Mager v. Secretary of Health and Human Services

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: April 19, 2022

*

SECRETARY OF HEALTH * Remand; entitlement; human

AND HUMAN SERVICES, * papillomavirus (“HPV”) vaccine;

* epilepsy; significant aggravation;

Respondent. * challenge-rechallenge; timing; death

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

Renee J. Gentry and Julie Kim, Vaccine Injury Clinic, George Washington

University Law School, Washington, DC, for petitioner;

Zoe Wade and Tyler King, United States Dep’t of Justice, Washington, DC, for

respondent.

RULING FINDING ENTITLEMENT TO COMPENSATION 1

Michael Mager alleged that the human papillomavirus (“HPV”) vaccine his

deceased daughter Victoria received on September 11, 2012, significantly

aggravated an epilepsy. He sought compensation pursuant to the National

Childhood Vaccine Injury Compensation Program.

After a previous decision found that Victoria did not suffer from a particular

form of epilepsy, autoimmune epilepsy, the Court of Federal Claims held that this

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 ruling on its

website. This posting will make the ruling 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.

focus on autoimmune epilepsy was erroneous. The Court, accordingly, vacated the

previous decision and remanded for an analysis of whether the 2012 vaccination

harmed Victoria.

On remand, the parties presented testimony from three people. Mr. Mager

called Yuval Shafrir, M.D., a neurologist. The Secretary called Michael H.

Kohrman, M.D., a neurologist, and Robert S. Fujinami, Ph.D., a specialist in

immunology, although not a medical doctor. Based upon this testimony as well as

the written material, the undersigned finds that Mr. Mager is entitled to

compensation.2

I. Facts

Victoria’s history can be separated into three periods. These are (A) from

birth to the first dose of the HPV vaccine at age 12, (B) from the first dose of the

HPV vaccine to the second dose of the HPV vaccine approximately five years

later, (C) from the second dose of the HPV vaccine to Victoria’s death.

A. Events and Health Before the First Dose of the HPV Vaccine on

October 2, 2007

Victoria Mager was born on July 29, 1995. Amend. Pet., filed Nov. 19,

2014, at ¶ 1. Victoria had a family history of epilepsy on her mother’s side. Three

cousins on her maternal line had seizures similar to the seizures that Victoria

eventually experienced. Exhibit 11 at 28, 40; exhibit 6 at 2. In addition, Victoria’s

maternal grandfather had epilepsy for which he was treated with surgery. Id. The

testifying neurologists recognize that Victoria had a family history of seizures. Tr.

218, 221 (Dr. Shafrir), 447-48 (Dr. Kohrman). In other words, she had a genetic

propensity to develop seizures. Id. at 221, 332 (both Dr. Shafrir). For Dr.

Kohrman, the family history contributes to Victoria’s relatively early onset of

juvenile myoclonic epilepsy (“JME”). Id. at 454, 502.

An early medical record from her four-year well-child exam indicates that

Victoria’s parents had been divorced for about six months. Exhibit 18 at 19. In

this November 2, 1999 well-child exam, Victoria’s mother informed the

pediatrician, Dr. Jason Wray-Raabolle, that Victoria “does not speak much, and

others will occ[asionally] have a hard time understanding her.” Id. Dr. Wray-

Raabolle offered Victoria an evaluation by a speech therapist, but Victoria’s

2

The undersigned has considered all the material in the record, although this

ruling does not discuss all the material. This ruling focuses upon the evidence that

the parties have emphasized.

2

mother stated that “she feel[s] her daughter is improving and does not wish to

[pursue] that at this time.” Id. at 21.

This concern about speech recurs about one year later as part of the five-year

well-child exam. By this time, Victoria had started kindergarten. Victoria’s

mother stated others had difficulty understanding Victoria’s speech. Id. at 12

(Sept. 6, 2000).

In another well-child exam about 18 months later, Victoria’s mother

reported that Victoria was receiving speech therapy. Exhibit 18 at 3 (Mar. 11,

2004). Victoria was in second grade, and she was earning Ds in some subjects. Id.

According to a neuropsychologist’s report created in 2008, Victoria had an

individualized education plan (“IEP”) from first to fourth grade, and an IEP in

speech and language from grades four through seven. Exhibit 6 at 1; accord Tr.

280 (Dr. Shafrir), 510 (Dr. Kohrman). However, any IEP is not among the

exhibits. Dr. Kohrman saw Victoria’s learning difficulties as consistent with JME.

Tr. 455; see also id. at 539.

In the March 11, 2004 appointment, Victoria’s mother informed the

pediatrician that Victoria was wetting the bed. Exhibit 18 at 3. At this time,

Victoria was eight years old. A non-contemporaneous medical record indicates

that the bedwetting started when Victoria was around six years old. Exhibit 6 at 25

(Dr. Koehn’s Feb. 21, 2008 report). It appears that Victoria was placed on

Ditropan.3 In addition to the bedwetting, Victoria’s pediatrician noted that she was

receiving speech therapy and experienced “poor performance” and “decreased

attention” at school. Exhibit 18 at 5.

Victoria was weaned off Ditropan in summer 2007, about three years after

bedwetting was first reported. See exhibit 6 at 25; exhibit 11 at 30. The records

indicate that Ditropan helped with Victoria’s bedwetting. Exhibit 6 at 25. After

stopping Ditropan, Victoria had a few episodes of bedwetting between summer and

November 2007. Id. One report states that the bedwetting

“stopped . . . completely” after Victoria began to use Depakote, an anti-seizure

medication, in November 2007. Id. When asked about these records at hearing,

Dr. Kohrman stated that the medical records indicate her bedwetting improved

with Ditropan before she received the first HPV vaccine but did not stop

completely. Tr. 515. He reasoned that the reference in the records that states the

3

Ditropan prevents bedwetting by relaxing the bladder, allowing it to

expand to contain more urine. Tr. 334. Ditropan is not an antiepileptic

medication. Id. at 242.

3

bedwetting stopped after starting Depakote implies that Victoria was wetting the

bed, at least to some degree, until she started taking Depakote. Id. Dr. Kohrman

further reasoned that the cessation of bedwetting after taking an anti-seizure

medication indicates that the bedwetting was due to seizures. Id. at 446, 511-12,

541.

On this point, Dr. Kohrman was persuasive. Episodes of bedwetting in a

child from age seven-years to approximately twelve-years is unusual. See Tr. 242,

329 (both Dr. Shafrir’s testimony that approximately 10% of children are wetting

the bed at age six and of this group, half stop by age seven). 4 Episodes of

bedwetting can be the only manifestation of nocturnal seizures. Exhibit H

(Margaret N. Shouse & Mark W. Mahowald, Epilepsy, Sleep, and Sleep Disorders,

in Principles and Practice of Sleep Medicine 863 (Meir H. Kryger et al. eds., 4th

ed. 2005)) at 870; see also Tr. 328 (Dr. Shafrir: bedwetting could be consistent

with a seizure), 501-02 (Dr. Kohrman: bedwetting that continues until age 13 and

is stopped after the introduction of anti-seizure medication indicates a nocturnal

seizure).

Based in part upon this information, Dr. Kohrman opined that Victoria’s

neurologic problems started before the first HPV vaccination. Exhibit A at 11-12.

The basis is threefold. First, Victoria had problems in school. Second, Victoria

was wetting the bed. Third, Victoria was biting her tongue. The first two points

were described above. Id.; see also Tr. 445-46; Spec. Mstr. Oral Arg. Tr. 618,

citing Tr. 543 (Dr. Kohrman’s testimony).

