndrome that was diagnosed twenty-one
months later. Id. at *20-21.
Besides finding that Mr. and Ms. Oliver did not meet their burden to show
causation-in-fact, the special master found that they failed to establish a vaccine
significantly aggravated E.O.’s epilepsy. Id. at *22-24; id. at 24 (noting that
“the vaccinations did not change his clinical course and thus did not significantly
aggravate his preexisting condition”). The special master reached this outcome
because of the overlap in the elements under both causes of action.
Likewise, the special master found that the Secretary “has put forth
preponderant evidence establishing that E.O.’s SCN1A mutation, a factor unrelated
to the administration of the vaccines, is the agent solely responsible causing his
Dravet syndrome.” Id. at *26. The special master analyzed that issue by looking
at the elements from Althen’s causation-in-fact test. For the first prong, the special
master stated: “The medical articles and studies filed in this case establish that the
international medical community generally agrees that vaccinations are not the
cause of Dravet syndrome and that the SCN1A mutation is responsible for causing
the disease.” Id. The special master credited Dr. Raymond’s testimony that the
type of mutation present in E.O., a splice-site mutation, causes “no protein
production and thus causes disease.” Id. at *27.
For the second prong, the special master recounted the testimony of Dr.
Raymond and Dr. Sachdeo that even if E.O.’s seizures started earlier because of
the vaccine, an earlier onset of E.O.’s seizure disorder would not have changed his
outcome. 2017 WL 747846, at *27. The special master accepted these opinions as
consistent with the McIntosh and Brunklaus articles.
Finally, with respect to timing, the special master noted that:
E.O. had no encephalopathy after the vaccinations at
issue. Therefore, E.O. did not have an injury that was
temporally associated with the vaccines on April 9, 2009.
His initial seizure was, in hindsight, a suspicious sign that
he might develop Dravet syndrome, or the initial
manifestation of his genetic mutation. That fact alone
does not establish a vaccine-related injury.
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Id. at *27. Therefore, based upon these findings, the special master found that the
Secretary met his burden to show that the mutation, not the vaccination, was the
sole cause of E.O.’s Dravet syndrome. Id.
Mr. and Ms. Oliver filed a motion for review. A judge from the Court of
Federal Claims denied the motion, essentially because the factual findings were not
arbitrary. Oliver v. Sec’y of Health & Hum. Servs., 133 Fed. Cl. 341 (2017). The
judge stated:
The Chief Special Master carefully considered the entire
record, including the opinions of the experts and the
medical literature. She explained her reasoning in detail.
Under the well-established principles set forth above, this
Court defers to the Chief Special Master’s ultimate
conclusion that the opinions of the government’s experts
were more persuasive than those of Dr. Shafrir, and that
E.O.’s SCN1A gene mutation and not a vaccine was the
cause of E.O.’s Dravet syndrome.
Id. at 354. Thus, judgment was entered against Mr. and Ms. Oliver.
Mr. and Ms. Oliver continued the litigation by appealing to the Federal
Circuit. The panel of Federal Circuit judges split with a majority affirming the
judgment to deny compensation. Oliver v. Sec’y of Health & Hum. Servs., 900
F.3d 1357 (Fed. Cir. 2018). The majority characterized the appellants’ argument
as “no more than a challenge to the weight afforded to their expert’s testimony and
supporting evidence.” Id. at 1361. The Federal Circuit determined that the
“factual findings were neither arbitrary nor capricious,” and under the standard of
review, the Federal Circuit “cannot review such challenges.” Id. at 1362. Thus,
the judgment was affirmed.
However, one judge from the Federal Circuit dissented. In this judge’s
view, the medical studies “show that both vaccination and the mutation have a role
in Dravet syndrome.” Id. at 1365 (Newman, J., dissenting). The dissenting judge
stated:
Science is at last providing answers to why some infants
manifest a severe reaction to vaccination. However,
these are the infants for whom the Vaccine Act was
enacted. Instead, HHS and the courts now exclude these
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infants from the Vaccine Act—in contravention of the
statute and the legislative purpose.
Id. at 1365.
The dissenting judge summarized eight articles, including the McIntosh and
Berkovic articles. According to this jurist, these articles showed “continuing
uncertainties” about “the role of vaccination when the SCN1A mutation is
present.” Id.
With respect to the facts for E.O., the dissent stated that: “It is not known
whether E.O. would have manifested Dravet syndrome without the vaccination.
The only certainty is that E.O. experienced a dramatic reaction within a few hours
of DTaP vaccination, that the seizures continued, and that there were
developmental consequences.” Id. at 1369. In the dissent’s view, the special
master erred in finding that “neither that initial seizure nor his vaccinations caused
his Dravet syndrome or neurological complications.” Id. (citation omitted).
After the panel from the Federal Circuit ruled against Mr. and Ms. Oliver,
they sought rehearing from the panel and a rehearing en banc. The Federal Circuit
denied this petition. Oliver v. Sec’y of Health & Hum. Servs., 911 F.3d 1381 (Fed.
Cir. 2019).
But, two judges from the Federal Circuit dissented from the rehearing en
banc. The dissent began with a statement from the legislative history of the
Vaccine Act that indicates a small number of children will be injured by a vaccine
but predicting who will be injured “is not always possible.” Id. at 1382 (Newman,
J., dissenting) (citing H.R. Rep. No. 99-908, at 4-6 (1986), as reprinted in 1986
U.S.C.C.A.N. 6344, 6345-46)). The dissent objected to the conclusion that “E.O.
would have been gravely injured due to his SNC1A mutation—that it is his
‘destiny’—and that it is irrelevant that the DTaP vaccinations initiated the seizures
and their consequences.” Id. at 1383.
In the dissent’s view, advances in genetics, “‘vaccinomics’ and
‘adversomics’” will, in the future, help doctors predict which children might be
harmed by a vaccination. Id. at 1384. But, until doctors test children’s genetic
mutations before the vaccination, a genetic test should not be the basis for an
award of compensation. Finally, the dissent called upon an en banc review to
correct the flawed outcomes in Snyder, Deribeaux, and Stone. Id. at 1385-86.
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F. Sharpe
Although not an SCN1A case, the next precedent from the Federal Circuit
involving a genetic mutation in a vaccinated child is Sharpe. Sharpe is the case on
which Mr. and Ms. Vinesar rely most heavily.
Sharpe began when Heidi Sharpe alleged that a vaccination with DTaP and
other vaccines on February 10, 2011 significantly aggravated a central nervous
system disorder affecting her child, L.M. Sharpe v. Sec’y of Health & Hum.
Servs., No. 14-65V, 2018 WL 7625360, at *1 (Fed. Cl. Spec. Mstr. Nov. 5, 2018).7
In 2016, Ambry Genetics determined that L.M. possessed a mutation in the
DYNC1H1 (“DYNC”) gene. Id. at *5. According to Ambry Genetics, the
mutation “is the cause of [L.M.’s] clinical symptoms.” Id. One reason for this
finding is that another female patient with the “same mutation . . . experienced a
phenotypic outcome very similar to L.M’s course.” Id. However, Ambry Genetics
also stated that “‘[n]o clear genotype-phenotype correlations have emerged,
although alterations associated with malformations of cortical development tend to
cluster in the motor domain, whereas alterations associated with SMA-LED [spinal
muscular atrophy with lower extremity predominance] tend to cluster in the stem
domain.’” Id. (quoting Ambry Genetics Rep., at 40).
The symptoms to which the Ambry Genetics report referenced started no
later than four days after the vaccination when L.M. had a seizure without a fever.
Id. at *2. An EEG showed that L.M. had hypsarrhythmia, which is characteristic
for a condition known as infantile spasms. Id. at *3. L.M. experienced significant
delays in her development, delays that are common in infantile spasms. Id.
To connect L.M.’s disorder to the vaccines she received, Ms. Sharpe
retained two experts. The first was Robert Shuman, a pediatric neuropathologist.
Id. at *7-12. Because Dr. Shuman formed his opinions before L.M.’s genetic
mutation was detected, he largely did not discuss that topic. Id. at *12; see also id.
at *8 (noting that “[t]he core of Dr. Shuman’s testimony and opinion was his
interpretation of L.M.’s various MRI’s”). The genetic issues were mostly left for
Ms. Sharpe’s second expert, Dr. Boles. Id. at *12-15. The main thrust of Dr.
Boles’s opinion was differentiating mutations in the stem (or tail) part of the gene
from mutations in other parts of the gene responsible for motor function. In Dr.
Boles’s opinion, a mutation in the tail was “far more likely to experience a severe
7 Ms. Sharpe also alleged that L.M. suffered an injury appearing on the Vaccine Table,
encephalitis. However, this allegation is not further discussed in the present decision because
Mr. and Ms. Vinesar have not claimed an on-Table injury.
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outcome than one with a mutation in the stem.” Id. at *13. Because L.M.’s
mutation was in the stem and because she had a severe outcome, something else (a
vaccine) made L.M.’s condition worse.
The Secretary also retained two experts. One was a pediatric neurologist
with extensive experience treating infantile spasms, John Zempel. 2018 WL
7625360 at *19, *22 n.36. Dr. Zempel opined “L.M.’s history to constitute a
‘classic presentation’ of an infantile spasm disorder only temporally coinciding
with the vaccines she received in February 2011.” Id. at *21. He briefly added
that the DYNC gene mutation was “more likely the cause of L.M.’s condition.” Id.
at *22.
The Secretary’s other expert, Maria Descartes, focused on the genetic issues
because she is board-certified in genetics and pediatrics. Id. at *16. Dr. Descartes
stated that de novo mutations in conserved regions are more frequently associated
with severe outcomes. Id. at *17. “However, she also acknowledged that it could
not be predicted in advance with complete certainty what any outcomes would be
for individuals bearing DYNC mutations, and that the possession of certain
mutations was not necessarily determinative of outcome.” Id. Dr. Descartes also
responded to Dr. Boles’s opinion regarding the location of the mutation by
maintaining that “a range of outcomes was always possible regardless of mutation
location.” Id.
At the beginning of the special master’s analysis of the evidence, the special
master discussed the (older) whole cell version of the pertussis vaccine (“DTP”)
and the (current) acellular version of the pertussis vaccine (“DTaP”). Although
Kottenstette v. Sec’y of Health & Hum. Servs., No. 15-1016V, 2017 WL 6601878
(Fed. Cl. Spec. Mstr. Dec. 12, 2017) “elide[d]” the differences between them, this
special master stated that “there is a significant distinction between the DPT
vaccine and the subsequent forms that use the acellular version of pertussis.”
Sharpe, 2018 WL 7625360, at *31. In support of this proposition, the special
master cited a series of cases from special masters, starting with Grace v. Sec’y of
Health & Hum. Servs., No. 04-[redacted], 2006 WL 3499511, at *9 (Fed. Cl. Spec.
Mstr. Nov. 30, 2006).
When considering how the DTaP might have harmed L.M., the special
master most importantly found that Ms. Sharpe “did not successfully establish that
L.M.’s post-vaccination condition was sufficiently worse to constitute a
‘significant aggravation’ of her DYNC mutation.” Id. at 36 (capitalization changed
without notation). As part of the third prong of Loving, the special master held
that a “claimant must demonstrate that his or her post-vaccination condition is
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overall qualitatively worse than what would be expected given what is known
about the preexisting condition (which might otherwise have deleterious effects on
its own).” Id. at 36 (citing Locane v. Sec’y of Health & Hum. Servs., 685 F.3d
1375, 1381-82 (Fed. Cir. 2012)). In interpreting the law regarding significant
aggravation, the special master held that he or she must evaluate “what is known
about the preexisting mutation and its likely impact on an affected individual’s
life.” Id. at *37. The special master found that “L.M.’s overall course is consistent
with what is known about the effects of a DYNC mutation. The evidence therefore
does not preponderate in favor of the conclusion that L.M.’s spasm disorder
otherwise attributable to her DYNC mutation was worsened by vaccination.” Id.
With respect to the DYNC mutation, the special master declined to credit
Dr. Boles’s opinion regarding the significance of location of the mutation.
Although the special master found that Dr. Boles’s opinion “raised interesting and
valid scientific points,” it was ultimately “flawed.” Id. at *38. One reason for
rejecting Dr. Boles’s opinion was the example of another patient, noted in the
Ambry Genetics report and subsequently described in an article by Helbig, with
“the precise same amino acid alteration location as L.M., and an outcome
comparable to that experienced by L.M.” Id. at *39.
For Loving’s fifth prong, the special master found that the vaccinations did
not worsen L.M.’s seizure disorder. The special master recognized that L.M.’s
infantile spasms became more obvious after the vaccination. But, this sequence
did not establish that the vaccinations caused any worsening. Id. at *41 (noting
that although the petitioner’s experts “found particularly compelling the fact that
L.M.'s West syndrome became most obvious after vaccination” it remains
“axiomatic in the Vaccine Program that a mere temporal relationship
between vaccination and illness does not establish causation”). Accordingly, for
these reasons, the special master denied compensation. The special master also
stated, in a footnote, that if Ms. Sharpe had met her burden to present a prima facie
case, then the Secretary had met his burden to establish a factor unrelated to the
vaccine (the genetic mutation) caused L.M.’s condition. Id. at *37 n.47. In this
lengthy footnote, the special master analogized the DYNC gene to the SCN1A
gene.
Ms. Sharpe filed a motion for review. Regarding her significant aggravation
claim, Ms. Sharpe argued that the special master “erred because he
‘unambiguously required [the petitioner] to predict [L.M.’s] current condition’ had
L.M. not been vaccinated.” Sharpe v. Sec’y of Health & Hum. Servs., 142 Fed. Cl.
630, 645 (2019) (quoting petitioner’s Motion for Review).
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The judge from the Court of Federal Claims disagreed, stating that Ms.
Sharpe’s argument did not present “a fair reading of the decision.” Id. In the
judge’s view:
[T]he Special Master had to evaluate what can be
attributed to her genetic mutation and what impact the
mutation would have on her life without the vaccinations.
Assessing an off-Table significant aggravation claim
therefore necessarily involves asking whether the
individual’s “clinical course and outcome [would have
been] any different than it would have been if [she] had
not been vaccinated[.]”
Id. (quoting Oliver v. Sec’y of Health & Hum. Servs., No. 10-394V, 2017 WL
747846, at *23). In assessing this issue, the Court ruled that the special master
“reasonably determined that L.M. was not guaranteed a mild outcome. Rather, her
outcome, as demonstrated by the medical literature, was consistent with children
who experienced infantile spams and specifically the condition of another little girl
with the same genetic mutation.” Id. at 645.
The Court also indicated that the special master alternatively found that the
Secretary had met his burden regarding the factor unrelated. But, the Court, itself,
did not review this finding because the special master’s primary finding (that Ms.
Sharpe had not met her burden) was based upon the “entire record” and a “rational
conclusion.” Id. at 646-47. Thus, the Court affirmed the judgment denying
compensation.
Ms. Sharpe appealed the judgment to the Federal Circuit. With respect to
the third Loving prong, which concerns comparing the vaccinee before and after
the vaccination, the Federal Circuit held that the special master erred. Based upon
Whitecotton v. Sec’y of Health & Hum. Servs., 81 F.3d 1099, 1105 (Fed. Cir.
1996), the Federal Circuit held that the special master made a mistake in requiring
“a petitioner to demonstrate an expected outcome and that her current-post
vaccination condition was worse than such expected outcome.” Sharpe v. Sec’y of
Health & Hum. Servs., 964 F.3d 1072, 1081 (Fed. Cir. 2020). The Federal Circuit,
however, allowed that a special master “should consider all evidence in the record,
including evidence of other possible sources of injury.” Id. at 1082. And a special
master may find that a vaccinee’s “condition ‘was not affected by the
vaccination.’” Id. (quoting Locane, 685 F.3d at 1378).
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The Federal Circuit’s panel in Sharpe was concerned about requiring a
petitioner to present information about an expected outcome in a gene mutation
cases because, according to this panel, “a clinical outcome is nearly impossible to
predict.” Id. at 1082. For this proposition, the Federal Circuit quoted testimony
from the Secretary’s expert in genetics, Dr. Descartes. She testified:
The dream of the geneticist is to find genotype-
phenotype correlation, because when a parent comes to
talk to me, the first thing they want to know, is my child
going to be able to do this and that? How long my child
is going to live? Do you have any answer to these
questions? The mutation that you found, what do you
know? And the answer, unfortunately, to all these
questions that parents ask all the time is we don’t know.
Id. at 1082 (internal citation omitted).
As to Loving’s fourth prong, the Federal Circuit stated that the special
master found that Ms. Sharpe had not met her burden of proof due to the presence
of the Ambry patient. The Federal Circuit held that the special master’s factual
finding was “arbitrary and capricious and must be set aside.” Id. at 1084.
The flaw in relying upon the Ambry / Helbig patient was:
[n]either party established whether the Ambry patient
faced any of the same environmental factors that
arguably affected the outcome of L.M.’s mutation,
including vaccination. If the Ambry patient was also
vaccinated, then the patient’s condition could also have
been caused by her vaccine. Additionally, even if the
Ambry patient suffered from the same condition as L.M.
without vaccination, a single example cannot establish
the typical progression of a disease; nor is such a singular
example sufficient to disprove a medical theory that a
vaccine can cause aggravation in some patients.
Id. at 1084. In this context, the Federal Circuit criticized the special master for
determining that “L.M. was destined to have a severe outcome” noting that a
“deterministic mindset does not belong in the Vaccine Injury Program.” Id. For
this proposition, the Federal Circuit cited the opinion dissenting from the denial of
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rehearing en banc in Oliver v. Sec’y of Health & Hum. Servs., 911 F.3d 1381,
1384 (Fed. Cir. 2009). Id., n.4.
For Loving’s fifth prong, the Federal Circuit again ruled that the special
master erred in his analysis. (It is not readily apparent whether the special master’s
mistake on prong five was an error of law or an error of fact.) The Federal Circuit
set aside the special master’s finding without making one of its own. Id. at 1086
(noting the fact “that L.M. experienced some seizure episodes before receiving
her vaccination should have no negative affect on Petitioner’s case”).
Finally, the Federal Circuit addressed the special master’s alternative
determination that the gene mutation was “the sole, substantial factor in causing
L.M.’s seizure disorder.” Id. The Federal Circuit found that the “record does not
support this finding.” Id. Here, the Federal Circuit summarized the evidence
regarding a mutation in the stem region of the gene. The Federal Circuit found that
the “science in the record uniformly supports . . . [a finding that] a stem mutation
in the DYNC1H1 gene is generally more likely than not going to lead to a non-
severe, non-cognitive disorder.” Id. at 1087. Therefore, “there is no substantial
evidence to support the conclusion that L.M.’s stem mutation was more likely than
not the sole, substantial factor causing her severe seizure disorder.” Id.
For these reasons, the Federal Circuit vacated the special master’s decision
regarding the off-Table claim. The Federal Circuit remanded for further
proceedings. Id. However, before the mandate issued, the Secretary sought a
panel rehearing or a rehearing en banc. A thrust of this argument was that the
panel erred in relying upon Whitecotton because Whitecotton was an on-Table
case and Ms. Sharpe as well as Locane are off-Table cases.8 Resp’t’s-Appellee’s
Pet. for Rehear’g and Rehear’g en Banc, No. 2019-1951, at 13 (Fed. Cir. filed
Sept. 8, 2020). However, after inviting and receiving a response from Ms. Sharpe,
the Federal Circuit denied the petition for a rehearing en banc. Sharpe v. Sec’y of
Health & Hum. Servs., No. 2019-1951 (Fed. Cir. 2020).
When Sharpe returned to the special master, he found that the Federal
Circuit’s opinion “unquestionably forecloses further consideration of Respondent’s
success in establishing alternative cause/factor unrelated based on the DYNC
8 The amount of evidence in on-Table cases differs from the amount of evidence in off-
Table cases. The Vaccine Act “‘relaxes proof of causation for injuries satisfying the Table, . . .
but does not relax proof of causation in fact for non-Table injuries.’” Boatmon v. Sec’y of
Health & Hum. Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019) (ultimately quoting Grant v. Sec’y
of Health & Hum. Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992)).
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mutation.” Sharpe v. Sec’y of Health & Hum. Servs., No. 14-65V, 2021 WL
1291720, at *6 (Fed. Cl. Spec. Mstr. Feb. 19, 2021). On the question that the
Federal Circuit left open, Loving prong 5, the special master relied on L.M.’s
transient reaction on the day of the vaccination and her seizure days later. Id. at
*7. While characterizing this evidence as “quite thin” and “weak[],” the special
master found that Ms. Sharpe met her burden. Id. at *7-8. In this context, the
special master distinguished L.M.’s genetic mutation from mutations in the
SCN1A gene because less is known about the DYNC mutation. Id. at *8; see also
id. (noting that the “admitted little that is still known about the DYNC mutation
and its possible interaction with vaccines is to no small extent another factor
favoring Petitioner”). Accordingly, the special master ruled that Ms. Sharpe was
entitled to compensation and ordered the parties to proceed to damages. Id. at *9.
G. Sanchez
Although not cited by the parties, the Federal Circuit’s 2022 opinion in
Sanchez is arguably more important than Sharpe. In a 2020 opinion in Sanchez,
the Federal Circuit vacated an October 9, 2018 decision that had led, after the
denial of a motion for review, to a judgment against Germain and Jennifer
Sanchez. A primary reason for the Federal Circuit’s vacatur was a significant
discrepancy in the [undersigned] special master’s finding of fact regarding the
neurological health of the Sanchezes’ child, Trystan, in mid-February 2009.
Sanchez v. Sec’y of Health & Hum. Servs., 809 F. App’x 843, 853 (Fed. Cir.
2020). Trystan’s activities in mid-February 2009 were important because Trystan
received a DTaP vaccination on February 5, 2009. Id. at 845. The Sanchezes and
the two experts whom they retained maintained that by mid-February 2009,
Trystan was displaying unusual arm movements that (a) were brought about by the
vaccination and (b) marked an early manifestation of a condition with which
Trystan was eventually diagnosed, Leigh’s syndrome. See, e.g., Sanchez v. Sec’y
of Health & Hum. Servs., No. 11-685V, 2020 WL 5641872, at *8 (Fed. Cl. Spec.
Mstr. Aug. 26, 2020).
In contrast, the Secretary and the experts whom he retained contended that
Trystan did not have any unusual arm movements, or, if there were unusual arm
movements, they were not associated with Leigh’s syndrome. Acting through Dr.
Raymond, the Secretary also argued that Trystan’s Leigh’s syndrome was solely
caused by mutations in a gene known as the SDHA gene. Id. at *1.
After the Federal Circuit’s 2020 Opinion, the special master’s August 26,
2020 decision focused predominantly on evaluating whether the Sanchezes
established that the DTaP vaccination caused Trystan to develop Leigh’s
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syndrome. Id. at *20-51. The special master found that the Sanchezes did not
meet their burden of proof under Althen. One reason was that Trystan did not
display symptoms of Leigh’s syndrome in mid-February 2019, which was an
assertion underpinning their expert’s opinions. Id. at *24, *28. Another reason
was that Trystan’s treating doctors linked his Leigh’s syndrome to the genetic
mutation. Id. at *50-51 (discussing Dr. Haas and Dr. Wong, a geneticist).
Although unnecessary to the outcome, the special master also evaluated the
parties’ evidence regarding the role of Trystan’s genetic mutations. Id. at *56-61.
As part of this analysis, the special master placed the burden of proof on the
Secretary to establish “‘that the factor unrelated, not the vaccination, actually
caused the injury alleged.’” Id. at *53 (quoting Deribeaux v. Sec’y of Health &
Hum. Servs., 717 F.3d 1363, 1369 (Fed. Cir. 2013)). In this context, the special
discussed Rachel Hammitt’s case in which the Federal Circuit ruled that the special
master was not arbitrary in crediting Dr. Raymond’s opinion. Id. at *54 (citing
Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373 (Fed. Cir. 2012)). The
special master also discussed L.M.’s case in which the Federal Circuit ruled that
the special master’s finding that “the genetic mutation was the likely sole
substantial factor causing L.M.’s severe seizure disorder was not supported by
substantial evidence.” Id. at *55 (citing Sharpe v. Sec’y of Health & Hum. Servs.,
964 F.3d 1072 (Fed. Cir. 2020) (noting the “record did not support the special
master's conclusion because the specific mutation in L.M. ‘generally result[s] in
non-severe, noncognitive disorders.’”)).
As to the significance of Trystan’s two SDHA mutations, the parties’
retained experts differed. Dr. Raymond’s opinion was that the gene mutations
entirely explained Trystan’s condition and for this proposition Dr. Raymond relied
primarily upon an article by Parfait. Id. at *56; see Beatrice Parfait et
al., Compound Heterozygous Mutations in the Flavoprotein Gene of the
Respiratory Chain Complex II in a Patient with Leigh Syndrome, 106 Human
Genetics 236 (2000). The geneticist whom the Sanchezes retained, Dmitriy
Niyazov, stated the “genetic mutations were not sufficient, by themselves, to cause
[Trystan] to suffer Leigh’s syndrome.” Sanchez, 2020 WL 5641872, at *56.
Instead, a second stressful event, such as a vaccination, was also needed. Id.; see
also id. at *15 (describing Dr. Niyazov’s qualifications). These experts extensively
discussed six articles, which the special master summarized. Id. at *56-57. Based
upon this evidence, the special master found that the Secretary carried his burden
to present preponderant evidence. Id. at *58. In doing so, the special master
recognized that Dr. Niyazov offered strong points. On the other hand, the
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Secretary’s burden was merely to present a persuasive case, not necessarily a clear
and convincing case. Id.
