Court Opinion

ID: 2816314
Source: CourtListenerOpinion
Date Created: 2015-07-10 16:09:11.771034+00
Date Added: 2024-06-11T12:25:36.526677
License: Public Domain

In the United States Court of Federal Claims
                               No. 07-605V
                     (Originally Filed: June 15, 2015)
                        (Reissued: July 10, 2015)

**********************

NANCY BARCLAY, as the legal
representative of her minor son,
MATTHEW RAMIREZ,                                 Vaccine case; petitioner’s
                                                 challenge to the Special
                     Petitioner,                 Master’s decision;
                                                 significant aggravation;
v.                                               DTaP vaccine; Dravet
                                                 syndrome; SCN1A
SECRETARY OF HEALTH AND                          mutation.
HUMAN SERVICES,

           Respondent.
**********************

       Curtis R. Webb, Twin Falls, ID for petitioner.

       Voris E. Johnson, Jr., Assistant Director in the Torts Branch of the
Civil Division, Department of Justice, Washington, DC, with whom are, Joyce
R. Branda, Acting Assistant Attorney General, Rupa Bhattacharyya, Director,
Vincent J. Matanoski, Deputy Director, and Catharine E. Reeves, Assistant
Director, for respondent.

                             _______________

                                OPINION1
                             _______________

       1
        Publication of this opinion was deferred pending the parties’ review
for redaction of protected information. See Rules of the Court of Federal
Claims (“RCFC”), App. B, Rule 18(b). Neither party submitted proposed
redactions, although the court made other minor editorial changes. The
opinion is now prepared for release.
BRUGGINK, Judge.

        On August 14, 2007, petitioner, Nancy Barclay, filed a petition for
compensation under the National Childhood Vaccine Injury Act, 42 U.S.C. §§
300aa-1 to-34 (2012) (“Vaccine Act”), on behalf of her minor son, Matthew
Ramirez. The petition alleges that the diphtheria-tetanus-acellular pertussis
(“DTaP”) vaccination caused Matthew to develop Dravet syndrome.2 Progress
on this case was stayed pending the resolution of a series of cases which relied
on the same theory of causation. See Barnette v. Sec’y of Health & Human
Servs., No. 06-868V, 2012 WL 5285414 (Fed. Cl. Spec. Mstr. Sept. 26, 2012)
(denying compensation); Snyder v. Sec’y of Health & Human Servs., No. 07-
59V, 2011 WL 3022544 (Fed. Cl. Spec. Mstr. May 27, 2011) (denying
compensation); Harris v. Sec’y of Health & Human Servs., No. 07-60V, 2011
WL 2446321 (Fed. Cl. Spec. Mstr. May 27, 2011) (denying compensation);
Hammitt v. Sec’y of Health & Human Servs., No. 07-170V, 2011 WL 1135878
(Fed. Cl. Spec. Mstr. Mar. 4, 2011) (denying compensation); Stone v. Sec’y of
Health & Human Servs., No. 04-1041V, 2011 WL 836992 (Fed. Cl. Spec.
Mstr. Jan. 20, 2011) (denying compensation).3 Once it became clear that
respondent had proven that a genetic factor unrelated to the vaccination was
the cause of Dravet syndrome in those cases, Ms. Barclay was permitted to
amend her theory of liability.

       Petitioner asserts that DTaP vaccine significantly aggravated Matthew’s
Dravet syndrome by provoking an earlier onset and by causing additional
damage to Matthew’s brain. Ms. Barclay argues that but for the vaccination,
Matthew would have experienced less developmental delay. Petitioner
presented her case to the Special Master in June of 2013. After conducting a
hearing, reviewing the evidence, weighing the testimony provided by the
experts, and considering post-hearing briefs, the Special Master concluded that
petitioner failed to establish a persuasive theory of causation, held that
respondent proved a defense, and denied petitioner’s request for compensation.
See Barclay v. Sec’y of Health & Human Servs., No. 07-605V, 2014 WL
7891493 (Fed. Cl. Spec. Mstr. Dec. 15, 2014) (hereinafter “Decision”).

       2
       Dravet syndrome is also referred to as SMEI, which stands for severe
myoclonic epilepsy in infancy. This condition is characterized by
unmanageable epilepsy and developmental regression. See Stone v. Sec’y of
Health & Human Servs., 676 F.3d 1373, 1375 n.1 (Fed. Cir. 2012).
       3
           See footnote 10 for precedent affirming these decisions.

