Ginn v. Secretary of Health and Human Services ( 2021 )

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
Filed: March 26, 2021
* * * * * * * * * * * * * * *
STACY GINN and JENNIFER GINN, * PUBLISHED
Parents of R.G., a minor, *
* No. 16-1466V
Petitioners, *
* Special Master Nora Beth Dorsey
v. *
* Entitlement; Diphtheria-Tetanus-Acellular-
SECRETARY OF HEALTH * Pertussis (“DTaP”) Vaccine; Inactivated
AND HUMAN SERVICES, * Polio (“IPV”) Vaccine; Haemophilus
* Influenzae Type B (“Hib”) Vaccine;
Respondent. * Measles-Mumps-Rubella (“MMR”)
* Vaccine; Influenza (“Flu”) Vaccine;
* * * * * * * * * * * * * * * Febrile Seizures; Epilepsy.
Ronald C. Homer, Conway, Homer, P.C., Boston, MA, for petitioners.
Terrence K. Mangan, U.S. Department of Justice, Washington, DC, for respondent.
RULING ON ENTITLEMENT1
I. INTRODUCTION
On November 7, 2016, Stacy Ginn and Jennifer Ginn (“petitioners”), on behalf of their
minor child, R.G., filed a petition under the National Vaccine Injury Compensation Program
(“Vaccine Act” or “the Program”), 42 U.S.C. § 300aa-10 et seq. (2012).2 Petitioners alleged that
as a result of receiving a diphtheria-tetanus-acellular-pertussis (“DTaP”), inactivated polio
(“IPV”), haemophilus influenzae type b (“Hib”), measles-mumps-rubella (“MMR”), and
1
Because this Ruling contains a reasoned explanation for the action in this case, the undersigned
is required to post it on the United States Court of Federal Claims’ website in accordance with
the E-Government Act of 2002. 44 U.S.C. § 3501 note (2012) (Federal Management and
Promotion of Electronic Government Services). This means the Ruling will be available to
anyone with access to the Internet. In accordance with Vaccine Rule 18(b), petitioners have
14 days to identify and move to redact medical or other information, the disclosure of which
would constitute an unwarranted invasion of privacy. If, upon review, the undersigned agrees
that the identified material fits within this definition, the undersigned will redact such material
from public access.
2
The National Vaccine Injury Compensation Program is set forth in Part 2 of the National
Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended,
42 U.S.C. §§ 300aa-10 to -34 (2012). All citations in this Ruling to individual sections of the
Vaccine Act are to 42 U.S.C. § 300aa.
influenza (“flu”) vaccines on November 15, 2013, R.G. suffered a neurological injury,
specifically epilepsy. Petition at 1 (ECF No. 1). Respondent argued against compensation,
stating that “petitioners have not provided preponderant evidence in support of their petition.”
Respondent’s Report (“Resp. Rept.”), filed May 24, 2017, at 7 (ECF No. 19).
After carefully analyzing and weighing the evidence presented in this case in accordance
with the applicable legal standards, the undersigned finds that petitioners have provided
preponderant evidence that the vaccines that R.G. received on November 15, 2013, triggered a
febrile seizure which caused or contributed to the development of a seizure disorder and
epilepsy, which satisfies their burden of proof under Althen v. Secretary of Health and Human
Services, 418 F.3d 1274, 1280 (Fed. Cir. 2005). Accordingly, petitioners are entitled to
compensation.
II. BACKGROUND
A. Summary of Relevant Facts
The facts have been covered in the parties’ pre- and post-hearing submissions and the
expert reports, and will not be repeated here in detail.3 A very brief chronology is helpful for
context.
R.G. was born on November 11, 2009, and was healthy prior to the vaccinations at issue.
At his four-year-old well child visit on November 15, 2013, he received MMR, DTaP, IPV, Hib,
and flu vaccinations. Petitioners’ Exhibit (“Pet. Ex.”) 1 at 1. Later that night R.G.’s parents
heard a strange noise and found R.G. shaking, unresponsive, and not breathing. Pet. Ex. 10 at 2.
His lips were blue. Id. They called 911, and R.G. was transported by ambulance to the hospital.
Id. He was seen by a physician in the emergency department (“ED”) who noted that R.G. likely
had a febrile seizure. Pet. Ex. 7 at 5. The ED physician noted that R.G. had received
vaccinations less than 24 hours before the seizure. Id. at 4-5.
On January 23, 2014, R.G. had a second seizure. Pet. Ex. 7 at 23. Again, he was seen in
the ED, where the physician noted that he had a seizure two months before, thought to be related
to fever and/or vaccinations. Id. R.G. was referred for an electroencephalogram (“EEG”). Id. at
24.