A reason for crediting Dr. Raymond was that the Parfait article reported the
case of a child with two genetic mutations of which one was exactly the same as
Trystan’s and the other was similar and the child in the Parfait article also
developed Leigh’s syndrome. Id. at *59. The authors of the Parfait also
experimented to determine the “‘deleterious effect’” of one mutation. Id. (quoting
Parfait, at 241). The special master also found unpersuasive Dr. Niyazov’s
criticisms of the Parfait article because Dr. Niyazov appeared to be demanding
scientific certainty “that exceeds the preponderance of the evidence standard.” Id.
A second reason for crediting Dr. Raymond’s opinion was the methodology he
used in analyzing Tristan’s genetic mutation matched his methodology in Rachel
Hammitt’s case. Notably, the Federal Circuit appeared to support this
methodology when determining that the special master reasonably relied upon Dr.
Raymond’s opinion in Stone, 676 F.3d 1373. See id. at *60. Finally, as noted
above, two doctors stated that Trystan suffered from a genetic disease. Id. at *61.
Accordingly, the special master found: “Trystan’s compound heterozygous
mutations are the sole substantial cause of his Leigh’s syndrome.” Id.
Mr. and Ms. Sanchez filed a motion for review. The judge found that the
special master’s finding about the lack of neurological symptoms in mid-February
was not arbitrary. Sanchez v. Sec’y of Health & Hum. Servs., 152 Fed. Cl. 782,
807 (2021). However, the judge of the Court of Federal Claims declined to review
the findings regarding genetics. Id. at 799. Thus, judgment was entered against
the Sanchezes.
For a second time, the Sanchezes appealed to the Federal Circuit. The
Federal Circuit’s panel divided. The majority ruled in favor of Mr. and Ms.
Sanchez. Sanchez v. Sec’y of Health & Hum. Servs., 34 F.4th 1350 (Fed. Cir.
2022). The majority’s analysis was divided into two parts. First, the majority
determined that the special master’s fact finding regarding a lack of neurologic
problems in mid-February 2009 was not logical. Because this was the foundation
for the special master’s finding that the Sanchezes did not establish their causation-
in-fact case, the special master’s determination was reversed. Id. at 1354-56.
Second, the majority addressed the special master’s alternative finding
regarding genetics. The majority stated: “There is no evidence . . . that Trystan’s
mutations would have resulted in the same progression and severity of his Leigh’s
syndrome absent the vaccine.” Id. at 1356. Quoting Sharpe v. Sec’y of Health &
Hum. Servs., 964 F.3d 1072, 1084 (Fed. Cir. 2020), the majority stated that “a
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single example does not establish the typical progression of a disease and is not
‘sufficient to disprove a medical theory that a vaccine can cause aggravation in
some patients.’” Id. The majority, accordingly, found that the Sanchezes were
entitled to compensation and remanded for damages.
The dissenting member’s opinion disagreed with the majority’s evaluation of
the special master’s fact-finding regarding Trystan’s condition in mid-February
2009. The dissent explained:
given the competing evidence regarding the etiology of
Trystan’s condition, it was not unreasonable for the
special master to conclude that Trystan’s Leigh’s
syndrome did not manifest itself until significantly later
than the date of his February 2009 vaccinations, and
therefore that no causal relationship was established
between the vaccinations and the triggering of Trystan’s
Leigh’s syndrome.
Id. at 1360 (Bryson, J., dissenting). Like the judge of the Court of Federal Claims,
the dissent did not comment on the genetics issue.
II. Events in A.V.’s Life
A. Before Allegedly Causal Vaccination
A.V. was born on September 23, 2014. Exhibit 9 at 25. Testing at birth was
normal. Id. at 25-33. However, according to a test report from approximately
three years later, A.V. suffered from two mutations in a gene, known as the
SCN1A gene. Exhibit 4 at 2. One of the polymorphisms was “consistent with the
diagnosis of an SCN1A-related disorder.” Id. Dr. Raymond opines that this
genetic problem is the basis for A.V.’s seizure disorder. Exhibit A at 6 (noting that
“a mutation in her SCN1A gene . . . is the sole cause of her epilepsy condition.”)
In contrast, Dr. Boles opines that this genetic problem made A.V. vulnerable to
developing a condition. Exhibit 153 at 1.
Throughout her first six months of life, A.V. was developing normally and
meeting her milestones. Exhibit 11 at 30-40.
B. Vaccination and First Seizure
As part of A.V.’s well-baby appointment for six-month-old children, A.V.
received the third round of the standard set of childhood vaccines, including DTaP.
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Exhibit 8 at 1 (Apr. 20, 2015). The time of vaccination was approximately 10:00
A.M. Exhibit 11 at 30. A.V. was given Tylenol prophylactically. According to
Ms. Vinesar’s declaration, filed on March 23, 2018, A.V. slept more than usual.
Exhibit 1.
At approximately 11:30 P.M. that day, A.V. suffered a seizure and an
ambulance was called. Exhibit 3-1 at 31. The emergency medical technicians
recorded that A.V.’s temperature was 102 degrees Fahrenheit. Exhibit 19 at 30.
Medical personnel gave A.V. a sedative, Versed 1.8 mg, to control the seizure.
Exhibit 3-1 at 32.
In the emergency department of Lutheran Hospital, A.V. had another
seizure. Id. Her temperature was 38.4 degrees Celsius (101.1 degrees Fahrenheit).
Id. An EEG and CT scan was normal. Exhibit 3-2 at 75-76. Testing on blood
cultures did not reveal any infections. Id. at 82, 85-88.
The doctors admitted A.V. to the hospital. The diagnosis was complex
febrile seizures because the seizures lasted more than fifteen minutes. Exhibit 3-2
at 78. The doctors indicated that the vaccinations from earlier that morning were
“the most likely source of her fever.” Exhibit 3-1 at 37.
Dr. Mohammad Ikramuddin discussed A.V.’s seizures “in detail with the
family, including mechanisms, known triggers, acute symptomatic measure . . . the
use of [seizure medicine], including the need to monitor for side effects, [and]
precautions and reoccurrence risk.” Exhibit 11 at 94. After spending one night in
the hospital, A.V. returned to her baseline. She was discharged home. Id. at 95-
98.
As discussed below, A.V.’s return to baseline, normal EEG, and normal CT
are emphasized by the Secretary in contending that A.V.’s initial febrile seizure did
not harm A.V. See Resp’t’s Br. at 38; Oral Arg. Tr. at 13. The perspective of Mr.
and Ms. Vinesar is that A.V.’s initial febrile seizure triggered a predisposition to
have seizures, which otherwise would not have happened. Pet’rs’ Br. at 9-10, Oral
Arg. Tr. at 44-45.
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A.V.’s response to the vaccination was reported to her pediatrician in an
April 24, 2015 appointment. Exhibit 11 at 28. The pediatrician indicated that she
would report the incident to drug manufacturers. Id. at 29.9
A.V. saw her pediatric neurologist, Dr. Ikramuddin, on May 14, 2015.
Exhibit 10 at 62. Dr. Ikramuddin provided an assessment that A.V. was suffering
from paroxysmal spells and recommended a follow-up in three months or earlier.
Id.
C. Second Seizure10
Around July 23, 2015, A.V. had cough and cold symptoms. Exhibit 12-1 at
39; see also Exhibit 11 at 25. A.V. suffered her second seizure on July 26, 2015.
Exhibit 12-1 at 23. She tested positive for parainfluenza type 3. Exhibit 12-2 at
99. This date was approximately three months after the previous seizure and A.V.
was approximately 10 months old.
When A.V. started seizing, her mother administered Diastat (2.5 mg) with
no initial relief. Exhibit 12-1. Emergency services recorded that A.V.’s clothing
was then removed to assist with cooling and then A.V. was given Versed (.16 mg)
at home and the medication stopped the seizure. Id. Personnel from an emergency
medical service recorded that A.V.’s temperature was 100.9 degrees Fahrenheit
and transported A.V. to a hospital. Id. at 27. In the hospital, A.V. underwent a
series of tests, of which one revealed A.V. was positive for parainfluenza. Exhibit
11 at 25, 92. A.V.’s July 27, 2015 EEG was normal. Exhibit 12-2 at 86. On July
27, 2015, the date A.V. was discharged, the parents were advised to follow up with
neurology and were given Diastat for home. Id. at 92.
Dr. Ikramuddin examined A.V. on August 20, 2015. Exhibit 10 at 54-56.
Dr. Ikramuddin reported A.V. as having “complex febrile seizure [and] nasty
cough.” Id. at 56. Dr. Ikramuddin discussed Diastat and the possibility of trial
medicine and side effects with Mr. and Ms. Vinesar. Id.
9 The Secretary noted that a VAERS report does not appear in the record. Resp’t’s Br. at
3 n.4. In response, Mr. and Ms. Vinesar did not identify its location. See Pet’rs’ Reply.
10 Mr. and Ms. Vinesar do not provide any details regarding seizures after the first
seizure. See Pet’rs’ Br. at 2. The lack of details seems consistent with their argument that the
only thing that matters is the trigger (alleged to be the vaccine) for the first seizure.
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D. Third Seizure
A.V.’s third seizure occurred on November 9, 2015. Exhibit 13 at 12.
When the seizure started, Ms. Vinesar administered diazepam rectally, which
stopped the seizure. Id. She told EMS personnel that A.V.’s temperature was 99.8
degrees Fahrenheit. Id.
A.V. again went to the hospital. Id. at 12. She tested positive for
parainfluenza type 1, but parainfluenza type 3 was not detected. Exhibit 13 at 52.
After several hours, A.V. was reported to be “awake, alert, [and] in no acute
distress.” Id. at 43. Ms. Vinesar told hospital staff that A.V. was “back to baseline
and she [wa]s comfortable taking [A.V.] home.” Id. Without staying overnight,
she was discharged after she returned to her baseline. Id. at 43-44.
E. Fourth Seizure
Another seizure happened approximately one month later. Exhibit 15 at 17
(Dec. 5, 2015). Ms. Vinesar again stopped the seizure by administering diazepam.
Id. She reported that A.V.’s temperature was 99.0 degrees Fahrenheit. She was
“mentating at baseline.” Id. at 21. Although A.V. was brought to the hospital, she
was discharged the same day. Id. at 31. Mr. and Mrs. Vinesar were instructed to
follow-up with A.V.’s primary care provider within two-to-four days. Id. at 34.
After Mr. and Ms. Vinesar informed A.V.’s pediatrician, Dr. Subramanian,
that A.V. had suffered four seizures, he recommended prescription medication.
Exhibit 11 at 19 (Dec. 18, 2015). However, the parents preferred herbal therapy.
Id. Dr. Subramanian’s records indicate that they would “follow with
lymphadenopathy if [seizures] persist past 2 weeks.” Id. at 20.
F. Events in 2016
In January 2016, because A.V. had experienced four seizures, A.V.’s
neurologist, Dr. Shah, recommended an MRI. Exhibit 10 at 49. Dr. Shah further
suggested that if febrile seizures reoccurred, “perhaps a 48 hour video EEG may be
of value.” Id. Mr. and Ms. Vinesar were willing to think about this suggestion.
Id.
In 2016, A.V. experienced two more confirmed seizures. The first was on
March 1, 2016, when she had a fever (101.3 degrees Fahrenheit) and symptoms
consistent with an upper respiratory infection. Exhibit 16 at 16-20. A.V. was
transported to the hospital. Id. at 16. The second was on September 12, 2016, and
also arose in the context of a low-grade fever. Exhibit 17 at 28. After both the
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March 2016 and September 2016 seizures, Dr. Shah saw A.V. Exhibit 10 at 39,
26-30 (noting A.V. saw Dr. Shah on both March 22, 2016 and September 22,
2016). A.V. may have had another seizure on July 19, 2016. See Exhibit 18 at 18.
A CT scan from the July 2016 emergency room visit was negative. Exhibit 11 at
82.
After turning two years old, A.V. was brought to her pediatrician for a well-
child appointment. Exhibit 11 at 14 (Nov. 4, 2016). She had reached her
developmental milestones. Id.
In December 2016, the family brought A.V. to see Dr. O’Connor at the
Epilepsy Center. Dr. O’Connor recommended an MRI, a longer EEG, and
metabolic studies. Id. at 69 (incomplete record); see also Exhibit 37 at 4 (also an
incomplete record for the visit with Dr. O’Connor). Dr. O’Connor also
recommended starting antiepileptic (“AEDs”) drugs. Exhibit 11 at 69. Dr.
O’Connor and the family also discussed that “if the neuroimaging metabolic
workup and EEG remain normal and [A.V.] continues to have recurrent seizures,
[Dr. O’Connor] would recommend doing some genetic testing specifically looking
at sodium channel abnormalities.” Id. Dr. O’Connor memorialized the family’s
response to her recommendations:
The parents do not want to do any imaging or lab work.
[They] do not want to start any medicines. They want to
use holistic methods and know a person in their
community who treats with multiple holistic medications.
As I do not know what these medications/treatments are I
am unable to recommend or comment on it.
Id. Dr. O’Connor concluded by stating that “As the family does not want to pursue
any of the recommendations I have made, follow up is not needed. . . . They should
follow up with . . . Dr. Shah primary neurologist at Lutheran General.” Id.
G. Events in 2017, including Genetic Testing
It appears that due to a dispute over whether A.V. should take anti-seizure
medication, Dr. Shah declined to continue to treat A.V. Exhibit 10 at 24 (Jan. 16,
2017). The family decided to transfer A.V.’s care to a doctor at the pediatric
epilepsy clinic at Lurie Children’s Hospital, Sunila O’Connor. Id.
On June 7, 2017, A.V. experienced more seizures for which she went to the
emergency room. Exhibit 11 at 66. According to Ms. Vinesar’s affidavit, the
doctors started her on Keppra. Exhibit 1 (Aff., dated Mar. 21, 2018) ¶ 6. But, Ms.
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Vinesar thought Keppra was causing adverse side effects and stopped
administering Keppra. Exhibit 20 at 65 (June 23, 2017).
While in Dr. Shah’s office on June 23, 2017, A.V. had a prolonged seizure
lasting roughly fifteen minutes and was taken to the Advocate’s Children’s
Hospital. Exhibit 10 at 12.11 A record from this facility stated A.V. “has never
been on any [anti-epileptic drug], and has instead been managed on a cocktail of
herbal meds that are prescribed by a naturopath which are currently not preventing
her seizures.” Exhibit 20 at 48. While in the hospital, A.V. was prescribed another
medication for preventing seizures, Trileptal. Id. at 66.
Following another seizure, which was on July 1, 2017, Dr. Shah diagnosed
A.V. with complex partial epilepsy with generalization. Exhibit 10 at 5. The
family planned to see Dr. O’Connor in the next few days. Id. But, a record from a
visit with Dr. O’Connor from around this time is not readily apparent.
A.V. had another seizure on August 23, 2017. Exhibit 23 at 20. While at
the Advocate Children’s Hospital, Ms. Vinesar told a staff member that Mr.
Vinesar and she had “weaned her off the Trileptal.” Id. They transferred care
from Advocate Children’s Hospital to the University of Chicago. Exhibit 34 at 3.
Upon a referral from A.V.’s pediatrician, A.V. underwent a 24-hour long-
term video EEG on August 24, 2017, at the University of Chicago. Exhibit 11 at
54. The doctor interpreting the EEG, Charles Marcuccilli, determined that it was
abnormal. Id. at 55-56. The potential multiple causes included: “structural or
vascular abnormalities, toxic, metabolic conditions, hydrocephalus or postictal
conditions.” Id. at 55.
Dr. Marcuccilli ordered genetic testing. Exhibit 4 at 1. The results, which
were reported by Gene Dx on October 24, 2017, are the foundation for the parties’
dispute over whether A.V.’s vaccinations in April 2015 harmed her. A.V.
possessed two SCN1A variants. Exhibit 4 at 2. The more significant variant was
c.811_815dupGGCAA. Id. This terminology means five base pairs are duplicated
in her DNA. Exhibit A at 2. The duplication, in turn, “creates a premature Stop
codon.” Exhibit 4 at 3. Because of either “protein truncation or nonsense-
mediated mRNA decay,” a loss of normal protein function is predicted. Id. Gene
Dx stated, “this variant is pathogenic.”12 Id. Overall, according to Gene DX, any
11 The circumstances by which Dr. Shah continued to treat A.V. are not readily apparent.
12 The second variant was c.2051 C>T. Exhibit 4 at 2. Gene DX classified this as a
“variant of uncertain significance.” Id. at 4. Later, other members of A.V.’s family also showed
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mutation in an SCN1A gene is associated with “70-80% of Dravet syndrome, 20-
24% early-onset cryptic epilepsy, 5-10% GEFS+.” Id. at 6 (footnotes omitted).
A.V. saw her pediatrician in September 2017 for a three-year-old well-child
appointment. A.V. was taking Keppra. Exhibit 11 at 7. Her development was
normal. Id. This normal development, in turn, is a basis for the Vinesar’s
questions about whether A.V. suffers from Dravet syndrome. See Pet’rs’ Br. at 3-
4; Pet’rs’ Reply at 4. The normal development continued despite abnormalities on
EEG and seizures.
H. Events after 2017
After the genetic testing detected the presence of an SCN1A variant, the
remaining medical records say relatively little about whether the vaccinations
harmed A.V. Thus, they are presented summarily. See Pet’rs’ Br. at 3-4; Resp’t’s
Br. at 8-11.
The family returned to the University of Chicago on April 4, 2018. A.V.
was taking an antiseizure medication Onfi (clobazam). Exhibit 34 at 389.
However, the family believed the medication was causing side effects such as
abdominal pain and sleepiness. Rather than maintain pharmacotherapy, the family
wanted to initiate a ketogenic diet. Id. at 390. The impression of the neurologist,
Dr. Alshaikh, was that A.V. was a three-year old female “with Dravet syndrome
(SCN1A mutation).” Id. at 385, 390. Because Ms. Vinesar was questioning the
diagnosis, Dr. Alshaikh advised the family to seek a third opinion at Lurie’s
Children’s Hospital. Id. at 390.
In June 2018, Dr. Marcuccilli from the Rush University saw A.V. He
obtained information about A.V.’s history of seizures, including that her longest
time without a seizure was 39 days. Exhibit 23 (Rush Univ. Ped. Neur.) at 46. Dr.
Marcuccilli also reviewed four EEGs. Id. at 48-49. Based upon this information
as well as the results of the genetic testing, which he had ordered, Dr. Marcuccilli
described A.V. as a “3 year old female with Dravet Syndrome with intractable
epilepsy secondary to an SCN1A mutation,” and that “her seizure semiology is
consistent with Dravet Syndrome given the prolonged seizures.” Id. at 49. While
A.V. was at risk for developmental delays, her problems were seizures, staring
spells, significant drowsiness, and some slurred speech. Exhibit 41 at 46.
this variant. Exhibit 144; Exhibit 145. Sometimes, Mr. and Ms. Vinesar refer to this variant,
instead of the pathogenic variant. See, e.g., Pet’rs’ Br. at 3-4.
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In June 2018, A.V. had additional genetic testing. Exhibit 39. These results
also identified a pathogenic SCN1A gene variant. Id. at 1.
On March 30, 2021, A.V. had a well-child examination when she was six
years old. She was being home schooled. Exhibit 147. Ms. Vinesar reported that
A.V. is “doing well with learning, speech and development, except she has periods
of set back following a seizure episode.” Id. at 5.13
A November 17, 2021 health summary from Lurie Children’s Hospital
describes A.V.’s active problems as “Dravet syndrome, intractable, with status
epilepticus.” Exhibit 148 at 1. She was noted to have a speech problem in
February 2020. Id. A.V. was taking antiseizure medication.
It appears that the parties have not attached any significance to more recent
medical records. Thus, although those records have been reviewed, they are not
further summarized in this decision.
III. Procedural History
Represented by Attorney John McHugh, Mr. and Ms. Vinesar alleged that a
series of vaccines given to their daughter, A.V., caused her to suffer a seizure
disorder or aggravated a pre-existing problem. Pet., filed Mar. 23, 2018. With the
petition, Mr. and Ms. Vinesar submitted a few medical records and an opinion
from Marcel Kinsbourne. Exhibits 1-6. Mr. and Ms. Vinesar periodically filed
additional medical records.
After the Secretary reviewed this material, the Secretary recommended
against an award of compensation. Resp’t’s Rep., filed Dec. 19, 2018, at 19. As
part of his analysis, the Secretary relied upon previous decisions from special
masters that found that vaccines do not cause Dravet syndrome, such as Oliver v.
Sec’y of Health & Hum. Servs., No. 10-394V, 2017 WL 747846, at *25-26 (Fed.
Cl. Spec. Mstr. Feb. 1, 2017) (noting that at least 16 other SCN1A cases had not
succeeded), mot. for rev. denied, 133 Fed. Cl. 341 (2017), aff’d, 900 F.3d 1357
(Fed. Cir. 2018). Id. at 10. In light of this history of unsuccessful claims, the
Secretary announced that he intended to challenge the reasonable basis for filing
the petition. Id. at 11 n.10.
13 The actual page numbers are not in consecutive order, so this cite is to a page number,
automatically generated by CM/ECF.
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With the Secretary’s report, he also filed an opinion from Dr. Gerald
Raymond, who had opined in other SCN1A cases. Dr. Raymond addressed the
opinion from Dr. Kinsbourne. Exhibit A. Dr. Raymond discussed the McIntosh
article.
Following a status conference to discuss the Secretary’s position and
evidence, Mr. and Ms. Vinesar were instructed to obtain additional medical records
and support. Order, issued Feb. 21, 2019. On successive days, they filed two
supplemental reports from Dr. Kinsbourne. Exhibit 45, filed July 24, 2019;
Exhibit 46, filed July 25, 2019. In the next status conference, Mr. and Ms. Vinesar
expressed an intention to obtain reports from other experts. Order, issued Aug. 9,
2019.
Mr. and Ms. Vinesar did not respond to several orders requesting
information regarding their plans for additional expert reports. See Orders, issued
Oct. 1, 2019 and Oct. 24, 2019. Consequently, on November 5, 2019, they were
directed to show cause why the case should not be dismissed for failure to
prosecute. Mr. and Ms. Vinesar addressed that order on December 4, 2019 by
submitting a report from Mark McNulty, a statistician. Exhibit 81. A primary
purpose of this report was to address the McIntosh article. Mr. and Ms. Vinesar
also sought an extension of time to file a report from a third person, Richard Boles.
They then filed the report from Dr. Boles. Exhibit 82. Dr. Boles opined that an
SCN1A gene did not determine the clinical traits a person would display. Id. at 4.
Instead, in the view of Dr. Boles, environmental factors, such as a fever, contribute
to the severity of any disorder. Id. at 6-7.
To address the reports from Dr. McNulty and Dr. Boles, the Secretary
submitted another report from Dr. Raymond. Exhibit C, filed June 29, 2020. Dr.
Raymond opined that the variations in clinical presentation were due to mosaicism,
rather than environmental factors. Id. at 4-5. He also touched upon Dr. McNulty’s
comments regarding the McIntosh article, noting his disagreement with Dr.
McNulty’s opinion that “McIntosh assumes that all children who developed Dravet
syndrome immediately following vaccination would have developed Dravet
syndrome even without vaccination…However, it is understood that not all
children with SCN1A mutations will develop Dravet syndrome and that a diversity
of outcomes is possible.” Id. at 10. Dr. Raymond noted that “[i]t is very clear from
the understanding of the biology of the variants in SCN1A and the impact on the
voltage-gated sodium channel that there is a spectrum of outcomes, but that the
severe end of that spectrum when fully expressed in animals, including humans,
results in a complex, neurologic presentation that may present with medically
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refractory seizures, intellectual disability, ataxia, sleep disturbances, and other
manifestations. Id.
On July 1, 2020, the Federal Circuit issued its opinion in Sharpe v. Sec’y of
Health & Hum. Servs., 964 F.3d 1072 (Fed. Cir. 2020). As discussed extensively
below, the parties differ in how they interpret Sharpe. Mr. and Ms. Vinesar
maintain that this case dictates a ruling in their favor. See Pet’rs’ Reply, filed Apr.
25, 2022. In contrast, the Secretary contends that it is distinguishable. See Resp’t’s
Response, filed Mar. 25, 2022.
The parties discussed Sharpe in the next status conference, which was held
on July 6, 2020. Mr. and Ms. Vinesar were directed to file responsive reports by
August 20, 2020. Order, issued July 6, 2020.
Mr. and Ms. Vinesar did not file any reports by the deadline, and they did
not seek additional time to comply with the order. But, in the October 7, 2020
status conference, their attorney represented that he had received a report and was
gathering the articles cited in the report. Mr. McHugh commented that the Federal
Circuit indicated in Sharpe that genetic mutations are factors that create a risk of an
adverse reaction in a vulnerable person receiving a vaccine. However, the
Secretary’s attorney countered that not all genetic mutations are the same and
judicial officers had already addressed SCN1A mutations, like the one A.V.
suffered.
In the ensuing order, Mr. and Ms. Vinesar were obligated to file an expert
report by October 9, 2020, which was the date Mr. McHugh proposed, and any
articles by November 6, 2020. Order, issued Oct. 7, 2020. The Secretary, in turn,
was directed to file a status report 30 days after Mr. and Ms. Vinesar submitted
their expert report. Id.
Over the next six weeks, Mr. and Ms. Vinesar filed multiple articles. See
Exhibits 110-121, 124-127. However, they did not submit the report that Mr.
McHugh represented he had on hand on October 7, 2020.
Mr. and Ms. Vinesar sought a statement of judicial notice that the
diphtheria-tetanus-acellular pertussis vaccine can cause the same adverse effects of
a predecessor vaccine, the diphtheria-tetanus-[whole cell] pertussis vaccine.
