The opinion
In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
*********************
MICHAEL MAGER, as parent of *
VICTORIA MAGER, *
* No. 14-820V
* Special Master Christian J. Moran
Petitioner, *
*
v. * Filed: July 29, 2021
*
SECRETARY OF HEALTH * Entitlement; human papillomavirus
AND HUMAN SERVICES, * (“HPV”) vaccine; autoimmune
* epilepsy; sudden unexpected death in
Respondent. * epilepsy (“SUDEP”); diagnosis.
**********************
Renee J. Gentry, Vaccine Injury Clinic, George Washington University Law
School, Washington, DC, for petitioner;
Laurie Wiesner, United States Dep’t of Justice, Washington, DC, for respondent.
DECISION DENYING COMPENSATION1
Michael Mager alleges that the human papillomavirus (“HPV”) vaccine his
deceased daughter Victoria received on September 11, 2012, caused her to suffer
autoimmune epilepsy leading to sudden unexpected death in epilepsy. He seeks
compensation pursuant to the National Childhood Vaccine Injury Compensation
Program.
As detailed below, the undersigned finds that Mr. Mager is not entitled to
compensation because based on the evidence submitted, he has not met his burden
1
The E-Government Act, 44 U.S.C. § 3501 note (2012) (Federal Management and
Promotion of Electronic Government Services), requires that the Court post this decision on its
website. This posting will make the decision available to anyone with the internet. Pursuant to
Vaccine Rule 18(b), the parties have 14 days to file a motion proposing redaction of medical
information or other information described in 42 U.S.C. § 300aa-12(d)(4). Any redactions
ordered by the special master will appear in the document posted on the website.
to show that Victoria suffered from autoimmune epilepsy. Furthermore, because
this is a threshold issue for which the evidence and briefing already submitted is
sufficient to make a determination, a hearing is not required.
I. Procedural History
Represented by attorney Mark Krueger, Mr. Mager asserted that the HPV
vaccination Victoria received on October 2, 2007, caused her to suffer a seizure
disorder leading to her death on January 11, 2014. Pet., filed Sept. 5, 2014, at
Preamble, ¶ 12. Mr. Mager filed an amended petition on November 19, 2014. He
then gathered medical records, including those requested by the Secretary in
advance of the Rule 4(c) report, and the record was complete on February 17,
2015.
The Secretary filed his Rule 4(c) report on April 1, 2015, contesting
causation and arguing that Victoria’s seizure disorder existed pre-vaccination.
Resp’t’s Rep. at 8-11. Mr. Krueger withdrew from the case on May 18, 2016. Mr.
Mager submitted a fact witness affidavit on July 7, 2015. Ms. Renee Gentry was
substituted as counsel of record for Mr. Mager on August 3, 2016, after which the
case proceeded to the expert report stage. After multiple extensions, Mr. Mager
filed his first expert report from Dr. Mikovits and Dr. Ruscetti on November 17,
2016.2 The Secretary then filed responsive expert reports from Dr. Fujinami and
Dr. Kohrman on March 2, 2017, and March 22, 2017, followed by supplemental
expert reports from Mr. Mager on May 25, 2017; October 12, 2017; and October
27, 2017. The Secretary submitted supplemental expert reports on March 19,
2018, and Mr. Mager submitted his final supplemental expert reports on May 25,
2018.
In a status conference held on June 19, 2018, the undersigned discussed the
relative weaknesses of Mr. Mager’s expert reports and his attorney requested
additional time to retain a pediatric neurologist to better support his claim. Mr.
Mager then filed an expert report from Dr. Shafrir on October 3, 2018. In this
report, Dr. Shafrir raised the potential helpfulness of obtaining the slides from
Victoria Mager’s autopsy. While Mr. Mager began the process of attempting to
obtain the autopsy slides and the exchange of expert reports continued, the case
was referred to alternative dispute resolution (“ADR”) on January 30, 2019.
However, the parties failed to reach a settlement agreement and the case was
2
Because Mr. Mager eventually chose not to rely on the opinions of Dr. Mikovits or Dr.
Ruscetti, all submissions from these expert witnesses were later stricken from the record.
2
removed from ADR on March 25, 2019. Respondent then filed supplemental
expert reports on April 22, 2019.
Dr. Shafrir asserted a diagnosis of autoimmune epilepsy based, in part, on
what he deemed neurological reactions to the vaccine that suggested underlying
autoimmune encephalitis. Exhibit 55 at 18. Dr. Kohrman, however, maintained a
diagnosis of juvenile myoclonic epilepsy (“JME”), based on his view that Victoria
suffered pre-vaccination seizure activity, non-focal (i.e. generalized) seizures, and
a lack of evidence regarding an autoimmune process in Victoria’s autopsy. Exhibit
Y at 7. Dr. Fujinami agreed with the JME diagnosis, highlighting that Victoria’s
seizures were not treatment resistant, as would be true of seizure activity involved
in autoimmune epilepsy. Exhibit CC at 1-2. Dr. Shafrir and Dr. Kohrman both
have significant experience in neurology and pediatric neurology, exhibit 56;
exhibit B, though Dr. Kohrman has particularly strong experience regarding
epilepsy and pediatric epilepsy, including a current board certification with the
American Board of Psychiatry and Neurology with a subspecialty in epilepsy.
Exhibit B at 2. Dr. Fujinami has significant experience as an immunologist.
Exhibit J.
After trying for an extended period to obtain the autopsy slides, Mr. Mager
filed a status report on October 28, 2019, stating that a supplemental expert report
from Dr. Shafrir would not be necessary. The undersigned issued an order for
submissions in advance of potential adjudication on November 20, 2019. After
multiple extensions, Mr. Mager filed a supplemental expert report from Dr. Shafrir
on July 25, 2020, and his brief on July 27, 2020. The Secretary, again after
multiple extensions, filed his supplemental expert reports from Dr. Fujinami and
Dr. Kohrman, as well as his brief, on February 10, 2021. Mr. Mager filed his reply
brief on March 26, 2021. With the briefing complete, this case is ripe for review.