With respect to tongue biting, the evidence is mixed, but favors a finding

that Victoria was biting her tongue before vaccination. Some evidence supports

this finding. On November 15, 2007, a neurologist, Dr. Uzma Sharif, obtained a

history in which she recorded, “Parents have noted tongue [difficult to read].”

Exhibit 11 at 40.5 Later, when seeing the family in follow-up, Dr. Sharif

recommended that Victoria’s stepmother (Kathy Mager) keep a journal,

documenting any episodes of bedwetting, tongue biting, soreness, and wet pillow

4

Mr. Mager takes a statement from Dr. Kohrman about the commonness of

bedwetting in young children out of context. Pet’r’s Posthear’g Br., filed Mar. 25,

2022, at 21, quoting Tr. 501-02.

5

During the hearing, the undersigned asked Dr. Kohrman whether he could

read the last word and Dr. Kohrman stated he could not. Tr. 515. On redirect, the

Secretary’s attorney leadingly asked whether the word could be “lacerations.” Id.

at 543. Mr. Mager’s attorney objected, and this objection was sustained. Id.

4

with saliva. Id. at 77. The November 15, 2007 history from Dr. Sharif is

consistent with a history obtained one day earlier in which a doctor recorded:

“Episodes waking up [with] cuts in mouth.” Id. at 28.

Thus, the evidence is clear and convincing that before Victoria’s generalized

tonic-clonic seizure on November 14, 2007, she was biting her tongue. Even Dr.

Shafrir agreed on this point. He wrote: “everybody agreed that she probably had

episodes of nocturnal seizures during the previous month.” Exhibit 55 at 17;

accord Tr. 254, 262 (Dr. Shafrir’s testimony that Victoria “quite likely” had

nocturnal seizures before November 14, 2007). Mr. Mager also agrees that

Victoria bit her tongue before the generalized tonic-clonic seizure on November

14, 2007. See Pet’r’s Posthear’g Br., filed Mar. 25, 2022, at 20-21; Spec. Mstr.

Oral Arg. Tr. 627-28. The ensuing question is whether the tongue biting also

started before the October 2, 2007 vaccination.

Two pieces of evidence support a finding that Victoria began biting her

tongue before the first vaccination. First, when Victoria went to the hospital on

November 14, 2007, in the context of explaining no history of seizures, her

stepmother informed the doctor that Victoria had

2 questionable episode[s] of

2 month[s] ago

2 week[s] ago

Exhibit 11 at 30.6 An episode that occurred two months before November 14,

2007 would be approximately September 14, 2007, meaning before the

vaccination.

Second, when the family sought care from a neurologist (Dr. Koehn) in

February 2008 (approximately three months after the tonic-clonic seizure), Mr.

Mager told this doctor “that months before this incident happened, Victoria did

complain that a couple of times she bit her tongue when she woke up in the

morning.” Exhibit 6 at 25; accord Tr. 445. Again, “months” before the November

14, 2007 tonic-clonic seizure places the onset of tongue biting before the

vaccination. See Tr. 266.

6

The doctor’s note regarding “month” is not clear. The number before

“month” could be a “1” or a “2.” See Tr. 266 (Dr. Shafrir, interpreting this note as

a “1”); id. at 541 (Dr. Kohrman, interpreting this note as a “2”).

5

Mr. Mager attempted to refute the accuracy of these records. Relying upon

Shapiro v. Secretary of Health & Human Services, 101 Fed. Cl. 532, 539 n.10

(2011), mot. for reconsideration denied after intervening remand, 105 Fed. Cl. 353

(2012), Mr. Mager argued a contemporaneous record cannot refer to events taking

place months earlier. Spec. Mstr. Oral Arg. Tr. 605-07; see also Pet’r’s Posthear’g

Br. at 20-21. The upshot to Mr. Mager’s argument appears to be that because

doctors first documented tongue biting months after the tongue biting reportedly

occurred, the tongue biting did not occur when the reports said it did.

The evidence that the tongue biting started after the vaccination was created

much later in time, and, therefore, is less reliable. In 2013, a neurologist (Dr.

Edgar) obtained a history that began with Victoria experiencing her first tonic-

clonic seizure in 2006. It continues: “One month prior to the seizure event, she

awoke and had bitten her tongue. A few weeks prior to this, she had received an

HPV shot.” Exhibit 9 at 6. Dr. Shafrir relies upon this record, despite its creation

approximately five years after the events in question. Tr. 241-42, 255; cf. id. at

542 (Dr. Kohrman: a person’s memory is altered by events). While this record

provides some evidence that the HPV vaccination preceded any tongue biting, this

record carries less weight because it was created many years later. Although Mr.

Mager may be correct that Dr. Koehn’s February 21, 2008 record is not

contemporaneous with events happening in July 2007, Mr. Mager has not

persuasively justified why Dr. Edgar’s record from 2013 is more likely to be

accurate. Moreover, an additional reason for not crediting the history Dr. Edgar

obtained in 2013 is that the history is erroneous in describing Victoria’s first

seizure as occurring in 2006, when the first tonic-clonic seizure was actually in

2007. Exhibit 9 at 6. Given these inaccuracies in recollections presented in 2013

about events occurring in 2007, crediting Mr. Mager’s affidavit from July 15, 2015

(exhibit 19 at ¶¶ 4-6) is also not possible. See O’Connell v. Sec’y of Health &

Hum. Servs., 40 Fed. Cl. 891, 893, 895 (1998) (denying motion for review when a

special master declined to credit the parents’ oral testimony because the passage of

time may have tainted their memories), aff’d in unpublished op., 217 F.3d 857,

1999 WL 1039699 (Fed. Cir. 1999).

For these reasons, a preponderance of evidence supports placing the tongue

biting before the vaccination. Furthermore, there is no meaningful dispute that

tongue biting can be a symptom of a seizure. Tr. 265, 328 (both Dr. Shafrir).

Consequently, preponderant evidence supports a finding that Victoria was

experiencing seizures before the vaccination. 7 This finding can be made despite

7

Mr. Mager argued against a finding that Victoria experienced seizures

before her first vaccination because, at least in part, there was no “clear evidence.”

6

the fact that a doctor treating Victoria before the vaccination did not diagnose her

as suffering from seizures. It appears that the family did not inform the doctors

that Victoria was biting her tongue until after the tonic-clonic seizure. See exhibit

11 at 30. More importantly, a retrospective analysis is not surprising. In Dr.

Shafrir’s second report, he quoted a treatise on neurology, stating, “Patients

frequently come to medical attention only after a generalized convulsion, and the

history of earlier myoclonic jerks is often obtained retrospectively.” Exhibit 85 at

3, quoting exhibit 87 (Eliane Kobayashi et al., Juvenile Myoclonic Epilepsy, in

Epilepsy: A Comprehensive Textbook (Jerome Engel & Timothy A. Pedley eds.,

2d ed. 2008)). As Dr. Kohrman explained, this is what happened in Victoria’s

case. Tr. 457-58. Dr. Kohrman’s testimony is persuasive.

The finding that Victoria suffered seizures before the October 2, 2007

vaccination does not alter her cause of action. Her cause of action is that a

vaccination in 2012 worsened her preexisting epilepsy. Spec. Mstr. Oral Arg. Tr.

604.

On September 4, 2007, Victoria received the meningococcal and tetanus-

diphtheria-acellular pertussis vaccines. Exhibit 4 at 2, 3. Mr. Mager has not

asserted that either of these vaccines harmed Victoria.