                                        2
       Currently before the court is petitioner’s motion for review of the
Special Master’s ruling of December 15, 2014, denying compensation. We
have jurisdiction pursuant to 42 U.S.C. § 300aa-12. In our review, we apply
the standard articulated in 42 U.S.C. § 300aa-12(e) and will only set aside the
special master’s findings of fact or conclusions of law that were “arbitrary,
capricious, an abuse of discretion, or otherwise not in accordance with law.”
42 U.S.C. § 300aa-12(e)(2); see Paluck v. Sec’y of Health & Human Servs.,
No. 2014-5080, 2015 WL 2403354 (Fed. Cir. May 20, 2015) (precedential);
see also Lampe v. Sec’y of Health & Human Servs., 219 F.3d 1357, 1360 (Fed.
Cir. 2000) ((holding that special masters have discretion to weigh the evidence
and “reversible error is ‘extremely difficult to demonstrate’” unless the special
master has failed to consider the relevant evidence of record, drawn
implausible inferences or failed to articulate a rational basis for the decision)
(quoting Hines v. Sec’y of Health & Human Servs., 940 F.2d 1518, 1528 (Fed.
Cir. 1999))).

       The matter is fully briefed and we heard oral argument on May 7, 2015.
For the reasons explained below, we deny petitioner’s motion for review.

                              BACKGROUND4

       Matthew was born on November 16, 2004. Although he appeared
normal and healthy, Matthew was born with a genetic mutation.5 Specifically,
there was a frameshift mutation in his SCN1A gene caused by the “deletion of
10 base pairs at nucleotide position 3867-3876 / codon position 1289-1292.”
Decision at *5 n.9. Without the missing base pairs, Matthew lacks the
necessary genetic material to support proper neurological function.

       In a healthy person, the SCN1A gene supplies the genetic code which
is used by the body to create Nav1.1 sodium channels.6 Sodium channels are

       4
        The background facts are derived from the Decision and are not in
dispute. The page numbers used in citations to the Decision refer to the
pagination provided by Westlaw.
       5
         The precise mutation that afflicts Matthew was revealed through
genetic testing in 2009.
       6
        For more information on transcription and translation, which are the
processes by which the body eventually produces the proteins proscribed by
                                                                   (continued...)

                                       3
integral to neurological function because they regulate electrical excitability.
Specifically, sodium channels transmit electrical signals throughout cells and
cell networks to achieve functions such as movement or thought. The
transmission is achieved when the membrane of a sodium channel becomes
depolarized because it increases permeability to sodium ions and thereby
permits the flow of these ions. Once the need for the excitability concludes,
permeability decreases and the sodium channel closes.

        Within the infant’s brain, sodium channels evolve in the first six months
of life. At birth, the human body relies on the Nav1.3 sodium channel instead
of the Nav1.1 channel. Around three months of age, there is a natural
transition to reliance on the Nav1.1 sodium channel. The Nav1.1 sodium
channel functions to maintain a neurological balance in the brain and
dysfunction in this channel can lead to seizures.

       Because Matthew’s body was not yet utilizing the Nav1.1 sodium
channel, Matthew was asymptomatic during his early development. He had
well-baby visits on November 30, 2004, January 21, 2005, and March 25,
2005, during which his pediatrician noted nothing out of the ordinary.

       During the March 25, 2005 well-baby checkup, Matthew received a set
of vaccinations, which included a second dose of the DTaP vaccine. Later that
night, Matthew developed a fever and, in response, Matthew’s mother gave
him infant Motrin. Around 6:00 a.m. on the morning of March 26, Matthew
had a seizure lasting about 20 minutes. Matthew lost consciousness during the
seizure, prompting his parents to bring him to the hospital. Upon arriving at
the local emergency room, Matthew was still seizing and remained feverish.
The doctor administered Versed, and the seizure abated within a minute.
Matthew’s seizure lasted approximately 45 minutes.

       While Matthew was in the hospital, the doctors ordered a series of tests
including an electroencephalogram (“EEG”), a computerized tomography
(“CT”) scan of his brain, magnetic resonance imaging (“MRI”), and X-rays.
The EEG and CT scan were normal, and the MRI was essentially normal. The
X-ray, however, revealed infiltrate in both lungs. The doctors concluded that
Matthew had pneumonia, and his final diagnosis was stated to be febrile
seizures due to pneumonia. On March 29, 2005, after being hospitalized for

       6
           (...continued)
the DNA, see Decision at *3-4.

                                       4
four days, Matthew was discharged with a course of antibiotics to treat the
pneumonia.