II. Standards for Adjudication
Petitioners are required to establish their cases by a preponderance of the
evidence. 42 U.S.C. § 300aa–13(1)(a). The preponderance of the evidence
standard requires a “trier of fact to believe that the existence of a fact is more
probable than its nonexistence before [he] may find in favor of the party who has
the burden to persuade the judge of the fact’s existence.” Moberly v. Sec’y of
Health & Human Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010) (citations
omitted).
To receive compensation, petitioners must establish five elements. 42
U.S.C. § 300aa–11(c)(1)(A) through (E); 42 U.S.C. § 300aa–13(a)(1)(A)
(authorizing special masters to award compensation when petitioners establish
3
items listed in section 11(c)(1)). To establish causation for off-Table injuries,
petitioners bear a burden “to show by preponderant evidence that the vaccination
brought about [the vaccinee’s] injury by providing: (1) a medical theory causally
connecting the vaccination and the injury; (2) a logical sequence of cause and
effect showing that the vaccination was the reason for the injury; and (3) a showing
of a proximate temporal relationship between vaccination and injury.” Althen v.
Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005).
The process for finding facts in the Vaccine Program begins with analyzing
the medical records, which are required to be filed with the petition. 42 U.S.C.
§ 300aa–11(c)(2). Medical records that are created contemporaneously with the
events they describe are presumed to be accurate. Cucuras v. Sec’y of Health &
Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).
Furthermore, as a threshold matter, a petitioner must establish she suffers
from the condition for which she seeks compensation. Broekelschen v. Sec’y of
Health & Human Servs., 618 F.3d 1339, 1346 (Fed. Cir. 2010). When a petitioner
fails to establish her diagnosis, there is no need for an analysis pursuant to Althen
v. Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005).
Lombardi v. Sec’y of Health & Human Servs., 656 F.3d 1343, 1353 (Fed. Cir.
2011).
III. Diagnostic Criteria
Mr. Mager alleges that Victoria Mager suffered from autoimmune epilepsy.
However, the Secretary contends that her condition was more likely indicative of
JME. See exhibit A at 13-14. The difference between autoimmune epilepsy and
JME affects the outcome of Mr. Mager’s case because his theory of causation
relies on an autoimmune disease causing neuroinflammation. To better assess
whether Mr. Mager has met his burden in establishing that Victoria suffered from
autoimmune epilepsy, as well as the Secretary’s assertion of JME as the more
likely diagnosis, it is necessary to set forth the diagnostic criteria for each.
A. Autoimmune Epilepsy
The three major indicators of autoimmune epilepsy are: (1) “demonstration
of autoantibodies against neuronal components in the patient’s blood”; (2) in most
patients, seizures that “may not respond to regular antiepileptic medications but
respond to immunomodulatory treatment”; and (3) “occurring in relation to an
autoimmune disease or autoimmune encephalitis.” Pet’r’s Br. at 9-10.3 With
3
Mr. Mager states that he gleaned these diagnostic criteria from exhibit 88 and exhibit 65
and that this specific list “does not appear” verbatim in the medical literature filed. Pet’r’s Status
4
respect to the third criterion, Mr. Mager alleges that Victoria suffered from
autoimmune encephalitis. The diagnostic indicators of autoimmune encephalitis
include:
(1) Focal seizures, particularly focal motor and focal dyscognitive,
secondary generalized seizures; (2) seizure clusters, status epilepticus; (3)
seizures and epilepsy of unknown cause; (4) refractory seizures; (5)
associated features of encephalopathy, movement disorders,
neuropsychiatric symptoms, cognitive or memory impairment; and (6)
history of autoimmune diseases (personal or family).
Exhibit 65 (Suleiman) at 3.4 Focal seizures are those in which the onset in the
brain is localized, while the onset of generalized seizures is not localized.
Secondary generalized seizures start out localized, but then spread to both sides of
the brain. Refractory are those which do not respond to anti-seizure medications.
As outlined above, focal, secondary generalized, and/or refractory seizures are
clinical indicators specific to autoimmune encephalitis, though both
focal/secondary generalized and primary generalized seizures can occur in people
with autoimmune encephalitis. Thus, while presence of a focal, secondary
generalized, and/or refractory seizure would necessarily indicate autoimmune
encephalitis, presence of a primary generalized seizure could indicate autoimmune
encephalitis or juvenile myoclonic epilepsy because primary generalized seizures
occur with both conditions. Mr. Mager points out that “it is not necessary to find
each of these attributes to come to a diagnosis of autoimmune encephalitis,” id.
(citing exhibit 65), “origin of seizure onset is difficult to determine with certainty,”
id. at 12 (citing exhibit BB (Dr. Kohrman’s report), tab 4, at 1), and autoimmune
epilepsy can occur in patients with milder presentations, see Pet’r’s Br. at 10
(citing exhibit 88).
B. Juvenile Myoclonic Epilepsy
In his brief, the Secretary sets out the clinical features of JME as: (1)
presence of myoclonic, tonic-clonic, and/or absence seizures; (2) an average onset
age of 15.1 years, although this metric is highly variable; and (3) myoclonic
seizures may precede the first generalized tonic-clonic seizure by 6-12 months,
although generalized tonic-clonic seizures occur as the first seizure type in
Rep., filed June 17, 2021, CM/ECF No. 188. Respondent did not challenge this list as the
criteria for autoimmune epilepsy in any of his briefs. Therefore, the undersigned will accept
these criteria for the purposes of this decision.
