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,

Petitioner,

v.

SECRETARY OF HEALTH AND

HUMAN SERVICES,

Respondent.

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

Vaccine case; petitioner’s

challenge to the Special

Master’s decision;

significant aggravation;

DTaP vaccine; Dravet

syndrome; SCN1A

mutation.

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 whomare, 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 Dravetsyndrome.

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 assertsthatDTaP vaccine significantly aggravatedMatthew’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 SpecialMaster concluded that

petitioner failed to establish a persuasive theory of causation, held that

respondent proved a defense, and denied petitioner’srequestfor 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, sodiumchannels 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-table7significant 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 offtable 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 drewsupport for his opinion fromscientific 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 postvaccination 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

sodiumions. When sodiumions 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 byBrunklaus,which tracked 355 SCN1Amutation-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, 

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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

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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).

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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

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