B. Events and Health from the First Dose of the HPV Vaccine (Oct.

2, 2007) to the Second Dose of the HPV Vaccine (Sept. 11, 2012)

Because this period encompasses approximately five years, it is further

divided into two subsections.

1. October 2007 to July 2008

Victoria received the HPV vaccine on October 2, 2007. Exhibit 4 at 2, 9. In

Mr. Mager’s first affidavit, he stated that following the HPV vaccine, Victoria

experienced headaches and muscle aches. Exhibit 2 at ¶ 2.

Approximately six weeks after the HPV vaccination, on November 14, 2007,

Victoria was attending a funeral. Exhibit 11 at 13. After the funeral while at a

restaurant, she experienced a seizure and was taken to the emergency room of

Children’s Hospital of Wisconsin. Id. at 13, 28. Her extremities shook, her eyes

rolled, her face turned blue briefly, and she was disoriented. Id. at 13. In her

admission notes, the description of her condition states that she experienced a

See, e.g., Pet’r’s Posthear’g Br. at 54-55 n.20. However, the evidentiary standard

for the finding of facts is a mere preponderance.

7

seizure followed by a second seizure approximately four minutes later. Id. at 28.

A head CT scan, urine toxicology screen, and chest x-ray were performed with

normal results. Id. at 3-4, 13.

The testifying neurologists differed in how they assessed the funeral. Dr.

Kohrman suggested that the stress of attending a funeral for a loved one could have

provoked a seizure. Exhibit Z at 2; exhibit BB at 13; Tr. 459-60, 516-17. On the

other hand, although Dr. Shafrir agreed that stress can lead to a seizure, he asserted

that a funeral is not the type of stressful event that could lead to a seizure within

hours. Tr. 329-30.

Dr. Shafrir identified this November 14, 2007 tonic-clonic seizure as the first

clinical manifestation of any adverse consequence to the HPV vaccination. Tr.

244. This testimony is consistent with his second report in which he asserted that

Victoria “would not have developed epilepsy [had] she not receiv[ed] the

vaccination.” Exhibit 85 at 6.

The histories given during this hospitalization shed some light on Victoria’s

health leading up to the tonic-clonic seizure for which she was treated in the

hospital. Her father reported that Victoria was a “previously healthy [female]

[with] new onset [of seizures].” Exhibit 11 at 19; accord id. at 28 (admitting note

stating no history of seizures). Yet, at the same time, the histories also contain

details that, as discussed above, contribute to the finding that Victoria had, in fact,

had nocturnal seizures before November 14, 2007. For example, the neurology

resident or fellow documented that Victoria was having enuresis and an issue with

her tongue. Id. at 39-40.

During her hospitalization, Victoria underwent an electroencephalogram

(“EEG”). Exhibit 11 at 16-17. The results were abnormal. Id. More specifically,

the EEG showed “[i]ntermittent epileptiform spike & slow 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 the 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. Dr. Shafrir emphasized that a

nationally renowned epileptologist interpreted this EEG as showing discharges in a

focal location, not generalized. Tr. 227, 230. Dr. Kohrman responded that a

person with primary generalized epilepsy can have intermittent focal discharges

“here-and-there, now-and-again.” Id. at 447. Dr. Kohrman also maintained that

the EEG showed a “classic” pattern for a primary generalized epilepsy. Id. at 517-

18.

8

Late in the evening of November 15, 2007, Mr. Mager requested that

Victoria be discharged from the hospital. Exhibit 11 at 36. While the doctors

agreed that Victoria could be discharged, they recommended that Victoria take

Depakote. Id. Mr. Mager agreed that Victoria would take Depakote for one

month. Id. Victoria was expected to follow up with the neurologist who saw her

in the hospital, Dr. Sharif, in about one month. See id. at 71.

The medication the doctors prescribed for Victoria, Depakote, is primarily

given to patients with generalized epilepsy. Tr. 444-45, 463, 531 (Dr. Kohrman);

id. at 557 (Dr. Shafrir). Patients with partial epilepsy are likely to be prescribed

levetiracetam (Keppra) or oxcarbazepine (Trileptal). Tr. 463, 531 (Dr. Kohrman);

id. at 557-58 (Dr. Shafrir). The doctor’s selection of Depakote “push[ed]” Dr.

Kohrman to favor a diagnosis of primary generalized epilepsy. Id. at 519.

The day after being discharged from the hospital, Mr. Mager observed

Victoria having a similar tonic-clonic generalized seizure while sleeping. Exhibit

6 (Dr. Koehn’s notes) at 24. This episode lasted approximately one minute and

then she was unconscious for approximately five minutes. Victoria did not

remember the event happening. Id. at 24-25.

The follow up appointment happened as expected, on December 12, 2007.

Exhibit 11 at 75-77. Dr. Sharif noted that after Victoria 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.” Id. at 75. Victoria’s stepmother also reported that there had been

no more bedwetting incidents after the prescription of Depakote between her

hospital admission and this appointment. Id. Dr. Sharif noted an impression of

“focal onset epilepsy by EEG” and “some frontal lobe dysfunction.” Id. at 77. Dr.

Sharif recommended neuropsychological testing. Id. Dr. Sharif wrote that

Victoria might be a candidate for surgery. Id. To Dr. Shafrir, the suggestion that a

surgery might improve Victoria’s epilepsy meant that Dr. Sharif believed that

Victoria’s epilepsy was focal. Tr. 230.

Victoria saw another pediatric neurologist, Dr. Monica Koehn,

approximately two months later on February 21, 2008. Exhibit 6 at 20. An EEG

was performed, the results of which were normal. Id. at 22; accord Tr. 231-32.

Referring to the original abnormal EEG taken during her hospital admission, Dr.

Koehn noted, “The 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.” Exhibit 6 at 20. Victoria’s father and

9

stepmother requested that she be weaned off Depakote, although the medication

appeared to be controlling her seizure activity. Id. at 24, 28. 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 Amend. Pet. at ¶ 4. Victoria stopped taking Depakote in March

2008. Exhibit 6 at 9.

On April 1, 2008, Victoria underwent neuropsychological testing with Dr.

Stuart Waltonen. Exhibit 6 at 1. 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 these 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. Dr. Kohrman indicated that the

results of the neuropsychological evaluation showed that Victoria suffered from

discrete learning problems and these discrete learning problems are consistent with

JME. Tr. 455.

In conjunction with the neuropsychological testing, Victoria saw her

neurologist, Dr. Koehn, again. Exhibit 6 at 8. Dr. Koehn noted that discerning the

type of seizure Victoria was experiencing was difficult. Id. at 11. When asked

about Dr. Koehn’s comment, Dr. Shafrir stated that different neurologists did not

agree on whether Victoria had “generalized epilepsy, symptomatic generalized

epilepsy or partial seizure with secondary generalization.” Tr. 341-42. Dr.

Kohrman recognized that at the time of Dr. Koehn’s assessment, she had limited

information about Victoria. Thus, he would have had questions similar to the ones

Dr. Koehn raised. Id. at 521.

Dr. Koehn planned to repeat the EEG in the summer when Victoria was not

taking Depakote. Exhibit 6 at 11. The next EEG happened on June 26, 2008. It

was normal. Id. at 13. Dr. Kohrman stated that the normalized EEG showed that

Victoria responded to Depakote. Tr. 464.8 Dr. Shafrir said that a “total

8

Dr. Kohrman also opined that the normal EEGs could have missed

seizures. Tr. 462.

10

disappearance of all discharges” would be “quite unusual,” although it does

happen. Id. at 558.