R.G. had the EEG on January 29, 2014. Pet. Ex. 5 at 389. The EEG was abnormal. Id.
It showed an “independent foci of spike activity in the right parieto posterior temporal occipital
and left occipital regions.” Id. The findings “indicate[d] the presence of a focal potentially
epileptogenic process in these regions.” Id. at 389-90.
Subsequently, on February 25, 2014, R.G. saw pediatric neurologist, Dr. Wilfred Castro-
Reyes, who noted that R.G.’s first seizure occurred in November with fever after receiving
3
See Petitioners’ (“Pet.”) Pre-Hearing Brief (“Br.”), filed July 21, 2020 (ECF No. 81); Resp.
Pre-Hearing Br., filed Aug. 20, 2020 (ECF No. 100); Pet. Post-Hearing Br., filed Nov. 30, 2020
(ECF No. 106); Resp. Post-Hearing Br., filed Jan. 4, 2021 (ECF No. 111).
2
vaccinations. Pet. Ex. 5 at 418. Dr. Castro-Reyes diagnosed R.G. with “[e]pilepsy with an
abnormal EEG that showed multifocal spikes.” Id. at 419. She prescribed anticonvulsant
therapy, Trileptal. Id.
Since then, R.G. has had more seizures and he continues to see his neurologist every six
months and remains on medication for treatment of his epilepsy. See generally Pet. Ex. 5. His
current neurologist, Dr. Garrett Burris, has opined that R.G. will require medication and
neurological follow-up until the age of twenty-two. Id.
B. Febrile Seizures and Epilepsy
Febrile seizures occur in 2-5% of children under the age of five. Resp. Ex. E at 3.4 A
febrile seizure is defined as “an epileptic seizure . . . occurring in childhood after age 1 month,
associated with a febrile illness not caused by an infection of the [central nervous system].”
Resp. Ex. D at 3.5 “In the past, it was believed that most febrile seizures represented a form of
epilepsy and that the prognosis was not favorable,” but over the last several decades, and with
the benefit of more research and data, “[t]he prognosis for febrile seizures usually has been found
to be good.” Resp. Ex. E at 3.
There are two types of febrile seizures: simple and complex. Resp. Ex. E at 3. A febrile
seizure is complex, “if it is focal, prolonged (lasting more than either 10 . . . or 15 minutes), or
multiple.” Id. Most febrile seizures are simple, and only approximately 20-30% are complex.
Id. A complex seizure is defined as a focal seizure, one or more seizures occurring within 24
hours, or a seizure lasting longer than 15 minutes. Transcript (“Tr.”) 72. The causes of febrile
seizures are multifactorial and include inflammation, brain pH, and genetic factors. See
generally Resp. Ex. M.6
Epilepsy is defined as two or more seizures, “unprovoked by any immediate identified
case.” Resp. Ex. D at 3. Evidence shows febrile seizures are associated with an increased risk of
subsequent epilepsy, and that epilepsy develops in 2-4% of children with a history of febrile
seizures. Resp. Ex. F at 2.7 The risk for development of epilepsy after a simple febrile seizure is
two times higher than the general population, and for a complex febrile seizure, the risk is
higher. Tr. 22. If a “febrile seizure is focal, that makes it complex. And the risk of subsequent
epilepsy is higher. It’s 5 to 10 percent.” Tr. 123.
4
Shlomo Shinnar, Febrile Seizures, in 1 Swaiman’s Pediatric Neurology: Principles and
Practice, 790 (Kenneth F. Swaiman et al. eds., 5th ed. 2018).
5
Comm’n on Epidemiology & Prognosis, Int’l League Against Epilepsy, Guidelines for
Epidemiologic Studies on Epilepsy, 34 Epilepsia 592 (1993).
6
S. Gatti et al., Mechanisms of Fever and Febrile Seizures: Putative Role of the Interleukin-1
System, in Febrile Seizures, 169 (Tallie Z. Baram & Shlomo Shinnar eds., 2002).
7
Anne T. Berg et al., A Prospective Study of Recurrent Febrile Seizures, 327 New Eng. J. Med.
1122 (1992).