4
For a more detailed analysis of the Suleiman article, see Moriarty v. Sec’y of Health &
Human Servs., No. 03-2876V, 2016 WL 5390172, at *28 (Fed. Cl. Spec. Mstr. Aug. 23, 2016),
vacated and remanded, 130 Fed. Cl. 573 (2017).
5
approximately one third of patients. Resp’t’s Br. at 13-14 (citing exhibit BB (Dr.
Kohrman’s report)). Unlike autoimmune epilepsy, JME produces seizures that
generally respond to anti-seizure medication and is characterized by the presence
of primary generalized, not focal or secondary generalized, seizures. See id. at 14
(citing exhibit BB).
IV. Facts
Victoria Mager was born on July 29, 1995. Pet. ¶ 1. Prior to receiving the
vaccination that is the subject of Mr. Mager’s claim on her behalf, Victoria
suffered from enuresis, or bed wetting, at approximately eight years old. Exhibit
18 at 5. Her primary care provider also noted that she was receiving speech
therapy at this time and experienced “poor performance” and “decreased attention”
at school during this time. Id. Other than this, Victoria’s pre-vaccination health
history appears relatively normal.
On September 4, 2007, Victoria received the meningococcal and tetanus-
diphtheria-acellular pertussis (“Tdap”) vaccines. Exhibit 4 at 2, 3. She then
received the HPV vaccine on October 2, 2007. Id. at 2, 9. On November 14, 2007,
Victoria experienced a seizure and was taken to the emergency room of Children’s
Hospital of Wisconsin. Exhibit 11 at 28. In her admission notes, the description of
her condition states that she experienced a seizure followed by a second seizure
approximately four minutes later. Id. A head CT scan, urine toxicology screen,
and chest x-ray were performed with normal results. Id. at 3-4, 13. An EEG was
then performed, the results of which were “[i]ntermittent epileptiform spike & low
wave discharges over the left frontal region, as well as the bifrontal region,
maximal on left” and “intermittent generalized spike and slow wave discharges,
maximum over left frontal region, seen predominantly during drowsiness and
sleep.” Id. at 17. It was noted that these discharges “indicate focal sites of cerebral
hyperexcitability which can be associated with partial seizures/epilepsy.” Id.
Victoria was prescribed Depakote, an anti-seizure medication, and discharged on
November 15, 2007. Id. at 38.
On December 12, 2007, Victoria saw a pediatric neurologist, Dr. Sharif, for
a follow-up. Dr. Sharif noted that, after she was discharged, her parents recalled
and reported to Dr. Sharif in this appointment that “for a while, [Victoria] was
waking up with big cuts in her tongue at least twice and also complaining of
soreness after waking up and it is possible that these might have been seizures.”
Exhibit 11 at 75. Victoria’s stepmother also reported that there had been no more
bed wetting incidents after the prescription of Depakote between her hospital
admission and this appointment. Id. Dr. Sharif noted an impression of “focal
6
onset epilepsy by EEG” and “some frontal lobe dysfunction.” Id. at 77. Dr. Sharif
recommended neuropsychological testing. Id.
Victoria saw another pediatric neurologist, Dr. Koehn, approximately two
months later on February 21, 2008. An EEG was performed, the results of which
were normal. Exhibit 6 at 22. Referring to the original abnormal EEG taken
during her hospital admission, Dr. Koehn noted that “[t]he first EEG pattern could
represent a fragment/a more lateralized pattern of an underlying generalized
discharge or it could in fact be a focal discharge. Therefore, leaving the possibility
open for this to have been a primary or secondarily generalized seizure.” Id. at 20.
Victoria’s father and stepmother requested that she be weaned off Depakote,
although the medication appeared to be controlling her seizure activity. They cited
poor performance and difficulties focusing in school, which they thought may have
been attributable to the Depakote. Id. at 24. Dr. Koehn therefore directed that she
be gradually weaned off Depakote and referred her for neuropsychological testing.
Id. at 28; see also Pet. ¶ 4.
On April 1, 2008, Victoria underwent neuropsychological testing with Dr.
Waltonen. Exhibit 6 at 6. Dr. Waltonen noted that she had “a history of some type
of learning difficulty at least in the speech and language area.” Id. at 6. He also
noted a family history of epilepsy and seizures on her maternal side. Id. at 2. With
respect to learning and school-related difficulties, he noted that Victoria’s
stepmother reported “increasing problems with doing well in school” and
Victoria’s teachers indicated “problems following directions.” Id. at 1, 4. Dr.
Waltonen ultimately concluded that “[o]verall, her examination does not reveal
evidence of significant cognitive impairment with the exception of very focal
language findings.” Id. at 6. He further recommended that “her language be
looked at a bit more extensively” and, under “Plan,” noted “Refer to the school for
speech and language evaluation.” Id. at 6-7.
Between April 2008 and her next medical event in October 2012, Victoria
appears to have been functioning normally. School records submitted from part of
this time period do not indicate any abnormalities. See exhibit 83. She received a
normal sports physicals and health maintenance exams on August 8, 2009, and
March 2, 2012. Exhibit 10 at 15-17; exhibit 14 at 1-2. She also saw Dr. Budde for
a physical exam and removal of hand warts on January 5, 2012, when she reported
that she had not experienced seizure activity in four years. Exhibit 10 at 18. On
September 11, 2012, she received her second HPV vaccination. Exhibit 4 at 1.
Approximately one month later, she was taken to the emergency department of
Theda Clark Medical Center on October 10, 2012, after suffering a seizure.
Exhibit 7 at 9. Her work-up, including an EKG, was normal. Id. at 13-14. She was
diagnosed with a “probable seizure” and discharged. Id. at 14.