Pet’rs’ Mot. for Jud. Notice, filed Nov. 27, 2020. For reasons not explained on the
docket, the Secretary did not respond to this motion promptly. Approximately
seven months later, Mr. and Ms. Vinesar repeated their arguments and suggested
that the case should settle. Pet’rs’ Status Rep., filed June 17, 2021.
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A comprehensive scheduling order was issued on August 5, 2021. With
respect to the opportunity for Mr. and Ms. Vinesar to respond to Dr. Raymond’s
June 29, 2020 report, the petitioners were ordered to file a status report by August
19, 2021. While Mr. and Ms. Vinesar were instructed that they could still address
the report from Dr. Raymond, if they did not respond by August 19, 2021 with a
proposed schedule, then they would have been deemed to have determined that
they did not want to respond. As to the November 27, 2020 motion for judicial
notice, the Secretary was directed to respond by August 26, 2021. Order, issued
Aug. 5, 2021.
The August 5, 2021 order also set a schedule to address a motion for an
award of attorney’s fees and costs on interim basis, which Mr. and Ms. Vinesar had
filed on July 12, 2021. The Secretary opposed an award of attorney’s fees and
costs on the ground that the petitioners had not established the reasonable basis for
their claim. Resp’t’s Resp., filed Aug. 25, 2021. Because the evidence supporting
the claim was being developed, an adjudication of the motion for an interim award
was deferred. Interim Fees Decision, filed Sept. 14, 2021.
The November 27, 2020 motion for judicial notice was denied because
reasonable people could dispute whether the acellular version of the pertussis
vaccine causes the same side effects as the whole cell version of the pertussis
vaccine. Order, issued Sept. 29, 2021. This same order also reminded Mr. and
Ms. Vinesar that their opportunity to respond to Dr. Raymond’s June 29, 2020
report was closing.
Following this reminder, Mr. and Ms. Vinesar submitted another report from
Dr. Boles. Exhibit 153.14 In his two-page report, Dr. Boles refers to a 2020
Federal Circuit opinion, although he does not identify the case by name. Dr. Boles
concluded that “the SCN1A gene variant confers vulnerability towards disease, not
causality for disease. The person carrying the gene variant is vulnerable to injury
leading from additional factors, including environmental triggers such as seizures,
infection, or vaccination.” Exhibit 153 at 2. Dr. Boles also maintained that “the
Federal Circuit has reached the conclusion that I had urged in my [previous]
report.” Id.
In a December 10, 2021 status conference, Mr. McHugh confirmed that Dr.
Boles had read Sharpe. When asked whether the Secretary wanted Dr. Raymond
14 Mr. and Ms. Vinesar first attempted to file this report from Dr. Boles on October 27,
2021. CM/ECF 114. However, due to various deficiencies, they did not actually file the report
until December 23, 2021.
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to respond to Dr. Boles’s recent report, the Secretary declined. The Secretary
suggested that the case could be resolved on the papers.
Mr. and Ms. Vinesar argued that the evidence in the record supported a
ruling that they are entitled to compensation. Pet’rs’ Mot. for Judgment, filed Jan.
12, 2022. This pending motion is eleven pages. This motion could be construed to
raise both a causation-in-fact and significant aggravation claim. The next day, an
order regarding the anticipated scope of briefs was issued. Order, issued Jan. 13,
2022. While that January 13, 2022 order arguably expanded the topics beyond
those which Mr. and Ms. Vinesar discussed in their motion, they declined to
submit a supplemental brief. See Order, issued Jan. 27, 2022.
The Secretary sought a decision that the petitioners are not entitled to
compensation. Resp’t’s Resp. to Pet’rs’ Mot. for Judgment, filed Mar. 25, 2022.
With this response, the Secretary filed another report from Dr. Raymond. Exhibit
D.
Mr. and Ms. Vinesar replied on April 25, 2022. The parties’ briefs raised
several questions. Thus, an oral argument was held on January 18, 2023. With the
completion of oral argument, the case is ready for adjudication.
IV. Standards for Adjudication
Petitioners are required to establish their case by a preponderance of the
evidence. 42 U.S.C. § 300aa–13(1)(a). The preponderance of the evidence
standard requires a “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 v. Sec'y of
Health & Human Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010) (citations
omitted). Proof of medical certainty is not required. Bunting v. Sec'y of Health &
Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991).
Distinguishing between “preponderant evidence” and “medical certainty” is
important because a special master should not impose an evidentiary burden that is
too high. Andreu v. Sec'y of Health & Human Servs., 569 F.3d 1367, 1379-80
(Fed. Cir. 2009) (reversing special master's decision that petitioners were not
entitled to compensation); see also Lampe v. Sec'y of Health & Human Servs., 219
F.3d 1357 (Fed. Cir. 2000); Hodges v. Sec'y of Health & Human Servs., 9 F.3d
958, 961 (Fed. Cir. 1993) (disagreeing with dissenting judge's contention that the
special master confused preponderance of the evidence with medical certainty).
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Whether petitioners have presented preponderant evidence is evaluated,
below, in two separate parts. Section V first examines whether Mr. and Ms.
Vinesar have met their burden of showing either that a vaccination was the cause-
in-fact of A.V.’s seizure disorder or a vaccination significantly aggravated A.V.’s
seizure disorder. Section VI then examines whether the evidence preponderates in
favor of finding that A.V.’s genetic mutation caused her seizure disorder.
V. Analysis Part 1: Whether Mr. and Ms. Vinesar Have Met Their Burden
of Proof to Show a Vaccination Either was the Cause-in-Fact of A.V.’s Seizure
Disorder Or Significantly Aggravated A.V.’s Seizure Disorder
Whether Mr. and Ms. Vinesar are asserting only a causation-in-fact claim,
only a significant aggravation claim, or a causation-in-fact claim and a significant
aggravation claim is not clear. See Pet’rs’ Br. at 4, 9-10. In such circumstance, the
analysis can follow the elements for a significant aggravation claim.
As confirmed in W.C. v. Sec'y of Health & Human Servs., 704 F.3d 1352,
1357 (Fed. Cir. 2013), the elements of an off-Table significant aggravation case
were stated in Loving v. Sec’y of Health & Hum. Servs., 86 Fed. Cl. 135, 144
(2009). There, the Court blended the test from Althen v. Sec'y of Health & Human
Servs., 418 F.3d 1274, 1279 (Fed. Cir. 2005), which defines off-Table causation
cases, with a test from Whitecotton v. Sec'y of Health & Human Servs., 81 F.3d
1099, 1107 (Fed. Cir. 1996), which concerns on-Table significant aggravation
cases. The resulting test has six components. These are:
(1) the person's condition prior to administration of the
vaccine, (2) the person's current 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.
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In resolving claims of significant aggravation, special masters may focus
their analysis on the last three prongs of the Loving test, which correspond to the
traditional Althen factors. Walker v. Sec’y of Health & Hum. Servs., No. 18-
299V, 2022 WL 11141194, at *3 (Fed. Cl. Spec. Mstr. Sep. 27, 2022) (citing
Hennessey v. Sec’y of Health & Hum. Servs., No. 01-190V, 2009 WL 1709053, at
*42 (Fed. Cl. Spec. Mstr. May 29, 2009), mot. for rev. denied, 91 Fed. Cl. 126
(2010)).
A. Althen Prong One / Loving Prong Four – A Medical Theory
The oral argument clarified the parties’ respective positions. Mr. and Ms.
Vinesar are putting forth one theory to explain how the vaccines could have
harmed A.V. This theory contains two steps: 1) a vaccine can cause a fever, and a
fever can cause a seizure and 2) the first febrile seizure causes the later seizures.
Tr. at 54-55, 61.15
The Secretary’s opposition focuses on the second step. Through Dr.
Raymond, the Secretary concedes that a vaccine can trigger a febrile seizure. Oral
Arg. Tr. at 12-13; Resp’t’s Br. at 32, citing Exhibit D (Dr. Raymond’s report). Dr.
Raymond’s concession regarding the first febrile seizure is consistent with his
previous testimony. Oral Arg. Tr. at 13; Exhibit A at 2. However, the Secretary
and Dr. Raymond maintain that the first febrile seizure did not cause A.V.’s
seizure disorder. Oral Arg. Tr. at 13; Exhibit D at 3.
A first seizure differs from a seizure disorder. See Stone, 676 F.3d 1373
(citing 2011 WL 836992 at *4); see also Holmes v. Sec'y of Health & Hum. Servs.,
No. 08-185V, 2011 WL 2600612 at *11 (Fed. Cl. Spec. Mstr. Apr. 26, 2011), mot.
for rev. denied, 115 Fed. Cl. 469 (2014); Deribeaux, 105 Fed. Cl. at 594. In some
cases, including A.V.’s, the first seizure does not cause any lasting harm.
Moreover, a seizure that resolves in approximately one day or two days without
any sequellae would not fit the Vaccine Program’s severity rule. 42 U.S.C.
§ 300aa–11(c)(1)(D); Oral Arg. Tr. at 18. Thus, to receive compensation, the
15 The Vinesars did not advance a theory based on cytokines. Pet’rs’ Br. Nevertheless,
the Secretary argued that this theory is not persuasive. Resp’t’s Br. at 37 (citing cases). The
Vinesars also did not present a theory based on cytokines in their April 25, 2022 Reply. When
asked to explain their theory in oral argument, the Vinesars did not refer to a theory based on
cytokines. See Oral Arg. Tr. at 10-11. Under these circumstances, discussion of a cytokine-
based theory is not required.
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Vinesars must claim (and have claimed) that the vaccination contributed to A.V.’s
seizure disorder.
In terms of vaccines and a generic (meaning non-genetic) seizure disorder,
the Vinesars have not presented strong evidence. They have emphasized a set of
three articles plus an abstract, of which all involve the DTaP vaccine, to support
their claim that the DTaP vaccine causes seizures. Pet’rs’ Br. at 5-7, Oral Arg. Tr.
at 11. They have also cited an article about the whole-cell version of the pertussis
vaccine. However, these articles do not link the acellular pertussis vaccine to a
seizure disorder. They are taken up in chronological order, starting with the
earliest.
The earliest published article is the only one of this set of articles that
focuses on the whole cell version of the pertussis vaccine. Bellman MH et al.,
Infantile spasms and pertussis immunization, 8332 Lancet 1031 (1983). However,
the Vinesars did not actually file this article as an exhibit. Moreover, neither Dr.
Kinsbourne nor Dr. Boles cited Bellman in their reports. See Exhibits 2, 45, 46,
82, 114, 153. Because it is not an exhibit, additional discussion is not necessary.
Sheller Est. of Sheller v. Sec’y of Health & Hum. Servs., No. 18-696V, 2022 WL
4075946, at *7 (Fed. Cl. Spec. Mstr. Aug. 15, 2022), mot. for rev. denied, 164 Fed.
Cl. 398 (2023), appeal docketed, No. 23-1746 (Fed. Cir. Apr. 12, 2023).
Regardless, Bellman considers the incidence of infantile spasms after the whole-
cell version of pertussis vaccines. See Exhibit D at 2. The Vinesars have not
presented any persuasive reason to extend Bellman to a different vaccine (the
acellular form of pertussis vaccines) and to a different condition (epilepsy). See
Resp’t’s Br. at 33-34 (citing cases declining to rely upon Bellman). While the
Vinesars cannot find support in Bellman primarily because Bellman is not an
exhibit, the Vinesars did at least file the three other articles and one abstract.
In 1999, Dennis A. Conrad and Hal B. Jenson compared the whole-cell
version of pertussis vaccines and the acellular version of pertussis vaccines.16 The
authors assembled data from several sources, including the Centers for Disease
Control and Prevention and the American Academy of Pediatrics Committee on
Infectious Disease. For children who received the acellular pertussis vaccine, the
16 The Vinesars filed this article without bibliographic information. It appears that the
appropriate citation is Dennis Conrad & Hal Jenson, “Using Acellular Pertussis Vaccines for
Childhood Immunization. Potential Benefits Far Outweigh Potential Risks,” 105 Postgrad Med.
165 (1995). See Kottenstette v. Sec’y of Health & Hum. Servs., No. 15-1016V, 2020 WL
3579995, at *2 n.2 (Fed. Cl. Spec. Mstr. June 2, 2020), mot. for rev. denied, 2020 WL 4592590
(Fed. Cl. July 27, 2020), reversed, 861 Fed. App’x. 433 (Fed. Cir. 2021).
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authors commented: “the number of subjects . . . has been too small to calculate the
risk of extremely rare but potentially life-threatening reactions (eg, immediate
anaphylaxis, encephalopathy).” Exhibit 138 at pdf 5.17 Nevertheless, they
concluded “DTaP vaccines do and will continue to cause undesirable effects, albeit
at reduced frequency and severity compared with whole-cell vaccines.” Id. at pdf
7.
In 2000, a set of researchers from the United States government used the
VAERS database to compare adverse events following the whole-cell version of
pertussis vaccines with adverse events following the acellular version of pertussis
vaccines. Exhibit 139.18 M. Miles Braun and colleagues found that the acellular
version was at least as safe as the prior version. Id. With respect to seizures or
convulsions, the researchers examined 34 VAERS reports. Id. at 4. (Although the
text is not clear about which type of vaccine preceded the seizures or conclusions,
it appears that the relevant VAERS reports concern the acellular pertussis vaccine.)
Of this group, “none of the 34 were reported to have developed a seizure disorder
or epilepsy.” Id.
The third exhibit comes from 2002.19 Exhibit 140. The Vinesars filed the
abstract, not the entire article. The abstract does not provide any information about
whether children who received the acellular pertussis vaccines experienced a
seizure disorder. See id.
In 2003, Nicole Le Saux and colleagues compared, among other points, the
frequency of seizures after the earlier whole-cell version of a pertussis vaccine
with the frequency of seizures after the modern acellular version of a pertussis
17 It appears that the Vinesars incorrectly labeled the Conrad article as exhibit number 32.
The Vinesars’ exhibit list, filed on December 23, 2021, reflects that this article is exhibit 138.
Since exhibit 32 is already associated with medical records, the Conrad article will be cited as
exhibit 138. The Vinesars submitted this article in manuscript form. Therefore, the page cites
are to the pdf version, rather than the version that appears in printed journals.
18 It appears that the Vinesars incorrectly labeled the Braun article as exhibit number 33.
The Vinesars’ exhibit list, filed on December 23, 2021, reflects that this article is exhibit 139.
Since exhibit 33 is already associated with medical records, the Braun article will be cited as
exhibit 139.
19 The Vinesars also filed this article without any bibliographic information. However,
their brief provides the following: LA Jackson et al., “Retrospective population-based
assessment of medically-attended injection site reactions, seizures, allergic responses and febrile
episodes after acellular pertussis vaccine combined with diphtheria and tetanus toxoids,” 21 The
Pediatric Infectious Disease Journal 781 (2002).
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vaccine in Canadian hospitals. They found “a 79% decrease in febrile seizures
associated with receipt of [acellular] pertussis vaccine.” Exhibit 137 at e348 (Le
Saux et al.). This finding supports the first aspect of the Vinesars’ theory: that
vaccines can cause a fever and a fever can cause a seizure. The problem is that Le
Saux and colleagues report only about hospitalizations for the febrile seizure.
They do not report about any long-term consequences. See id. Thus, Le Saux
does not meaningfully contribute to analyzing whether an initial febrile seizure can
cause other seizures.
Against these three articles and one abstract, the Secretary and Dr. Raymond
point to a 2010 paper by Wan-Ting Huang and others, including people from the
Centers for Disease Control and Prevention. Exhibit D at 3, citing Exhibit D-2; see
also Resp’t’s Br. at 33-34. In this article, researchers accessed information
contained by managed health organizations and kept in the Vaccine Safety
Datalink. Exhibit D-2 at e264 (Huang). The researchers identified nearly one-half
million children (433,654) who received the DTaP vaccine. Id. at e265. After
searching medical records for various diagnostic codes, the researchers determined
that 5,205 patients had 7,191 seizure events. Id. The researchers used two
methods to analyze whether the DTaP vaccine was associated with an increased
incidence of seizures within four days of the vaccination: the risk-interval cohort
method and the self-controlled case series. Id. The authors concluded: “Our study
did not observe a significantly increased risk of seizures within 0 to 3 days after
DTaP vaccination.” Id. at e266. The increased relative risk was below 1.0. Id. at
e267, Table 2 (risk interval cohort analysis) and Table 3 (self-controlled case
series). This study did not address whether children who received a DTaP vaccine
had a greater incidence of seizure disorders. However, any decline in seizures
would seem to mean a decline in seizure disorders.
In short, the collection of evidence the Vinesars submitted (three older
articles plus an older abstract) does not persuasively support the Vinesars’ theory
that DTaP vaccines can cause a seizure disorder. The Vinesars seem to assume
that proving a vaccine causes a seizure is the same as proving a vaccine causes a
seizure disorder. For example, the Vinesars do not argue that a febrile seizure can
lower a person’s seizure threshold. See Pet’rs’ Br. The Vinesars have not
advanced that argument despite Dr. Kinsbourne’s assertion that the younger a child
experiences a first febrile seizure, the greater likelihood of developing epilepsy.
Exhibit 45 at 7-8, citing Berg and Van Stuijvenberg. The absence of this argument
is construed as a waiver of any argument based upon that evidence. See Vaccine
Rule 8(f).
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If the only question were “have the Vinesars established, by a preponderance
of evidence, that DTaP vaccines can cause a seizure disorder?,” the answer to that
question would be “no.” For the reasons explained above, evidence connecting the
acellular form of pertussis vaccines to a seizure disorder is lacking. Under this
understanding, the Vinesars have not met their burden of proof regarding Althen
prong one.
However, the question might be recast as asking whether preponderant
evidence shows that DTaP vaccines can cause (or significantly aggravate) a seizure
disorder in a child with an SCN1A mutation. Because this version implicates a
factor (the mutation) unrelated to the DTaP vaccination as the cause of A.V.’s
seizure disorder, this analysis is separated and can be found in section VI.C. below.
B. Althen Prong Two / Loving Prong Five – A Logical Sequence of
Cause and Effect
Just as the definition of the condition for which the Vinesars are seeking
compensation affects the determination on Althen prong one (or Loving prong
four), a distinction between a seizure and a seizure disorder (epilepsy) influences
the analysis of Althen prong two (or Loving prong five). To repeat, the Vinesars
are not seeking compensation for the immediate effects A.V. suffered from her
April 2015 seizure. These immediate effects dissipated within a few days. Exhibit
11 at 94-98 (noting A.V. had returned to her baseline and discharging her from the
hospital). As such, the Vinesars cannot receive compensation for this transient,
although frightening, incident. See 42 U.S.C. § 300aa–11(c)(1)(D); Barclay v.
Sec'y of Health & Hum. Servs., 122 Fed. Cl. 189, 198 (2015); Santini v. Sec'y of
Health & Hum. Servs., No. 06-725V, 2014 WL 7891507, at *19 (Fed. Cl. Spec.
Mstr. Dec. 15, 2014), mot. for rev. denied, 122 Fed. Cl. 102, 109 n.12 (2015).
Thus, the abundant evidence that the DTaP vaccine triggered A.V.’s first seizure is
beside the point.20
The actual issue is whether the DTaP vaccination triggered (or caused or
significantly aggravated) A.V.’s epilepsy. On this critical question, the Vinesars
have not identified any treating doctor who indicated that the vaccination caused
any lasting harm to A.V. Oral Arg. Tr. at 38; see also Pet’rs’ Br. at 9 (discussion
of prong two consisting of an (accurate) assertion that a doctor who treated A.V.
20 An example of evidence showing that the DTaP vaccine caused her fever is the report
when A.V. was first admitted to the hospital in April 2015. Exhibit 3-1 at 36-37. The Secretary
does not dispute this evidence. Resp’t’s Br. at 38.
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during her first hospitalization attributing her fever to the vaccine), Pet’rs’ Reply at
2 (similar).
The Secretary emphasizes that the Vinesars have not established that the
April 20, 2015 seizure caused “any lasting injury.” Resp’t’s Br. at 38. In support,
the Secretary points to a normal EEG and a normal CT scan. Exhibit 3-2 at 75-76.
By the time of A.V.’s discharge, she appeared normal. This information, in turn, is
the evidentiary foundation for Dr. Raymond’s assertion that “there was no
evidence of altered mental status or other evidence of encephalopathy.” Exhibit C
at 2.
The Vinesars have not countered the contention that A.V. returned to her
baseline shortly after her April 20, 2015 seizure. Their reply brief ends its
discussion regarding events in A.V.’s life with the febrile seizure. See Pet’rs’
Reply at 2. The Vinesars do not discuss the normal EEG and the normal CT scan.
See id. So, too, the reports from the Vinesars’ experts are relatively quiet on this
topic. For example, while Dr. Kinsbourne acknowledged the normal EEG and CT
scan (Exhibit 45 at 2), he does not explain how these results fit with his theory that
the febrile seizure harmed A.V. Dr. Boles also recognized A.V.’s normal EEG and
CT scan in his first report. Exhibit 82 at 2. Yet, in a later report, Dr. Boles states
that the “vaccination was the environmental trigger for brain injury.” Exhibit 153
at 2. However, Dr. Boles cites no evidence of brain injury (other than the seizure).
To the extent that Dr. Boles’s opinion assumes that the first febrile seizure
injured A.V.’s brain, then this case is analogous to Stone. There, Dr. Kinsbourne
maintained that a vaccine-induced complex febrile seizure harmed the child. 2010
WL 1848220 at *2. But, in Dr. Kinsbourne’s testimony, he could not point to any
clinical manifestation of the brain damage that he asserted occurred. Id. at *36. In
response, Dr. Raymond acknowledged that complex febrile seizures could injure
the brain, but “‘we have no evidence that the complex febrile seizures actually
injure the brain.’” Id., quoting the transcript. Thus, the chief special master found:
“There is simply no evidence that Amelia’s initial seizure caused any brain
damage.” Id. at *38. When the case reached the Federal Circuit, the Federal
Circuit summarized that a “key component of Dr. Kinsbourne’s theory is that the
initial seizure caused some form of lasting brain injury that had downstream
consequences for both children, specifically a lower seizure threshold.” Stone, 676
F.3d at 1384. The Federal Circuit reviewed the evidence discussed above and
found the chief special master’s analysis was not erroneous. The chief special
master could find that “Dr. Kinsbourne’s inference of brain damage, in the face of
clinical records showing no brain damage, was unpersuasive.” Id. at 1385.
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Just as in Stone, the evidence that the first febrile seizure harmed A.V. is
lacking. A.V. had a normal EEG, a normal CT scan, and was discharged a day
after her seizure. In a follow-up appointment, A.V.’s pediatric neurologist did not
seem particularly worried and recommended the next appointment occur in three
months or earlier. Exhibit 10 at 65. A.V. did not have her second seizure until
approximately three months after the first seizure and that second seizure occurred
in the context of a parainfluenza infection. Exhibit 11 at 25.
In addition to the lack of clinical manifestations of the harm potentially
caused by the first febrile seizure, another cause has been proposed. After A.V.’s
genetic mutation was discovered, a treating doctor associated her condition with
the genetic mutation. Exhibit 23 (Rush Univ. Ped. Neur.) at 49 (describing A.V. as
a “3 year old female with Dravet Syndrome with intractable epilepsy secondary to
an SCN1A mutation”) (emphasis added).
Accordingly, the Vinesars have not established with preponderant evidence
that the DTaP vaccine caused or worsened A.V.’s seizure disorder. They have not
met their burden of proof regarding Althen prong two / Loving prong five.
C. Althen Prong Three / Loving Prong Six -- Timing
A striking aspect about the chronology of events in A.V.’s case is that she
experienced her first febrile seizure about thirteen hours after vaccination. See
Exhibit 11 at 30 (time of vaccination), Exhibit 3-2 at 80-81 (time of seizure).
While this short latency is notable, an interval of less than one day between the
vaccination and the first seizure in children with an SCN1A mutation is common.
See Oliver, 2017 WL 747846, at *4; Snyder, 2011 WL 3022544, at *2; Deribeaux,
2011 WL 6935504, at *3; Hammitt, 2010 WL 3735705, at *2; Stone, 2010 WL
1848220, at *2-3. Yet, in all these cases, the Federal Circuit ultimately found that
the special master was not arbitrary in not awarding compensation. The denial of
compensation was based, in whole or in part, on a finding that the Secretary had
established with preponderant evidence that the SCN1A mutation caused the
child’s seizure disorder. That critical question is discussed as the second part of
the analysis in section VI.
D. Synopsis Regarding Petitioners’ Burden
Regardless of whether Mr. and Ms. Vinesar are proceeding under an off-
Table causation-in-fact case or an off-Table significant aggravation case, they bear
a burden of proof for two critical aspects. Here, first, they have not met their
burden to present a medical theory to explain how an acellular pertussis vaccine
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can harm a recipient, either by causing a seizure disorder or by aggravating a
seizure disorder. Mr. and Ms. Vinesar have focused much (if not all) their
attention on whether a vaccination might lead to a febrile seizure. But, proof of an
isolated febrile seizure differs from proof regarding a seizure disorder. Mr. and
Ms. Vinesar have not persuasively explained any mechanism by which a
vaccination might cause a seizure disorder. This lack of persuasive evidence
means that Mr. and Ms. Vinesar cannot prevail on Althen prong one / Loving
prong four. Without proof on this element, Mr. and Ms. Vinesar cannot receive
compensation.