Dr. Koehn reviewed the EEG in an appointment on July 10, 2008. Exhibit 6

at 15-18. Dr. Koehn documented that Victoria was failing almost all her subjects

in school. Id. at 16. The neurologic exam was normal. Id. at 17-18; see also Tr.

521. Dr. Koehn recommended that Victoria continue not taking medication and

return in about one year. Exhibit 6 at 18; see also Tr. 342 (Dr. Shafrir’s agreement

that he would have recommended not continuing medication).

Within one week of the July 10, 2008 appointment with Dr. Koehn,

Victoria’s stepmother inquired whether the HPV vaccination was related to

Victoria’s seizures. Exhibit 6 at 19 (call log). Dr. Koehn responded that the HPV

immunization was not related to the seizure. Id.

2. July 2008 to September 2012

From July 2008 to September 2012, Victoria attended eighth, ninth, tenth,

and eleventh grades. While there is no academic record for Victoria in eighth

grade, see exhibit 83, her high school transcript shows her academic performance.

Exhibit 83 at 1. During these years, Victoria’s grades were mixed, including many

Cs and Ds. Id. 9

During these four years, relatively few medical records were created. A

doctor indicated that Victoria was healthy enough to play volleyball in 2009.

Exhibit 14 at 1-2.

Victoria established a relationship with a new doctor, Dr. David Budde, on

January 5, 2012. Dr. Budde’s history indicates that Victoria had not had any

seizures in four years. Victoria was not taking any medications. Exhibit 10 at 18.

Victoria returned to Dr. Budde for an annual maintenance exam on March 6,

2012. Id. at 15. Dr. Budde recorded that Victoria was doing “fairly well in

school,” although there was “room for some improvement.” Id. He also noted,

9

Dr. Shafrir noted that after the seizures initially disappeared, Victoria

continued to have problems with learning. Tr. 238. He also opined that “it tells us

that the [vaccine] was associated with encephalopathy and was most likely the

cause of encephalopathy, the situation.” Id.; accord id. at 278. However, Dr.

Shafrir appears to overlook that Victoria had difficulties in school before the first

HPV vaccination.

11

“Mother has no concerns about her.” Id. The medical record from this visit

contains no information about seizures. See id.

Dr. Shafrir emphasized that Victoria was seizure-free for nearly five years.

During this period, she likely experienced stress and likely was deprived of sleep at

least sometimes. Tr. 215, 338. However, she did not experience seizures. This

seizure-free time helps Dr. Shafrir isolate the vaccinations as the triggers for

Victoria’s seizures.

Dr. Kohrman had less confidence in the assertion that Victoria did not

experience seizures during these approximately five years. He noted that after her

death, Mr. Mager recounted that Victoria did not always perceive having seizures

during sleep. Tr. 491; see also exhibit 13 at 2; exhibit 16 at 3 (Mr. Mager’s report

to medical examiners). 10

On September 11, 2012, Victoria received her second HPV vaccination.

Exhibit 4 at 1. Mr. Mager alleges that this vaccination aggravated her seizure

disorder. Amend. Pet. at ¶ 12; Spec. Mstr. Oral Arg. Tr. 605.

C. Events and Health from October 2012 Until January 2014

Approximately one month after the second HPV vaccination, Victoria 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

electrocardiogram (“EKG”), was normal. Id. at 13-14. She was diagnosed with a

“probable seizure” and discharged. Id. at 14. When she was discharged, Victoria

was recommended to see a neurologist in follow-up. Id. Because Victoria already

had a seizure disorder, the doctors at the emergency room did not need to order an

EEG. Tr. 525.

It appears that Victoria experienced two other seizures for which she did not

seek medical attention emergently. She had a seizure at school on October 19,

2012. Exhibit 9 at 6 (report to Dr. Edgar); exhibit 2 at ¶ 7 (Mr. Mager’s first

affidavit). She had a third seizure on November 7, 2012. Exhibit 9 at 39 (Dr.

Budde’s Nov. 8, 2012 report); id. at 6 (report to Dr. Edgar listing seizure on

November 8, 2012).

10

Dr. Kohrman also asserted, “There is no medical record during that

period.” Tr. 491. However, this assertion overlooks records from Dr. Budde. See

id. at 522-23.

12

Following a third seizure, Victoria 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 emergency room visit on October 19, 2012, and

November 7, 2012. Id. Dr. Budde recorded that although the doctors at Theda

Clark had recommended an appointment with a neurologist, Victoria had not seen

one. Id. Dr. Budde noted that Victoria “adamantly denies any drug or alcohol

use.” Id.

Dr. Budde also stated that Victoria felt “spacy” and may have been “losing

some time during lectures or conversations that could represent absence-type

seizures.” Id. Dr. Kohrman interpreted the history of feeling “spacy” as consistent

with Victoria experiencing absence type seizures. Tr. 450. Dr. Shafrir disagreed,

stating that feeling “spacy” “is not evidence for absence.” Id. at 313.

In the history obtained by Dr. Budde, he wrote, “Sometimes, [Victoria]

thinks she can feel them coming on as she will get an unusual sensation. She had a

cramping sensation in her calf prior to one seizure.” Exhibit 9 at 39. Dr. Shafrir

interpreted this information as an “aura.” Tr. 232, 309, 559-60. An aura, in turn,

makes the diagnosis of JME less likely. Id. In contrast, Dr. Kohrman considered

Victoria’s unusual sensation (or aura) as consistent with an absence seizure and her

cramping as a myoclonic jerk. Id. at 529, 567. At the end of the appointment, Dr.

Budde prescribed Depakote and facilitated a referral to a local neurologist, Dr.

Terence Edgar. Exhibit 9 at 39.

Victoria saw Dr. Edgar on January 14, 2013. Exhibit 9 at 6-8. Dr. Edgar

recorded that “Mom does report occasional staring spells, but it is unclear if there

are absence seizures.” Id. at 8. Dr. Shafrir relied upon this statement to opine that

Victoria did not have absence seizures. Tr. 311-12.

An EEG was also performed. Exhibit 9 at 24-25. 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. Shafrir

indicated that the January 2013 EEG supports a diagnosis of partial seizures with

secondary generalization. Tr. 347-48. Dr. Kohrman recognized that this EEG was

not typical for juvenile myoclonic epilepsy. Id. at 545-46.

Dr. Edgar’s impression was a 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.”

Exhibit 9 at 8. Dr. Edgar also noted that he “inquired into the myoclonic seizures.”

Id. He recommended Depakote but, after Victoria specified that she did not wish

13

to remain on Depakote, Dr. Edgar directed her to begin weaning off Depakote and

prescribed a different anti-seizure medication, Keppra. Id. at 8. Dr. Edgar

instructed Victoria to follow up in one year. Id. In Dr. Kohrman’s opinion,

Keppra was likely to be a less effective medication. Tr. 467.

To Dr. Shafrir, Dr. Edgar’s record that Victoria did not report myoclonic

seizures was important. Victoria could not suffer from JME without having

myoclonic seizures. Tr. 232-33. Dr. Kohrman was less concerned about the lack

of reports about myoclonic seizures because myoclonic seizures can be difficult to

detect. Id. at 443, 451-52, 457-58, 496. Dr. Kohrman gave much more weight to

Dr. Edgar’s (and Dr. Koehn’s) diagnosis of primary generalized epilepsy. Id. at

496; see also exhibit A at 13.