        Matthew experienced another seizure on April 15, 2005, although this
episode was not provoked by a fever or other identifiable trigger. Shortly after
this episode, Matthew had an EEG which “indicated that Matthew had some
slowing in the background and was interpreted as abnormal.” Decision at *7.
After Matthew suffered another unprovoked seizure on April 25, 2005, he fit
the criteria for being epileptic.

       Matthew continues to suffer from epilepsy. The Special Master
summarized Matthew’s condition as follows: “Since he started having
seizures, Matthew has not developed normally. Various anticonvulsant
medicines have not controlled his seizures. He experiences approximately ten
seizures each month. He speaks sentences that are three or four words in
length. He can walk but has difficulty catching a ball.” Id.

        In 2009, Matthew underwent genetic testing to explore the cause of his
epilepsy. The genetic testing report issued by Athena Diagnostic, Inc. stated,
“This individual possesses a DNA sequence variant that is either a previously
reported disease-associated mutation or is predicted to be a disease-associated
mutation. This test result is consistent with a diagnosis of, or a predisposition
to develop, SMEI or SMEB, the severe phenotypes associated with SCN1A
mutations.” Id. at * 5 (quotation and citation omitted). Upon receiving these
test results, Matthew’s treating physicians diagnosed him as suffering from
Dravet syndrome.

       The presentation of Dravet syndrome includes onset of seizures
sometime between four and eight months of age. These initial seizures are
typically clonic or hemi-clonic and last for over five minutes or occur multiple
times in a five-minute period. “In the second or third year of life, the seizures
evolve into different types of seizures including myoclonic seizures, absence
seizures, and complex partial seizures. Although the initial development is
normal, by the time the child becomes a toddler, his or her development
stagnates.” Id. at *4. The severity of Dravet syndrome occurs along a
spectrum with some children experiencing milder outcomes than others. There
are subtypes of Dravet syndrome that serve to categorize presentations within
the spectrum. These subtypes include “generalized epilepsy with febrile
seizures (GEFS), severe myoclonic epilepsy borderline (SMEB), and severe
myoclonic epilepsy in infancy (SMEI).” Id. As discussed below, the location

                                       5
and nature of the genetic mutation may be indicative of the child’s outcome
along the spectrum.

        After the test results revealed that Matthew had a severe mutation to his
SCN1A gene, his parents were also tested in order to determine if the mutation
was hereditary. If one or both of Matthew’s parents had a similar mutation
that would suggest a more hopeful prognosis for Matthew; the assumption is
that the parent with the mutation has developed normally enough to function
and reproduce. For example, there are some SCN1A mutations that are
associated with conditions such as migraines. These more benign mutations
could be inherited. The test results showed that neither of Matthew’s parents
had a SCN1A gene abnormality.

       The alternative to an inherited abnormality is a genetic mutation that
occurred spontaneously and for the first time, de novo, in Matthew’s
development. While a de novo mutation does not automatically mean a severe
outcome, it is not as promising as a hereditary mutation.

       Another indicator that the outcome might be severe is location on a
conserved region of DNA. A conserved region is one that is preserved through
evolution in many species, which suggests that changes in these sequences of
DNA are not easily tolerated. Some mutations that occur in conserved regions
are not consistent with life.

       The type of genetic mutation also impacts outcome. While some types
of mutations are harmless, such as when one amino acid is substituted for a
similar amino acid, other types, such as frame shift mutations in which base
pairs are missing and the DNA sequence shifts in their absence, might be
predictive of worse outcomes.

                                DISCUSSION

       To receive compensation for a vaccine related injury, petitioner bears
the burden of proving by a preponderance of the evidence the elements of his
or her petition, which are listed in 42 U.S.C. § 300aa-11(c)(1). 42 U.S.C. §
300aa-13(a)(1)(A). In a non-table7 significant aggravation claim, petitioner

       7
      See 42 U.S.C. § 300aa-14(a) (injury table); W.C. v. Sec’y of Health &
Human Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013) (explaining that “[i]n a
                                                                   (continued...)

                                       6
must prove that he or she “had significantly aggravated any illness, disability,
injury, or condition not set forth in the Vaccine Injury Table but which was
caused by a vaccine.” § 300aa-11(c)(1)(C)(ii)(I). “Significant aggravation”
is defined in § 300aa-33(4) as “any change for the worse in a preexisting
condition which results in a markedly greater disability, pain, or illness
accompanied by a substantial deterioration of health.”

        A critical step in petitioner proving her case is showing that the vaccine
caused the significant aggravation. The Court of Appeals for the Federal
Circuit in W.C. v. Secretary of Health and Human Services, 704 F.3d at 1357,
endorsed the factors for establishing causation in a significant aggravation case
set forth in Loving v. Secretary of Health and Human Services, 86 Fed. Cl. 135
(2009). The Loving case suggests an examination of the following factors:

       (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
       casually 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 proximate temporal relationship
       between the vaccination and the significant aggravation.