7
She saw her primary care doctor, Dr. Budde, on November 8, 2012. Exhibit
9 at 39. At this appointment, she reported two additional seizures following her
ER visit on October 19, 2012, and November 7, 2012. Id. Dr. Budde prescribed
Depakote and referred her to a neurologist. Id.
Victoria saw neurologist Dr. Edgar on January 14, 2013. Exhibit 9 at 24-25.
An EEG was also performed. Dr. Edgar noted that the “EEG is normal during
wakefulness. During sleep there is activation of infrequent potentially epileptiform
activity over the left frontal and bioccipital head regions, consistent with the
patient’s history of generalized seizures.” Id. at 25. Dr. Edgar’s impression was
primary generalized seizure disorder and he noted “age of onset at approximately
11 years of age suggests the possibility of juvenile myoclonic epilepsy, although
no myoclonic seizures are reported.” Id. at 9. He recommended Depakote but,
after Victoria specified that she did not wish to remain on Depakote, Dr. Edgar
directed her to begin weaning off Depakote and prescribed Keppra, a different anti-
seizure medication. Id. at 8.
During a follow-up appointment with Dr. Edgar on July 8, 2013, he stated
that Victoria’s compliance with her Keppra prescription had been “less than ideal,”
with a sub-therapeutic level of the medication in her blood documented from a test
on May 30, 2013. Exhibit 9 at 3. Victoria expressed a desire to discontinue use of
Keppra, but Dr. Edgar persuaded her to remain on the drug given her history of
seizures. Id. at 4. Dr. Edgar noted “probable juvenile myoclonic epilepsy” at this
appointment due to age of onset. Id.
On January 11, 2014, Victoria was rushed to the emergency department after
being discovered unresponsive at a friend’s house. Exhibit 8 at 2. She was
pronounced dead upon her arrival at the ER. Id. As part of an investigation of the
death by the Waukesha Police Department, a witness reported that Victoria had
been “missing a lot of doses of her medication” and Mr. Mager reported that “she
was having seizures more frequently.” Exhibit 13 at 2.
An autopsy was performed by Dr. Okia on January 13, 2014. Exhibit 12 at
1. The findings included pulmonary edema and brain changes consistent with a
seizure disorder. Exhibit 16 at 1. Sections of the brain showed focal areas of
subpial gliosis. Id. at 6. Furthermore, a toxicology screen showed levels of
Keppra in her blood. Exhibit 13 at 11. According to the toxicology report, regular
dosing of Keppra results in 3-37 mcg/mL in the blood, with peak levels of 10-60
mcg/mL within 1.5 hours after dosage. Id. Victoria’s toxicology results revealed
26 mcg/mL of Keppra in her blood at the time of death. Id. Victoria’s death
certificate listed “seizure disorder” as her cause of death. Exhibit 1 at 1.
8
V. Analysis
This section will first analyze the relative qualifications of the experts,
specifically Dr. Shafrir and Dr. Kohrman, as their expertise is relevant to their
diverging opinions regarding Victoria’s diagnosis. Next, this section will consider
whether Mr. Mager has met his burden to prove each diagnostic criterion for
autoimmune epilepsy: presence of autoimmune antibodies, response to anti-
seizure medications, and co-existing autoimmune disorder. Because in order to
satisfy the third criterion, Mr. Mager asserts that Victoria suffered from
autoimmune encephalitis, section B. includes an analysis of whether he has met his
burden to show each of the six diagnostic criteria for autoimmune encephalitis.
Finally, section C. discusses statements from treating doctors.
A. Qualifications of Experts
Because a determination regarding whether Mr. Mager has met his burden to
prove Victoria suffered from autoimmune epilepsy hinges in part on the diagnostic
opinions of Dr. Shafrir and Dr. Kohrman, it is helpful to compare their
qualifications as a preliminary matter. Special masters may consider the relative
expertise of testifying experts when weighing the value of their opinion. See
Depena v. Sec’y of Health & Human Servs., No. 13-675V, 2017 WL 1075101
(Fed. Cl. Spec. Mstr. Feb. 22, 2017), mot. for rev. denied, 133 Fed. Cl. 535, 547-48
(2017), aff’d without op., 730 Fed. App’x 938 (Fed. Cir. 2018); Copenhaver v.
Sec’y of Health & Human Servs., No. 13-1002V, 2016 WL 3456436 (Fed. Cl.
Spec. Mstr. May 31, 2016), mot. for rev. denied, 129 Fed. Cl. 176 (2016).
Though both Dr. Shafrir and Dr. Kohrman have ample experience and
expertise in pediatric neurology, Dr. Kohrman has a notable special expertise in
epilepsy. For example, Dr. Kohrman holds a current board certification with the
American Board of Psychiatry and Neurology with a subspecialty in epilepsy.
Exhibit B at 2. Dr. Shafrir’s board certifications include pediatrics, neurology, and
psychiatry with a special qualification in child neurology, and clinical
neurophysiology. Exhibit 56 at 2. Both experts have published in the areas of
epilepsy and pediatric epilepsy. However, Dr. Kohrman’s publication history
specific to issues involving pediatric epilepsy appears more extensive. See exhibit
B at 3-9; exhibit 56 at 4-6. Though Dr. Shafrir’s certifications and topics of focus
in his publications are certainly relevant and helpful to this case, Dr. Kohrman’s
specialty in epilepsy—particularly his board certification with a subspecialty in
epilepsy and focus on pediatric epilepsy—makes him particularly qualified to
opine on a case in which potential diagnoses of autoimmune epilepsy or juvenile
myoclonic epilepsy are at play.
9
B. Diagnosis of Autoimmune Epilepsy
The three major indicators of autoimmune epilepsy are: (1) “demonstration
of autoantibodies against neuronal components in the patient’s blood”; (2) in most
patients, seizures that “may not respond to regular antiepileptic medications but
respond to immunomodulatory treatment”; and (3) “occurring in relation to an
autoimmune disease or autoimmune encephalitis.” Pet’r’s Br. at 9-10. Each of
these indicators will be addressed in turn.