3
“There seems to be a consensus that seizures affect brain function.” Pet. Ex. 13, Tab HH
at 7.8 “The vulnerability of the brain to seizure-induced injury is age-specific . . . . Experimental
studies show that immature brains are highly prone to develop seizures . . . but are more resistant
to seizure . . . induced damage than adult brains.” Id. at 8. Recent animal data suggest that
seizures “may produce age-specific changes that are not confined to cell loss.” Id. “Structural,
functional, and neurochemical changes have been reported after brief and prolonged seizures in
human beings. However, the significance of these changes is unclear.” Id.Epileptogenesis “refers to [the] process in which an initial brain damaging insult triggers
a cascade of molecular and cellular changes that eventually lead to the occurrence of
spontaneous seizures.” Pet. Ex. 13, Tab TT at 1.9 In other words, “epileptogenesis is a process
determined by conversion of the healthy brain into the epileptic brain. In epileptic seizure
development . . . abnormal and excessive electronic discharges” occur. Pet. Ex. 13, Tab E at 3.10
The immune system is suggested to play a role in seizure development. Id.C. Experts Qualifications
Both experts are well qualified to opine on the causation issues presented by the facts and
circumstances presented in this case.
1. Petitioners – Dr. Mahbubul Huq
Dr. Huq is a clinical geneticist and a board certified pediatric neurologist at Children’s
Hospital of Michigan. Pet. Ex. 13 at 1. He completed pediatrics and neurology residencies at
Wayne State University, as well as clinical and postdoctoral fellowships in genetics at Baylor
College of Medicine and the University of British Columbia. Pet. Ex. 14 at 1. Dr. Huq is a
Professor of Pediatrics and Neurology at Wayne State University in the “Clinician Educator
track.” Pet. Ex. 13 at 1. He has an active clinical practice and has authored or co-authored over
75 publications including published peer reviewed articles on the genetics of epilepsy and
neurodevelopmental disorders. Id.; Pet. Ex. 14 at 14-21.
2. Respondent – Dr. Shlomo Shinnar
Dr. Shinnar is board certified in Pediatrics and Neurology with an added Qualification in
Epilepsy. Resp. Ex. A at 2. He completed residencies in Pediatrics and Neurology at Johns
Hopkins Hospital. Id. Dr. Shinnar is a Professor of Neurology, Pediatrics and Epidemiology,
8
Sheryl R. Haut et al., Susceptibility of Immature and Adult Brains to Seizure Effects, 3 Lancet
Neurology 608 (2004).
9
Asla Pitkanen A & Katarzyna Lukasiuk, Molecular and Cellular Basis of Epileptogenesis in
Symptomatic Epilepsy, 14 Epilepsy & Behavior 16 (2009).
Feyza Alyu & Miriş Dikmen, Inflammatory Aspects of Epileptogenesis: Contribution of
10
Molecular Inflammatory Mechanisms, 29 Acta Neuropsychiatrica 1 (2017).
4
and Population Health, and the Hyman Climenko Professor of Neuroscience Research and the
Director of the Comprehensive Epilepsy Management Center at Montefiore Medical Center and
the Albert Einstein College of Medicine. Resp. Ex. A at 2. He has authored or co-authored more
than 200 publications, a majority which relate to seizure disorders. Id.III. DISCUSSION
A. Standards for Adjudication
The Vaccine Act was established to compensate vaccine-related injuries and deaths. §
10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as
a simple, fair and expeditious means for compensating vaccine-related injured persons. The
Program was established to award ‘vaccine-injured persons quickly, easily, and with certainty
and generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996) (quoting
H.R. Rep. No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).
Petitioners burden of proof is by a preponderance of the evidence. § 13(a)(1). The
preponderance standard requires petitioners to demonstrate that it is more likely than not that the
vaccine at issue caused the injury. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315,
1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health
& Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In particular, petitioners must prove that the
vaccine was “not only [the] but-for cause of the injury but also a substantial factor in bringing
about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Hum.
Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)); see also Pafford v. Sec’y of Health & Hum.
Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). A petitioner who satisfies this burden is entitled to
compensation unless respondent can prove, by a preponderance of the evidence, that the
vaccinee’s injury is “due to factors unrelated to the administration of the vaccine.” §
13(a)(1)(B).
B. Causation
To receive compensation through the Program, petitioners must prove either (1) that R.G.
suffered a “Table Injury”—i.e., an injury listed on the Vaccine Injury Table—corresponding to a
vaccine that he received, or (2) that R.G. suffered an injury that was actually caused by a
vaccination. See §§ 13(a)(1)(A), 11(c)(1); Capizzano v. Sec’y of Health & Hum. Servs., 440
F.3d 1317, 1319-20 (Fed. Cir. 2006). Because petitioners do not allege that R.G. suffered a
Table Injury, they must prove that the vaccinations R.G. received caused his injury. To do so,
they must establish, by preponderant evidence: (1) a medical theory causally connecting the
vaccines and R.G.’s injury (“Althen Prong One”); (2) a logical sequence of cause and effect
showing that the vaccines were the reason for R.G.’s injury (“Althen Prong Two”); and (3) a
showing of a proximate temporal relationship between the vaccine and R.G.’s injury (“Althen
Prong Three”). § 13(a)(1); Althen, 418 F.3d at 1278.