86 Fed. Cl. at 144.8 Additionally, petitioner must show that “the residual
effects or complications of such illness, disability, injury, or condition”

       7
           (...continued)
table claim, the petitioner benefits from a statutory presumption of causation
upon showing that the injury is listed in the Vaccine Injury Table for the
vaccine received and occurred within the time period in the table” but that “[i]f
the injury is not listed in the table, the petitioner must prove actual causation
by a preponderance of the evidence”).
       8
         The Loving standard combines the traditional causation factors
outlined in Althen v. Secretary of Health and Human Services, 418 F.3d 1274,
1278 (Fed. Cir. 2005), with three additional factors for establishing an off-
table significant aggravation claim derived from Whitecotton v. Secretary of
Health and Human Services, 81 F.3d 1099, 1107 (Fed. Cir. 1996).

                                        7
continued “for more than 6 months after the administration of the vaccine.”
§ 300aa-11(c)(1)(D)(i). If petitioner proves these factors, she has established
a prima facie case for compensation.

        At any point, whether it is before or after petitioner has established her
prima facie case, the Special Master may consider whether a factor unrelated
to the vaccine was the cause of the injury. Stone, 676 F.3d at 1379-80. The
Secretary bears the burden of proving the “factors unrelated” defense, which
requires a showing “also by a preponderance of evidence, that the injury was
in fact caused by factors unrelated to the vaccine.” Knudsen v. Sec’y of Health
& Human Servs., 35 F.3d 543, 547 (Fed. Cir. 1994) (citation and quotation
omitted).

       The anomaly in using this approach here, however, is that Matthew had
a preexisting condition which had not manifested itself prior to the
vaccination. Asking the question, “what was Matthew’s condition prior to the
vaccination?” therefore, requires addressing the issue of his genetic
abnormality. Does the fact that the abnormality had not manifested and was
therefore unknown mean that his condition prior to vaccination was that of a
normal, healthy child? The result of the before and after comparison posed by
questions one and two in the Loving analysis is different depending on whether
or how the genetic abnormality is taken into account.

        Petitioner does not contend that the vaccine caused the Dravet
syndrome. In other words, she concedes that Matthew’s “before” condition is
that of a child with a genetic abnormality, which, as we consider below, means
that he will develop one of the severe disease types associated with SCN1A
mutations. She contends, however, that the vaccination triggered the earlier
onset of the manifestations of Dravet and that those symptoms were, on a
continuing basis, more serious than they otherwise would have been.

        Further complicating the application of the Loving factors, however, is
that it is undisputed that the vaccine caused the fever which preceded the
seizure on the day of vaccination. There is thus no question that Matthew’s
condition immediately prior to vaccination was that he was free of fever and
seizures, and that after the vaccination he had a fever (briefly), but continued
to have seizures. Under these circumstances, determining whether or not the
causation test is met depends on how the question is framed. Is it sufficient
that there is a connection between the vaccination and the first seizure, or must
the first seizure have had an impact on Matthew’s ultimate prognosis? What
specific condition must have persisted at least six months to establish

                                        8
causation, and what must petitioner prove, if anything, with respect to whether
the genetic abnormality alone explains the ongoing seizures?

       I.     Before the Special Master

              A.      The Parties’ Arguments and Experts

       Before the Special Master, petitioner presented three overlapping
theories of causation. First, that individuals “with an SCN1A mutation are
vulnerable or susceptible to developing an adverse reaction to the DTaP
vaccine.” Decision at *12. Second, that “vaccines cause Dravet syndrome to
manifest earlier by bringing about seizures before they would have occurred
otherwise.” Id. Third, that “vaccines cause a more prolonged seizure and the
prolonged seizure inflicts additional damage.” Id.