1. Presence of autoimmune antibodies
Mr. Mager concedes, based on Dr. Shafrir’s report that, with the respect to
the first element of autoimmune epilepsy, Victoria was not tested for autoimmune
antibodies in her blood. Exhibit 85 at 4. Thus, there is no affirmative evidence on
this point. Mr. Mager asserts potentially valid reasons why Victoria’s treating
doctors may not have thought to perform tests relevant to an autoimmune epilepsy
diagnosis. Specifically, he asserts that autoimmune epilepsy is a relatively
“emerging field.” Pet’r’s Reply at 18. He refers vaguely to comments made by
both his and respondent’s experts. However, it is unclear where these assertions
regarding the emerging nature of this diagnosis are located in any of the reports.
Still, even assuming this is true and that there is a valid reason for the lack of
testing, a lack of evidence on this point does not help Mr. Mager’s case. While this
fact is not dispositive as to the determination of whether Victoria had autoimmune
epilepsy, and does not rule out autoimmune epilepsy, a lack of testing also does not
provide any affirmative evidence supporting an autoimmune epilepsy diagnosis.
Mr. Mager also concedes via Dr. Shafrir’s report that no autoimmune
process was detected from Victoria’s autopsy. Exhibit 85 at 4. However, Dr.
Shafrir in his first report pointed to the finding of gliosis in Victoria’s autopsy as
an indicator of an inflammatory process. Specifically, he stated:
Gliosis is typically an inflammatory mechanism which is induced by various
brain insults. Although we do not have a good description of the extent,
cellular components, and the localization of the gliosis in the postmortem
examination of Victoria’s brain, it definitely supports an inflammatory
mechanism as a cause of epilepsy.
Exhibit 55 at 20. He argues that this constitutes evidence of autoimmunity because
of the connection between autoimmunity and inflammatory responses. Id. at 19-
20. In response, Dr. Fujinami contended that gliosis found in Victoria’s autopsy is
a “common finding in epilepsy and represents the result of a neuronal injury and
cell death . . . and not an acute or chronic inflammatory process related to
10
vaccination.” Exhibit Y at 7. Mr. Mager states that medical literature relied upon
by Dr. Fujinami contradicts this contention. In his reply brief, he states that
astrogliosis, like that detected in Victoria’s autopsy, can indicate inflammatory
attacks. Pet’r’s Reply at 19 (citing exhibit Y-15 at 8). Dr. Kohrman agrees that
gliosis is a “regular finding in juvenile myoclonic epilepsy” and that the
pathologist “concluded this was a typical finding in epilepsy and [Victoria] ha[d]
primary generalized epilepsy.” Exhibit BB at 15. Thus, the experts dispute the
significance of the gliosis finding as it pertains to evidence of autoimmunity.
The connection made between the gliosis found in Victoria’s autopsy and
the potential for an inflammatory response, which may indicate autoimmunity is
tenuous. While there may be some chance of an inflammatory process—and thus,
in Dr. Shafrir’s opinion, evidence of autoimmunity—indicated by the gliosis in
Victoria’s autopsy, this does not tip the scale persuasively in the direction of an
autoimmune disease, as evidenced by the conclusions of the pathologist
performing the exam. It also does not provide evidence of autoimmune antibodies
in Victoria’s blood, which is the actual relevant criterion in terms of testing for a
diagnosis of autoimmune epilepsy.
2. Response to anti-seizure medications and refractory
seizures
The second clinical feature of autoimmune epilepsy is seizures that do not
respond to anti-seizure medication, also called refractory seizures. See Pet’r’s
Reply at 13-14. As detailed in the facts, Victoria was prescribed Depakote after
her first emergency room visit in November 2007 and weaned off the medication at
her father’s request starting in February 2008. She was then prescribed Keppra,
another seizure medication, in November 2012 after her second emergency room
visit for a seizure. She maintained the Keppra prescription until her death in
January 2014.
To support the contention that Victoria’s seizures were resistant to anti-
seizure medication, Mr. Mager points to two particular incidents: (1) Victoria
suffered a seizure the night she was discharged from the hospital in November
2007, after she had been prescribed and started on Depakote; and (2) levels
commensurate with prescriptive use of Keppra were found in her blood upon her
death.
To the first point, while Mr. Mager did report that Victoria experienced a
seizure after being discharged from the hospital, there is also evidence that, after
she began taking Depakote, her seizure-related activity, such as enuresis, stopped.
Exhibit 11 at 75 (report by stepmother in December 2007 appointment with Dr.
11
Sharif). Her providers, including Dr. Sharif and Dr. Koehn, recommended
continuation of Depakote. At her appointment with Dr. Koehn in February 2008,
she had a normal EEG and no reports of seizure activity since the night of her
hospital discharge. Exhibit 6 at 20. Victoria’s parents requested that she be
weaned off Depakote, however, against Dr. Koehn’s recommendations, see id. at
20-21 (noting a discussion of potential recurrent seizures if not on Depakote and
recommending Keppra if seizures recur), and Victoria did not take Depakote or
experience seizure activity between approximately February 2008 and October
2012 when she began to experience her second bout of seizure activity. Thus, the
single seizure occurring the night of her hospital discharge after she had just begun
taking Depakote does not outweigh the months of a lack of seizure activity while
on Depakote, that was further supported by a normal EEG and recommendations to
continue anti-seizure medication at her appointment with Dr. Koehn in late
February 2008.
To the second point, regarding presence of Keppra in her blood upon death,
Victoria was prescribed Keppra after her seizure and hospitalization in October
2012, as an alternative to Depakote. However, multiple medical records discuss
Victoria’s irregular use or lack of adherence to her Keppra prescription. After Dr.