The causation theory must relate to the injury alleged. Petitioners must provide a sound
and reliable medical or scientific explanation that pertains specifically to this case, although the
explanation need only be “legally probable, not medically or scientifically certain.” Boatmon v.
5
Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019); see also Knudsen v.
Sec’y of Health & Hum Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994). Petitioners cannot
establish entitlement to compensation based solely on their assertions; rather, a vaccine claim
must be supported either by medical records or by the opinion of a medical doctor. § 13(a)(1).
In determining whether petitioners are entitled to compensation, the special master shall consider
all material in the record, including “any . . . conclusion, [or] medical judgment . . . which is
contained in the record regarding . . . causation.” § 13(b)(1)(A). The undersigned must weigh
the submitted evidence and the testimony of the parties’ proffered experts and rule in petitioners’
favor when the evidence weighs in their favor. See Moberly, 592 F.3d at 1325-26 (“Finders of
fact are entitled—indeed, expected—to make determinations as to the reliability of the evidence
presented to them and, if appropriate, as to the credibility of the persons presenting that
evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are resolved in petitioners’
favor).
C. Diagnosis
As Federal Circuit precedent establishes, in certain cases it is appropriate to determine the
nature of an injury before engaging in the Althen analysis. Broekelschen v. Sec’y of Health &
Hum. Servs., 618 F.3d 1339, 1346 (Fed. Cir. 2010). Since “each prong of the Althen test is
decided relative to the injury[,]” determining facts relating to the claimed injury can be
significant in a case like this, where R.G. has an evolving course of symptoms, resulting in a
diagnosis of epilepsy. Id. Thus, before determining if petitioners have met each prong of
Althen, the undersigned addresses whether they have established, by a preponderance of the
evidence, that R.G. suffered from epilepsy.
Prior to the hearing, there was a question as to whether R.G. had epilepsy. Petitioners’
expert, Dr. Huq, opined that R.G. did have epilepsy; however, respondent’s expert, Dr. Shinnar,
did not agree. Instead, Dr. Shinnar opined that R.G. had a mild seizure disorder. At the hearing
however, after Dr. Shinnar had the opportunity to review R.G.’s medical records from August
10, 2018, he agreed that R.G. does have epilepsy. Tr. 101. Dr. Shinnar changed his opinion
based on the August 2018 records that showed that R.G. had an unprovoked seizure.
However, Dr. Shinnar disagreed that R.G.’s diagnosis of epilepsy was appropriate before
2018. He disagreed with the diagnosis of epilepsy made by R.G.’s treating physician, Dr.
Castro-Reyes. Tr. 106. Specifically, Dr. Shinnar disagreed with Dr. Castro-Reyes’ diagnosis of
epilepsy on February 24, 2014, based on R.G.’s clinical course and his initial EEG done January
29, 2014. Id.; see Pet. Ex. 5 at 416-19.
A treating physician’s opinions are considered “quite probative,” and are entitled to some
weight. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1326 (Fed. Cir. 2009);
Capizzano, 440 F.3d at 1326 (“[M]edical records and medical opinion testimony are favored in
vaccine cases, as treating physicians are likely to be in the best position to determine whether a
‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury.’”
(quoting Althen, 418 F.3d at 1280)). Medical records are generally viewed as trustworthy
evidence since they are created contemporaneously with the treatment of the vaccinee. Cucuras
v. Sec’y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).
6
The undersigned defers to the diagnosis of R.G.’s treating physician, Dr. Castro-Reyes,
and finds that Dr. Castro-Reyes’ diagnosis of epilepsy was appropriate and correct at the time
that she made the diagnosis on February 24, 2014.
D. Causation Analysis
The petitioners assert that the vaccinations R.G. received on November 15, 2013,
caused a febrile seizure which triggered the process by which he developed epilepsy. Both Dr.
Huq and Dr. Shinnar agree that the vaccinations R.G. received on November 15, 2013, likely
caused his initial seizure. Tr. 85, 120. They disagree, however, as to whether that initial
seizure caused or contributed to the development of his epilepsy. Dr. Shinnar testified that
whether a febrile seizure is the “starting point” of epilepsy is a much debated issue. Tr. 114.
However, he does agree that in rare cases, patients with febrile seizures can develop epilepsy.
Tr. 115.