Second, Mr. and Ms. Vinesar also have not met their burden of showing the
vaccination was the logical reason for either the development of the seizure
disorder or worsening of A.V.’s seizure disorder. The evidence does not
preponderate in favor of finding that the April 20, 2015 vaccination caused any
lasting harm. The EEG and CT were normal, and the hospital doctors discharged
A.V. the next day. This evidence points away from implicating the vaccination as
causing a lasting harm.
For these reasons, Mr. and Ms. Vinesar have failed to meet their burden of
proof regarding Althen prong one (corresponding to Loving prong four) and
Althen prong two (corresponding to Loving prong five).21 Without this showing,
the burden of proof has not shifted to the Secretary. LaLonde v. Sec’y of Health &
Hum. Servs., 746 F.3d 1334, 1340 (Fed. Cir. 2014).
VI. Analysis Part Two – Did the Secretary Meet His Burden to Establish a
Factor Unrelated to the Vaccinations Caused (or Worsened) A.V.’s Seizure
Disorder
If for the sake of argument it were assumed that Mr. and Ms. Vinesar had
met their burden of proof, then the Secretary may show A.V.’s “condition . . . is
due to factors unrelated to the administration of the vaccine.” 42 U.S.C. § 300aa–
13(1)(B). “If a petitioner successfully satisfies the Loving inquiry, the burden
shifts to the government to prove by a preponderance of the evidence that a ‘factor
unrelated’ to the vaccine caused the petitioner’s injuries.” Sharpe, 964 F.3d at
1080.
21 The analysis of Althen prong two / Loving prong five does not consider whether the
SCN1A genetic mutation provides “compelling evidence of a different cause for the injury.”
Stone, 676 F.3d at 1380. The genetics issue is discussed in section VI.A. below.
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Here, the Secretary through Dr. Raymond has identified A.V.’s genetic
mutation as the cause of her seizure disorder. Exhibit D at 3; Exhibit A at 6. To
understand this claim, basic information about genes is provided in section VI. A.
Then, three types of evidence (animal models, information about A.V.’s genetic
mutation, and human studies) are discussed in section B, section C, and section D,
respectively. Then, the leading cases---including cases involving an SCN1A
mutation---are again examined in section E.
A. Genes
Previous decisions have set forth foundational, if complicated, information
about genes and why genetic mutations cause a disease. See Snyder, No. 7-59V,
2011 WL 3022544, *13-15 (Fed. Cl. Spec. Mstr. May 27, 2011); Oliver, No. 10-
394V, 2017 WL 747846, at *7-9, *20; Deribeaux, No. 05-306V, 2011 WL
6935504, at *7–9. Genes contain segments of DNA. Through a process involving
RNA, the gene provides instructions for cells to assemble sequences of amino
acids into proteins. Exhibit A at 2.
The relevant protein here is a sodium channel. The sodium channel controls
the flow of sodium molecules across a neuron’s cell membrane. Exhibit A at 3.
To be more detailed, when less sodium than expected is conducted, certain neurons
that inhibit excitation are not activated, resulting in over-excitement. Exhibit 82 at
5; Exhibit 45 at 4; Exhibit A at 3.
In general, mutations in SCN1A genes are associated with different
neurological conditions, such as Dravet syndrome, which is also known as severe
myoclonic epilepsy in infancy (“SMEI”); generalized epilepsy with febrile seizures
plus (“GEFS+”); other types of epilepsy; and migraines. Exhibit A at 3, Exhibit 82
at 3.
The parties and their experts differ in their interpretation about the variation
in conditions.22 For Dr. Kinsbourne and Dr. Boles, the range of potential outcomes
in people with SCN1A mutations means that genes do not tell the whole story.
Something else, an environmental factor (such as an infection or a vaccination),
can modify or worsen a person’s outcome. See Exhibit 45 (Dr. Kinsbourne’s
report) at 5-10, Exhibit 82 (Dr. Boles) at 6-8. In contrast, Dr. Raymond states that
22 The experts and medical literature sometimes use the term "phenotype." Phenotype
means "the observable morphologic, biologic, and physiologic characteristics of an individual,
either in whole or with respect to a single or a few traits, as determined by a combination of the
genotype and the environment." Dorland's Illus. Med. Dictionary (33 ed. 2012) at 1410.
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the variability in outcome is more readily explained by differences in the genetic
mutation. See Exhibit C at 4.
Dr. Raymond asserts that “More recent papers… have demonstrated an
increase in predictability.” Exhibit C at 5. For example, Dr. Raymond stated
mosaicism can explain apparently disparate outcomes. Id. at 4, citing Francesco
Nicita et al. (Exhibit C-7). Dr. Boles did not respond to Dr. Raymond’s discussion
of mosaicism or predictability. See Exhibit 153; Oral Arg. Tr. at 41.
Thus, the crux of this issue could be viewed as whether the evidence
preponderates in favor of finding a genetic mutation in an SCN1A gene either (1)
constitutes a predisposition toward a disease or (2) constitutes a cause sufficient by
itself to cause disease.
Four sources support a finding that A.V’s SCN1A mutation is likely to be
the sole cause of her epilepsy. The first three are evidentiary – articles about
animal models, articles about the genetic mutations, and articles about
developmental delays in children with SCN1A disorders.23 The fourth category
consists of prior adjudications.
B. Animal Models
In his first report, Dr. Raymond put forward two animal models for Dravet
syndrome. The first animal model is used by researchers in the Catterall group.
See Exhibit A at 3-4 (citing, among others, an article by Oakley and an article by
Yu). Another mouse model was used by Ito. Exhibit A-15.
In response, Dr. Kinsbourne did not challenge the usefulness of the Catterall
group’s mouse model. See Exhibit 45. Dr. Kinsbourne endorsed articles using a
different animal model. Exhibit 45 at 8, citing Dutton et al. (Exhibit 58). The
same is true for Dr. Boles. He did not criticize the Catterall model. See Exhibit
82. Dr. Boles also relied upon Dutton and an extension of that work by Salgueiro-
Pereira. Exhibit 82 at 7-8.
23 The parties have filed an abundance of articles about SCN1A mutations, which have
been reviewed. The Vinesars did not discuss any article about SCN1A mutations in their briefs.
However, the Secretary has an extensive discussion. Furthermore, the parties were asked to
identify the articles that were most helpful to their positions and the parties identified those
supporting articles at oral argument. Oral Arg. Tr. at 58-61. Thus, this decision focuses on the
most important articles in the record.
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Thus, a preponderance of evidence supports analogizing the human
condition of Dravet syndrome to the mouse models used by the Catterall group in
Oakley and Yu. See also Exhibit 48 at 81 (Auvin); Snyder, No. 7-59V, 2011 WL
3022544, at *32-33. Of these two articles, Yu carries more weight.
Yu, which was published in 2006, reports on two experiments in mice. In
one set of mice, researchers created mice in which both SCN1A genes were
knocked out. In other words, these mice were homozygotes. These mice died
within eighteen days of being born. Exhibit A-11 at 1143 (Yu). What happened
with the other mice matches more closely with what could be happening in
humans. In mice with only one SCN1A gene knocked out (meaning the mice were
heterozygotes), they “first showed recurring behavioral seizures and sporadic
deaths during the weaning period between P21 and P27.” Id. at 1144. “The
seizures were spontaneous.” Id.
In Oakley, which was published in 2009, the researchers continued working
with heterozygous mice. (Yu is reference 14 in Oakley.) This article begins:
“Heterozygous loss-of-function mutations in the… sodium channel cause severe
myoclonic epilepsy in infancy (SMEI).” Exhibit A-9 at 3994. (Oakley et al.). In
discussing the manifestations of SMEI in humans, the researchers stated: “A
crucial feature of human SMEI is increasing severity of seizures with age.” Id. at
3995. “Infants with SMEI frequently have febrile seizures before developing
spontaneous seizures. This suggests a developmentally regulated seizure
susceptibility in which initial seizures are usually realized only with an additional
provoking factor such as elevated temperature.” Id. at 3996.
The researchers “tested susceptibility to temperature-induced seizures for 3
age groups.” Id. at 3995. They found that increases in temperature could provoke
a seizure. With respect to the different days, the researchers connected the age of
vulnerability to temperature-induced seizures to an age when a sodium channel
found in prenatal and early postnatal development (Na 1.1) is replaced with the
v
mature sodium channel (Na 1.3). Id. at 3998.
v
Collectively, Yu and Oakley demonstrate that mice lacking one SCN1A
gene will have seizures spontaneously at a certain age. If the mice are heated (an
increase in temperature serving as a proxy for a fever), then the mice can have
seizures earlier than they would have in the absence of the heating. While Dr.
Raymond cited these articles in his first report, neither Dr. Kinsbourne nor Dr.
Boles contested the points of the articles. See Exhibits 45 and 82. Rather, they
rely upon different animal models.
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The set of animal models on which Dr. Kinsbourne and Dr. Boles rely were
used in two experiments led by Andrew Escayg. See Exhibit 45 at 8 and Exhibit
82 at 7-8. The lead authors for the two studies are Stacey Dutton and Ana Rita
Salgueiro-Pereira.
The genetic mutation of these mice (R1648H) causes human children to
develop GEFS+. Exhibit 45 at 8; Exhibit C at 7; see also Exhibit 82 at 7 (asserting
this mutation could lead to SMEI or GEFS+). Thus, Dr. Raymond challenges the
usefulness of this model. Exhibit C at 7-8. In Dr. Raymond’s view, experiments
with this model do “not recapitulate the features of [Dravet syndrome].” Id. at 7.
He also notes that this mutation was not the mutation in A.V. Id. at 8.
In support of the difference with R1648H mice, Dr. Raymond cited a 2010
article by Martin. Exhibit C at 7. These researchers found that among fourteen
mice with a heterozygous mutation, two mice experienced seizures spontaneously.
Exhibit C-22 at 9827 (Martin et al.). The authors indicated that the low frequency
of seizures “is likely due, in part, to the mixed genetic background and is
consistent with the variability observed among affected members of GEFS+
families.” Id.24 Dr. Raymond also asserted that the R1648H model has “none of
the other associated features reported of [Dravet syndrome] phenotype.” Exhibit C
at 7.
On these points, Dr. Raymond’s criticisms miss their mark. It appears that
Dr. Raymond is requiring a high level of similarity. For example, although he may
accurately state A.V. does not possess a R1648H mutation, Dr. Raymond has not
shown that the Scn1a knockout model used in the Yu and Oakley experiments is
the same as A.V.’s mutation. Further, as Dr. Kinsbourne comments, Dravet
syndrome and GEFS+ are on a spectrum and A.V has not experienced the
developmental delays of Dravet syndrome. Exhibit 45 at 13. However, as
discussed below, Dr. Raymond has an additional criticism of the Escayg group,
which is more on target.
The earlier of the two papers from the Escayg group is by Dutton. The
purpose of the experiments about which Dutton reported was to determine whether
early-life febrile seizures lead to more severe epilepsies. Exhibit 58 at 159. The
researchers conducted two experiments of which both involved RH heterozygous
mice and wild-type littermates. Id. at 160.
24 Citing Yu (reference 15), the researchers also stated that spontaneous seizures were
detected in 3 of 7 Scn1a+/- mice.
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The first paradigm (“prolonged febrile event”) involved heating the mice
gradually and maintaining an elevated body temperature for thirty minutes. The
researchers counted the seizures and rated the severity of the seizures. Id. In the
second paradigm (“acute/prolonged febrile event”), the researchers on the first day
gradually elevated the mice’s temperature until a seizure occurred. On the second
day, the researchers again gradually increased the temperature but then maintained
the high temperature for thirty minutes. The researchers again counted and scored
the seizures. Id.
Two months later, the researchers gave the groups of mice that were heated
plus mice that were not heated a drug to induce a seizure. The researchers then
tested the mice in a variety of ways. The mice that were not heated experienced
fewer seizures and the seizures were of less severity compared with the A/PFE
mice. Id. at 164 (table 2). The researchers summarized their conclusion: “early
life [febrile seizures] resulted in lower latencies to induced seizures, increased
severity of spontaneous seizures, hyperactivity, and impairments in social behavior
and recognition memory during adulthood.” Id. at 159 (abstract). Based upon
their conclusions, the researchers recommended pharmacological intervention to
prevent febrile seizures in patients with SCN1A mutations. Id. at 169.
The lead author for the second article from the Escayg group relevant here is
Ana Rita Salgueiro-Pereira. In the introduction, the authors begin: “SCN1A
(Na 1.1 sodium channel) mutations cause Dravet syndrome (DS) and GEFS+
v
(which is in general milder).” Exhibit C-21 at 31 (abstract). Citing the Dutton
article, these researchers indicated that “hyperthermic long seizures/status
epilepticus can worsen the mild phenotype of Scn1a knock-in mice carrying the
R1648H mutation (Scn1aRH/+).” Id. at 32.
The researchers divided mice into six categories: wild-type, heterozygous
mutant, wild-type that had seizures induced by temperature, heterozygous mutant
that had seizures induced by temperature, wild-type which had seizures induced by
a drug, and heterozygous mutants that had seizures induced by a drug. Id. at 32.
For the temperature-induced seizure group and the drug-induced seizure group, the
mice experienced a seizure once per day for ten days. Id. The researchers found
the mice with hyperthermia-induced seizures developed long-lasting epilepsy and
long-lasting dysfunction in behavior and cognition. Id. at 34. The researchers
concluded that “Our results are not consistent with the concept of [Dravet
syndrome] as pure channelopathy.” Id. at 41.
Dr. Raymond criticized Dr. Kinsbourne’s reliance on this paper because A.V
“did not have an initial prolonged seizure or a train of daily seizures as the mouse
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model in the experiments of Salgueiro-Pereira et al. were exposed to.” Exhibit C
at 8. Dr. Boles did not answer this criticism, leaving Dr. Raymond’s point
unrebutted. See Exhibit 147.
C. Factors about the Genetic Mutation in A.V.
GeneDx reported a frameshift in exon 6 of the SCN1A gene. Exhibit 4 at 3.
GeneDx also recommended more testing and when the Vinesars were tested, this
genetic mutation was only found in A.V and was not present in other family
members. Id. at 4; see also Exhibit D at 1. The parties agreed that a mutation
arising de novo is more likely to cause a disease. See Oral Arg. Tr. at 41-45; see
also Exhibit 82 at 3.
This genetic mutation prevents the entire protein from forming, due to a
premature stop codon. Without a full structure, A.V. will have a loss of function.
Exhibit C at 2. Dr. Boles does not dispute that A.V.’s body system will not
assemble the entire protein. Instead, he asserts “Loss-of-function (LOF) SCN1A
mutations can be associated with very different outcomes, and are not exceptions
to the fact that the SCN1A mutation alone does not confer destiny on the
individual.” Exhibit 82 at 5. In support, he cites three articles.
Of these three articles, Jiang supports the Vinesars’ claim the most. Jiang,
which was published in 2016, reports “a case of [Dravet syndrome] with an
unusually favorable cognitive and behavioral development with a novel SCN1A
frameshift mutation.” Exhibit C-11 at 144 (abstract). The child was born with a
frameshift mutation. Id. at 144-45. This mutation “lead[s] to early protein
truncation.” Id. at 146. The authors stated: “Logically, the patient would have the
more severe phenotype. However, she has exceptionally favorable intellectual
ability.” Id.
Jiang et al. suggested that “other mechanisms may be existed to influence
the SCN1A phenotype, such as modifier genes, developmental variability,
accumulation of somatic mutation in lifetime and environmental insults can all
contribute to the cognitive outcome.” Id. at 144 (abstract).
Dr. Raymond’s response to Jiang was contained in a single sentence: “I
agree the case reported by Jiang et al shares similarities with [A.V.] which raises
the question of a degree of potential somatic mosaicism in both children.” Exhibit
C at 5.
Assessing the value of evidence concerning loss of function is difficult. Dr.
Raymond might be able to infer that from the limited information available that the
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child has mosaicism. Alternatively, Dr. Raymond’s supposition could be rejected
as speculation in that the Jiang authors present no information about mosaicism in
their subject.
In oral argument, the Secretary emphasized that the location of the protein
that the gene encodes supports a finding that the SCN1A in a mutation caused
A.V’s outcome. Oral Arg. Tr. at 28. In connection with this argument, the
Secretary cited two articles, Claes and Mulley, for the proposition that mutations
corresponding to the S4-S6 region of the sodium channel “lead to the more severe
phenotypes.” Oral Arg. Tr. at 28.
As to the importance of the protein’s location, the Secretary’s disclosure
could have been more explicit. Dr. Raymond’s first report states: “Mutations that
… affect the primary function of the channel such as the pore region have been
demonstrated to have a more severe disease or phenotype associated with them.”
Exhibit A at 3, citing Guilia Bechi et al. (Exhibit A-8). He did not cite either Claes
or Mulley for this proposition. Furthermore, the Secretary did not press an
argument about the location or the pore region. Neither “location” nor “pore”
appear in his brief.
More problematically, whether A.V’s mutation, which is in exon 6, aligns to
the S4-S6 region is not clear. The GeneDx report places the mutation in exon 6.
Exhibit 4 at 3. However, the SCN1A gene has 26 exons. Exhibit A-7 at 536
(Mulley). Dr. Raymond’s reports do not assert that exon 6 corresponds to S4-S6
region of the sodium channel. See Exhibits A, C, D. Without this evidence, a step
in the Secretary’s argument is missing.
In sum, the evidence regarding the nature of the genetic mutation might tip
slightly in the Secretary’s favor. One aspect of the A.V.’s genetic mutation
supports the Secretary’s position: A.V.’s mutation arose de novo and the parties
agreed that de novo mutations are more likely to be associated with worse clinical
manifestations. However, the significance of two other attributes is less clear.
A.V. has a genetic mutation that prevents the creation of the expected protein in its
entirety. The location of A.V.’s genetic mutation should, according to
respondent’s argument, lead to a severe phenotype. But, A.V.’s functioning is
relatively good. In other words, she is better than anticipated. The Secretary has
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not explained persuasively how A.V. can have developed as well as she has while
having the genetic mutation.25 See Oral Arg. Tr. at 50-51.
D. Human Studies
Through their experts, the parties advance many studies on children with
SCN1A mutations. Some of those investigated whether a vaccine affected the
outcome.
1. McIntosh
The earliest study and the one that received the most attention is by
McIntosh. Special masters have cited McIntosh. See Snyder, No. 7-59V, 2011
WL 3022544 at *23 (Fed. Cl. Spec. Mstr. May 27, 2011) (finding McIntosh
confirms Dr. Raymond’s opinion); see also Deribeaux, No. 05-306V, 2011 WL
6935504 at *45; Faoro, No. 10-704V, 2016 WL 675491 at *16 (Fed. Cl. Spec.
Mstr. Jan. 29, 2016) (relying upon McIntosh and other articles to find respondent
established an SCN1A mutation was the sole cause of a child’s Dravet syndrome);
Oliver, No. 10-394V, 2017 WL 747846 at *16 (finding the “existing medical
literature has established that vaccination does not affect the clinical course or
prognosis of Dravet syndrome”). Dr. Raymond relied upon McIntosh in his first
report. Exhibit A at 6.
The reliance on McIntosh drew a triple response from Dr. Kinsbourne, Dr.
Boles, and Dr. McNulty. First, Dr. Kinsbourne asserted that vaccines triggered an
earlier onset of seizures in children with Dravet syndrome. Exhibit 45 at 8.
Relying upon a study by Yuval Shafrir, Dr. Kinsbourne extended this claim by
stating “the earlier onset was associated with the more severe outcome.” Id. at 9.
Second, like Dr. Kinsbourne, Dr. Boles maintains: “Vaccination in children
with an SCN1A mutation is associated with earlier onset of seizure, generally on
the same or the next day.” Exhibit 82 at 9. Dr. Boles next uses data from
McIntosh to propose that McIntosh was unlikely to detect “poor long-term
developmental prognosis.” Id. at 12.
Dr. Boles’s use of statistics is expanded on by the petitioners’ third expert to
discuss McIntosh, Mark S. McNulty, PhD. Unlike other experts, who are medical
25 Mr. and Ms. Vinesar also failed to present a persuasive account for A.V.’s relatively
good development. The thrust of their claim is that the vaccine caused A.V. to be worse than she
would have been but for the vaccination. Yet, A.V. fortunately does not seem severely injured.
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doctors, Mr. McNulty earned a PhD in economics and statistics. Exhibit 81 at 6
(curriculum vitae). Mr. McNulty questions what inferences can be drawn from the
data McIntosh presents:
The direct interpretation is that there is no evidence in
this data that DTP vaccinations do impact outcomes, as
McIntosh states. However, there is also no evidence that
DTP vaccinations do not impact outcomes, and this is the
conclusion that McIntosh implicitly makes. McIntosh
ignores the fundamental premise of statistical hypothesis
testing that failing to reject the null hypothesis does not
imply that the null is true.
Exhibit 81 at 2-3. Dr. Raymond agrees. Exhibit C at 10.
One of Mr. McNulty’s conclusions is that the “information in the [McIntosh]
study data is very limited because of the small sample sizes.” Exhibit 81 at 5.
2. Human Studies Other than McIntosh
Dr. Raymond adds other human studies in which the populations were
larger. Exhibit C at 12-13, citing Tro-Baumann, Spiczak, Verbeek. Among
studies involving human children, Dr. Kinsbourne appears to favor a study by V.
Cetica. Exhibit 2 at 1, Exhibit 45 at 9-10.26
a) Tro-Baumann
The Tro-Baumann authors retrospectively examined the occurrence of
vaccination-related seizures in 70 children with Dravet syndrome with known
SCN1A mutations. Exhibit C-30 at 176-77 (Tro-Baumann). All participants
received at least one routine vaccination. These vaccines were DTP (diphtheria,
tetanus, pertussis), MMR (measles, mumps, rubella), influenza, and pneumococcal
vaccine. Id. The results were as follows:
In total, 34 seizures following vaccination were reported in 19 (27%) of 70
patients at a median age of 6 months (range 3 months to 4.5 years). In 11
(16%) of 70 patients, that is, 58% of all patients with seizures following
vaccination, the vaccination-related seizure was the first manifestation of
26 Dr. Kinsbourne also emphasized two studies involving animal models. Dutton and
Salgueiro-Pereira are discussed above.
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Dravet syndrome, with a median interval between vaccination and seizure of
24 h. Twenty-three (68%) of 34 seizures were accompanied by fever,
occurring in 10 of 19 patients.
Id.
The authors cited to the McIntosh article, stating that in one patient,
“antipyretics were systematically administered before and after all follow-up
vaccinations without further vaccination-related seizures.” Id. Although McIntosh
presents this single case, this example may indicate that vaccination-related
seizures might be preventable at least in patients with febrile episodes. Id.
The researchers’ “findings highlight seizures after vaccinations as a common
feature in Dravet syndrome and emphasize the need for preventive measures for
seizures triggered by vaccination or fever in these children.” Id. at 175. The
authors did not explicitly state whether the vaccinations caused or altered the onset
or subsequent course of seizures.
Neither Dr. Kinsbourne nor Dr. Boles opined on Tro-Baumann’s article.
b) Brunklaus
Three articles by Brunklaus appear in the record. They are presented in
chronological order, starting with the earliest.
(1) Prognostic, clinical and demographic features in
SCN1A mutation-positive Dravet syndrome (Exhibit 51
and Exhibit C-25)
In 2012, Brunklaus et al. conducted an ordinal logistic regression analysis on
355 patients with Dravet syndrome in order to identify predictors of developmental
outcome. Exhibit 51 and Exhibit C-25 at 2331 (Brunklaus). They discovered that
the “presence of a motor disorder, abnormal interictal EEG findings in Year 1,
status epilepticus and early focal seizures with impairment of awareness (≤ 24
months), were each positively associated with the tendency of a worse
developmental outcome.” Id. They further noted that “[a] young age at onset of
myoclonic seizures and a young age at onset of developmental delay were each
associated with the tendency for worse developmental outcome.” Id. It does not
appear that the authors expressly link this “worse developmental outcome” to the
severity of the genetic condition. They also stated that “the different seizure
precipitants, photosensitivity, MRI abnormalities or mutation class had no
significant effect on developmental outcome.” Id.
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The authors explained that their analysis of “clinical features reveals an
evolution of different seizure types over the first 3 years that corresponds to early
descriptions by Charlotte Dravet in 1978.” Id. at 2333. The authors found that the
“[m]ajority of seizures had been precipitated by fever or illness, however, one-third
had no precipitant and 7% had been triggered by vaccination.” Id. Pertussis
vaccination was once thought to cause vaccine encephalopathy, but “recent
evidence demonstrated that the encephalopathy is, in the majority of cases, truly a
presentation of Dravet syndrome caused by SCN1A gene mutation (Berkovic et al.,
2006).” Brunklaus et al. “found that vaccination-triggered seizures presented
significantly earlier than those without precipitant or with fever/illness,
nevertheless vaccination itself had no impact on the developmental outcome.” Id.
at 2334. Based on this finding, the authors commented: “[t]his supports the
argument that children carrying a SCN1A mutation are destined to develop the
disease, which in turn can be precipitated by a series of factors such as
fever/illness, vaccination or a bath.” Id. “However, the nature of the trigger has no
effect on overall developmental outcome and thus not seem to be responsible for
the subsequent encephalopathy.” Id.
Brunklaus et al. does not explicitly state that a vaccination-induced initial
seizure alters the course of Dravet syndrome. Rather, they explain that it is
inevitable that children with a SCN1A mutation will have Dravet syndrome.
(2) SCN1A variants from bench to bedside improved
clinical prediction from functional characterization.