Victoria was supposed to have blood drawn at Berlin Hospital on March 1,

2013. However, she did not appear. Exhibit 9 at 15.

To obtain more information, Dr. Edgar ordered additional labs. On June 18,

2013, Victoria’s stepmother told Dr. Edgar that Victoria may miss a dose of

Keppra “here and there.” Exhibit 9 at 13.

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 subtherapeutic 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. Because Victoria was concerned about not having insurance, Dr.

Edgar gave her a three-month supply of Keppra. Id. Dr. Edgar noted “probable

juvenile myoclonic epilepsy” at this appointment due to age of onset. Id.11

The summer of 2013 was the summer after Victoria had graduated from high

school. During her senior year, she earned a mixture of grades. Exhibit 83 at 1.

According to Victoria’s obituary, Victoria planned to enter military service.

Exhibit 110. At Waukesha County Technical College in the fall 2013, Victoria did

not earn any credits as she failed two classes and withdrew from a third. Exhibit

82 at 1.

11

Mr. Mager asserted that “Dr. Edgar only suggests the possibility of JME.”

Pet’r’s Posthear’g Br. at 25 (emphasis added). However, Dr. Edgar stated, “The

age of onset at 11 years of age suggests probable juvenile myoclonic epilepsy.”

Exhibit 9 at 4, 27 (emphasis added).

14

In November 2013, Victoria called Dr. Edgar’s office to say that she was

running out of medication. Exhibit 9 at 11. Due to the lack of records, Dr. Shafrir

could not comment on Victoria’s compliance with her medication in the fall 2013.

Tr. 349-50. According to an account Mr. Mager provided shortly after Victoria’s

death, she picked up more medication over the holidays. Exhibit 13 at 2. On

January 2, 2014, Kathy Mager informed Dr. Edgar’s office that Victoria intended

to transfer her care to a doctor closer to her, although the doctor was not identified.

Exhibit 9 at 9; see also Tr. 355.

Mr. Mager told medical examiners that in November 2013, Victoria was

occasionally having seizures in her sleep unknowingly. Exhibit 13 at 2; exhibit 16

at 3; see also Tr. 354. How Mr. Mager reached this conclusion is not clear as it

appears that Mr. Mager was not living with Victoria at this time. Tr. 354.

On January 11, 2014, after being discovered unresponsive at a friend’s

house, Victoria was rushed to the emergency department. Exhibit 8 at 1-2. She

was pronounced dead upon her arrival. Id. at 2. 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. Zelda Okia on January 13, 2014. Exhibit

12 at 1. The findings included pulmonary edema and brain changes consistent

with a seizure disorder. Id. at 2; exhibit 16 at 10. 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.; see also Tr. 302 (Dr. Shafrir: Victoria did not have low levels of medication in

her blood at the time of her death); id. at 467 (Dr. Kohrman: Keppra level of 26 is

in the middle of the therapeutic range).

Sections of the brain showed focal areas of subpial gliosis. Exhibit 16 at 16.

Gliosis occurs when glial cells cause structural changes to the central nervous

system in response to trauma to the brain, such as seizures. Tr. 395-96. Subpial

gliosis is found in areas of the brain associated with surface pia, including the

superior temporal gyrus and inferior temporal gyrus. Id. at 479-80. All the experts

agreed that epileptic seizures can cause gliosis. Id. at 288 (Dr. Shafrir), 394-97,

415 (Dr. Fujinami). Seizures can cause gliosis with or without an inflammatory

process. Id. at 289-90.

15

Beyond those foundational points, gliosis was the topic for a great deal of

(conflicting) testimony. See Spec. Mstr. Oral Arg. Tr. 633-37. Dr. Shafrir stated

that the amount of gliosis exceeded the amount expected in a person having

infrequent seizures. The presence of this excessive gliosis, in turn, meant that

Victoria was suffering from a process other than JME. Tr. 287.

Dr. Fujinami noted that the neuropathologist did not report gliosis around

the blood vessels in the brain. According to Dr. Fujinami, neuropathologists would

report this abnormal finding if they saw it. Tr. 388. From the lack of reporting,

Dr. Fujinami inferred that Victoria’s blood-brain barrier was intact. Id. A secure

blood-brain barrier undermines Dr. Shafrir’s theory that an antigen from the

periphery disturbed Victoria’s central nervous system. Id. at 397. On cross-

examination, Mr. Mager’s attorney ably pointed out that the record does not

contain an actual report from a neuropathologist. Id. at 412-14. Instead, the

autopsy simply states that a neuropathologist from Froedert Hospital, Dr. Cochran,

reviewed the microscopic slides of the brain. Exhibit 16 at 15. In rebuttal

testimony, Dr. Shafrir indicated that there is only one sentence in the autopsy

report about gliosis. Thus, deriving any information from it is difficult. Tr. 555-

57.

Victoria’s death certificate listed “seizure disorder” as her cause of death.

Exhibit 1 at 1. The testifying neurologists agreed that Victoria suffered sudden

unexpected death in epilepsy (“SUDEP”) as a consequence of her epilepsy. Tr.

355 (Dr. Shafrir), 533-34 (Dr. Kohrman adding factors that placed Victoria at

greater risk for a sudden and unexpected death); see also Spec. Mstr. Oral Arg. Tr.

648-49.

II. Procedural History

Represented by attorney Mark Krueger, Mr. Mager alleged that a dose of the

HPV vaccine given to Victoria on September 11, 2012 “aggravated a prior seizure

disorder leading to and causing her death.” Amend. Pet. at ¶ 12. 12 He then

12

The original petition, which was filed roughly two months earlier, had

alleged that a dose of the HPV vaccination given on October 2, 2007 caused

Victoria’s seizure disorder. However, the statute of limitations barred proceeding

on a claim based upon the 2007 vaccination. Thus, Mr. Mager’s attorney, Mr.

Krueger, amended the petition to assert a claim that the 2012 vaccination

significantly aggravated the seizure disorder. Although the amended petition also

asserts that the 2012 vaccination caused Victoria’s seizure disorder, Victoria was

already suffering from a seizure disorder before 2012.

16

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 contested Mr. Mager’s entitlement, arguing that Mr. Mager

had not established the elements for a significant aggravation claim. Resp’t’s Rep.,

filed Apr. 1, 2015, 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.

Mr. Mager’s initial effort to obtain competent reports from experts was not

successful. After multiple extensions, Mr. Mager filed his first expert report from

Dr. Mikovits and Dr. Ruscetti on November 17, 2016. Eventually, Mr. Mager

moved to strike the reports from these partners as well as an expert report from

their colleague, Dr. Aliffe. Thus, the details of these reports from people whom

Mr. Mager retained are no longer evidence and do not need to be discussed further.

However, before Mr. Mager ceased his reliance on Drs. Mikovits, Ruscetti, and

Aliffe, the Secretary responded with reports from Dr. Fujinami and Dr. Kohrman

on March 2, 2017, and March 22, 2017. While Dr. Fujinami and Dr. Kohrman

primarily responded to opinions expressed by Drs. Mikovits, Ruscetti, and Aliffe,

Dr. Kohrman presented some opinions that remained relevant after the withdrawal

of the earlier reports. Dr. Kohrman asserted that (1) the appropriate diagnosis for

Victoria was JME, (2) Victoria’s epilepsy began when she was five years old, and

(3) Victoria’s death was not caused by the HPV vaccination and was more likely

related to Victoria’s actions before her death, such as failing to take her anti-

seizure medication, smoking, drinking beer, and staying up late. Exhibit A at 11-

13; see also exhibit Y (Dr. Kohrman’s report, dated Mar. 18, 2018) at 2, 7.