1. Althen Prong One
Under Althen Prong One, petitioners must set forth a medical theory explaining how the
received vaccine could have caused the sustained injury. Andreu, 569 F.3d at 1375; Pafford, 451
F.3d at 1355-56. Petitioners’ theory of causation need not be medically or scientifically certain,
but it must be informed by a “sound and reliable medical or scientific explanation.” Knudsen, 35
F.3d at 548; Boatmon, 941 F.3d at 1359; see also Veryzer v. Sec’y of Health & Hum. Servs., 98
Fed. Cl. 214, 223 (2011) (noting that special masters are bound by both § 13(b)(1) and Vaccine
Rule 8(b)(1) to consider only evidence that is both “relevant” and “reliable”). If petitioners rely
upon a medical opinion to support their theory, the basis for the opinion and the reliability of that
basis must be considered in the determination of how much weight to afford the offered opinion.
See Broekelschen, 618 F.3d at 1347 (“The special master’s decision often times is based on the
credibility of the experts and the relative persuasiveness of their competing theories.”); Perreira
v. Sec’y of Health & Hum. Servs., 33 F.3d 1375, 1377 n.6 (Fed. Cir. 1994) (stating that an
“expert opinion is no better than the soundness of the reasons supporting it” (citing Fehrs v.
United States, 620 F.2d 255, 265 (Ct. Cl. 1980))).
From a chapter authored by Dr. Shinnar, he quotes data showing that in “children with
febrile seizures[,] . . . epilepsy subsequently develops in 2-10 percent.” Resp. Ex. E at 6. There
is a “slightly but statistically significant increased risk of subsequent epilepsy” after febrile
seizures. Id. at 7. This risk is increased to 5-10% where the febrile seizure is a complex or focal
seizure. Tr. 123.
Dr. Huq explained the mechanism by which epilepsy is thought to occur following an
initial vaccine-induced febrile seizure. See Pet. Ex. 13 at 5-9. Pro-inflammatory cytokines are
produced in response to vaccinations. Id. at 5. These cytokines lead to an inflammatory state in
the brain, which causes enhanced neuronal excitability and contributes to a disruption of the
blood brain barrier. Id. Some of the pro-inflammatory cytokines are involved in the
“precipitation of seizures,” while others are implicated in the process by which the brain
becomes predisposed to recurrent seizures. Id. at 2. While the exact cause of epilepsy is not
7
clear, genetic factors are also thought to be at play. Pet. Ex. 15 at 1. “A genetic predisposition to
develop sustained inflammatory reactions” has been suggested in children with febrile seizures.
Id. at 2. It is thought that genetic factors play a role in decreasing the seizure threshold by either
activating excitatory pathways or by disturbing inhibitory systems. See Resp. Ex. J at 2.11
“[B]rain inflammation is associated with the breakdown in the [blood brain barrier], and [blood
brain barrier] leakages ha[ve] been implicated both in the induction of seizures and in the
progression to epilepsy.” Pet. Ex. 13 at 6. A seizure can cause blood brain barrier (“BBB”)
leakage. See Tr. 52-53, 75-77.
Dr. Shinnar explained the mechanism of the development of epilepsy in a manner similar
to Dr. Huq. Dr. Shinnar agreed that pro-inflammatory cytokines are produced in response to
vaccination and that the cytokine profile IL-beta affects neuronal excitability. Tr. 108. He also
agreed that brain inflammatory processes contribute to a decrease in the seizure threshold. Tr.
109.
The central question for Dr. Shinnar is whether febrile seizures cause or contribute to the
development of epilepsy or whether they are simply markers for epilepsy. Tr. 111-12.
According to Dr. Shinnar, only prolonged seizures can initiate or contribute to the development
of epilepsy. Tr. 110-11. The undersigned finds that based on the opinions of Dr. Huq, along
with the medical literature filed by both parties, in rare cases, a brief febrile seizure triggered by
vaccinations can be the starting point for the development of epilepsy.
For example, in the Doose article, the authors state that, in rare cases, febrile seizures
form the starting point of epilepsy by activation of excitatory pathways or disturbance of
inhibitory systems. Resp. Ex. J at 7. Other factors, such as genetics, may also play a role. See
Tr. 45, 114. In the Pitkanen article, the authors explain that “[i]n animals, it has been shown that
even brief induced or spontaneous seizures, in addition to [status epilepticus], can trigger
neurogenesis.” Pet. Ex. 13, Tab TT at 3. And in the Virta article, the authors opine that
“[c]hildren with febrile seizures may therefore have an increased pro-inflammatory reaction
during fever,” which “may predispose some children to the development of epilepsy.” Pet. Ex.