Edgar initially prescribed Keppra in January 2013, Victoria returned to him for a
follow-up in July 2013. In this appointment, Dr. Edgar noted that Victoria’s
compliance with her Keppra prescription had been “less than ideal,” with a sub-
therapeutic level of the medication in her blood documented from a test on May
30, 2013. Exhibit 9 at 3. Based on the notes from this visit, it also appears that
Victoria was generally averse to continuing her Keppra prescription, perhaps
because of unwanted side effects. Id. at 4. However, Dr. Edgar persuaded her to
continue with the medication in light of potential recurrent seizure activity.
Though there were what appear from the toxicology report to be levels of Keppra
detected in Victoria’s blood during her autopsy that were consistent with the range
present as a result of normal dosing, a source noted that Victoria had been “missing
a lot of doses of her medication” and Mr. Mager reported that “she was having
seizures more frequently” leading up to her fatal seizure in January 2014. Exhibit
13 at 2. Thus, multiple sources of evidence show that Victoria did not take Keppra
as prescribed and was having seizures leading up to her death. Because of this, the
contention that levels of Keppra in her blood at death shows the presence of
refractory seizures is unpersuasive, given the evidence against regular adherence to
anti-seizure medication. There is no other evidence, besides these two instances
which appear unpersuasive, that Victoria’s seizures were resistant to anti-seizure
medications. In fact, there is some contradictory evidence from the few months
when she was taking Depakote as prescribed, that this anti-seizure medication was
effective in controlling her seizure activity.
12
3. Association with autoimmune encephalitis
The third and final clinical indicator of autoimmune epilepsy is association
with an autoimmune disease. To this point, Mr. Mager specifically asserts that
Victoria suffered concurrently from autoimmune encephalitis. The diagnostic
criteria for autoimmune encephalitis are:
(1) Focal seizures, particularly focal motor and focal dyscognitive,
secondary generalized seizures; (2) seizure clusters, status epilepticus; (3)
seizures and epilepsy of unknown cause; (4) refractory seizures; (5)
associated features of encephalopathy, movement disorders,
neuropsychiatric symptoms, cognitive or memory impairment; and (6)
history of autoimmune diseases (personal or family).
Pet’r’s Reply at 11 (citing exhibit 65). According to Mr. Mager, “It is not
necessary to find each of these attributes to come to a diagnosis of autoimmune
encephalitis, but ‘the suspicion of autoimmune encephalitis should be
predominantly based upon clinical characteristics and supportive investigations.’”
Pet’r’s Reply at 11 (quoting exhibit 65 at 1).
i. Focal vs. Generalized Seizures
Focal seizures, or seizures which begin in a localized part of the brain, are
clinical indicators of autoimmune encephalitis. Exhibit 65 (Suleiman) at 1.
Secondary generalized seizures, or seizures that start out localized and then spread
to both sides of the brain, are also included as clinical indicators of autoimmune
encephalitis. Id. Generalized seizures, which do not have a localized onset,
however, can occur in people with autoimmune encephalitis or juvenile myoclonic
epilepsy.
Victoria’s EEG results indicated that her seizures were not focal or
secondary generalized. To counteract this lack of evidence, Mr. Mager argues,
citing respondent’s medical literature, that “EEGs of patients suffering from
autoimmune epilepsy ‘may have variable findings including normal, focal, and
generalized slow activity, periodic discharges, and focal epileptiform discharges.’”
Id. at 12 (quoting exhibit BB, tab 4, at 1). Additionally, “in a study of children
with new-onset epilepsy, over 40% of these children experienced generalized
seizures.” Id. at 16 (citing exhibit 65). However, Dr. Kohrman states that
“generalized discharges are the hallmark of [primary or idiopathic generalized
epilepsies].” Exhibit BB at 2-3.
Though the classification of Victoria’s seizures as generalized does not rule
out autoimmune encephalitis, it also does not constitute affirmative evidence of
13
autoimmune encephalitis. In other words, the presence of generalized seizures
could indicate either autoimmune encephalitis or juvenile myoclonic epilepsy,
whereas only the presence of focal or secondary generalized seizures would point
specifically to a diagnosis of autoimmune epilepsy. After factoring in Dr.
Kohrman’s comment that generalized seizures are also the “hallmark” of primary
or idiopathic generalized epilepsies (i.e. epilepsies without an autoimmune
component), as well as the fact that Dr. Kohrman possesses superior expertise with
respect to epilepsy, see supra Part V.A, this makes Mr. Mager’s argument even less
persuasive.
ii. Seizure Clusters, Status Epilepticus
Mr. Mager states that Victoria may have suffered one seizure cluster,
referring to her first hospital admission in November 2007. Pet’r’s Reply at 12-13.
Specifically, he states that, after her ER visit, which was precipitated by a seizure,
“she suffered a three-minute seizure followed very closely by a shorter seizure,
without recovering between the two.” Id. at 13 (citing exhibit 6 at 24). It is not
clear whether “status epilepticus” was applicable to this particular “cluster.”
However, it also does not appear that “status epilepticus” is necessarily present in a
case of autoimmune encephalitis. Id. (citing exhibit 65 at 4). Still, while this
incident following Victoria’s November 2007 hospitalization could constitute a
seizure cluster, it also does not provide persuasive evidence regarding this
particular indicator of autoimmune encephalitis, or evidence of autoimmune
encephalitis as a whole, given the inconclusiveness of a classification of this
incident as a “cluster” and the fact that, if it was, it was an isolated incident.
iii. Seizures of Unknown Cause
It does appear that treaters in this case were not uniform in their assessment
of the cause of her seizures. During her first hospitalization, it was noted that the
discharges detected in her EEG “indicate focal sites of cerebral hyperexcitability
which can be associated with partial seizures/epilepsy.” Exhibit 4 at 17. At her
second hospitalization, the reason for her visit was noted as “probable seizure.”