(Exhibit C-16)
In October 2019, Brunklaus et al. state that it is difficult to predict disease
outcomes based on variant type in the SCN1A gene. Exhibit C-16 at 363
(Brunklaus). Although thousands of SCNIA variants have been reported, “only a
minority has been functionally assessed.” Id. The authors “review[ed] the
functional SCN1A work performed to date, critically appraise[d]
electrophysiological measurements, compare[d] this to in silico predictions, and
relate[d] [their] findings to the clinical phenotype.” Id. Their results revealed that,
“regardless of the underlying phenotype, that conventional in silico software
correctly predicted benign from pathogenic variants in nearly 90% . . . [but it] was
unable to differentiate within the disease spectrum [Dravet syndrome, genetic
epilepsy with febrile seizures plus vs. familial hemiplegic migraine].” Id. “In
contrast, patch-clamp data from mammalian expression systems revealed
functional differences among missense variants allowing discrimination between
disease severities.” Id. “Those presenting with milder phenotypes retained a
degree of channel function measured as residual whole-cell current, whereas those
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without any whole-cell current were often associated with [Dravet syndrome].” Id.
Based on these findings, the authors concluded that “electrophysiological data
from mammalian expression systems can serve as useful disease biomarker when
evaluating SCN1A variants, particularly in view of new and emerging treatment
options in [Dravet syndrome].” Id.
This article did not discuss whether a vaccination-induced initial seizure
alters the course of Dravet syndrome.
(3) Biological concepts in human sodium channel
epilepsies and their relevance in clinical practice.
(Exhibit C-29)
In January 2020, Brunklaus et al. discussed a study where out of 504 patients
with SCN1A variants, 490 had Dravet syndrome and 14 had “generalized epilepsy
with febrile seizure plus.” Exhibit C-29 at 390 (Brunklaus). “Nearly all [protein-
truncating variant] carriers (99.6%) had [Dravet syndrome].” Id. “The authors
discussed that “[t]he majority of SCN1A-related epilepsies are caused by [loss of
function] missense variants, full gene deletions, and [protein-truncating variants].”
Id. at 392.
The authors found that SCN1A steadily increases throughout childhood into
adulthood. Id. at 396. “SCN1A is predominantly expressed in inhibitory
neurons.” Id. The authors explained that “induced pluripotent stem cell work has
shown that increased excitability of principal neurons equally contributes to
network hyperexcitability in [Dravet syndrome] [and] [t]he distinct developmental
and neuronal type-specific expression of SCN1A may explain the phenotypic
differences and variations in drug response with exacerbation of seizures in
[Dravet syndrome] patients due to [sodium channel blocker] therapy.” Id.
This article did not discuss vaccinations.
(4) Parties’ Comments on Brunklaus articles
Petitioners did not discuss the Brunklaus articles in their briefs. Petitioners’
expert, Dr. Kinsbourne, cited to Brunklaus’ Prognostic, clinical and demographic
features in SCN1A mutation-positive Dravet syndrome to demonstrate that the
worst developmental outcomes are not associated with the earliest seizure onset.
Exhibit 45 at 10. Age at which the first seizure occurred was a more accurate
factor in predicting the severity of subsequent developmental delay. Id.
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Respondent referred to all three Brunklaus articles and concluded that they
do not show a vaccination-induced initial seizure alters the course of Dravet
syndrome. Resp’t’s Br. at 28, 34.
c) Verbeek
Verbeek wrote three articles, discussing the role of vaccination, febrile
seizures, and Dravet syndrome, contained in the record.
(1) Prevalence of SCN1A-Related Dravet Syndrome
among Children Reported with Seizures following
Vaccination: A Population-Based Ten-Year Cohort Study
(Exhibit C-32)
Verbeek et al. conducted a study “to determine the prevalence of Dravet
syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with
seizure onset after vaccination, among infants reported with seizures following
vaccination . . . [and] differences in characteristics of reported seizures after
vaccination in children with and without SCN1A-related Dravet syndrome.”
Exhibit C-32 at 127 (Verbeek). In the study, the researchers identified: “SCN1A-
related Dravet syndrome [was] the underlying cause in 1.2% of children reported
with seizures following vaccinations in the first two years of life, including 2.5%
of seizures reported after vaccination in the first year of life, and 0.3% in the
second year of life. Among seizures reported after the second or third DTP-
IPV(-)Hib vaccination, the proportion of SCN1A-related Dravet syndrome was the
highest.” Id. at 6. The authors reported: “The seizure had occurred within 24 h
(median 7.5 h) after administration of DT(P)-IPV(-)Hib vaccines in the majority of
children diagnosed with SCN1A-related Dravet syndrome. Children diagnosed
with SCN1A-related Dravet syndrome had a younger age at first seizure following
vaccination, and more often had second and third seizures reported after
subsequent vaccinations than other children. Both short or prolonged, generalized
or unilateral, and febrile or afebrile vaccination-related seizures occurred in
children with SCN1A-related Dravet syndrome. Seizures occurred more often with
a body temperature below 38.5°C, illustrating the high sensitivity also to minor
temperature increase in children with SCN1A-related Dravet syndrome.” Id. The
authors concluded:
27 The Secretary submitted this article in manuscript form. Therefore, the page cites in
Exhibit C-32 are to the pdf version, rather than the version that appears in printed journals.
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In children with Dravet syndrome, vaccinations might induce the first
and following seizures. Physicians and co-workers of immunization
safety surveillance should have knowledge of the prevalence of
Dravet syndrome among children reported with seizures following
vaccinations, and of the discriminating seizure characteristics in this
subgroup. This will promote earlier diagnoses of Dravet syndrome
which is appropriate treatment and genetic counseling. Moreover, an
early diagnosis will prevent parents and professionals from assuming
that vaccination is the cause of the epilepsy, and will thereby promote
faith and participation in immunization programs.
Id. at 8 (emphasis added).
(2) Etiologies for Seizures Around the Time of
Vaccination (Exhibit C-33)
Verbeek et al. assessed “the incidence, course, and etiology of epilepsy with
vaccination-related seizure onset in a population-based cohort of children.”
Exhibit C-33 at 658 (Verbeek). In a study of 23 children with epilepsy onset after
vaccination, 12 of them developed epileptic encephalopathy, 8 had benign
epilepsy, and 3 had encephalopathy before seizure onset. Id. The authors
identified underlying causes in 15 children (65%), which included SCN1A-related
Dravet syndrome or genetic epilepsy with febrile seizures plus syndrome, a
protocadherin 19 mutation, a 1qter microdeletion, neuronal migration disorders,
and other monogenic familial epilepsy. Id. The authors reasoned that the
“administered vaccines could have acted as a trigger for the first seizure, thereby
unmasking the genetic seizure predisposition in the children [in their cohort
study].” Id. at 663 (emphasis added). The authors stated that “[s]eizure
precipitation by vaccination or fever is a hallmark of SCN1A-related Dravet
syndrome.” Id. These findings led the authors to conclude that “in most cases,
genetic or structural defects are the underlying cause of epilepsy with onset after
vaccination, including both cases with preexistent encephalopathy or benign
epilepsy with good outcome.” Id.
(3) Effect of vaccinations on seizure risk and disease
course in Dravet syndrome (Exhibit 78 and Exhibit C-34)
Verbeek et al. studied “the effect of vaccination-associated seizure onset on
disease course and estimate[d] the risk of subsequent seizures after infant pertussis
combination and measles, mumps, and rubella (MMR) vaccinations in Dravet
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syndrome.” Exhibit C-34 at 596 (Verbeek).28 In a study, “[c]hildren who had
[Dravet syndrome] with and without vaccination-associated seizure onset (21%
and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months)
but not in age at first nonvaccination-associated seizure, age at first report of
developmental delay, or cognitive outcome.” Id. The authors found: “The risk of
subsequent vaccination-associated seizures was significantly lower for acellular
pertussis (9%) and nonpertussis (8%) than whole-cell pertussis (37%) vaccines.
Self-controlled case series analysis showed an increased incidence rate ratio of
seizures of 2.3 (95%) within the risk period of 5 to 12 days following MMR
vaccination.” Id. These findings “suggest that vaccination-associated earlier
seizure onset does not alter disease course in [Dravet syndrome], while the risk of
subsequent vaccination-associated seizures is probably vaccine-specific.” Id.
(4) Parties’ Comments on Verbeek Articles
While petitioners did not cite to Verbeek in the briefs, Dr. Boles cited to
Verbeek, stating that “35% of the cases having SCN1A-related [Dravet syndrome]
does suggest that this gene is an important part of the vaccine-associated epilepsy
population.” Exhibit 82 at 9. Dr. Kinsbourne also stated Verbeek and colleagues
“misinterpreted negative statistical outcomes as flagrantly as did McIntosh and
colleagues.” Exhibit 45 at 9; accord Exhibit 109 at 9.
Respondent and Dr. Raymond cited to all three Verbeek articles, concluding
that they do not show a vaccination-induced initial seizure alters the course of
Dravet syndrome. Resp’t’s Br. at 36; Exhibit C at 12-13.
d) Spiczak
Spiczak et al. recognized that “little is known about the type and frequency
of seizures and epilepsy syndromes following vaccination” and strove to
understand it better by conducting a study with a goal “to describe the clinical
features of children presenting with seizures after vaccination using a register-
based cohort.” Exhibit C-31 at 1506 (Spiczak). In a study of 247 patients with
seizures of epilepsy, the authors found that severe childhood epilepsies (Dravet
syndrome, West syndrome, Lenox-Gastaut syndrome, or Doose syndrome) were
diagnosed in 29 (11.7%) of those 247 patients, with the vaccination-associated
event being the first documented seizure in 15 (51.7%) of 29 patients. Id. Clinical
28 Although Exhibit 78 and Exhibit C-34 are the same article, only Exhibit C-34 is cited
to because it is the entire article.
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history was strongly suggestive of Dravet syndrome in 8 (3.2%) of 247 cases. Of
these, SCN1A mutations were reported in four cases (1.6%, referred to as
"confirmed Dravet syndrome"). Results of the SCN1A mutation analysis were not
available in 3 of 8 cases and were negative in 1 of 8 cases (all referred to as
"suspected Dravet syndrome"). Id. at 1509.
Because the clinical information provided was strongly suggestive of Dravet
syndrome in . . . 1.6% [cases] and genetic factors are increasingly identified
in patients with West syndrome (Watanabe, 1998), [Spiczak et al.] suggest
that causal genetic factors could potentially be identified in a sizeable subset
of patients with severe childhood epilepsies and vaccination-associated
seizures, helping to further demystify the concept of "vaccine
encephalopathy.
Id. at 1510.
Spiczak et al. explained that “[i]n a recent study, the majority of cases of
alleged ‘vaccine encephalopathy’ had Dravet syndrome following reevaluation
(severe myoclonic epilepsy of infancy; Dravet et al., 2005) and mutations in
SCN1A, encoding the alpha-1 subunit of the sodium channel (Claes et al., 2001;
Suls et al., 2006; Harkin et al., 2007), were identified in 11 of 14 patients
(Berkovic et al., 2006), showing that genetic epilepsy syndromes might
masquerade as vaccination-related epilepsies.” Id. at 1507 (emphasis added).
Spiczak et al. concluded that “[v]accination-associated seizures present in
the setting of various epilepsy syndromes, including severe childhood epilepsies in
>10% of cases [and] [e]arly diagnosis of the corresponding epilepsy syndromes
and confirmation of an underlying etiology is important for treatment decisions,
genetic counseling, and public health evaluation of vaccine safety.” Id. at 1506.
Dr. Raymond discussed the Spiczak article, but Dr. Kinsbourne and Dr.
Boles did not.
e) Cetica
Cetica et al. retrospectively “studied 200 individuals with SCN1A mutations
and explored the prognostic value of mutational data and early clinical findings
that may help clinicians to set up management choices adapted to individuals at
higher risk of progressing to Dravet syndrome, without delaying them until the
epileptic encephalopathy has become obvious.” Exhibit C-37 at 1038 (Cetica).
They found: “Age at seizure onset, analyzed as both a continuous and a categorical
variable, was distributed differently in patients with Dravet and those without
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Dravet syndrome. Mean age at first seizure was 5.19 months for patients with
Dravet and 18.4 months for those without Dravet syndrome . . . . None of the
patients who experienced their first seizure after 12 months of age developed
Dravet syndrome.” Id. at 1040. This study led the authors to conclude that age at
seizure onset appears to be a reliable indicator of outcome. Id. at 1043. They
recommended “early recognition and treatment that mitigates prolonged/repeated
seizures in the first year of life,” limiting the progression to epileptic
encephalopathy, because outcome is not predetermined by genetic factors only. Id.
at 1037.
While Dr. Kinsbourne cited to the Cetica article for support, petitioners did
not mention any argument based upon this article in their briefs. Exhibit 2 at 1,
Exhibit 45 at 9-10.
Dr. Raymond and respondent, however, address the Cetica study. Exhibit A
at 5, Exhibit C at 14, Resp’t’s Br. at 35. Dr. Raymond discussed that a subsequent
review in 2019 by the same individuals as Cetica et al. “recognize[d] the major
significant finding of their paper in finding the ability to predict the significance of
a mutation was whether it resulted in earlier onset of seizures or not.” Exhibit C at
14. Dr. Raymond stated the authors did not “appear to be endorsing that their
review demonstrates any role of early seizure in a change of outcome.” Id.
In this 2019 study by the Cetica group, the researchers stated that “[i]t has
now been clarified that the clinical spectrum of the [Dravet] syndrome does not
have firmly established boundaries.” Exhibit C-38 at S2 (Mei). They explained
that “[c]ognitive impairment is invariably present when the full syndrome is
manifested . . . [amd] [t]his complex of symptoms is related to mutations in the
SCN1A gene . . .” Id. They stated: “Inheritance from less severely affected
individuals, at times only having experienced a few febrile seizures, and
differences in severity, even within the same family, with a subset of patients only
showing fragments of the syndrome, testify to a remarkable phenotypic
heterogeneity as far as severity, but less so clinical phenomenology, are
concerned.” Id. They opined that the SCN1A gene-Dravet syndrome association
is “highly specific” and reasoned that “because the syndrome spectrum is wide,
fragments of it can at times also be manifested in other genetic epilepsy
syndromes, thereby leading to overdiagnosis of Dravet syndrome beyond SCN1A.”
Id. They concluded that “Dravet syndrome is in turn a severe SCN1A phenotype
within a continuum of SCN1A-related clinical phenomenology.” Id.
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3. Synopsis
Overall, this category of evidence (studies involving human children) favors
the Secretary’s position. It must be recognized that these studies are not perfect.
For example, the researchers did not withhold a vaccine from children with a
mutation to see whether they developed seizures in the absence of vaccination.
The creation of this type of control group would raise ethical questions. The
studies also do not include thousands of subjects. See Exhibit C at 11 (Dr.
Raymond’s discussion of the challenges of studying rare disorders). However, a
perfect study is not a requirement. See Sullivan v. Sec'y of Health & Hum. Servs.,
No. 10-398V, 2015 WL 1404957, at *20 (Fed. Cl. Spec. Mstr. Feb. 13, 2015)
(discussing that “the possibility of a better study is not an effective critique of an
existing, otherwise valid study”); see also Harris v. Sec'y of Health & Hum. Servs.,
No. 10-322V, 2014 WL 3159377, at *13 (Fed. Cl. Spec. Mstr. June 10, 2014)
(stating that the “perfect scientific study is not required by the relevant legal
standards”), but see Sanchez, 34 F.4th 1350, 1356 (“a single example does not
establish the typical progression of a disease and is not ‘sufficient to disprove a
medical theory that a vaccine can cause aggravation in some patients’”).
Multiple groups have explored whether childhood vaccines cause or worsen
seizures in children with SCN1A mutations. Using different approaches,
investigators have not detected any evidence that vaccines alter the child’s seizure
pattern. Instead, the large studies tend to show that the genetic mutation causes the
seizures.
E. Previous Cases
The foregoing four sections (parts VI.A through VI.D) of analysis largely
matches the findings by special masters in other cases involving a SCN1A
mutation. See Stone, 2010 WL 1848220, at *42; see also Hammitt, 2010 WL
3735705, at *47; Deribeaux, 2011 WL 6935504, at *46, Harris, 2011 WL
2446321, at *35. In two precedential opinions and one non-precedential opinion,
the Federal Circuit ruled that the finding of a genetic mutation was the sole cause
of a child’s epilepsy was not arbitrary. Stone, 676 F.3d at 1381-86, Deribeaux, 717
F.3d at 1369, Snyder, 553 Fed. App’x at 1002-04. The panels from the Federal
Circuit acknowledged the deferential standard of review for findings of fact.
In the decisions underlying those Federal Circuit opinions, special masters
considered multiple factors:
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• Details about what is known about the nature of the mutation, such as
arising de novo and occurring in a well conserved region. Stone, No. 04-
1041V, 2010 WL 1848220, at *19; Harris, 2011 WL 2446321, at *15-16
• The mutation’s effect on the resulting structure of the sodium channel.
Deribeaux, 2011 WL 693-5504, at *35-36, 40-41
• Dr. Raymond’s expertise in genetics. Stone, 2010 WL 1848220, at *40;
Harris, 2011 WL 2446321, at *6.
The special masters also:
• Determined a showing of a specific genotype – phenotype combination
was not required. Stone, 99 Fed. Cl. at 190; Deribeaux, 2011 WL
6935504, at *42, mot. for review denied on this point, 105 Fed. Cl. at
596; but see Harris, 102 Fed. Cl. at 302 (2011) (“a one-to-one
relationship has not been established”), rev'd sub nom. Snyder, 553 F.
App'x 994 (Fed. Cir. 2014).
• Concluded that definitive proof of mutations’ causative effect was not
required. Deribeaux, 2011 WL 6935504, at *32.
• Rejected a theory that the genetic mutation only created a predisposition
or vulnerability to developing epilepsy. Hammitt, 2010 WL 3735705, at
*10 (Dr. Kinsbourne); Deribeaux, 2011 WL 6935504, at *27 (Dr.
Tornatore).
These cases were a foundation for the special master’s decision in Oliver,
No. 10-394V, 2017 WL 747846. There, the petitioners advanced the theory that
the genetic mutation created susceptibility to a further injury. Id. However, the
special master rejected that theory and found the genetic mutation caused the
child’s epilepsy.
A majority of the Federal Circuit panel ruled that the special master’s
finding was not arbitrary. Accordingly, the panel affirmed the judgment, denying
compensation. Oliver, 900 F.3d at 1361–62.
When the petitioners/appellants in Oliver requested en banc review, the
Federal Circuit denied the petition. But, a dissent from a denial of the rehearing en
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banc maintained that Snyder, Deribeaux, and Stone were flawed and should be
overruled. Oliver, 911 F.3d at 1385-86 (Newman, J., dissenting).
In short, before 2018, the Federal Circuit had ruled in four opinions
(reflecting six cases) in which a child-vaccinee possessed an SCN1A mutation that
a special master could reasonably find the mutation was the sole cause of the
child’s epilepsy. But, in the Vinesars’ view, Sharpe changes everything. See
Pet’rs’ Br. at 10-11, Pet’rs’ Reply at 3-4.
From one perspective, the Vinesars’ argument matches what the Federal
Circuit did and said. The Federal Circuit stated that a “deterministic mindset does
not belong in the Vaccine Injury Program.” 964 F.3d at 1084. For this
proposition, the Federal Circuit cited the dissent in Oliver’s denial of a rehearing
en banc. The Federal Circuit in Sharpe did not reconcile its rejection of genetic
determinism with its earlier acceptance of findings from special masters in Stone,
Deribeaux, Harris, and Oliver.
One way that Sharpe differs from Stone etc. is that the genetic mutation in
Sharpe was a mutation in the DYNC gene. Sharpe, 2018 WL 7625360, at *3. In
Stone, Deribeaux, Harris, and Oliver, the genetic mutation was in the SCN1A
gene.
Another potential distinction between Sharpe and Stone etc. could be that
the opinions from the government’s experts differed. In the SCN1A cases, the
government’s expert, Dr. Raymond, opined the genetic mutation was the sole
reason for the child’s epilepsy. In contrast, in Sharpe, the government’s expert, Dr.
Descartes, was more equivocal. The Federal Circuit quoted this aspect of her
testimony:
The dream of the geneticist is to find genotype-
phenotype correlation, because when a parent comes to
talk to me, the first thing they want to know, is my child
going to be able to do this and that? How long my
child is going to live? Do you have any answer to these
questions? The mutation that you found, what do you
know? And the answer, unfortunately, to all these
questions that parents ask all the time is we don't know.
964 F.3d at 1082 (emphasis supplied by the Federal Circuit).
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This equivocation from the Secretary’s expert is not present in the Vinesars’
case. Dr. Raymond has consistently explained that the SCN1A mutation is the
cause for A.V.’s seizure disorder. Exhibit A at 6; Exhibit D at 3.
The potential distinction between the evidence as a basis to harmonize, on
the one hand, Stone, Deribeaux, Snyder, and Oliver with, on the other hand, Sharpe
is less apparent with respect to Sanchez. In Sanchez, Dr. Raymond opined
“Trystan’s genetic mutations, and solely his genetic mutations, caused Trystan’s
Leigh’s syndrome.” Sanchez, No. 11-685V, 2020 WL 5641872, at *59. This
testimony contributed to approximately ten pages of analysis following the
methodology the Federal Circuit appeared to endorse in Stone. Sanchez, 2020 WL
5641872, at *60. Nevertheless, the Federal Circuit determined “There is no
evidence … that Trystan’s mutations would have resulted in the same progression
and severity of his Leigh’s syndrome absent the vaccine.” Sanchez, 34 F.4th at
1356.
The result in Sanchez is, the undersigned respectfully submits, difficult to
understand. Can Dr. Raymond’s opinion satisfy the preponderance of the evidence
standard? What is the minimum quantity and quality of evidence required for the
Secretary to prevail on an alternative factor defense? Is the Secretary required to
present a study involving people with the genetic mutation who did and did not
receive a vaccine? In this respect, the Federal Circuit in Sanchez criticized the
(undersigned) special master for relying in part upon a gene expression study in
which researchers determined a relevant genetic mutation would cause a disease.
However, this level of proof was not available in Stone and Deribeaux.29
Understanding the view of the Federal Circuit would help this special master
comply with the instructions and expectations of the controlling Circuit Court.
To the extent that the two more recent precedential opinions (Sharpe and
Sanchez) cannot be reconciled with the three earlier precedential opinions (Stone,
Deribeaux and Oliver), the earlier panel controls. Robert Bosch, LLC v. Pylon
Mfg. Corp., 719 F.3d 1305, 1316 (Fed. Cir. 2013) (en banc); Johnston v. IVAC
Corp., 885 F.2d 1574, 1579 (Fed. Cir. 1989). Thus, a finding that an SCN1A
mutation was the sole cause of an epilepsy would seem consistent with the
outcomes in Stone, Deribeaux, and Oliver and would seemingly not necessarily
violate any dictates set out in Sharpe and Sanchez.
29 Although the Federal Circuit affirmed the judgments denying compensation, the
Federal Circuit did not comment on whether a specific genotype-phenotype precedent was
required.
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The Federal Circuit’s rulings that a special master was not capricious do not
preclude a different outcome. See Lampe v. Sec'y of Health & Hum. Servs., 219
F.3d 1357, 1368 (Fed. Cir. 2000); Bean-Sasser v. Sec'y of Health & Hum. Servs.,
127 Fed. Cl. 161, 167 (2016); [M.S.B.] by Bast v. Sec'y of Health & Hum. Servs.,
117 Fed. Cl.104, 124 (2014) (discussing opinions from the Court of Federal
Claims). Outcomes could differ because the underlying evidence is different.
However, the outcome in the Vinesars’ case resembles the evidence in those other
cases. For example, Dr. Raymond has testified in all the SCN1A cases. This
evidence, which has been discussed at length above, still preponderates in favor of
finding that the SCN1A mutation, by itself, causes a child’s epilepsy.
After scientists discovered an association between SCN1A mutations and
Dravet’s syndrome, scientists have, in many contexts, determined that the mutation
caused the seizure disorder. For example, in 2012, Brunklaus and others
concluded: “children carrying a SCN1A mutation are destined to develop the
disease.” Mr. and Ms. Vinesar have not presented persuasive evidence to
contradict the scientific conclusion reached by multiple sets of researchers.
F. Summary regarding Factor Unrelated
If the Secretary bore a burden to demonstrate that a factor unrelated to the
vaccination caused A.V.’s seizure disorder, the Secretary met that burden. With
preponderant evidence, the Secretary demonstrated that the A.V.’s genetic
mutation was the sole cause of her seizure disorder. This evidence primarily
consists of experiments on animals that model SCN1A mutations, information
about the details of A.V.’s specific mutation, and results of multiple studies about
children with SCN1A mutations published in peer-reviewed journals. Dr.
Raymond, who has more experience treating children and their families for
genetic-based neurologic problems than either Dr. Kinsbourne or Dr. Boles,
persuasively supported his opinion that a mutation in A.V.’s SCN1A gene “is the
sole cause of her epilepsy.” Exhibit D at 3.
Furthermore, the result in A.V.’s case (a finding that a genetic mutation
caused a seizure disorder) is the result reached in all other cases involving an
SCN1A mutation. While those results do not dictate the outcome here, they do
provide some persuasive precedent.
VII. A Hearing Is Not Required
Special masters possess discretion to decide whether an evidentiary hearing
will be held. 42 U.S.C. § 300aa-12(d)(3)(B)(v) (promulgated as Vaccine Rule 8(c)
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& (d)). A special master may decline to conduct a hearing when each party has
enjoyed a full and fair opportunity to present its position. Kreizenbeck v. Sec’y of
Health & Hum. Servs., 945 F.3d 1362, 1366 (Fed. Cir. 2020); Bello v. Sec’y of
Health & Hum. Servs., 158 Fed. Cl. 734, 748-49 (2022). A key question is
whether the special master has considered all the relevant evidence. Mager v.