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 support his claim better. Mr.

Mager then filed an expert report from Dr. Shafrir on October 3, 2018. The

presentation of Dr. Shafrir’s opinion essentially begins Mr. Mager’s development

of experts.

In this report, Dr. Shafrir reviewed Victoria’s medical history in detail.

Exhibit 55 at 1-16. In the course of this summary, Dr. Shafrir raised the potential

helpfulness of obtaining the slides from Victoria Mager’s autopsy. 13 Id. at 14. Dr.

13

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

17

Shafrir emphasized that Victoria’s case was an example of challenge-rechallenge

in that she “suffered seizures twice within 1 month of each of her HPV

vaccinations.” Id. at 16. As for how the HPV vaccination can cause seizures /

epilepsy, Dr. Shafrir stated the “mechanism is likely based on molecular mimicry

which could be supplemented by activation of the innate immune system.” Id. at

20. He asserted that “Victoria had an abnormal immune reaction to the HPV

vaccination produced brain inflammation in autoimmune epilepsy.” Id.

In response to Dr. Shafrir, the Secretary obtained reports from the people

who had previously responded to Drs. Mikovits, Ruscetti, and Aliffe. 14 Dr.

Kohrman began, “As I have stated in my previous report Victoria had a preexisting

encephalopathy dating to first grade.” Exhibit Z at 2. Dr. Kohrman also

commented on Victoria’s activities just before she died: “when she was prescribed

meds, she did not take them regularly prior to her death per Mr. Mager’s report.

On the night she died she had stayed up until 4 am drinking beer and smoking.

Again, her death is associated with a seizure in the face of sleep deprivation.” Id.15

Dr. Fujinami stated that Dr. Shafrir “is opining that components contained

in the vaccine caused an autoimmune epilepsy that resulted in seizures.” Exhibit

AA at 3. Dr. Fujinami questioned whether Victoria suffered an autoimmune

process because “there is no indication of autoimmune indicators being present.”

Id. Dr. Fujinami also raised doubts about molecular mimicry because one article

(Ruiz) showed that peptides from the human papillomavirus “could actually

protect from autoimmune neuroinflammation.” Id. at 3-4, citing exhibit AA, tab 5

(Pedro J. Ruiz et al., Microbial Epitopes Act as Altered Peptide Ligands to Prevent

Experimental Autoimmune Encephalomyelitis, 189 J. Experimental Med. 1275

(1999)).16

Given that the Secretary submitted reports from Dr. Kohrman and Dr.

Fujinami, the next step was for Mr. Mager to respond. This process was delayed

failed to reach a settlement agreement and the case was removed from ADR on

March 25, 2019.

14

The reports from Dr. Kohrman and Dr. Fujinami also addressed the most

recent reports from Drs. Mikovits, Ruscetti, and Aliffe. But, again, these

comments are no longer relevant.

15

Dr. Kohrman’s response to Dr. Shafrir’s report was essentially one page.

16

Like Dr. Kohrman, Dr. Fujinami responded to Dr. Shafrir in essentially

one page.

18

as Mr. Mager attempted to get the autopsy slides. 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. Thus, it appeared that the submission of reports from experts was

concluded.

The undersigned issued an order for submissions in advance of potential

adjudication on November 20, 2019. This order informed the parties that the case

might be decided without a hearing. Order, issued Nov. 20, 2019, at 1. Citing

Broekelshen v. Secretary of Health & Human Services, 618 F.3d 1339, 1346 (Fed.

Cir. 2010), the undersigned directed the parties to comment upon the appropriate

diagnosis for Victoria. This discussion was requested because Dr. Kohrman

“proposed that Victoria suffered from juvenile myoclonic epilepsy. . . . While [Dr.

Shafrir] seems to be opining that Victoria suffered an encephalopathy and Victoria

suffered from an autoimmune epilepsy, not juvenile myoclonic epilepsy.” Order,

issued Nov. 20, 2019, at 5, citing exhibit A at 13 and exhibit 55 at 18-22. In this

context, the parties were instructed to identify the diagnostic criteria for any

relevant condition. The parties also were instructed to address the six Loving

factors concerning whether a vaccine significantly aggravated an underlying

condition. Id. at 6-11. The order also raised, in a separate section, the topic of

how Victoria would have been but for the vaccination. Id. at 11.

This order prompted Mr. Mager to obtain another report from Dr. Shafrir,

which Mr. Mager filed on July 25, 2020, after receiving multiple extensions. This

new report is approximately six pages with another two pages devoted to

references. Exhibit 85. Dr. Shafrir began with the “importance of

challenge/rechallenge.” Id. at 1. Consistent with the November 20, 2019 order,

Dr. Shafrir commented upon the appropriate diagnosis. He stated that Victoria

“suffered SUDEP [sudden unexpected death in epilepsy] as a result of the acquired

autoimmune epilepsy, which was the result of her repeated HPV vaccination.” Id.

at 2. Dr. Shafrir explained why the diagnosis that Dr. Kohrman proposed, JME,

does not fit. Id. at 2-3. Rather, the “basis for the presumed autoimmune epilepsy

is the striking relationship of the seizures to the HPV immunization.” Id. at 3. Dr.

Shafrir also added approximately a dozen articles to support “the role of HPV

vaccination in Ms. Mager[’s] autoimmune epilepsy.” Id. at 4.

Two days after filing Dr. Shafrir’s supplemental report, Mr. Mager made his

arguments. Under the topic of “diagnosis,” Mr. Mager asserted, “Petitioner

contends Victoria suffered from autoimmune epilepsy that resulted in sudden

unexpected death with epilepsy.” Pet’r’s Prehear’g Br., filed July 27, 2020, at 9.

After discrediting the diagnosis of JME, Mr. Mager contended that “Victoria’s

most likely, most appropriate diagnosis would be autoimmune epilepsy.” Id. Mr.

19

Mager presented three ways in which autoimmune epilepsy is typically diagnosed.

However, Mr. Mager did not identify any evidence supporting the ways

autoimmune epilepsy is typically diagnosed. Id. at 9-10. Mr. Mager asserted, “as

demonstrated by Suleiman et al. (Exhibit 88), autoimmune epilepsy can also be

present as milder epilepsy cases.” Id. at 10.

In introducing his analysis of the Loving factors, Mr. Mager stated,

“Petitioner’s theory of causation is a neurological autoimmune process triggered

by the HPV vaccine, causing autoimmune epilepsy, which is strongly supported by

the challenge/ rechallenge.” Id. at 16. “Molecular mimicry is the most likely

mechanism” by which the HPV vaccine triggered seizures. Id. at 21. Although

Mr. Mager discussed aspects of this theory for several pages, he stated, “all of this

underpins Petitioner’s theory of causation which is based on

challenge/rechallenge.” Id. at 23. Mr. Mager added that “while he alleges the first

HPV [dose] caused Victoria’s onset of autoimmune epilepsy, his claim is for the

significant aggravation of her epilepsy (largely controlled and seizure-free for five

years) by her second dose of HPV. Petitioner is not precluded from using the first

dose of HPV vaccination as part of her challenge/rechallenge claim as she is not

claiming injury from the initial insult.” Id. at 46.

Due to the presentation of a new report from Dr. Shafrir, the Secretary had a

chance to respond and did so by filing a report from Dr. Kohrman and a report

from Dr. Fujinami. Dr. Kohrman opined about the appropriate diagnosis. He set

forth the diagnostic criteria for JME. Exhibit BB at 2. Dr. Kohrman also defined

the diagnostic criteria for autoimmune epilepsy. Id. at 11-12. He extensively

summarized the events in Victoria’s medical history. Id. at 3-10. He concluded, as

he did in other reports, that Victoria’s seizure disorder is consistent with JME. Id.

at 14.