Exhibit 7 at 14. Dr. Sharif noted an impression of “focal onset epilepsy by EEG.”
Exhibit 11 at 77. Dr. Koehn, in her assessment, elected to “leave[] the possibility
open for this to have been a primary or secondarily generalized seizure.” Exhibit 6
at 20. Finally, Dr. Edgar diagnosed her with “probable juvenile myoclonic
epilepsy” based on age of onset. Exhibit 9 at 4. Thus, this clinical factor does
appear to be present in Victoria’s case in that no treater gave her a certain
diagnosis or cause of her seizures and there is some disagreement on ultimate
conclusions among treaters. However, because this factor represents a lack of
information by definition, rather than information pointing specifically to a
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diagnosis of autoimmune encephalitis, it appears to be a less persuasive indicator
than some of the other factors discussed.
iv. Refractory Seizures
As explained above, see supra Part V.B.2, Mr. Mager has not met his burden
to show that Victoria’s seizures were refractory, or in other words resistant to anti-
seizure medication.
v. Movement Disorders, Neuropsychiatric Symptoms,
and/or Cognitive or Memory Impairment
Mr. Mager asserts that Victoria experienced cognitive impairment and bases
this assertion on neuropsychological testing performed by Dr. Waltonen in April
2008. Pet’r’s Reply at 14-15. Dr. Waltonen ultimately concluded that “overall,
her examination does not reveal evidence of significant cognitive impairment with
the exception of very focal language findings.” Exhibit 6 at 6. In his brief, Mr.
Mager emphasizes the language findings as proof that the results of this testing
were irregular. However, Victoria has a documented history of “some type of
learning difficulty at least in the speech and language area.” Id.; see also exhibit
18 at 5 (pre-vaccination notation from a primary care provider regarding “poor
performance” and “decreased attention” at school). It does not appear that the
results of Dr. Waltonen’s assessment, which were very narrowly limited to
language-related deficits, can rise to the level of a cognitive impairment indicative
of autoimmune encephalitis, especially when these language issues existed to some
degree long before her vaccination. See exhibit A at 12 (Dr. Kohrman opining that
Victoria’s normal range IQ “argues against a neurodegenerative disorder as a cause
for the seizures”).
vi. History of Autoimmune Diseases
Mr. Mager concedes that Victoria did not have any significant personal or
family history of autoimmune disease. Pet’r’s Reply at 15. While, as Mr. Mager
points out and as is true with the other diagnostic indicators of autoimmune
encephalitis, this fact is not dispositive, the absence of a family or personal history
of autoimmune disease further adds to the lack of persuasiveness with respect to
the existence of autoimmune encephalitis.
vii. Summary: Autoimmune Encephalitis
Thus, with respect to autoimmune encephalitis, the only diagnostic criterion
that Mr. Mager has met his burden to show is that Victoria’s seizures were of an
unknown cause. It follows that Mr. Mager has then not met his burden in showing
15
that Victoria suffered from autoimmune encephalitis, as this is only one of six
diagnostic criteria, and one that is relatively less weighty given that it by definition
indicates a lack of information regarding Victoria’s condition.
C. Lack of Support from Treating Doctors
The opinions of treating doctors regarding the diagnosis of a petitioner’s
condition are generally favored given that, having examined the petitioner, they are
in the best position to opine on the petitioner’s condition. See Capizzano v. Sec’y
of Health & Human Servs., 440 F.3d 1317, 1326 (Fed. Cir. 2006). In this case, no
treating doctors diagnosed Victoria with autoimmune epilepsy.
On December 12, 2007, pediatric neurologist Dr. Sharif noted an impression
of “focal onset epilepsy by EEG.” Exhibit 11 at 77. On February 21, 2008,
pediatric neurologist Dr. Koehn assessed her abnormal EEG during her
hospitalization as indicating a possible “primary or secondarily generalized
seizure,” but did not diagnose her with any specific type of epilepsy. Exhibit 6 at
20.
Later, she was assessed with “probable seizure” during her hospitalization in
October 2012, exhibit 4 at 14, and subsequently visited her primary care doctor
who prescribed anti-seizure medication, exhibit 9 at 39. Again, no diagnoses of
epilepsy were made. On January 14, 2013, neurologist Dr. Edgar noted an
impression of primary generalized seizure disorder and stated: “age of onset at
approximately 11 years of age suggests possibility of juvenile myoclonic
epilepsy.” Exhibit 9 at 9. Dr. Edgar again noted “probable juvenile myoclonic
epilepsy” at a second appointment on July 8, 2013. Id. at 4.
Thus, as evidenced by these records, none of Victoria’s treating doctors
diagnosed her with autoimmune epilepsy, or in fact made a definitive diagnosis at
all. The closest Victoria came to receiving a diagnosis were Dr. Edgar’s
impressions. However, Dr. Edgar specifically stated that he suspected probable
juvenile myoclonic epilepsy, not autoimmune epilepsy. The lack of support from
treating doctors regarding a diagnosis of autoimmune epilepsy is yet another factor
that weighs against finding that Victoria suffered from autoimmune epilepsy.
D. Conclusion: Autoimmune Epilepsy
As explained above, Mr. Mager advanced the presence of autoimmune
encephalitis as an associated autoimmune disease as one of three overall diagnostic
indicators of the asserted diagnosis—autoimmune epilepsy. Mr. Mager has not
met his burden to show either the presence of autoimmune antibodies in Victoria’s
blood or that Victoria’s seizures were refractory. See supra Parts V.B.1, V.B.2.