Sec’y of Health & Hum. Servs., 158 Fed. Cl. 136, 149 (2022). Here, two
considerations lead to the conclusion that a hearing is not required.
First, the parties (particularly the Vinesars) have had ample opportunity to
submit evidence supporting their position. The Vinesars have submitted more than
a half-dozen reports, from a total of three experts. Exhibits 2, 45, 46, 81, 82, 109,
114, 153. These reports allowed Dr. Kinsbourne, Dr. Boles, and Dr. McNulty a
chance to respond to opinions Dr. Raymond had expressed. After the submission
of expert reports concluded, the Vinesars were given an opportunity to submit a
comprehensive brief but declined. See Orders, issued Jan. 13, 2022 (proposing
topics for a brief) and Jan. 27, 2027 (reporting comments from a status
conference). To the extent that the Vinesars proposed a hearing to address topics
that they had not previously addressed, see Oral Arg. Tr. at 37, those requests are
too late. The proper time to disclose an expert’s opinion is in the written report.
Simanksi v. Sec’y of Health & Human Servs., 671 F.3d 1368, 1382 (Fed. Cir.
2012) (stating “the special master can order the experts to confine their testimony
to the issues addressed in their reports”). Accordingly, the Vinesars have had a fair
and full opportunity to present evidence.
Second, from the Vinesars’ perspective, they do not need any additional
evidence. The Vinesars stated that the matter could be resolved on the papers “as
no material fact is in dispute.” Pet’rs’ Br. at 1. The essence of their claim is that
(1) an SCN1A mutation creates a propensity (or predisposition or vulnerability) to
developing seizures, and (2) a vaccine can induce a fever and a fever can trigger
the propensity for a seizure.
For their argument that the SCN1A mutation predisposes a person to having
seizures (as opposed to causing the seizures), the Vinesars largely emphasize the
Federal Circuit’s opinion in Sharpe. (As noted earlier, the Federal Circuit’s
opinion in Sanchez, arguably, helps them even more than Sharpe does.) If an
appellate authority were to determine that the Sharpe and Sanchez approach to
analyzing cases with genetic mutations were the correct approach, then the
Vinesars could prevail on the component regarding petitioners’ burden to explain
how a vaccine can cause a previously unmanifest condition to become manifest
and/or petitioners’ burden to explain how a vaccine can significantly aggravate a
clinically silent genetic condition. On the other hand, if an appellate authority
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were to determine that the Stone, Deribeaux, and Oliver approach were correct,
then the Vinesars could not prevail.
VIII. Conclusion
As with other parents whose children have genetic mutations and seizure
disorders, the Vinesars have endured and are enduring complicated and
challenging medical situations. They merit sympathy for everything they and their
beloved daughter have suffered.
However, sympathy is not the standard for awarding compensation. For the
reasons explained above, they have not demonstrated that the vaccination caused
any lasting harm in A.V. In addition, the Secretary has demonstrated with
preponderant evidence that the SCN1A mutation is the sole cause of her seizure
disorder. Accordingly, the Vinesars are not entitled to compensation.
The Clerk’s Office is instructed to issue judgment in accord with this
decision unless a motion for review is filed. Information about filing a motion for
review, including the deadline, is found within the Vaccine Rules, which are
available on the website for the Court of Federal Claims.
IT IS SO ORDERED.
s/Christian J. Moran
Christian J. Moran
Special Master
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DOCUMENT 2: USCOURTS-cofc-1_18-vv-00440-2
Date issued/filed: 2024-03-25
Pages: 22
Docket text: JUDGE VACCINE REPORTED OPINION (PUBLIC VERSION) re: 147 Sealed Opinion/Order on Pet'rs' Corrected Motion for Review. Signed by Chief Judge Elaine D. Kaplan. (tbs) Service on parties made. (Main Document 149 replaced on 4/18/2024) (vds).
--------------------------------------------------------------------------------
Case 1:18-vv-00440-EDK Document 149 Filed 03/25/24 Page 1 of 22
In the United States Court of Federal Claims
)
ANGELICA VINESAR and MARIUS )
VINESAR as best friends of their daughter, )
A.V., )
) No. 18-440V
Petitioners, ) (Filed Under Seal: March 6, 2024;
) Re-issued: March 25, 2024)*
v. )
)
SECRETARY OF HEALTH AND HUMAN )
SERVICES, )
)
Respondent. )
)
John F. McHugh, New York, NY, for Petitioners.
Julia M. Collison, Assistant Director, Torts Branch, Civil Division, U.S. Department of Justice,
with whom were Lara A. Englund, Assistant Director, Heather L. Pearlman, Deputy Director, C.
Salvatore D’Alessio, Director, and Brian M. Boynton, Principal Deputy Assistant Attorney
General, for Respondent.
OPINION AND ORDER
KAPLAN, Chief Judge.
Petitioners in this case, Angelica L. and Marius Vinesar, seek review of the decision of
Special Master Christian Moran finding that they failed to prove that their daughter, A.V.,
suffered a vaccine-related injury that would entitle her to compensation under the National
Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa–1 to –34 (“Vaccine Act” or “Act”),
as amended. See Decision of Spec. Mstr., ECF No. 136 [hereinafter “Dec.”]; see also Vinesar v.
Sec’y of Health & Hum. Servs., No. 18-440V, 2023 WL 5427935 (Fed. Cl. Spec. Mstr. July 28,
2023). Specifically, they challenge the Special Master’s findings: (1) that they did not establish
by preponderant evidence that the diphtheria-tetanus-acellular pertussis (“DTaP”) vaccine A.V.
received in April 2015 caused her to develop Dravet syndrome (a seizure disorder); (2) that the
DTaP vaccine did not significantly aggravate her pre-existing genetic susceptibility to
developing Dravet syndrome, see Dec. at 52; and (3) that, in any event, the Secretary of Health
* Pursuant to Vaccine Rule 18(b) of the Court of Federal Claims, the Court initially filed this
opinion and order under seal on March 6, 2024, and the parties were afforded fourteen days to
propose redactions. Neither party proposed any redactions. The Court therefore publicly reissues
the opinion and order initially filed under seal without any redactions.

Case 1:18-vv-00440-EDK Document 149 Filed 03/25/24 Page 2 of 22
and Human Services (“Secretary”) demonstrated by preponderant evidence that a pathogenic
genetic mutation was the sole cause of A.V.’s Dravet syndrome, see id. at 74.
For the reasons set forth below, the Court concludes that the evidence of record taken as a
whole supports the Special Master’s decision and that his conclusions are neither arbitrary and
capricious nor contrary to law. Petitioners’ Motion for Review, ECF No. 143, must therefore be
denied.
BACKGROUND
I. Medical History
A. A.V.’s First Febrile Seizure
A.V. was born without complications or medical problems on September 23, 2014.
Pet’rs’ Ex. 1, at 1, ECF No. 1-2. Newborn screening and the physical exam completed the day
after her birth were normal. See Pet’rs’ Ex. 9, at 25–33, ECF No. 12-2.
Some seven months later, on April 20, 2015, A.V. underwent a periodic well-child check-
up. Pet’rs’ Ex. 11, at 30, ECF No. 12-4. During that check-up, A.V. received her third scheduled
dose of the DTaP vaccine along with additional doses of the standard panel of recommended
childhood vaccines. See id.; Pet’rs’ Ex. 8, at 1, ECF No. 12-1. Just over twelve hours later, A.V.
experienced a seizure. Pet’rs’ Ex. 3 pt. 1, at 36, ECF No. 1-4 (Apr. 20, 2015). Ms. Vinesar called
911. Id. The emergency responders (“EMS”) administered the sedative Diastat (diazepam) to
A.V. while en route to the hospital. Id. at 32.
About ten minutes after her arrival at the hospital, A.V.’s seizure-like activity resumed
and she was given another dose of diazepam. See id. Her temperature was recorded as 101.1°
Fahrenheit. See id. (recording A.V.’s temperature as 38.4° Celsius). A computerized tomography
(“CT”) scan of A.V.’s head was taken and interpreted as unremarkable. See Pet’rs’ Ex. 3 pt. 2, at
88, ECF No. 1-5. No signs of infection appeared on A.V.’s chest x-ray or in the results of rapid
blood tests. See id. at 85–86, 89.
A.V. was admitted to the hospital with a diagnosis of complex febrile seizures. See
Pet’rs’ Ex. 3 pt. 1, at 32. Based on A.V.’s history, physical exam, and the diagnostic studies
completed in the emergency department (“ED”), A.V.’s attending physician concluded that the
vaccinations A.V. received earlier that day were “the most likely source of her fever.” See id.1
A.V. exhibited no further seizure-like symptoms during the remainder of her time at the
hospital. She also had no fever, and the electroencephalogram (“EEG”) study of her brain
activity was unremarkable. See Pet’rs’ Ex. 3 pt. 2, at 57, 76. After about forty-two hours of
observation, A.V. was prescribed diazepam for use as needed to treat acute seizure activity and
was discharged with instructions to follow up with her pediatrician, Dr. Subramanian, in one to
1 Because A.V.’s symptoms began within twenty-four hours of administration of vaccinations,
hospital staff later contacted her pediatrician to recommend reporting A.V.’s febrile seizures as
an adverse vaccine reaction to the Centers for Disease Control and Prevention. See Pet’rs’ Ex. 3
pt. 2, at 75–76.
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three days. See id. at 69 (admitting A.V. on April 21, 2015, 2:46 a.m.); id. at 78 (discharging
A.V. on April 22, 2015, 8:23 p.m.).
As recommended, A.V. was examined by Dr. Subramanian on April 24, two days after
her discharge from the hospital. See Pet’rs’ Ex. 11, at 28. Dr. Subramanian listed epilepsy with
complex seizures as her diagnosis. See id. at 29. She also noted a “possible diagnosis” of adverse
effects from a bacterial vaccine. Id. Dr. Subramanian advised the Vinesars to have A.V.
evaluated for complex seizures by a neurology specialist and instructed them to follow up in two
months or as needed. See id.
B. A.V.’s Second Febrile Seizure
The following month, on May 14, 2015, A.V. presented for a pediatric neurology consult
with Dr. Mohammad Ikramuddin. Pet’rs’ Ex. 10, at 65, ECF No. 12-3. Dr. Ikkramuddin
diagnosed A.V. with “[p]aroxysmal spells” and recommended that the Vinesars follow up with
him in three months or earlier if necessary. Id. He also counseled the Vinesars on the
“mechanism, known triggers, acute symptomatic measure[s], [and] chronic prophylaxis [of
seizures], . . . [and on] the use of anti-seizure medication, including side effects, the need to
monitor for side effects, seizure precautions[,] and reoccurrence risk.” Id.
In late July 2015, two months after her visit with Dr. Ikramuddin, A.V. experienced a
second seizure after a cold she had contracted a few days earlier caused her to develop a fever.
See Pet’rs’ Ex. 12 pt. 1, at 39, ECF No. 12-5 (July 26, 2015); Pet’rs’ Ex. 11, at 25. At this point,
A.V. was about ten months old. See Pet’rs’ Ex. 12 pt. 1, at 27. A.V.’s mother administered
diazepam after the seizure began, but it did not resolve A.V.’s symptoms. See id. EMS arrived,
administered another sedative, and A.V.’s seizure activity stopped about ten minutes later. Id.
On route to the hospital and in the ED, A.V.’s temperature was recorded at 100.9°
Fahrenheit. Id. at 27, 29. A.V. was admitted to the hospital and underwent an extensive
diagnostic workup. See id. at 63–64 (EEG results); Pet’rs’ Ex. 12 pt. 2, at 96–101, ECF No. 12-6
(complete blood count, comprehensive metabolic panel, respiratory viral panel, blood culture,
urine culture, and chest x-ray results).
Notably, A.V. tested positive for parainfluenza virus type 3. Pet’rs’ Ex. 12 pt. 2, at 99.
Based on the test results, A.V.’s doctors concluded that the seizure she had experienced was
caused by the fever brought on by her viral infection. See id. at 85. An EEG study of A.V.’s
brain activity recorded the next day was “essentially unremarkable.” Pet’rs’ Ex. 12 pt. 1, at 63.
A.V. was discharged that same day with a prescription for diazepam and instructions to follow
up with Dr. Ikramuddin. Pet’rs’ Ex. 12 pt. 2, at 86; see also Pet’rs’ Ex. 12 pt. 1, at 9
(documenting A.V.’s discharge date and length of stay).
C. A.V.’s Third Febrile Seizure
A.V. had her follow-up exam with Dr. Ikramuddin on August 20, 2015. See Pet’rs’ Ex.
10, at 54–56. He documented the details of A.V.’s recent seizure episode and discussed treating
A.V.’s condition with anticonvulsant medication. See id. at 56. Given the possible side effects of
the medication, however, A.V.’s parents declined this treatment option. Id.
Just under three months after this follow-up exam, on November 8, 2015, A.V.
experienced a third seizure. See Pet’rs’ Ex. 13, at 32, ECF No. 12-7. A.V.’s mother administered
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diazepam, and A.V.’s seizure activity stopped one to two minutes thereafter. Id. EMS was called
and once again transported A.V. to the ED. Id. In the ED, A.V.’s temperature was 102.6°
Fahrenheit. Id. at 33 (recording A.V.’s temperature as 39.2° Celsius). Several hours later, A.V.’s
initial labs were negative, her temperature had returned to normal, and she appeared “more
awake and alert.” Id. at 34.
Although the results of viral testing were still pending, the ED physician concluded that
A.V. “likely has a virus, given sick contacts at home.” Id. at 34. A.V. did not spend the night but
was instead discharged, again with a prescription for diazepam and instructions to follow up with
Drs. Subramanian and Ikramuddin within two to four days. Id. at 34–35.
The Vinesars met with Dr. Subramanian the next day. See Pet’rs’ Ex. 11, at 21. She
documented A.V.’s recent febrile seizure symptoms and advised the Vinesars to follow up with
A.V.’s neurologist. Id.
D. A.V.’s Fourth Febrile Seizure
A.V.’s fourth seizure occurred about a month later, on December 5, 2015. See Pet’rs’ Ex.
15, at 17, 37, ECF No. 13-2. On this occasion, A.V. had a temperature of 99.4° Fahrenheit and
experienced a seizure about five minutes after she took Tylenol (acetaminophen) to reduce it.
See id. Her mother administered diazepam one minute after the seizure-like symptoms began,
and they ended about two minutes later. See id. at 17, 32, 37.
When A.V. presented in the ED after this episode, her temperature was 101.3°
Fahrenheit. Id. at 20 (documenting A.V.’s arrival on Dec. 5, 2015, at 5:03 p.m.; recording A.V.’s
temperature was 38.5° Celsius). A few hours later, however, A.V. was alert, eating normally, and
no longer had a fever. Id. at 20–23. The ED discharged A.V., again with a prescription for
diazepam and instructions to follow up with Drs. Subramanian and Ikramuddin within two to
four days. Id. at 20, 22 (documenting A.V.’s discharge on Dec. 5, 2015, at 6:27 p.m.).
E. A.V.’s Seizures Continue; Seizure Disorder Diagnosed
On December 18, 2015, Dr. Subramanian conducted a follow-up exam of A.V. See
Pet’rs’ Ex. 11, at 19. Dr. Subramanian diagnosed A.V. with epilepsy. Id. at 19–20. Dr.
Subramanian noted that A.V.’s fourth seizure was afebrile because her temperature just prior to
the episode was only 99° Fahrenheit. See id. at 19. She advised the Vinesars to make an
appointment with A.V.’s neurologist and encouraged them to start A.V. on prescription anti-
seizure medication. Id. 19–20. The Vinesars rejected this suggestion and advised Dr.
Subramanian that they wanted to pursue herbal therapy instead. Id. at 19.
In January 2016, the Vinesars presented to pediatric neurology specialist Dr. Nishant
Shah for a re-evaluation of A.V.’s seizure disorder. See Pet’rs’ Ex. 10, at 50 (Jan. 25, 2016).
During the visit, Dr. Shah recommended that the Vinesars pursue magnetic resonance imaging
(“MRI”) of A.V.’s brain. See id. at 53. The Vinesars agreed to consider the recommendation. See
id. Dr. Shah also opined that a forty-eight-hour video EEG “may be of value” if A.V.
experiences a recurrence of seizure activity, especially if febrile. Id.
Later that year, A.V. experienced at least four more seizures with low or no fever present.
See Pet’rs’ Ex. 16, at 16–20, 27–29, ECF No. 13-3 (documenting seizure on Mar. 1, 2016);
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Pet’rs’ Ex. 17, at 16–17, 28–30, ECF No. 13-4 (documenting seizure on Sept. 12, 2023); Pet’rs’
Ex. 10, at 20 (documenting seizures on Dec. 5, 2016, and Dec. 24, 2016).2
After the first two confirmed seizures in 2016, the Vinesars followed up with Dr. Shah.
See Pet’rs’ Ex. 10, at 41–45 (Mar. 22, 2016); id. at 31–35 (Sept. 22, 2016). During both visits,
Dr. Shah reiterated his recommendations that the Vinesars obtain an MRI of A.V.’s brain and a
forty-eight-hour video EEG. See Pet’rs’ Ex. 10, at 34, 44. Nonetheless, as of the time A.V.
experienced her third seizure in 2016, neither study had been performed. See id. at 34, 39. Dr.
Shah also advised that given A.V.’s “recurrent seizures with no convincing fever or mild fever,
and [her] subsequent diagnosis of epilepsy, [A.V.] will need to be on long-term antiseizure
medic[ation].” See id. at 34. The Vinesars, however, remained “quite reluctant” to accept this
recommendation. Id.
In November 2016, A.V. presented in Dr. Subramanian’s clinic for her two-year well-
child check-up. See Pet’rs’ Ex. 11, at 14 (Nov. 4, 2016). In the notes from that check-up, Dr.
Subramanian opined that A.V. continued to meet developmental milestones and noted that her
seizure disorder was being followed by neurology. See id. at 14–15.
The next month, the Vinesars sought another opinion, this time with pediatric epilepsy
specialist Dr. Sunila O’Connor. See id. at 69; see also Pet’rs’ Ex. 37, at 4, ECF No. 41-1 (Dec.
13, 2016). Dr. O’Connor recommended obtaining an MRI of A.V.’s brain, a longer EEG, and
certain metabolic studies to investigate the etiology of A.V.’s seizure disorder. See Pet’rs’ Ex.
11, at 69. Based on A.V.’s history of prolonged seizures, Dr. O’Connor also recommended
starting A.V. on antiepileptic medication after the diagnostic workup was complete. See id.
Further—if neuroimaging, EEG, and metabolic studies were unremarkable—Dr. O’Connor felt
that “genetic testing specifically looking at sodium channel abnormalities” would be prudent.
See id.
The Vinesars rejected these suggestions and declined to pursue any radiological or
laboratory studies or to start A.V. on medication. Id. Instead, the Vinesars told Dr. O’Connor that
they intended to pursue “holistic methods” from “a person in their community who treats with
multiple holistic medications.” Id. Given that A.V.’s family did not want to pursue any of Dr.
O’Connor’s recommendations, Dr. O’Connor did not schedule a follow-up appointment and
advised the Vinesars to pursue another opinion elsewhere or follow up with Dr. Shah as needed.
See id.
The next month, the Vinesars brought A.V. to see Dr. Shah again. See Pet’rs’ Ex. 10, at
20 (Jan. 16, 2017). Dr. Shah noted that A.V. had experienced febrile seizures on five occasions,
that her first episode was prolonged when she “perhaps” had a mild fever, but that her more
recent episodes occurred—or “quite likely” occurred—without fever. Id. at 24. Based on this
recent history of recurrent seizures “with minimal or no fever,” Dr. Shah concluded that A.V.
had “epilepsy/seizure disorder” and again recommended anti-seizure medication. Id. Yet again,
2 A.V. may have also had a seizure in July when she fell to the floor while playing on a couch,
but it was never confirmed by her doctors. See Pet’rs’ Ex. 18, at 18–19, ECF No. 13-5
(documenting A.V.’s possible seizure on July 19, 2016). In this instance, A.V. did not have a
fever or lose consciousness, but her father reported she was unresponsive with her eyes rolling
back and that she had difficulty standing up afterward. See id.
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the family declined, and Dr. Shah informed them he could no longer participate in A.V.’s care if
they did not follow his diagnostic and therapeutic recommendations. Id.
According to Ms. Vinesar, A.V.’s next seizures occurred in April and June 2017. Pet’rs’
Ex. 1, at 3 (Apr. 1, June 7, and 23, 2017); see also Pet’rs’ Ex. 11, at 61–66 (medical records
regarding A.V.’s seizures on June 7 and 23, 2017). After the first seizure in June 2017, doctors
started A.V. on Keppra (levetiracetam), an anticonvulsant. Pet’rs’ Ex. 1, at 3.
On June 15, the Vinesars followed up with Dr. Subramanian. See Pet’rs’ Ex. 11, at 12.
During this visit, Ms. Vinesar reported that A.V. was receiving her anticonvulsant medication as
prescribed but expressed concerns about the side effects of the medication. Id. Dr. Subramanian
advised Ms. Vinesar about the benefits of anticonvulsant therapy and about how to avoid side
effects. Id. She also recommended following up with neurology. Id.
Ms. Vinesar nonetheless discontinued the levetiracetam one week later because she
believed A.V. was experiencing side effects. Pet’rs’ Ex. 20, at 45.3 The next day, June 23, 2017,
the Vinesars brought A.V. to see Dr. Shah. See Pet’rs’ Ex. 10, at 12.
At the outset of her visit with Dr. Shah, A.V. experienced “a prolonged seizure lasting at
least [fifteen] minutes” and was transferred to the pediatric intensive care unit (“ICU”). Id. After
examining A.V. in the ICU, the pediatric intensivist opined that A.V.’s seizure was “likely due to
medical noncompliance” rather than “infectious etiology at this time.” Pet’rs’ Ex. 20, at 50.
While in the hospital, the Vinesars consented to an MRI of A.V.’s brain and a brief EEG,
but the results from both studies were unremarkable. See id. at 25, 92. Hospitalists also
transitioned A.V. off levetiracetam and started another anticonvulsant, Trileptal (oxcarbazepine),
to manage her seizures. Id. at 55.
According to Ms. Vinesar, A.V. had ten more seizures in the two months that followed
her discharge from the hospital. See Pet’rs’ Ex. 1, at 3 (July 1, 6, 11, 16, 26, Aug. 4, 6, 11, and
23, 2017); see also Pet’rs’ Ex. 10, at 2 (July 6, 2017); Pet’rs’ Ex. 22, at 19–20 (July 1, 2017);
Pet’rs’ Ex. 23, 19–22 (Aug. 23, 2017); Pet’rs’ Ex. 34, at 3 (“Patient had been having seizures
every 5–10 days leading to the events of [August 23, 2017].”).4
In late August, EMS brought A.V. to the ED during a seizure that lasted over half an
hour. See Pet’rs’ Ex. 23, at 17, 20 (noting that A.V.’s seizure activity started twenty minutes
before EMS arrival at 8:32 PM and did not stop until Ativan (lorazepam) was administered upon
arrival in the ED at 8:46 PM). While in the ED this time, Ms. Vinesar told A.V.’s doctor that she
had taken A.V. off the oxcarbazepine against Dr. Shah’s advice. See id. at 20.
3 Petitioners’ Exhibit 20 is not accessible on the electronic docket. This exhibit is stored on a
compact disc that Petitioners filed with the Clerk of the Court on June 25, 2018. See Pet’rs’
Notice of Intent to File at 1, ECF No. 18.
4 Petitioners’ Exhibits 22–23 and 34 are not accessible on the electronic docket. These exhibits
are stored on a compact disc that Petitioners filed with the Clerk of the Court on June 25, 2018.
See Pet’rs’ Notice of Intent to File at 1.
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The next day, A.V. underwent a “24-hour long-term video EEG monitoring study.”
Pet’rs’ Ex. 11, at 54–55 (Aug. 24–25, 2017). According to the neurology specialist at the
University of Chicago who interpreted the results, Dr. Charles Marcuccilli, A.V.’s brain activity
demonstrated “focal sites of cerebral hyperexcitability,” possibly associated “with partial
seizures/epilepsy,” and “diffuse cerebral dysfunction” potentially caused by “structural or
vascular abnormalities, toxic, metabolic conditions, hydrocephalus or postictal conditions.” Id. at
55.
A few weeks later, the Vinesars brought A.V. to see Dr. Subramanian for her three-year
well-child check-up. See id. at 7 (Sept. 15, 2017). At this visit, Dr. Subramanian noted that the
University of Chicago now followed A.V.’s seizure disorder, A.V. was taking levetiracetam, and
she continued to meet developmental milestones. See id.
F. Genetic Testing and Dravet Syndrome Diagnosis
In October, after yet another series of seizures, see Pet’rs’ Ex. 1, at 3 (Sept. 8, 23, 27,
Oct. 21, and 28, 2017), Dr. Marcuccilli ordered neurogenetic testing, see Pet’rs’ Ex. 4, at 2, ECF
No. 1-9. The testing included sequencing and deletion/duplication analysis on a panel of eighty-
seven genes. Id. The results indicated that A.V. has “a novel pathogenic variant and a variant of
uncertain significance in the SCN1A gene.” Id.