       In order to establish its prima facie case, petitioner relied on the expert
opinion of Jean-Ronel Corbier, a pediatric neurologist. Dr. Corbier offered his
medical opinion that “a prolonged seizure, especially a prolonged febrile
seizure, can change the infant’s brain” and thereby significantly aggravate a
preexisting condition such as a SCN1A genetic mutation. Id. at *9.
Specifically, Dr. Corbier testified that a person with a SCN1A mutation could
potentially experience a range of outcomes from benign migraines to much
more severe conditions. He opined that the broad spectrum of disorders was
not explained solely by genetics and was likely caused to some extent by
environmental factors. In Matthew’s case, Dr. Corbier testified that the second
dose of the DTaP vaccine was an environmental factor that caused a fever and
a prolonged febrile seizure, which damaged Matthew’s brain and significantly
aggravated his ultimate outcome. While Dr. Corbier acknowledged that
Matthew’s EEG and MRI test results were normal shortly after receiving the
second dose of DTaP, he asserted that the March 26, 2005 seizure altered
Matthew’s brain. “In Dr. Corbier’s view, ‘an immature brain exposed to
prolonged febrile seizure will then not have just an isolated event but will have
further seizures.’” Id. at *8 (quoting Tr. 99). Dr. Corbier conceded that
Matthew was at risk for epileptic conditions because of his SCN1A mutation,
but asserted that the vaccine triggered an earlier onset of epilepsy, which
damaged Matthew’s brain and altered his outcome for the worse.

       Dr. Corbier drew support for his opinion from scientific material related
to SCN1A mutations. Specifically, Dr. Corbier relied on the Tro-Baumann
study for the proposition that there is a connection between vaccination and
Dravet syndrome. See Blanca Tro-Baumann et al., A Retrospective Rtudy of

                                        9
the Relation Between Vaccination and Occurrence of Seizures in Dravet
Syndrome, 52 Epilepsia 175 (2011). Tro-Baumann and colleagues studied 70
patients with Dravet syndrome and SCN1A mutations and noted that 27% of
them experienced seizures after vaccination. In more than half of the patients
who reported a seizure following vaccination, it was their first clinical
manifestation of Dravet syndrome. While the authors of the study concluded
that drawing a causal connection between vaccination and onset of Dravet
syndrome would be a misinterpretation of the data, Dr. Corbier presented this
study as support for his opinion that vaccination is an inciting factor that could
trigger early disease onset in genetically susceptible individuals like Matthew.

       Dr. Corbier’s theory that vaccines cause a more prolonged seizure and
that the prolonged seizure inflicts additional damage was based on medical
studies which examined whether febrile seizures damage HCN channels. Dr.
Corbier testified that “‘these articles show that we have an explanation for
prolonged febrile seizures causing permanent changes, permanent epileptic
changes in a brain that may start out normal, for example, Dravet patients.’”
Decision at *18 (quoting Tr. 50). Dr. Corbier testified that Matthew had
suffered some sort of alteration to his brain during his initial seizure, even
though he could not point to any medical evidence showing the alleged
damage and despite the fact that the neurological tests performed directly after
Matthew’s initial epileptic episode yielded normal results.

        Respondent’s position is that Matthew’s genetic mutation is a factor
unrelated to the vaccine and that the mutation is the sole cause of his present
condition. The Secretary is willing to concede that the vaccination caused a
fever, and that the fever may have triggered a seizure, but whether the seizures
started immediately upon the vaccination or later, she argues that Matthew’s
outcome is the same as it would have been absent the vaccination. Respondent
relies on two experts: Max Wiznitzer, a pediatric neurologist, and Gerald
Raymond, a neurologist and geneticist. Both experts supported the Secretary’s
position that the vaccine neither caused nor significantly aggravated
Matthew’s Dravet syndrome. Dr. Wiznitzer testified about the course of
Matthew’s condition and Dr. Raymond supplied information about the
interplay between Matthew’s genetic mutation and the function of sodium
channels. Both respondent experts agreed with Dr. Corbier only to the extent
that the vaccination most likely provoked a fever that triggered the first
seizure.

      Dr. Wiznitzer was of the opinion that Matthew’s SMEI condition was
caused solely by the mutation in his SCN1A gene. He asserted that there is no

                                       10
medical or scientific evidence that environmental factors can aggravate a
SCN1A gene mutation. To the contrary, the Secretary presented a medical
study conducted by Yu and his colleagues. See Frank H. Yu et al., Reduced
Sodium Current in GABAergic Interneurons in a Mouse Model of Severe
Myoclonic Epilepsy in Infancy, 9 Nat. Neuroscience 1142 (2006). It showed
how mice with a severe SCN1A mutation were destined to develop seizures
even in the absence of a fever or other triggering event. In light of this study
and his medical experience, Dr. Wiznitzer concluded that “the initial post-
vaccination fever did not affect Matthew’s development because children with
SMEI always manifest the disorder even if they do not have a fever.” Decision
at *8 (citation and internal quotation omitted). Dr. Wiznitzer also relied on the
McIntosh study, which examined 40 patients with Dravet syndrome to see if
there was an association between vaccination and disease onset. See Anne M.
McIntosh et al., Effects on Vaccination on Onset and Outcome of Dravet
Syndrome: A Retrospective Study, 9 Lancet Neurology 592 (2010). The study
concluded that there were “no differences in intellectual outcome, subsequent
seizure type, or mutation type between” those whose disease manifested
directly following vaccination and those whose disease manifested later. Id.
at 592. Additionally, McIntosh and her colleagues found “no evidence that
vaccinations before or after disease onset affect outcome.” Id.