16
Because he also could not persuasively show that Victoria suffered from
autoimmune encephalitis, and therefore an associated autoimmune disease, see
supra Part V.B.3, it follows that he has not shown by a preponderance of the
evidence that Victoria suffered from autoimmune epilepsy. Because he has not
established the threshold issue of diagnosis, it also follows that further analysis
regarding causation is unnecessary. See Lombardi v. Sec’y of Health & Human
Servs., 656 F.3d 1343, 1353 (Fed. Cir. 2011); Broekelschen v. Sec’y of Health &
Human Servs., 618 F.3d 1339, 1346 (Fed. Cir. 2010).
If an Althen analysis were performed, then one element is that Mr. Mager
establish, by preponderant evidence, “a proximate temporal relationship between
vaccination and injury.” Althen, 418 F.3d at 1278. Here, relying upon a post-
marketing study, Slade, Mr. Mager asserts that a window of 4-42 days was
“‘biologically plausible.’” Pet’r’s Br. at 45, quoting exhibit 59 (Slade) at 5.
Mr. Mager further maintains that Victoria developed seizures within the
appropriate time. In 2007, she received her first dose of the HPV vaccine on
October 2, 2007. Exhibit 4 at 2, 9. She suffered a seizure on November 14, 2007.
Exhibit 11 at 3. The interval between these events is 43 days.
Five years later, Victoria received a second dose of the HPV vaccine on
September 11, 2012. She then experienced a seizure on October 10, 2012. The
interval between these events is 29 days.
In response, the Secretary does not strenuously argue that the seizures
occurred outside an expected window. Instead, the Secretary points out that
“temporal proximity alone is insufficient to establish causation.” Resp’t’s Br. at
23, citing Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1323 (Fed.
Cir. 2010) and Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148
(Fed. Cir. 1992).
The sequence of events in Victoria’s life in that she twice experienced
seizures after receiving the HPV vaccine seems to underlie Mr. Mager’s good faith
belief that the vaccinations harmed his daughter and, ultimately, caused her death
much too soon. However, Congress has not allowed special masters to award
compensation based upon a petitioner’s belief alone. 42 U.S.C. § 300aa–13(a)(1);
see Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1349 (Fed. Cir.
1999). Although Mr. Mager has present opinions from a qualified expert, Dr.
Shafrir, his opinion that Victoria suffered autoimmune epilepsy is not persuasive
for the reasons explained at length above. And, without this predicate showing,
examination of Dr. Shafrir’s opinions regarding all Althen prongs is not required
according to Federal Circuit precedent.
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VI. Ruling on the Record is Appropriate
Special masters may rely on accumulated knowledge in the Vaccine
Program to make entitlement decisions on the papers. Thus, special masters,
“based upon their accumulated expertise in the field, judg[e] the merits of
individual claims.” Whitecotton v. Sec’y of Health & Human Servs., 81 F.3d
1099, 1104 (Fed. Cir. 1996) (quoting Hodges v. Sec’y of Health & Human Servs.,
9 F.3d 958, 961 (Fed. Cir. 1993)). Additionally, special masters retain wide
discretion in determining whether an evidentiary hearing is necessary.
Kreizenbeck v. Sec’y of Health & Human Servs., 945 F.3d 1362, 1365 (Fed. Cir.
2020) (citing 42 U.S.C. § 300aa-12(d)(3)(B)(v) (“In conducting a proceeding on a
petition a special master . . . may conduct such hearings as may be reasonable and
necessary.”)). The special master must only determine “that the record is
comprehensive and fully developed before ruling on the record.” Id. at 1366
(citing Simanski v. Sec’y of Health & Human Servs., 671 F.3d 1368, 1385 (Fed.
Cir. 2012)).
A hearing to determine the threshold issue of diagnosis in this case is not
needed. The parties have had ample opportunity to develop their positions through
submissions of evidence (primarily medical records) about Victoria, lengthy and
multiple expert reports, and thorough briefing.
Mr. Mager’s claim fails for reasons that a hearing could not cure given the
paucity of evidence establishing a diagnosis of autoimmune epilepsy, which is
essential for the remainder of Mr. Mager’s claim to proceed. He has had a full and
fair opportunity to present his case. Thus, a disposition on the papers is
appropriate. See Kreizenbeck, 945 F.3d at 1365.
VII. Conclusion
For the foregoing reasons, the undersigned finds that Mr. Mager has not met
his burden to show, by a preponderance of the evidence, that Victoria suffered
from autoimmune epilepsy. Therefore, Mr. Mager has not shown that the HPV
vaccination caused her to suffer autoimmune epilepsy resulting in sudden
unexpected death in epilepsy. Accordingly, the claim for compensation is
DENIED.
The Clerk’s Office is instructed to enter judgment in accord with this
decision unless a motion for review is filed. Information about the submission for
a motion for review, including deadlines, is presented in the Vaccine Rules, which
are available through the Court’s website.
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IT IS SO ORDERED.
s/Christian J. Moran
Christian J. Moran
Special Master
19
Appendix of Articles Cited
Barbara A. Slade et al., Postlicensure Safety Surveillance for Quadrivalent
Human Papillomavirus Recombinant Vaccine, 302 J. Am. Med. Ass’n 750 (2009),
filed as exhibit 59.
Jehan Suleiman et al., The recognition and treatment of autoimmune
epilepsy in children, 57 Dev. Med. & Child Neurology 431 (2015), filed as exhibit
65.
Jehan Suleiman et al., Autoantibodies to neuronal antigens in children with
new-onset seizures classified according to the revised ILAE organization of
seizures and epilepsies, 54 Epilepsia 2091 (2013), filed as exhibit 88.
Alexei Verkhratsky & Arthur Butt, General Pathophysiology of Neuroglia,
in Glial Physiology and Pathophysiology 431 (2013), filed as exhibit Y, tab 15.
20