According to the report, A.V.’s variant of unknown significance was predicted to damage
protein structure or function. Id. at 4. However, the report stated “[b]ased on the currently
available information, it is unclear whether this variant is a pathogenic variant or a rare benign
variant.” Id. A.V.’s pathogenic variant was deemed consistent with the “diagnosis of a SCN1A-
related disorder” as it “is predicted to cause loss of normal protein function either through
protein truncation or nonsense-mediated mRNA decay.” Id. at 2–3. Additionally, the report notes
that 70–80% of Dravet syndrome, 20–24% of early-onset cryptic epilepsy, and 5–10% of genetic
epilepsy with febrile seizures plus (“GEFS+”) are associated with mutations in the SCN1A gene.
See id. at 6.5
In April 2018, the Vinesars brought A.V. to the neurology clinic at the University of
Chicago for follow-up. See Pet’rs’ Ex. 34, at 385 (Apr. 4, 2018). The neurologist’s impression
was that A.V. had Dravet syndrome due to her SCN1A gene mutation. See id. at 390. By this
point, A.V.’s doctors had swapped levetiracetam for ONFI (clobazam), a sedative medication
used to treat certain types of seizures. See id. at 389. But because the Vinesars felt the new
medication was causing A.V. to experience abdominal pain and somnolence, the family sought
to initiate a ketogenic diet to treat A.V.’s seizures in lieu of pharmacotherapy. Id. at 390. At the
5 A.V. had repeat genetic testing performed at a different laboratory in June 2018. See Pet’rs’ Ex.
39, at 1, ECF No. 42-1. This test provided “[s]equence analysis and deletion/duplication testing”
of 133 genes. Id. Repeat testing identified the same “[p]athogenic variant” and “[v]ariant of
[u]ncertain [s]ignificance” that the first test identified in A.V.’s SCN1A gene. Compare id. with
Pet’rs’ Ex. 4, at 2. Likewise, the report indicates that “[t]he SCN1A gene is associated with a
spectrum of autosomal dominant seizure disorders ranging from simple febrile seizures and
genetic epilepsy with febrile seizures plus (GEFS+) to Dravet syndrome and intractable
childhood epilepsy with generalized tonic-clonic seizures.” Pet’rs’ Ex. 39, at 1 (citations
omitted).
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end of the visit, the neurologist lowered A.V.’s dose of clobazam and referred her to the
ketogenic diet clinic. See id. Additionally, since Ms. Vinesar continued to express doubt about
A.V.’s diagnosis, the doctor advised the Vinesars to seek a third opinion at a nearby Dravet
syndrome specialty clinic. See id.
Dr. Marcucilli examined A.V. once again in June 2018. See Pet’rs’ Ex. 41, at 46, ECF
No. 42-3 (June 21, 2018). During this visit, the Vinesars updated Dr. Marcucilli on A.V.’s
medical history. Id. They shared that “[t]he longest [A.V.] has gone seizure free [was] 39 days.”
Id. Nevertheless, despite “significant drowsiness” and “some slurred speech,” A.V. was
“otherwise developing normally.” Id. Dr. Marcucilli then reviewed A.V.’s medical history of
prolonged seizures, her genetic profile, and the results of four EEG studies. Id. at 48–49. Based
on this information, Dr. Marcucilli diagnosed A.V. with “Dravet [s]yndrome with intractable
epilepsy secondary to an SCN1A mutation.” Id.
G. A.V.’s Subsequent Medical History
A.V. continued to experience two to three seizures per month over the next few years.
See Pet’rs’ Ex. 147, at 2, ECF No. 115-4 (Nov. 11, 2021). Nevertheless, Ms. Vinesar reported at
A.V.’s six-year well-child checkup that A.V. was being homeschooled and “doing well with
learning, speech[,] and development” except for “periods of set back following a seizure
episode.” See id. at 5 (Mar. 30, 2021). As of November 2021, A.V. had a “[s]peech problem”
and was taking antiseizure medication for “Dravet syndrome, intractable, with status
epilepticus.” See Pet’rs’ Ex. 148, at 1, ECF No. 115-5 (Nov. 17, 2021).
II. Procedural Background
A. Proceedings Before the Special Master
On March 23, 2018, Petitioners filed a petition for compensation under the National
Vaccine Injury Compensation Program, 42 U.S.C. §§ 300aa-1 to -34, on A.V.’s behalf. See
Petition at 1, ECF No. 1. In their petition, they alleged that “covered vaccinations” administered
to A.V. on April 20, 2015, caused a seizure disorder that first presented “within half a day of the
vaccination and continues to afflict [A.V.].” Id. at 1.
Along with their petition, the Vinesars attached A.V.’s medical records and a letter from
their expert, Dr. Marcel Kinsbourne. See Pet’rs’ Ex. 2, at 2, ECF No. 1-3. In that letter, Dr.
Kinsbourne opined that recent progress in the understanding of SCN1A mutations have
undermined several assumptions that special masters relied on in the past when denying
compensation to children with SCN1A mutations. Id. at 1–2; see also Oliver v. Sec’y of Health
& Hum. Servs., No. 10-394V, 2017 WL 747846, at *25–26 (Fed. Cl. Spec. Mstr. Feb. 1, 2017)
(noting compensation has been denied in at least sixteen cases involving children with SCN1A
mutations), review denied, 133 Fed. Cl. 341 (2017), aff’d 900 F.3d 1357 (Fed. Cir. 2018).
The Secretary filed his Vaccine Rule 4(c) report on December 19, 2018. See Resp’t’s
Rep. at 1–2, 19, ECF No. 29; see also RCFC App. B, Vaccine Rule 4(c). He recommended the
denial of compensation, contending that Petitioners had “failed to proffer a medical opinion or
theory sufficient to establish a logical cause and effect relationship between [A.V.’s] vaccines
and her condition.” Resp’t’s Rep. at 19. Specifically, the Secretary observed that A.V. possesses
a known pathogenic variant “consistent with the diagnosis of an SCN1A-related disorder” and
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that “[A.V’s] own treating doctors have attributed [her] seizure disorder to a mutation in her
SCN1A gene.” See id. at 17.
Along with his recommendation, the Secretary submitted an expert report by Dr. Gerald
Raymond, a pediatric neurologist and clinical geneticist. See generally Resp’t’s Ex. A, ECF No.
30-1. Dr. Raymond responded to Dr. Kinsbourne’s opinion and the medical literature on which
he relied. See id. at 4–6. According to Dr. Raymond, the mutation in A.V.’s SCN1A gene was
“the sole cause” of her seizure disorder and “[i]t was not caused nor exacerbated by any of the
immunizations that she received.” See id. at 6.
The Vinesars subsequently filed additional medical records, Pet’rs’ Exs. 35–41, ECF
Nos. 38, 41–42, and two supplemental reports by Dr. Kinsbourne, Pet’rs’ Exs. 45–46, ECF Nos.
51, 55. They also submitted expert reports from Dr. Mark McNulty, a statistician, Pet’rs’ Ex. 81,
ECF No. 64-1, and Dr. Richard Boles, a pediatrician and medical geneticist, Pet’rs’ Exs. 82, 153,
ECF Nos. 68-1, 121-2. In addition, they further supplemented the record by filing additional
medical literature. See Pet’rs’ Exs. 110–121, 124–127, ECF Nos. 92–94.
In January 2022, Petitioners filed a motion for a ruling on the record, Pet’rs’ Mot. for J.
on Admin. R., ECF No. 124 [hereinafter “Pet’rs’ MJAR”], to which the Secretary responded on
March 25, 2022, Resp’t’s Resp. to MJAR, ECF No. 127. On January 18, 2023, the Special
Master held oral argument on several questions raised by the parties’ briefs. See generally Oral
Arg. Tr., ECF No. 135.
The Special Master denied Petitioners’ motion for a ruling on the record on July 28,
2023. See Dec. at 1. In his view, Petitioners failed to prove the DTaP vaccine that A.V. received
either caused or significantly aggravated her Dravet syndrome. See id. at 51–52. He also found,
in the alternative, that the Secretary proved that a factor unrelated to the vaccine—namely her
SCN1A variant—was the sole reason why she developed Dravet syndrome. See id. at 74.
B. The Present Motion for Review
Petitioners filed their motion for review of the Special Master’s decision with the Court
on August 14, 2023, and the Secretary filed a response urging the Court to affirm the Special
Master’s decision. See generally Pet’rs’ Mot. for Rev., ECF No. 138 [hereinafter “Pet’rs’ Mot.
for Rev. I”]; Respt’s Resp. to Pet’rs’ Mot. for Rev., ECF No. 141 [hereinafter “Gov’t’s Resp. I”].
Petitioners’ motion did not comply with the requirements of the Vaccine Rules of the
United States Court of Federal Claims. The Court therefore ordered Petitioners to file a corrected
motion for review and granted the Secretary leave to file a supplemental response to the
corrected motion. See Order, Sept. 26, 2023, ECF No. 142. Shortly thereafter, Petitioners timely
filed their “corrected” motion, and the Secretary subsequently supplemented his initial response.
See generally Pet’rs’ Corrected Mot. for Rev., Oct. 1, 2023, ECF No. 143 [hereinafter “Mot. for
Rev. II”]; Respt’s Resp. to Pet’rs’ Corrected Mot. for Rev., Oct. 5, 2023, ECF No. 144
[hereinafter “Gov’t’s Resp. II”].
The Court has considered the arguments in Petitioners’ “corrected” motion for review
and concludes that Petitioners have failed to demonstrate that the Special Master’s decision was
arbitrary, capricious, an abuse of discretion, or contrary to law. The Motion for Review is
therefore denied, and the Special Master’s decision is sustained.
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DISCUSSION
I. Jurisdiction
Congress established the National Vaccine Injury Compensation Program in 1986 to
provide a no-fault compensation system for vaccine-related injuries and deaths. Figueroa v.
Sec’y of Health & Hum. Servs., 715 F.3d 1314, 1316–17 (Fed. Cir. 2013); see also 42 U.S.C.
§§ 300aa–10 to –34. The Act is “[r]emedial legislation” which “should be construed in a manner
that effectuates its underlying spirit and purpose.” Figueroa, 715 F.3d at 1317 (alteration in
original) (citing Cloer v. Sec’y of Health & Hum. Servs., 675 F.3d 1358, 1362 (Fed. Cir. 2012)).
A petition seeking compensation under the Vaccine Act must be filed in the Court of
Federal Claims, after which the Clerk of the Court forwards it to the Office of Special Masters
for assignment. 42 U.S.C. § 300aa–11(a)(1). The special master to whom the petition is assigned
“issue[s] decision on such petition with respect to whether compensation is to be provided under
the [Vaccine Act] and the amount of such compensation.” Id. § 300aa 12(d)(3)(A).
–
The Vaccine Act grants the Court of Federal Claims jurisdiction to review the decisions
of special masters (subject to further review in the Federal Circuit). Mahaffey v. Sec’y of Health
& Hum. Servs., 368 F.3d 1378, 1383 (Fed. Cir. 2004) (citing 42 U.S.C. § 300aa–12(d)(3)(A)).
On review, the Court may:
(1) uphold the findings of fact and conclusions of law of the special master and
sustain the special master’s decision[;]
(2) set aside any findings of fact or conclusion of law of the special master found to
be arbitrary, capricious, an abuse of discretion, or otherwise not in accordance
with law and issue its own findings of fact and conclusions of law[;] or
(3) remand the petition to the special master for further action in accordance with the
court’s direction.
42 U.S.C. § 300aa–12(e)(2); see also RCFC App. B, Vaccine Rule 27.
II. Standard of Review
The Court reviews a special master’s legal determinations de novo, applying the “not in
accordance with law” standard. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1321
(Fed. Cir. 2010); Althen v. Sec’y of Health & Hum. Servs., 418 F.3d 1274, 1278–79 (Fed. Cir.
2005); see also Carson v. Sec’y of Health & Hum. Servs., 727 F.3d 1365, 1368 (Fed. Cir. 2013)
(instructing the reviewing court to “give no deference to the . . . Special Master’s determinations
of law”). Review of a special master’s factual determinations, on the other hand, is
circumscribed. Such determinations will be set aside only if they are arbitrary, capricious, and/or
reflect an abuse of discretion. Moberly, 592 F.3d at 1321.
The standard of review of a special master’s factual determinations is a “uniquely
deferential” one. Milik v. Sec’y of Health & Hum. Servs., 822 F.3d 1367, 1376 (Fed. Cir. 2016)
(quoting Hodges v. Sec’y of Health & Hum. Servs., 9 F.3d 958, 961 (Fed. Cir. 1993)). The Court
does not reweigh the evidence nor examine its probative value or the credibility of the witnesses;
those “are all matters within the purview of the fact finder.” Porter v. Sec’y of Health & Hum.
Servs., 663 F.3d 1242, 1249 (Fed. Cir. 2011) (citing Broekelschen v. Sec’y of Health & Hum.
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Servs., 618 F.3d 1339, 1349 (Fed. Cir. 2010)). Therefore, if a special master “‘has considered the
relevant evidence of record, drawn plausible inferences and articulated a rational basis for the
decision,’ then reversible error is ‘extremely difficult to demonstrate.’” Milik, 822 F.3d at 1376
(quoting Hines v. Sec’y of Health & Hum. Servs., 940 F.2d 1518, 1528 (Fed. Cir. 1991)).
III. The Petitioners’ Burden of Proof
To make a prima facie case of entitlement to compensation under the Vaccine Act, a
petitioner must prove by preponderant evidence that the “illness, disability, injury, or condition”
at issue was caused—or significantly aggravated—by a vaccine. See 42 U.S.C. §§ 300aa–
11(c)(1), –13(a)(1). There are two avenues by which a petitioner may establish causation: the on-
table claim and the off-table claim. Broekelschen, 618 F.3d at 1341–42 (citing 42 U.S.C. §
300aa-11(c)(1)(C)(i); Andreu ex rel. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367
(Fed. Cir. 2009)).
In an on-table claim, causation is presumed if the petitioner can show (1) that he or she
received a vaccination listed in the Vaccine Injury Table, 42 U.S.C. § 300aa–14, as revised by 42
C.F.R. § 100.3(a), and (2) that he or she suffered an injury associated with that vaccine within
the period of time prescribed by the table. See Andreu, 569 F.3d at 1374 (citing 42 U.S.C.
§ 300aa–11(c)(1)(C)(i)).
Petitioners’ claim that the third dose of the DTaP vaccine administered to A.V. caused
the development or worsening of her Dravet syndrome does not allege an on-table injury. See 42
C.F.R. § 100.3(a). There is no presumption of causation for off-table claims. For off-table
claims, the petitioner must prove by preponderant evidence that any claimed injury was either
caused or significantly aggravated by a vaccine. See W.C. v. Sec’y of Health & Hum. Servs.,
704 F.3d 1352, 1356–57 (Fed. Cir. 2013) (quoting Althen, 418 F.3d at 1278; Loving v. Sec’y of
Health & Hum. Servs., 86 Fed. Cl. 135, 144 (2009)); see also Sharpe v. Sec’y of Health & Hum.
Servs., 964 F.3d 1072, 1078 (Fed. Cir. 2020) (citing 42 U.S.C. § 300aa–11(c)(1)(C); Whitecotton
ex rel. Whitecotton v. Sec’y of Health & Hum. Servs., 81 F.3d 1099, 1102–03 (Fed. Cir. 1996)).
To prove that a vaccine caused an injury, petitioners must establish: (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 “proximate temporal
relationship between vaccination and injury.” Althen, 418 F.3d at 1278.
Petitioners asserting significant aggravation claims must produce preponderant evidence
showing: (1) the vaccine recipient’s “condition prior to administration of the vaccine”; (2) their
“current condition (or the condition following the vaccination if that is also pertinent)”; and (3)
whether their “current condition constitutes a ‘significant aggravation’ of [their] condition prior
to vaccination.” W.C., 704 F.3d at 1357 (quoting Loving, 86 Fed. Cl. at 144).
If these elements are proven, then petitioners must make a showing similar to the one
required to prove causation under Althen. They must demonstrate by a preponderance of
evidence: (1) a “medical theory causally connecting such a significantly worsened condition to
the vaccination”; (2) a “logical sequence of cause and effect showing that the vaccination was
the reason for the significant aggravation”; and (3) a “proximate temporal relationship between
the vaccination and the significant aggravation.” Id.
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A failure to establish any one of the required elements set forth in Althen or Loving, “is
necessarily fatal to a petitioner’s case.” See Hodge ex rel. Elson v. Sec’y of Health & Hum.
Servs., 168 Fed. Cl. 117, 124 (2023). On the other hand, if a petitioner has satisfied the criteria
required to show causation-in-fact under Althen, or significant aggravation under Loving, he or
she is entitled to compensation “unless the government can show by a preponderance of the
evidence that the injury is due to factors unrelated to the vaccine.” See Broekelschen, 618 F.3d at
1342 (citing Doe v. Sec’y of Health & Hum. Servs., 601 F.3d 1349, 1351 (Fed. Cir. 2010)); see
also 42 U.S.C. § 300aa-13(a)(1)(B).
IV. The Expert Opinions
The parties submitted dueling expert opinion reports for the Special Master’s
consideration. Petitioners’ experts included Dr. Marcel Kinsbourne, a pediatric neurologist, Dr.
Mark McNulty, a statistician, and Dr. Richard Boles, a pediatrician and medical geneticist. See
generally Pet’rs’ Exs. 2, 45–46, 81–82, 153. The Secretary’s expert was Dr. Gerald Raymond, a
pediatric neurologist and clinical geneticist. See generally Resp’t’s Exs. A, C–D.
The Court notes for context that Drs. Raymond, Kinsbourne, and Boles have frequently
appeared as experts in cases involving claims that a vaccine caused a child with the SCN1A
genetic defect to develop Dravet syndrome. See Dec. at 2–32 (summarizing cases). Based in part
on findings that Dr. Raymond’s qualifications were superior to those of the other experts in the
cases, the special masters reviewing the claims in every one of these cases have credited his
opinion that a defect in the SCN1A gene, and not a vaccine, caused the vaccine recipient to
develop Dravet syndrome. See id.
In his first report, Dr. Kinsbourne cited a study described by Cetica et al., which he
interpreted as showing that febrile seizures (whether or not caused by the DTaP vaccine) increase
the chances that a child with the genetic mutation will develop Dravet syndrome. See Pet’rs’ Ex.
2, at 1 (citing Valentina Cetica et al., Clinical and Genetic Factors Predicting Dravet Syndrome
in Infants with SCN1A Mutations, 88 Neurology 1037 (2017)). Further, he stated, when the
DTaP vaccine triggers Dravet syndrome, it accelerates the onset of the disorder by some two
months. Id. Dr. Kinsbourne also cited Dutton et al., which studied mice with the mutation and
found that “early-life [febrile seizures] resulted in lower latencies to induced seizures, increased
[the] severity of spontaneous seizures, hyperactivity, and impairments in social behavior and
recognition memory during adulthood.” Id. (quoting Stacey B.B. Dutton et al., Early-Life Febrile
Seizures Worsen Adult Phenotypes in SCN1A Mutants, 293 Experimental Neurology 159, 159
(2017)).
Dr. Raymond prepared a report expressing disagreement with Dr. Kinsbourne’s opinion
and his interpretation of the medical literature he cited in support of that opinion. See Resp’t’s
Ex. A, at 4–6. He specifically addressed and rejected Dr. Kinsbourne’s interpretation of, and
reliance on, the Cetica and Dutton articles. See id. at 5. He stated that it was his view “to a
reasonable degree of medical certainty” that a mutation in A.V.’s SCN1A gene “is the sole cause
of her epilepsy condition,” and that “[i]t was not caused nor exacerbated by any of the
immunizations that she received.” See id. at 6.
Dr. Raymond stated that his opinion—that a genetic mutation and not a vaccine causes
Dravet syndrome—was supported by a study on early seizure events secondary to vaccination in
Dravet syndrome by McIntosh et al. See id. at 5–6. Dr. Raymond noted that the researchers for
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that article found that “although vaccination might sometimes seem to trigger the onset of Dravet
syndrome,” there was no evidence that “vaccination itself affect[ed] the severity of the disorder.”
See id. at 6. He also stated that “[t]here is no evidence that the timing of the first seizure in any
way alters the tragic course of this genetic disorder.” Id. Children with Dravet syndrome, he
opined, typically have the onset of seizures in their first year of life and those seizures
subsequently “escalate in type and severity.” Id.
Dr. Kinsbourne provided two supplemental reports in which he responded to Dr.
Raymond’s opinion. See generally Pet’rs’ Exs. 45–46. In the first report, he reviewed A.V.’s
medical history and described what he understood to be the mechanism by which the DTaP
vaccination that A.V. received caused, or at least exacerbated, her seizure disorder. See Pet’rs’
Ex. 45, at 7–14, ECF No. 51-1. Dr. Kinsbourne disagreed with Dr. Raymond’s conclusion that
A.V.’s SCN1A mutation was the sole cause of her Dravet syndrome. See id. at 13. He also
opined that Dr. Raymond’s opinions were contradicted by the medical literature Dr. Kinsbourne
summarized in his supplemental report. See id. at 12–13. He concluded that “[a]bsent the
vaccinations [A.V. received,] a later onset, if any, of a milder seizure disorder would have been
expected.” Id. at 14.
In his second supplemental report, Dr. Kinsbourne summarized a recent article by
Salgueria-Pereira et al. and discussed how the findings in the article were relevant to A.V.’s
clinical condition. See Pet’rs’ Ex. 46, at 1–2, ECF No. 55. He observed that Salgueria-Pereira
found that “seizures are important contributors to the development of severe phenotypes in
carriers of SCN1A variants” and that therapeutic approaches “should aim [to] . . . reduce[] their
occurrence as much as possible.” See id. at 2. Applying these findings to A.V.’s case, Dr.
Kinsbourne opined that it was “more likely than not” that A.V.’s condition would be
“significantly more benign had . . . routine vaccinations not initiated or triggered her . . . seizure
disorder.” Id. at 2.
As noted, Dr. McNulty, a statistician, also submitted a report for Petitioners. See
generally Pet’rs’ Ex. 81. He discussed the McIntosh article that Dr. Raymond cited and noted
several flaws in the investigators’ statistical analyses. See id. at 2. Dr. McNulty asserted that the
investigators “incorrectly implie[d] that [DTaP] vaccinations have no long-term impacts on
outcomes.” Id. (footnote omitted). In his view, “the data in this study are not strong enough to
reach meaningful conclusions regarding the impacts of vaccination due to the small sample sizes
. . . analyzed.” Id.
Petitioners’ third expert, Dr. Boles, submitted a report discussing several articles that
addressed SCN1A mutations and Dravet syndrome. See generally Pet’rs’ Ex. 82. Dr. Boles
opined that “SCN1A mutations are associated with a wide range of neurological disease
phenotypes” and that environmental factors, such as fever, contribute to greater disease severity.
See Pet’rs’ Ex. 82, at 4, 6–9. Accordingly, it was Dr. Boles’ opinion that “vaccinations
significantly aggravated [A.V.’s] epilepsy, . . . resulting in the early []onset of seizures and a
worsened clinical outcome” and that, “if she had not been vaccinated, . . . her outcome would
have been better than it is today, and projected to be in the future.” See id. at 13.
In response to the foregoing, the Secretary filed another report by Dr. Raymond. See
generally Resp’t’s’ Ex. C, ECF No. 77. Dr. Raymond discussed the reports of Drs. Kinsbourne,
McNulty, and Boles, and provided citations to medical literature that he said contradicted their
opinions. See id. at 3–15. Among other things, he challenged Dr. McNulty’s critique of the
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statement in the McIntosh article that “it is unknown whether [patients with Dravet syndrome
that first presented less than one day after vaccination] would have had milder outcomes had
they not been vaccinated at all.” Id. at 10 (citing Pet’rs’ Ex. 81, at 5). Dr. Raymond agreed that
“[i]t is very clear from the understanding of the biology of the variants in SCN1A . . . that there
is a spectrum of outcomes.” Id. However, he noted, “the severe end of that spectrum . . . may
present with medically refractory seizures, intellectual disability, ataxia, sleep disturbances, and
other manifestations.” Id. He added that a recent study of 504 patients with SCN1A variants by
Brunklaus et al. demonstrated that 99.6% of the patients with protein truncation variants—like
the variant A.V. has—had Dravet syndrome. See id. (citing Andrea Brunklaus et al., Biological
Concepts in Human Sodium Channel Epilepsies and Their Relevance in Clinical Practice, 61
Epilepsia 387 (2020)). According to Dr. Raymond, these results illustrated “how knowledge of
the genetic variant and its action on the particular channel produced direct clinical information.”
Id. He again opined, “to a reasonable degree of medical certainty,” that A.V.’s SCN1A mutation
“[wa]s the sole cause of her epilepsy disorder” and none of the immunizations that she received
caused or exacerbated it. Id. at 15.
V. The Special Master’s Decision
As reflected in his decision, the Special Master reviewed A.V.’s medical records and the
reports of both parties’ experts. He also reviewed the medical literature on which the experts
relied. Applying the Althen and Loving frameworks, he concluded that Petitioners failed to
establish that A.V.’s seizure disorder was caused or significantly aggravated by the DTaP
vaccination she received in April 2015. See Dec. at 44–52. Therefore, he found, Petitioners had
not established a prima facie case of a vaccine-related injury. See id. at 51–52
The Special Master’s findings rest on two independent grounds: (1) that Petitioners did
not provide a reliable medical theory that explained how the DTaP vaccine “can harm a
recipient, either by causing . . . or by aggravating a seizure disorder” (Althen prong 1; Loving
prong 4); and (2) that they had also not shown that the vaccination A.V. received “was the
logical reason for either the development . . . or worsening of [her] seizure disorder” (Althen
prong 2; Loving prong 5). Id. at 51–52.