        Dr. Wiznitzer opined that McIntosh suggests that children with Dravet
syndrome who have an initial seizure in temporal proximity to a vaccination
still have similar clinical outcomes to children whose initial seizures are not
temporally related to vaccination. Furthermore, Dr. Wiznitzer saw no
evidence that Matthew’s brain had been affected by the March 26, 2005
seizure. Dr. Wiznitzer was therefore of the opinion that Matthew returned to
baseline and had no readily identifiable lasting effects from the March 26
episode. Dr. Wizniter opined that Matthew’s faulty “wiring” and not the
vaccine caused his present condition.

        Dr. Wiznitzer also addressed Dr. Corbier’s testimony that the medical
literature supported his conclusion that prolonged febrile seizures had damaged
Matthew’s brain. First, Dr. Wiznitzer pointed out that HCN channels are not
the same as sodium channels, with the latter and not the former being altered
by the SCN1A mutation. Dr. Wiznitzer explained that HCN channels are
located in the hippocampal region of the brain and exist to limit the cell’s
excitability through the movement of sodium and potassium ions across the
cell membrane. The exchange of sodium and potassium ions balances and
polarizes the cell. Sodium channels, by contrast, only regulate the flow of
sodium ions. When sodium ions are present, the cell becomes hyper-polarized.

                                       11
According to Dr. Wiznitzer, the two types of channels are prescribed by
different genes, built differently, and have different components. Dr.
Wiznitzer was not comfortable extrapolating the medical studies regarding
HCN channels to sodium channels.

       Respondent’s second expert, Dr. Raymond, explained how sodium
channels normally function and how a genetic defect can alter their proper
functioning. According to Dr. Raymond, the dysfunction of sodium channels
was sufficient to explain Matthew’s outcome, and “it is very clear that based
on the present animal investigations, that there is no need to invoke
environmental modifiers to explain disease onset or progression.” Decision
at *10 (internal quotations omitted).

         Additionally, Dr. Raymond challenged Dr. Corbier’s assertion that an
earlier onset of Dravet syndrome caused a worse outcome by pointing to
medical studies supporting an opposite conclusion. The Berkovic group
studied 14 patients who experienced their first seizure within 72 hours of
receiving the pertussis vaccination and thereafter suffered an alleged
encephalopathy and found that 11 of those patients had an SCN1A mutation.
Samuel F. Berkovic et al., De-novo Mutations of the Sodium Channel Gene
SCN1A in Alleged Vaccine Encephalopathy: A Retrospective Study, 5 Lancet
Neurology 488 (2006). Eight of those 11 patients had severe phenotypes of
the SCN1A mutation, which correlates to SMEI. Another 3 patients had an
SCN1A mutation that was linked to borderline SMEI. This led the researchers
to conclude that genetics, rather than the vaccine, caused the epileptic
encephalopathy. Berkovic wrote that “individuals with such mutations seem
to develop SMEI or SMEB whether or not they are immunized in the first year
of life. We do not think that avoiding vaccination, as a potential trigger, would
prevent onset of this devastating disorder in patients who already harbour the
SCN1A mutation.” Id. at 491. Additionally, Dr. Raymond relied on the study
conducted by Brunklaus, which tracked 355 SCN1A mutation-positive patients
with Dravet syndrome over 5 years to gather data on disease presentation and
manifestation. A. Brunklaus et al., Prognostic, Clinical and Demographic
Features in SCN1A Mutation-positive Dravet Syndrome, 135 Brain 2329
(2012). The authors found that the following variables predicted a worse
outcome: “status epilepticus, interictal electroencephalography abnormalities
in the first year of life, and motor disorders.” Decision at *16. By contrast,
variables such as mutation class and the event precipitating seizure did not
correlate to a worse outcome. The authors concluded that developmental
outcome was not affected by vaccination.

                                       12
        Dr. Raymond also testified about the location, type, and severity of
Matthew’s mutation. Specifically, Dr. Raymond drew on his experience as a
geneticist and explained that the following factors would lead him to expect
that Matthew’s condition would be severe, irrespective of the vaccination: the
fact that the mutation arose de novo; that Matthew’s mutation was the deletion
of ten base pairs of nucleotides; and that the mutation arose in a conserved
region. Dr. Raymond’s analysis about the significance of Matthew’s genetic
mutation is consistent with the laboratory that provided Matthew’s genetic
screening, which concluded that the mutation was indicative of a severe
manifestation of SMEI.