13, Tab LLL at 1.12
11
H. Doose et al., EEG Longitudinal Studies in Febrile Convulsions, 14 Neuropediatrics 81
(1982).
12
Miia Virtua et al., Increased Frequency of Interleukin-1Beta (-511) Allele 2 in Febrile
Seizures, 26 Pediatric Neurology 192 (2002).
8
The mechanism is illustrated below:
Pet. Ex. 13, Tab JJJ at 2 fig.1.13 In the schematic illustration above, Vezzani and her co-authors
defined the phrase “inciting event” as an event with “epileptogenic properties.” Id. Examples of
inciting events were listed and specifically included “febrile seizures.” Id.During the hearing there was discussion about whether a brief febrile seizure could
disrupt the BBB and contribute to the development of epilepsy. Van Vliet et al. describe that in
an animal model, “it has been shown that a single bicuculline-induced14 seizure is sufficient to
compromise the BBB.” Pet. Ex. 13, Tab FFF at 6.15 In another article by Van Vliet et al., the
authors opine that there is “ample evidence from experimental animal studies that BBB
dysfunction can be caused by seizure activity . . . [and] that BBB disruption can also lead to
epilepsy.” Pet. Ex. 13, Tab GGG at 1.16 They were able to show that a “long lasting increase in
BBB permeability [occurred] after a single seizure.” Id. at 2. Further, they state that although
BBB leakage gradually decreases, it can persist even weeks or months after the initial insult. Id.
at 4.
13
Annamaria Vezzani et al., The Role of Inflammation in Epileptogenesis, 69
Neuropharmacology 16 (2013).
14
Bicuculline is a neurotoxin that is a convulsant. Bicuculline, Dorland’s Med. Dictionary
Online, https://www.dorlandsonline.com/dorland/definition?id=6028&searchterm=bicuculline
(last visited Mar. 15, 2021).
15
E.A. Van Vliet et al., Role of Blood-Brain Barrier in Temporal Lobe Epilepsy and
Pharmacoresistance, 277 Neuroscience 455 (2014).
16
E.A. Van Vliet et al., Blood-Brain Barrier Dysfunction, Seizures and Epilepsy, 38 Seminars
Cell & Developmental Biology 26 (2015).
9
These articles support Dr. Huq’s theory of why and how a febrile seizure caused by
vaccinations can cause changes in the brain that contribute to the development of epilepsy.
Accordingly, the undersigned finds that petitioners have set forth a sound and reliable medical
theory, satisfying Althen Prong One.
2. Althen Prong Two
Under Althen Prong Two, petitioners must prove by a preponderance of the evidence that
there is a “logical sequence of cause and effect showing that the vaccination was the reason for
the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). “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.’” Pafford, 451 F.3d at 1356 (internal citations omitted).
The petitioners need not make a specific type of evidentiary showing, i.e., “epidemiologic
studies, rechallenge, the presence of pathological markers or genetic predisposition, or general
acceptance in the scientific or medical communities to establish a logical sequence of cause and
effect.” Capizzano, 440 F.3d at 1325. Instead, petitioners may satisfy their burden by presenting
circumstantial evidence and reliable medical opinions. Id. at 1325-26.
Here, both experts agree that the vaccinations likely caused R.G.’s initial seizure. The
undersigned has found that petitioners presented a sound and reliable theory as to how, in rare
cases, a febrile seizure can trigger changes in the brain that can lead to epilepsy. Here, the
undersigned extends that finding to R.G., and holds that R.G.’s vaccinations caused his initial
febrile seizure which caused or contributed to changes in the brain that caused his epilepsy.
R.G. had his first seizure on November 15, 2013, within 24 hours of his vaccinations.
Pro-inflammatory cytokines were released after these vaccinations, causing fever, and the initial
seizure. Of note, R.G. received the flu vaccine in addition to the nine childhood vaccines he was
scheduled to receive. R.G. had his next seizure nine weeks later. After the second seizure, his
EEG was abnormal and consistent with epilepsy. R.G. was diagnosed with epilepsy and put on
anticonvulsants. This chronology suggests that R.G. had changes in the brain after his initial
seizure, which caused or contributed to his second seizure, as well as the abnormalities seen on
his initial EEG. Specifically, the EEG showed a focal epileptogenic process in the “right parieto
posterior temporal occipital and left occipital regions.” Pet. Ex. 5 at 389-90. As described by
Dr. Huq, the time frame from seizure onset to the diagnosis of epilepsy was just over two
months. This clinical course is consistent with the effect of the pro-inflammatory cytokines
released after vaccination, affecting neuronal excitability, and creating changes in the brain that
caused epilepsy. The fact that R.G. received the flu vaccine along with the other vaccines
increased the risk of his initial febrile seizure. Tr. 30-32.