Dr. Kohrman disputed the presence of challenge-rechallenge. He

maintained that Victoria’s case did not constitute an example of challenge-

rechallenge. He explained, “Given the diagnosis of a primary generalized

epilepsy, that was never adequately treated [due] to family request and behavior,

and the lack of patient taking meds, [h]er history and clinical course cannot be

considered a challenge rechallenge. It was never documented medically that she

was seizure free prior to [the] second vaccination.” Id. at 12.

Dr. Kohrman also maintained, as he had in previous reports, that before the

first vaccination Victoria had nocturnal seizures. Id. at 13, citing exhibit 6 at 25

and exhibit 11 at 22. Dr. Kohrman did not address the medical theory that Dr.

Shafrir had proposed to explain how a HPV vaccine can aggravate a preexisting

seizure disorder. See exhibit BB at 14.

20

In conjunction with Dr. Kohrman’s report, the Secretary also submitted a

report from Dr. Fujinami, which is essentially one and a half, single-spaced pages.

Dr. Fujinami also disputed whether Victoria’s case is an example of challenge-

rechallenge. Dr. Fujinami argued “there is no clear information linking the

occurrence of seizures to [the] HPV vaccination, let alone an enhanced immune

response occurring against the second HPV vaccination due to immunological

memory present after the first vaccination with HPV.” Exhibit CC at 1.

While Dr. Fujinami recognized that he is not a physician, Dr. Fujinami

opined that Victoria “was not consistently taking her anti-seizure medications,

which led to the increase of seizures.” Id. He also indicated that Victoria did not

suffer from autoimmune epilepsy, which was the diagnosis given by Dr. Shafrir.

Id.

With the reports from Dr. Kohrman and Dr. Fujinami, the Secretary also

filed his brief. A central portion of the Secretary’s argument was that Victoria did

not suffer from autoimmune epilepsy and that her diagnosis is JME. Resp’t’s

Prehear’g Br., filed Feb. 10, 2021, at 10-15. The basic diagnostic criteria,

according to the Secretary and Dr. Kohrman, came from the Higdon and Steriade

articles. Id. at 11-12, citing exhibit BB, tab 4 (Lindsay M. Higdon, Autoimmune

Epilepsy: More than Just a Paraneoplastic Syndrome, Practical Neurology, Oct.

2018) and exhibit BB, tab 5 (Claude Steriade et al., Acute Symptomatic Seizures

Secondary to Autoimmune Encephalitis and Autoimmune-Associated Epilepsy:

Conceptual Definitions, 61 Epilepsia 1341 (2020)). In his brief, the Secretary also

addressed the Loving prongs. Id. at 17-26.

Mr. Mager replied to the Secretary’s arguments. Under the heading,

“VICTORIA’S DIAGNOSIS,” Mr. Mager asserted that “Victoria suffered from

autoimmune epilepsy, which caused SUDEP.” Pet’r’s Prehear’g Reply, filed Mar.

26, 2021, at 10. He continued, “Victoria suffered from autoimmune epilepsy based

on her well-documented systems [sic, “symptoms” might have been intended] and

the appropriate diagnostic criteria.” Id. With respect to the diagnostic criteria, it

appeared that Mr. Mager cited reference 9 in exhibit 65 multiple times. However,

that reference was not an exhibit. Mr. Mager also maintained that he satisfied the

Loving factors. Id. at 37-50.

Because Mr. Mager had cited, but not filed, reference 9 in exhibit 65, he was

directed to file it as an exhibit. Mr. Mager was also instructed to identify “the

source of the diagnostic criteria for autoimmune epilepsy.” Order, issued June 16,

2021.

21

In response, Mr. Mager clarified that “Pet. Ex. 65. Ref. 9 . . . does not refer

to the ninth reference in Pet. Ex. 65. Rather, Pet. Ex. 65 is also Ref. 09 in Dr.

Shafrir’s first expert report, filed as Pet. Ex. 55.” Pet’r’s Status Rep., filed June 17,

2021. For the diagnostic criteria, Mr. Mager stated that “the list itself does not

appear – it was derived from Pet. Ex. 88 along with Pet. Ex. 65. The criteria are

discussed in that section solely to demonstrate that autoimmune epilepsy can

present as milder epilepsy.” Id.

The undersigned denied compensation. Decision, 2021 WL 3737056 (Fed.

Cl. Spec. Mstr. July 29, 2021). The undersigned found that there was insufficient

evidence to support a diagnosis of autoimmune epilepsy. Id. at *11. The

undersigned reasoned that Mr. Mager had not met his burden to show either the

presence of autoimmune antibodies in Victoria’s blood or that Victoria’s seizures

were refractory. Id. at *7-8, 10. Additionally, the undersigned found that Mr.

Mager did not establish that Victoria suffered from autoimmune encephalitis. Id.

at *9. Accordingly, since the undersigned found that Mr. Mager did not establish

the threshold issue of diagnosis and analysis of causation was therefore

unnecessary, compensation was denied. Id. at *11.

Mr. Mager filed a motion for review on August 27, 2021. Mr. Mager argued

that the undersigned mischaracterized Victoria’s diagnosis. Mot. for Rev., filed

Aug. 27, 2021, at 2. He asserted that the undersigned conflated Victoria’s pre-

death diagnosis and her alleged injury and focused only on autoimmune epilepsy

with respect to Dr. Shafrir’s causation theory instead of considering the theory in

its full context. Id. at 20. Mr. Mager acknowledged that Victoria did not meet the

criteria for autoimmune epilepsy but maintained that Victoria’s epilepsy was

“autoimmune in nature.” Id. at 21.

The Court granted Mr. Mager’s motion for review and vacated the

undersigned’s decision denying compensation. Opinion and Order, issued Jan. 21,

2022, at 2, 158 Fed. Cl. 136, 137 (2022). The Court noted that the undersigned

was thorough in explaining why Victoria did not have autoimmune epilepsy. Id. at

19, 158 Fed. Cl. at 155. However, the Court concluded that the undersigned

mischaracterized Victoria’s diagnosis and misunderstood Mr. Mager’s argument

that “the vaccine caused an autoimmune response triggered recurrence and

aggravation of [Victoria’s] epilepsy disorder.” Id. Accordingly, the case was

remanded to the undersigned to consider whether Mr. Mager can satisfy the

elements for an off-Table claim under Althen v. Secretary of Health & Human

Services, 418 F.3d 1274, 1278 (Fed. Cir. 2005). Id. at 24, 158 Fed. Cl. at 160.

22

Following the Court’s Opinion and Order, the case was promptly scheduled

for a hearing.17 The hearing was held via videoconferencing over two days, March

8-9, 2022. Dr. Shafrir, Dr. Kohrman, and Dr. Fujinami testified.

After the hearing, the parties argued their positions in briefs, filed on an

expedited basis. Mr. Mager submitted his primary brief on March 25, 2022 and his

reply on April 5, 2022. In between, the Secretary filed his brief on April 1, 2022.

An oral argument was held on April 8, 2022.