                B.     The Special Master’s Decision

       In his decision, the Special Master did not perform an analysis as to
each of the Loving factors. Of the six Loving factors, the Special Master
focused his analysis on the fourth factor, which corresponds to the first prong
of Althen.9 The question asked by the fourth Loving factor is whether
petitioner has proven “a medical theory causally connecting such a
significantly worsened condition to the vaccination.” 86 Fed. Cl. at 144. The
Special Master was not persuaded by petitioner’s theory that the vaccination
aggravated the symptoms of the SCN1A mutation, and he accepted
respondent’s argument that Matthew’s presentation of Dravet syndrome is
completely explained by his genetic mutation.

        The Special Master thus accepted respondent’s proof of two things,
either of which would be inconsistent with a recovery: that the vaccination did
not cause any brain damage making the onset of Dravet more serious; and that
the manifestation of the SCN1A mutation would not have been any different
if the vaccine had not been administered. The first finding is inconsistent with
petitioner’s case in chief. The second accepts respondent’s defense.

       The Special Master considered the parties’ arguments and the expert’s
presentations and concluded that the opinions of respondent’s experts were
more persuasive than the expert opinion furnished by petitioner: “Dr.
Wiznitzer and Dr. Raymond explained the relevant medical concepts and
showed how those principles were the foundations for their opinions,” while
“Dr. Corbier did not.” Decision at *1. The Special Master summarized his
conclusion regarding the weight of the evidence as follows:

       9
           418 F.3d at 1278.

                                      13
       Thus, there is no reliable basis for crediting Dr. Corbier’s first
       theory that people with an SCN1A mutation are vulnerable to
       developing an adverse reaction to the DTaP vaccine. Similarly,
       there is no reliable basis for crediting Dr. Corbier’s second
       theory that vaccines worsen Dravet syndrome by bringing about
       seizures before they would have occurred otherwise. Although
       there may be an earlier manifestation, Dr. Corbier has not
       demonstrated how it affects the child’s outcome. Dr. Raymond
       and Dr. Wiznitzer rested their opinion on Berkovic, McIntosh,
       and Brunklaus. Dr. Corbier, on the other hand, had no support
       for his opinions that the vaccines change the outcome. These
       studies showed that children with SCN1A mutations have
       consistent symptoms, regardless of whether the initial seizure
       followed a [vaccine].

Id. at *17 (citations omitted). Without a medical theory causally connecting
the significant aggravation of Matthew’s condition to the vaccine, the Special
Master concluded that petitioner had not carried her burden. On the other
hand, the Special Master found that respondent had proved by a preponderance
of the evidence that a factor unrelated, Matthew’s SCN1A mutation, was the
sole cause of his present condition. The Special Master considered the age at
which the body switches from reliance on the Nav1.3 channel to the Nav1.1
channel and found that it was consistent with Matthew’s onset.

        The Special Master also held that petitioner had not established that, but
for the vaccine, Matthew’s outcome would not be as severe. According to the
Special Master, Dr. Corbier was unable to provide any meaningful information
about how Matthew’s present condition was different than a typical
presentation of Dravet syndrome. Instead, the Special Master found
respondent’s expert testimony that vaccination does not affect Dravet
syndrome to be more persuasive.

        Although the aforementioned rationales were sufficient for denying
compensation, the Special Master went on to evaluate whether petitioner had
established the severity requirement. All of the experts agreed that the vaccine
caused Matthew’s fever, which triggered the initial seizure. The Special
Master noted, however, that following this initial episode Matthew’s tests
results were normal and upon discharge from the hospital, Matthew was in
good condition. According to the Special Master, the effects of this initial
fever and isolated seizure did not continue for more than six months. Instead,

                                       14
the disease that Matthew continues to experience was caused by his genetic
mutation.

       II.    On Review

        As we suggested earlier, the Loving analysis may not be an ideal fit in
dealing with a child who has a genetic mutation that is asymptomatic prior to
vaccination. It is not entirely clear from the Special Master’s analysis what
conclusions he came to with respect to the first three Loving factors: “(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), [and] (3) whether the person’s current condition constitutes a
‘significant aggravation’ of the person’s condition prior to vaccination.” 86
Fed. Cl. at 144. Dealing with the fourth factor whether petitioner has proved
a causal connection between the aggravation and the vaccination would seem
to assume that petitioner has established an after condition that is a significant
aggravation of the before condition. Although the outcome in this case is the
same, we are not persuaded that petitioner has proved that Matthew’s current
condition is a significant aggravation of his prior condition, if that prior
condition assumes a genetic anomaly which will manifest in Dravet syndrome.