Dr. Shinnar agreed that R.G.’s initial seizure “may well have been related” to the
vaccines administered to him on November 15, 2013. Tr. 84. However, Dr. Shinnar
characterized it as a “benign febrile seizure.” Tr. 85. While the literature states that most febrile
seizures are benign, it is also clear that not all febrile seizures are harmless.
10
Dr. Shinnar agreed that fever after vaccination is caused by cytokines. In particular, Il-
1beta is responsible for producing fever. It is also known to be a pro-convulsive that lowers
seizure threshold. Tr. 88-89. The cytokine profile is what leads to a seizure. With fever, the
profile is primarily IL-1beta cytokine. Tr. 90-91. Cytokines stay in the system after seizure. Dr.
Shinnar explained that after prolonged febrile seizures, a sequence of events involving cytokines,
which cause chronic inflammation, can contribute to the development of epilepsy.17 Tr. 91-92.
Dr. Shinnar does not believe these changes can occur after a brief febrile seizure. Instead, he
argued that they only occur after prolonged seizures or status epilepticus. However, as briefly
discussed above, relative to Althen Prong One, medical literature specifically identifies febrile
seizures as potential triggers for epilepsy. These articles support Dr. Huq’s position that in rare
cases, a febrile seizure can lead to changes in the brain, as happened here.
The second reason for the undersigned’s finding as to Prong Two, is that R.G.’s initial
seizure had characteristics of a complex seizure, which increased his risk of developing epilepsy.
Dr. Huq explained that the “initial seizure was characterized by unusual vocalization, stiffening
of the trunk and extremities, slow breathing, cyanosis, and unresponsiveness.” Pet. Ex. 15 at 1;
see also Tr. 13. Dr. Huq testified that based on the fact that R.G.’s subsequent seizure was
similar in character to the initial one, and the fact that his EEG showed focal abnormalities, it is
more likely than not that R.G.’s initial vaccine related seizure was also a focal (complex) seizure.
Tr. 73. This increased the risk that R.G. would develop epilepsy. Tr. 74.
Dr. Shinnar testified that there was no way to know whether R.G.’s initial seizure was
focal, and thus, complex. Tr. 129. Even if R.G.’s first seizure was focal, that did not change Dr.
Shinnar’s opinion as to causation. Tr. 133. However, Dr. Shinnar agreed with Dr. Huq that a
focal seizure increases the risk of epilepsy. Id. Thus, there is evidence that R.G.’s initial vaccine
related seizure was focal and thus complex, and as such, his risk of epilepsy was higher.
The third reason for the undersigned’s finding as to Prong Two, is that there was no
alternative cause identified for R.G.’s epilepsy. As explained by Dr. Huq:
The pregnancy and delivery were uncomplicated. [R.G.] did not have any trauma
or any genetic syndromes or past medical problems that would predispose him to
develop epilepsy. Family history was negative on both paternal and maternal
sides with regards to epilepsy or any neurodevelopmental disorders. His brain
MRI did not show any developmental anomaly, cortical dysplasia or brain
malformation. Sodium channel mutation (SCN1A gene mutations) have been
identified in some individuals as a cause of epilepsy after vaccination. The
treating physicians of [R.G.] did not think SCN1A gene mutation as a likely cause
of [R.G.’s] epilepsy and chose not to perform the genetic testing for SCN1A.
Seizures associated with SCN1A mutations are aggravated by sodium channel
blockers like Trileptal (Wirrell, 2016). However, [R.G.’s] seizures were
17
Dr. Shinnar further opined, however, that the cytokines present at the time of a febrile seizure
would not be present nine weeks later. Tr. 91. He further stated that the cytokine IL-1beta was
not involved in chronic inflammation. Tr. 92.
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controlled with Trileptal which makes it unlikely that he has a SCN1A gene
mutation.
Pet. Ex. 13 at 9.
R.G. had had two MRI studies. The first one was done March 10, 2014. Pet. Ex. 5 at
348. The report mentioned a possible T2 flare change that could represent an artifact, however
Dr. Huq testified that he would have considered the study normal. Tr. 49. Dr. Shinnar testified
that it was possible that the MRI was abnormal, but his opinion did not rise to the level of more
likely than not. Tr. 95.
The second MRI was performed on May 28, 2019, and it was also interpreted as normal.