Finally, the Special Master concluded, even if Petitioners had proven a prima facie case
of a vaccine-related injury, the Secretary had established by preponderant evidence that a factor
unrelated to a vaccination—i.e., an SCN1A gene mutation—was the sole cause of A.V.’s seizure
disorder. Id. at 52–74. Therefore, he ruled, A.V. was not entitled to compensation under the
Vaccine Act. Id. at 76.
VI. Petitioners’ Objections to the Special Master’s Decision
Under Vaccine Rule 24, a motion for review of the decision of a special master must
include a memorandum of “numbered objections,” which “fully and specifically state and
support each objection . . . [with] citations to the record” and “set forth any legal arguments the
party desires to present to the reviewing judge.” See RCFC App. B, Vaccine Rule 24(a), (b)(1)–
(2). As noted above, the first motion for review that Petitioners filed did not meet these
requirements. It consisted largely of conclusory statements, did not contain numbered objections
to the Special Master’s decision, and did not support each of Petitioners’ objections with
citations to the record and controlling law. See Vaccine Rule 24(b); see generally Pet’rs’ Mot.
for Rev. I.
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At the Court’s direction, Petitioners filed a corrected motion for review. The corrected
motion includes three numbered objections to the Special Master’s decision. See Pet’rs’ Mot. for
Rev. II, at 1–2. Beyond that, it was not much of an improvement, if at all, over the original
motion. Petitioners’ corrected motion does not provide specific citations to the record or the
Special Master’s decision for the vast majority of the assertions it contains, leaving the Court to
guess their basis. See generally id. It also contains misspellings, odd capitalization, words that
run together, and multiple difficult—if not impossible—passages to follow. See, e.g., id. at 1–2,
6, 8, 10.
As best the Court can understand them, Petitioners’ first two objections to the Special
Master’s decision challenge the factual determinations that underly his conclusion that
Petitioners failed to establish a prima facie showing of causation under Althen and Loving. They
contend, for example, that the Special Master erroneously found that the seizure A.V. suffered
shortly after receiving the DTaP vaccine was a “one off” that caused no lasting harm. See id. at
1. This was error, according to Petitioners, because under the diagnostic criteria for Dravet
syndrome, EEG studies in children with Dravet syndrome are initially normal. See id. Second,
Petitioners object to the Special Master’s finding that there was insufficient support for their
contention that A.V.’s vaccine-induced seizure aggravated her seizure disorder by causing its
early onset, which in turn had the effect of increasing its severity. See id.
Petitioners’ third objection to the Special Master’s decision appears to be a legal one. The
Special Master ruled that—even assuming Petitioners had established a prima facie case of either
causation or significant aggravation under Althen or Loving—they would nonetheless not be
entitled to compensation because the Secretary has shown by preponderant evidence that a factor
unrelated to the vaccine—namely A.V.’s genetic mutation—was the sole cause of her Dravet
syndrome. See Dec. at 74; see also Broekelschen, 618 F.3d at 1342 (citing Doe, 601 F.3d at 1351
(explaining that once a petitioner has demonstrated causation or significant aggravation, he or
she “is entitled to compensation unless the government can show . . . the injury is due to factors
unrelated to the vaccine”)); 42 U.S.C. § 300aa-13(a)(1)(B). Petitioners contend that the Special
Master’s determination that the Secretary met his burden of showing that factors unrelated to the
vaccine caused A.V.’s Dravet syndrome conflicts with the court of appeals’ decision in Sharpe v.
Sec’y of Health & Hum. Servs., 964 F.3d 1072 (Fed Cir. 2020). See Pet’rs’ Mot. for Rev. II at 2.
Petitioners have a steep hill to climb to demonstrate reversible error based on their first
two objections to the Special Master’s decision. As noted above, the scope of judicial review of
the Special Master’s factual findings is exceptionally narrow and deferential. The Court does not
reweigh the evidence. Nor does it second-guess the Special Master’s assessment of the
credibility of expert witnesses. Its role is instead to ensure that the Special Master reviewed all of
the relevant evidence, drew plausible inferences, provided an adequate explanation for his
conclusions, and made factual findings that are not arbitrary and capricious or an abuse of
discretion.
Moreover, unless Petitioners have satisfied their burden of establishing causation under
Althen or significant aggravation under Loving, the burden to prove that some other factor (e.g.,
an SCN1A gene mutation) was the sole cause of A.V.’s injury does not shift to the Secretary.
LaLonde v. Sec’y of Health & Hum. Servs., 746 F.3d 1334, 1340 (Fed. Cir. 2014) (citing Althen,
418 F.3d at 1278). Therefore, to the extent that Petitioners do not prevail as to the fact-based
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challenges they present in their first two objections, it is unnecessary for the Court to address
their third objection.
For the reasons set forth below, the Court concludes that the Special Master’s findings
that Petitioners did not satisfy their burden of establishing causation under Althen or significant
aggravation under Loving are supported by the relevant evidence of record. Their motion for
review must therefore be denied.
A. The Special Master’s Finding that Petitioners Failed to Supply a Sound and
Reliable Medical Theory Explaining How the DTaP Vaccine Could Have
Caused A.V. to Develop a Seizure Disorder (Althen Prong 1)
As discussed above, to make a prima facie case of a vaccine-related injury under Althen,
a petitioner must set forth a medical theory explaining how the vaccine caused the injury
allegedly suffered. The theory of causation need not be “medically or scientifically certain,” but
it must be informed by a “sound and reliable medical or scientific explanation.” See Knudsen ex
rel. Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548–49 (Fed. Cir. 1994) (quoting
Bunting v. Sec’y of Health & Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991)); see also
Boatmon v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1360 (Fed. Cir. 2019); W.C., 704
F.3d at 1356 (“[T]he petitioner must do more than demonstrate a ‘plausible’ or ‘possible’ causal
link between the vaccination and the injury; [they] must prove [their] case by a preponderance of
the evidence.” (quoting Moberly, 592 F.3d at 1322)).
In this case, Petitioners have argued that the DTaP vaccine can cause a fever and that
fevers can cause seizures. Dec. at 45; see also Pet’rs’ MJAR at 4–5; Oral Arg. Tr. at 9–10, 58;
Pet. at 5. This contention is supported by the medical literature and was endorsed by both parties’
experts, as well as the Special Master. See Dec. at 45–49. But the dispute under Althen prong 1
is not about whether the vaccine could have caused A.V.’s first seizure. It concerns whether
Petitioners supplied a reliable medical or scientific theory to explain how the vaccine could have
caused A.V.’s seizure disorder. And based on the medical literature the Special Master
examined, as well as the opinions of Dr. Raymond, he found that Petitioners had not. Id. at 49.
The Special Master began his discussion of the medical literature with the earliest article
Petitioners cited: M.H. Bellman et al., Infantile Spasms and Pertussis Immunisation, 321 Lancet
1031 (1983). The authors of that article studied the diphtheria-tetanus-whole-cell-pertussis
(“DTwP”) vaccine. See Dec. at 46. Petitioners did not file the article as an exhibit and their
experts did not cite it. Nonetheless, the Special Master reviewed and discussed it. He credited the
opinion of the Secretary’s expert, Dr. Raymond, that the Bellman article was inapposite because
it studied persons who were administered a different vaccine and who experienced a specific
subtype of seizures that does not share any clinical characteristics with Dravet syndrome. See id.
(citing Resp’t’s Ex. D, at 1–2, ECF No. 128-1 (explaining that A.V. “did not develop infantile
spasms nor did she receive [the DTwP] vaccine”)).
The Special Master was also unpersuaded that the other articles Petitioners and their
experts cited provided a sound and reliable medical theory tying the DTaP vaccine to the
development of seizure disorders like Dravet syndrome. At best, he found, the other articles
showed that the vaccine can cause fevers, which in turn cause seizures, which is, as noted above,
a point that is not in dispute. See id. at 46–48.
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The Conrad & Jenson article, for example, examined data from the Centers for Disease
Control & Prevention and the American Academy of Pediatrics Committee on Infectious
Disease. See id. at 46. Based on that data, the authors concluded that “DTaP vaccines do and will
continue to cause undesirable effects[, including seizures], albeit at reduced frequency and
severity compared with [DTwP] vaccines.” Id. at 46–47 (quoting Pet’rs’ Ex. 138, at 7, ECF No.
97-2).6 An abstract by Jackson et al. includes similar findings. See id. at 47 n.19 (citing Pet’rs’
Ex. 140, 1–2, ECF No. 97-4).7
Braun et al. noted that seizures were a known side effect of both the DTwP and DTaP
vaccines. See id. at 47 (citing Pet’rs’ Ex. 139, at 4, ECF No. 97-3).8 But of the thirty-four post-
DTaP seizures reported in the Vaccine Adverse Event Reporting System that Braun et al.
studied, “none of the [study subjects] were reported to have developed a seizure disorder or
epilepsy.” See id. (quoting Pet’rs’ Ex. 139, at 4).
Another study that Petitioners cited—Le Saux et al.—“found a 79% decrease in febrile
seizures associated with receipt of [the DTaP] vaccine” compared to the DTwP vaccine. See
Pet’rs’ Ex. 137, at e348, ECF No. 97-1; Pet’rs’ MJAR at 5.9 But since Le Saux et al. only
examined hospitalizations for febrile seizures, the Special Master found that their research did
not meaningfully contribute to his analysis because it did not include any long-term follow-up to
determine whether any study subjects subsequently developed a seizure disorder. See Dec. at 48
(citing Pet’rs’ Ex. 137, at e348).
These studies support the theory that there is an association between the DTaP vaccine
and postimmunization seizures, albeit less than was true with the DTwP vaccine. But, as Dr.
Raymond observed, they do not provide any support for Petitioners’ theory that the vaccine can
cause a recipient to develop a seizure disorder, such as Dravet syndrome. See Resp’t’s Ex. D, at
3, ECF No. 128-1 (report of Dr. Raymond’s emphasizing that “none of the[se] studies state that
6 Although Petitioners’ Exhibit 138, ECF No. 97-2, was filed without bibliographic information,
the Special Master determined that the appropriate citation is: Dennis A. Conrad & Hal B.
Jenson, Using Acellular Pertussis Vaccines for Childhood Immunization: Potential Benefits Far
Outweigh Potential Risk, 105 Postgraduate Med. 165 (1995).
7 The full citation for Petitioners’ Exhibit 140, ECF No. 97-4, is: Lisa Jackson et al.,
Retrospective Population-Based Assessment of Medically Attended Injection Site Reactions,
Seizures, Allergic Responses and Febrile Episodes After Acellular Pertussis Vaccine Combined
with Diphtheria and Tetanus Toxoids, 21 Pediatric Infectious Disease J. 781 (2002).
8 The full citation for Petitioners’ Exhibit 139, ECF No. 97-3, is: M. Miles Braun et al., Infant
Immunization with Acellular Pertussis Vaccines in the United States: Assessment of the First
Two Years' Data from the Vaccine Adverse Event Reporting System (VAERS), 106 Pediatrics
e51 (2000).
9 The full citation for Petitioners’ Exhibit 137, ECF No. 97-1, is: Nicole Le Saux et al., Decrease
in Hospital Admissions for Febrile Seizures and Reports of Hypotonic-Hyporesponsive Episodes
Presenting to Hospital Emergency Departments Since Switching to Acellular Pertussis Vaccine
in Canada: A Report from IMPACT, 112 Pediatrics e348 (2003).
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epilepsy or an ongoing seizure disorder occurs as an adverse event following immunization with
any pertussis containing vaccine”). Rather, the Special Master found, the evidence shows that
Dravet syndrome is caused by a defect in the SCN1A gene. Dec. at 74. And in deciding whether
Petitioners made a prima facie case under Althen, it is appropriate to consider all evidence,
including that of alternative cause. See Sharpe, 964 F.3d at 1082.
The Court concludes, therefore, that the Special Master reasonably found that Petitioners
failed to provide a sound and reliable medical or scientific basis to support their theory that the
DTaP vaccine can cause recipients to develop seizure disorders, including Dravet syndrome.
Accordingly, his finding that Petitioners failed to satisfy Althen prong 1 was neither arbitrary
and capricious nor contrary to law.
B. The Special Master’s Finding that Petitioners Failed to Supply a Sound and
Reliable Medical Theory to Explain How the DTaP Vaccine Could Have
Aggravated A.V.’s Seizure Disorder (Loving Prong 4)
In addition to rejecting Petitioners’ argument that the DTaP vaccine can cause a recipient
to develop a seizure disorder like Dravet syndrome, the Special Master concluded that Petitioners
failed to provide a sound and reliable medical theory to explain how the vaccine might aggravate
or worsen such a disorder. See Dec. at 49, 52, 74. Therefore, he found, Petitioners failed to
satisfy Loving prong 4. Id. at 52.
In so finding, the Special Master credited the opinion of the government’s expert, Dr.
Raymond, and rejected the opinions of Petitioners’ medical experts, Drs. Boles and Kinsbourne.
Cf. Dec. at 49, 52 with id. at 74. Drs. Boles and Kinsbourne acknowledged that the mutation in
A.V.’s SCN1A gene caused alterations in her neurophysiology that increased her risk of
developing Dravet syndrome. See Pet’rs’ Ex. 45, at 7; Pet’rs’ Ex. 82, at 5; Pet’rs’ Ex. 153, at 1,
ECF No 121-2. But in their view, exposure to an environmental factor, such as a vaccine or viral
infection, is necessary to trigger the disorder’s onset. See Pet’rs’ Ex. 82, at 7–9, 13; Pet’rs’ Ex.
45, at 7–10; Pet’rs’ Ex. 46, at 1–2. They also opined that whether—and with what severity—
A.V. would develop Dravet syndrome, turned on if—and how early in life—she encountered the
environmental factor. See Oral Arg. Tr. at 11, 19–20; Pet’rs’ Ex. 45, at 7–9, 12; Pet’rs’ Ex. 46, at
1; Pet’rs’ Ex. 82, at 4–9, 13; Pet’rs’ Ex. 153, at 1–2.
In the views of Drs. Kinsbourne and Boles, research in genetics, animal models, and
human studies all demonstrate that the earlier onset of seizures in children with Dravet syndrome
results in worsened clinical outcomes. See Pet’rs’ Ex. 45, at 13 (Dr. Kinsbourne opining that
A.V.’s Dravet syndrome “would have been less severe had the [DTaP] vaccination[] not
triggered the onset of her seizure disorder” “at seven months of age”); Pet’rs’ Ex. 82, at 13 (Dr.
Boles opining that “if [A.V.] had not been vaccinated [with DTaP], . . . her outcome would have
been better than it is today”).
Also citing animal models as well as studies of children with the SCN1A mutation, Dr.
Raymond disagreed with the opinions of Drs. Boles and Kinsbourne that earlier onsets of seizure
disorders negatively impact clinical outcomes. See Resp’t’s Ex. C, at 6, 9, ECF No. 77-1. He
emphasized that “while . . . [a] fever may occur in young children following vaccination as an
adverse event, . . . [no] studies state that [Dravet syndrome] occurs as an adverse event following
immunization with [DTaP].” Resp’ts’ Ex. D, at 3. He added further that “an overwhelming body
of scientific literature” continues to show that the timing of the first seizure does not “alter[] the
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tragic course of this genetic disorder.” See Resp’ts’ Ex. A, at 6. In Dr. Raymond’s view, the
variability in outcomes that are experienced by individuals with the mutation of the SCN1A gene
can be explained by differences in the nature of the mutations, as opposed to environmental
factors. See Resp’t’s Ex. C, at 9–10, 14.
The Special Master also engaged in a detailed discussion of the medical literature on
which the competing experts relied. See Dec. at 53–70. Ultimately, he found Dr. Raymond’s
views more persuasive than the opinions of Petitioners’ medical experts, Drs. Kinsbourne and
Boles. See id. at 74. He reasoned that Dr. Raymond “has more experience treating children and
their families for genetic-based neurologic problems” and “supported his opinion that a mutation
in A.V.’s SCN1A gene ‘[wa]s the sole cause of her [seizure disorder]’” more persuasively than
Petitioners’ experts supported their own. Id. at 74 (quoting Resp’t’s Ex. D, at 3).
In their Motion for Review, Petitioners criticize the Special Master’s finding that the
studies performed by Brunklaus et al. and McIntosh et al. supported Dr. Raymond’s opinion. See
Pet’rs’ Mot. for Rev. II, at 6–8. The Brunklaus article, Petitioners contend, does not show that
the SCN1A mutation was the sole cause of A.V.’s injury because the study was too small. Id. at
6–7. Petitioners further note that the McIntosh article, which found that vaccinations have no
long-term impacts on outcomes of Dravet syndrome, has been criticized as invalid by
Petitioners’ statistical expert, Dr. McNulty. Id. at 7–8.
Of course, these were not the only two studies that the Special Master considered when
he addressed whether the DTaP vaccine can aggravate an existing seizure disorder. As he
observed, “[m]ultiple groups have explored whether childhood vaccines cause or worsen seizures
in children with SCN1A mutations.” Dec. at 70. Investigators have used a variety of approaches,
and yet they “have not detected any evidence that vaccines alter the child’s seizure pattern.” Id.
Instead, he observed, “the large studies tend to show that the genetic mutation causes the
seizures.” Id.
As the court of appeals has noted, “[f]inders of fact are entitled—indeed, expected—to
make determinations as to the reliability of the evidence presented to them.” Moberly, 592 F.3d
at 1326. It has explained that:
Congress assigned to a group of specialists, the Special Masters within the Court
of Federal Claims, the unenviable job of sorting through these painful cases and,
based upon their accumulated expertise in the field, judging the merits of the
individual claims. The statute makes clear that, on review, the Court of Federal
Claims is not to second guess the Special Masters[’] fact-intensive conclusions; the
standard of review is uniquely deferential for what is essentially a judicial process
. . . . That level of deference is especially apt in a case in which the medical evidence
of causation is in dispute.
Deribeaux v. Sec’y of Health & Hum. Servs., 717 F.3d 1363, 1366–67 (Fed. Cir. 2013) (quoting
Hodges, 9 F.3d at 961); see also de Bazan v. Sec’y of Health & Hum. Servs., 539 F.3d 1347,
1354 (Fed. Cir. 2008) (upholding the special master’s determination that respondent’s expert
testimony was more credible and probative than that of the petitioner’s expert); Lampe v. Sec’y
of Health & Hum. Servs., 219 F.3d 1357, 1361–62 (Fed. Cir. 2000) (upholding the special
master’s determination that the Secretary’s medical expert was more persuasive than the
petitioners’ medical expert because “[t]hose findings, which are at the core of the special
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master’s decision in this case, are largely based on his assessments of the credibility of the
witnesses and the relative persuasiveness of the competing medical theories of the case. As such,
they are virtually unchallengeable on appeal.”).
The Special Master here drew upon his expertise in the field, and, giving greater weight
to the opinions of Dr. Raymond, found no reliable medical or scientific basis for Petitioners’
theory that a DTaP vaccine can aggravate or worsen the condition of an individual with Dravet
syndrome. And because Petitioners failed to satisfy both Althen prong 1 and Loving prong 4, the
Special Master acted within his discretion when he found that they failed to establish a prima
facie case that the DTaP vaccine either caused or aggravated A.V.’s seizure disorder.
C. The Special Master’s Finding that Petitioners Failed to Prove a Logical
Sequence of Cause and Effect Showing that the DTaP Vaccine Caused or
Aggravated A.V.’s Seizure Disorder (Althen Prong 2/Loving Prong 5)
As described above, in addition to supplying a reliable scientific or medical basis for their
theory of causation, Petitioners must show under Althen prong 2 and Loving prong 5 that there is
a “logical sequence of cause and effect” between receiving the DTaP vaccine and the
development or aggravation of Dravet syndrome. Sharpe, 964 F.3d at 1085; see also Capizzano
v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1324 (Fed. Cir. 2006) (quoting Althen, 418
F.3d at 1278); Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d at 1356 (Fed. Cir. 2006)
(stating that “petitioner[s] must show that the vaccine was the ‘but for’ cause of the harm . . . or
in other words, that the vaccine was the ‘reason for the injury’”). The sequence of cause and
effect must be “‘logical’ and legally probable, not medically or scientifically certain.” Knudsen,
35 F.3d at 548–49.
As noted above, Petitioners’ theory is that the DTaP vaccine aggravated A.V.’s Dravet
syndrome because it induced the initial febrile seizure, which caused brain injury that triggered
or at least accelerated the onset of her seizure disorder. See Pet’rs’ Ex. 45, at 7; Pet’rs’ Ex. 82, at
5; Pet’rs’ Ex. 153, at 1. The Special Master rejected Petitioners’ argument that this theory
provides a logical sequence of cause and effect between the DTaP vaccine and either the
development or aggravation of A.V.’s seizure disorder. See Dec. at 48–49.
The primary flaw in this theory, according to the Special Master, was that there was no
evidence that A.V. suffered a brain injury as a result of her initial seizure. Id. at 50. He observed
that A.V. was examined by her pediatrician, Dr. Subramanian, and had a consultation with Dr.
Ikramuddin, a pediatric neurologist, shortly after her initial seizure. See Dec. at 33–34; see also
Pet’rs’ Ex. 11, at 28; Pet’rs’ Ex. 10, at 65. The Special Master explained that neither of these
“treating doctor[s]” “indicated that the vaccination caused any lasting harm to A.V.” Dec. at 49
(emphasis added) (citing Oral Arg. Tr. 37:6–38:12; Pet’rs’ MJAR at 9; Pet’rs’ Reply to Resp’t’s
Resp. to MJAR at 2); see also Pet’rs’ Ex. 11, at 28–29; Pet’rs’ Ex. 10, at 65. To the contrary, the
“immediate effects [of A.V.’s initial febrile seizure] dissipated within a few days,” Dec. at 49,
and it was not until she developed a fever from a confirmed viral infection nearly three months
later that she experienced another seizure, id. at 51 (citing Pet’rs’ Ex. 11, at 25).
The Special Master appropriately gave substantial weight to the fact that A.V.’s treating
physicians believed that A.V. had not suffered lasting, much less permanent, harm as a result of
the vaccine-induced seizure. As the court of appeals has observed, “medical records and medical
opinion testimony are favored in vaccine cases, as treating physicians are likely to be in the best
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position to determine whether ‘a logical sequence of cause and effect show[s] that the
vaccination was the reason for the [significant aggravation of the condition at issue].’”
Capizzano, 440 F.3d at 1326 (quoting Althen, 418 F.3d at 1280); see also Andreu, 568 F.3d at
1375.
Further, A.V. exhibited no clinical signs of recent seizure activity just hours after her
initial seizure. During her brief hospital stay, A.V.’s temperature returned to normal, and her
head CT scan, EEG study, and routine blood testing were all unremarkable. See Pet’rs’ Ex. 1 pt.
2, at 57, 76, 88; see also Pet’rs’ Ex. 3 pt. 2, at 69, 78 (reflecting A.V.’s discharge less than forty-
eight hours after arriving at the ED). She also exhibited “no evidence of altered mental status or
. . . encephalopathy” shortly after her initial seizure. See Dec. at 50 (quoting Resp’t’s Ex. C, at
2).
Because A.V. did not show any signs of brain injury after her initial febrile seizure, Dr.
Raymond reported that it was his opinion, “to a reasonable degree of medical certainty,” that
A.V.’s Dravet syndrome “was n[either] caused nor exacerbated by any of the immunizations that
she received.” See Resp’t’s Ex. C, at 15. The Special Master credited Dr. Raymond’s opinion,
because Petitioners did not “counter[] the contention that A.V. returned to her baseline shortly
after [her initial febrile seizure].” Dec. at 50. Further, he found that neither Dr. Kinsbourne nor
Dr. Boles attempted to reconcile A.V.’s normal EEG and CT scan with their theory that the
vaccine-induced initial seizure caused A.V. to suffer brain injury. Id.
Petitioners argue in their Motion for Review that it is of no moment that the EEG study
and CT scan showed no evidence that A.V. suffered brain injury after the DTaP vaccine induced
her first febrile seizure. See Pet’rs’ Mot. for Rev. II at 1, 3–4. They observe that under the
diagnostic criteria for Dravet syndrome, EEG studies are initially normal until additional seizures
have occurred over several months. See id. They also observe that none of A.V.’s treating
physicians or experts “reached the conclusion that the first seizure was not related to her long-
term seizure disorder.” See id. at 3.
Petitioners’ observations miss the mark. Neither the Special Master nor Dr. Raymond
denied that the seizure A.V. suffered after she received the DTaP vaccine was “related” to her
Dravet syndrome. To the contrary, as Dr. Raymond explained, “[f]ebrile seizures are common as
the initial manifestation of Dravet syndrome and may be secondary to any event which raises the
child’s temperature.” Resp’t’s Ex. D, at 3. He was of the view, however, that the vaccine did not
cause A.V.’s Dravet syndrome, and that her rapid return to baseline after the initial seizure
showed that the vaccine did not make her seizure disorder worse. See id.
In short, A.V.’s medical records reflect that she rapidly recovered after her initial seizure.
They provide no evidence that she suffered brain damage as a result of the initial seizure; indeed
they show that she did not. The Special Master’s conclusion—that Petitioners did not establish
that the DTaP vaccine “was the logical reason for the . . . worsening of A.V.’s seizure
disorder”—was not arbitrary and capricious but was instead consistent with A.V.’s medical
records and the opinion of the Secretary’s expert, Dr. Raymond. See Dec. at 52. Accordingly, the
Court has no basis for setting it aside.
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CONCLUSION
Based on the foregoing discussion, Petitioners’ Corrected Motion for Review, ECF No.
143, is DENIED, and the Special Master’s decision is SUSTAINED. The Clerk is directed to
enter judgment accordingly.
IT IS SO ORDERED.
s/ Elaine D. Kaplan
ELAINE D. KAPLAN
Chief Judge
22