       We sympathize with the challenge to the parties and Special Master in
dealing with the present tragic circumstances. For her part, petitioner
concedes, as she must, that in his condition before vaccination, Matthew had
a genetic defect, although he appeared asymptomatic at the time. The Special
Master concluded, based on sound medical evidence, that this fact meant that
Matthew would develop Dravet syndrome.

       Respondent, for its part, concedes that before the vaccine Matthew did
not have seizures, but that after the vaccination, he quickly developed a fever
and a seizure which can be causally linked to the vaccination. It is also
undisputed that Matthew continued to have seizures. From this, petitioner
asserts that Matthew’s preexisting genetic condition was significantly
aggravated because he experienced a change for the worse on March 26, 2005,
when Matthew “change[d] from a child who did not have seizures to a child
who has frequent seizures.” Mot. for Review at 7.

       Characterizing Matthew’s condition before and after as petitioner
proposes would appear to suggest a significant aggravation. The problem for
petitioner, however, is that implicit in Matthew’s before condition is the
genetic anomaly which, as a practical matter, undisputedly will lead to

                                       15
continuing seizures. The subsequent seizures and development of Dravet
syndrome, given the findings on the lack of connection to the vaccination,
cannot be attributed to the vaccine. In sum, if we view the significant
aggravation as the ongoing seizures, Matthew’s condition prior to vaccination
included the genetic abnormality and the inevitable Dravet syndrome. There
is thus no significant aggravation and no causal connection.10

        If we view the initial fever and seizure as the aggravation, there is a
causal connection but no significance to the aggravation. The seizure was
short-lived. Matthew had recovered from this episode within a few days, and
the injury is thus not severe under § 300aa-11(c)(1)(D)(i). The causal
connection between the vaccination and the initial fever, in other words, is
insufficient to establish liability.

       Petitioner’s best hope for establishing liability was to attempt to prove
that Matthew’s before condition was that of a child who would ultimately
develop seizures, but who, after the vaccination, is a child whose seizures and
developmental delay are more severe because of the vaccine. We have
reviewed the Special Master’s careful analysis of the evidence about this
connection and find no basis for overturning his finding that petitioner did not
demonstrate a causal connection between the vaccine and a heightened
severity of symptoms. He found Drs. Wiznitzer and Raymond’s evidence
more persuasive than that of Dr. Corbier. We find no basis for overturning his
analysis.

       Petitioner also argues that the Special Master elevated her burden of
proof by requiring her to establish that the vaccine affected Matthew’s ultimate
outcome. Petitioner is correct that it is not her burden to prove what
Matthew’s ultimate prognosis would have been, but for the vaccination.
Indeed, even if the ultimate prognosis were the same with and without the

       10
         There have been numerous prior determinations that the SCN1A
mutation was the sole cause of the child’s Dravet syndrome. See, e.g.,
Stone/Hammitt v. Sec’y of Health & Human Servs., 676 F.3d 1373 (Fed. Cir.
2012), reh’g en banc denied 690 F.3d 1380, cert. denied sub nom. Stone v.
Sebelius, 133 S.Ct. 2022 (Apr. 29, 2013); Deribeaux v. Sec’y of Health &
Human Servs., 717 F.3d 1363 (Fed. Cir. 2013); Snyder/Harris v. Sec’y of
Health & Human Servs., 553 Fed. App’x 994 (Fed. Cir. 2014); Barnette v.
Sec’y of Health & Human Servs., 110 Fed. Cl. 34 (2013).

                                      16
vaccination, there would still be room, presumably, to argue that for at least six
months the child’s condition was significantly worse than it would have been
without the vaccination. We view the Special Master’s statements concerning
ultimate outcome, however, in the context of respondent’s theory of alternative
causation. In the circumstances of this case, the “ultimate” outcome and the
significant aggravation petitioner attempted to prove were one and the same
and neither can be attributed to the vaccination.

                               CONCLUSION

        Because the Special Master’s decision was in accordance with the law,
and was not otherwise arbitrary or capricious, we affirm. For the reasons set
forth above, we deny petitioner’s motion for review. The clerk is directed to
enter judgment accordingly. No costs.

                                            s/Eric G. Bruggink
                                            ERIC G. BRUGGINK
                                            Judge

                                       17