Tr. 49. Dr. Huq testified that it did not show cortical dysplasia, stroke, mass lesion, or vascular
lesions. He testified that these two normal MRIs ruled out a host of causes of epilepsy. Id. Dr.
Shinnar testified that if R.G.’s second MRI was normal, the cause of R.G.’s epilepsy was
unknown, which he opined was true for the majority of cases of epilepsy. Tr. 102. Therefore,
the diagnostic work-up and MRIs did not provide any evidence of an alternative cause.
The last reason for the undersigned’s finding is based on the appropriate temporal
association between R.G.’s vaccinations and his initial seizure, as well as the time frame from his
initial seizure to his diagnosis of epilepsy, discussed below.
For these reasons, the undersigned finds that petitioners, by preponderant evidence, have
shown that the vaccinations were the cause for R.G.’s initial seizure and epilepsy. Accordingly,
petitioners have satisfied Althen Prong Two.
3. Althen Prong Three
Althen Prong Three requires petitioners to establish a “proximate temporal relationship”
between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been
equated to mean a “medically acceptable temporal relationship.” Id. The petitioners must offer
“preponderant proof that the onset of symptoms occurred within a timeframe which, given the
medical understanding of the disease’s etiology, it is medically acceptable to infer causation-in-
fact.” De Bazan v. Sec’y of Health & Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The
explanation for what is a medically acceptable time frame must also coincide with the theory of
how the relevant vaccine can cause the injury alleged (under Althen Prong One). Id.; Koehn v.
Sec’y of Health & Hum. Servs., 773 F.3d 1239, 1243 (Fed. Cir. 2014); Shapiro v. Sec’y of
Health & Hum. Servs., 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand, 105 Fed. Cl.
353 (2012), aff’d mem., 503 F. App’x 952 (Fed. Cir. 2013).
Dr. Huq opined that for the DTaP and flu vaccinations, the onset of R.G.’s initial seizure
was appropriate. Tr. 50-51. Dr. Shinnar agreed that a seizure occurring within 24 hours of
vaccinations was a medical appropriate time frame to infer a causal relationship. Tr. 120.
Thus, there is expert agreement that there was a proximately temporal relationship between
R.G.’s vaccinations and his initial seizure.
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The next question is whether the time frame between R.G.’s initial seizure and the
development of his epilepsy was appropriate. Dr. Huq opined that R.G.’s initial seizure began
the process of epileptogenesis—the process by which R.G. developed epilepsy. Tr. 18. When
R.G. was seen by Dr. Castro-Reyes after his first EEG, she diagnosed him with epilepsy based
on his clinical course and abnormal EEG. Tr. 20. Dr. Huq testified that this time frame of nine
weeks was appropriate in terms of epileptogenesis. Tr. 51.
Dr. Huq cited the 2015 Van Vliet article to support his opinion. In that article, the
authors concluded that BBB leakage may continue for weeks to months after an initial insult
such as a seizure. Pet. Ex. 13, Tab GGG at 1. This sustained dysfunction of the BBB leads to
an altered micro-environment of neurons with increased excitability and lowered firing
threshold that contribute to the emergence of seizures. Tr. 52-53 (citing Pet. Ex. 13, Tab GGG
at 1.)
Further, the undersigned notes that R.G.’s treating neurologist routinely documented
that the onset of his seizure disorder was the date of his vaccinations and initial seizure,
November 15, 2013. See Tr. 118.
For the above reasons, the undersigned finds that petitioners have provided
preponderant evidence of a proximate temporal relationship between R.G.’s November 15,
2013 vaccinations and his initial seizure, as well as his epilepsy.
E. Alternative Causation
Because the undersigned concludes that petitioners have established a prima facie case,
petitioners are entitled to compensation unless respondent can put forth preponderant evidence
“that [R.G.’s ] injury was in fact caused by factors unrelated to the vaccine[s].” Whitecotton v.
Sec’y of Health & Hum. Servs., 17 F.3d 374 (Fed. Cir. 1994), rev’d on other grounds sub nom.,
Shalala v. Whitecotton, 514 U.S. 268 (1995); see also Walther v. Sec’y of Health & Hum. Servs.,
485 F.3d 1146, 1151 (Fed. Cir. 2007). As discussed above, respondent did not prove by a
preponderance of evidence that R.G.’s injury was “due to factors unrelated to the administration
of the vaccine[s].” § 13(a)(1)(B).
IV. CONCLUSION
For the reasons discussed above, the undersigned finds that petitioners have established
by preponderant evidence that they are entitled to compensation. A separate damages order will
issue.
IT IS SO ORDERED.
s/Nora Beth Dorsey
Nora Beth Dorsey
Special Master
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