III. Standards for Adjudication

A petitioner is required to establish his case by a preponderance of the

evidence. 42 U.S.C. § 300aa-13(1)(a). The preponderance of the evidence

standard requires a “trier of fact to believe that the existence of a fact is more

probable than its nonexistence before [he] may find in favor of the party who has

the burden to persuade the judge of the fact’s existence.” Moberly v. Sec’y of

Health & Hum. Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010) (citations

omitted). Proof of medical certainty is not required. Bunting v. Sec’y of Health &

Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991).

Distinguishing between “preponderant evidence” and “medical certainty” is

important because a special master should not impose an evidentiary burden that is

too high. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1379-80 (Fed.

Cir. 2009) (reversing a special master’s decision that petitioners were not entitled

to compensation); see also Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d

1357 (Fed. Cir. 2000); Hodges v. Sec’y of Health & Hum. Servs., 9 F.3d 958, 961

(Fed. Cir. 1993) (disagreeing with the dissenting judge’s contention that the special

master confused preponderance of the evidence with medical certainty).

As confirmed in W.C. v. Secretary of Health & Human Services, 704 F.3d

1352, 1357 (Fed. Cir. 2013), the elements of an off-Table significant aggravation

case were stated in Loving v. Secretary of Health & Human Services, 86 Fed. Cl.

135 (2009). There, the Court blended the test from Althen, which defines off-

Table causation cases, with a test from Whitecotton v. Secretary of Health &

Human Services, 81 F.3d 1099, 1107 (Fed. Cir. 1996), which concerns on-Table

significant aggravation cases. The resulting test has six components. These are:

(1) the person’s condition prior to administration of the vaccine, (2) the

person’s current condition (or the condition following the vaccination if that

is also pertinent), (3) whether the person’s current condition constitutes a

17

The cooperation of the attorneys and witnesses is appreciated.

23

“significant aggravation” of the person’s condition prior to vaccination, (4) a

medical theory causally connecting such a significantly worsened condition

to the vaccination, (5) a logical sequence of cause and effect showing that

the vaccination was the reason for the significant aggravation, and (6) a

showing of a proximate temporal relationship between the vaccination and

the significant aggravation.

Loving, 86 Fed. Cl. at 144.

Additional details about how to evaluate each prong are provided in the

analysis section below.

IV. Analysis

The analysis consists of eight sections. The first section reviews the topic of

diagnosis, which is no longer disputed. The next six sections concern the elements

of significant aggravation set forth in Loving. Mr. Mager bears the burden of

proof on each of these six elements. The final section (section IV.H) considers

whether the Secretary has met his burden of proof in showing that Victoria’s

epilepsy followed the natural course of the disease.

A. Diagnosis

1. Procedural Aspects to Diagnosis and the Parties’ Arguments

Among the experts testifying in this case, Dr. Kohrman presented the first

opinion regarding diagnosis. 18 He opined that Victoria suffered from juvenile

myoclonic epilepsy (“JME”). Exhibit A at 11-13.

In response, Dr. Shafrir disagreed with the opinion that Victoria suffered

from JME. Dr. Shafrir opined that “Victoria had an abnormal immune reaction to

the HPV vaccination which produced brain inflammation in autoimmune

epilepsy.” Exhibit 55 at 20. The term “generalized epilepsy” does not appear in

Dr. Shafrir’s first report. See id. Dr. Shafrir also did not indicate that Victoria’s

epilepsy was either “mild” or “not severe.”

Perceiving a dispute over diagnosis, the undersigned ordered the parties to

comment on the condition the HPV vaccination aggravated. Order, issued Nov.

20, 2019, at 5, citing Broekelschen, 618 F.3d at 1346. This direction was based

upon a view that Dr. Kohrman had “proposed that Victoria suffered from juvenile

18

The reports from an earlier set of experts were struck.

24

myoclonic epilepsy . . . . While [Dr. Shafrir] seems to be opining that Victoria

suffered an encephalopathy and Victoria suffered from an autoimmune epilepsy,

not juvenile myoclonic epilepsy.” Id. The parties were also ordered to identify the

diagnostic criteria for any relevant condition.

Mr. Mager filed a second report from Dr. Shafrir. Dr. Shafrir opined that

Victoria “suffered SUDEP as a result of the acquired autoimmune epilepsy, which

was the result of her repeated HPV vaccination.” Exhibit 85 at 2. Dr. Shafrir also

indicated that SUDEP “can occur in patients whose epilepsy is not that severe.”

Id. at 1. Dr. Shafrir, however, did not explicitly state that Victoria’s epilepsy was

either mild or not severe. Dr. Shafrir added, “The epilepsy diagnosis (not relating

to specific etiology) is either secondary generalized epilepsy or symptomatic

generalized epilepsy. The etiology of this epilepsy is autoimmune, induced by [an]

abnormal immune reaction to the HPV vaccination.” Id. at 4.

When Mr. Mager advocated his position, he argued, “Petitioner contends

Victoria suffered from autoimmune epilepsy that resulted in sudden unexpected

death with epilepsy.” Pet’r’s Prehear’g Br., filed July 27, 2022, at 9, citing exhibit

55 (Dr. Shafrir’s first report) at 18. Mr. Mager further argued that Dr. Shafrir

“strongly disagrees” with the assertion that Victoria suffered from JME. Id. Mr.

Mager maintained that “Victoria’s most likely, most appropriate diagnosis would

be autoimmune epilepsy.” Id. Mr. Mager also presented three factors by which

autoimmune epilepsy “is typically diagnosed.” Id. at 9-10. Citing the Suleiman

article (exhibit 88), Mr. Mager asserted that “autoimmune epilepsy can also be

present as milder epilepsy cases.” Id. at 10. In this brief, Mr. Mager did not argue

that an analysis of diagnosis pursuant to Broekelschen was inappropriate. See id.

In contrast, the Secretary explicitly argued that whether Mr. Mager had

persuasively established that Victoria suffered from JME was a fundamental point.

“As the Federal Circuit has made clear, ‘the statute places the burden on petitioner

to make a showing of at least one defined and recognized injury.’” Resp’t’s

Prehear’g Br., filed Feb. 10, 2022, at 14, quoting Lombardi v. Sec’y of Health &

Hum. Servs., 656 F.3d 1343, 1353 (Fed. Cir. 2011). The Secretary further

maintained that Victoria did not suffer from autoimmune epilepsy but rather

suffered from JME. Id. at 10-15. This position was in accord with Dr. Kohrman’s

most recent report. See exhibit BB.

Mr. Mager quoted the portion of the Secretary’s prehearing brief that cited

Broekelschen and Lombardi. Mr. Mager argued that Lombardi was an “unusual”

case. Pet’r’s’ Prehear’g Reply, filed Mar. 26, 2021, at 10, citing Contreras v. Sec’y

of Health & Hum. Servs., 107 Fed. Cl. 280, 294 (2012). Otherwise, Mr. Mager

advanced the position that “Victoria suffered from autoimmune epilepsy.” Id. at

25

10. Mr. Mager did not qualify this assertion by describing Victoria’s epilepsy as

either “mild” or “not severe.” See id. Concomitantly, Mr. Mager argued that the

Secretary “failed to show Victoria suffered from juvenile myoclonic epilepsy.” Id.

at 16 (capitalization changed without notation).

In response to an order, Mr. Mager provided additional information

regarding the diagnostic criteria for autoimmune epilepsy. He stated that the

diagnostic criteria in his briefs were derived from two exhibits, exhibits 88 and 65.

“The criteria are discussed in that section solely to demonstrate that autoimmune

epilepsy can present as milder epilepsy.” Pet’r’s Status Rep., filed June 16, 2021.

The undersigned found that Mr. Mager asserted that Victoria suffered from

autoimmune epilepsy and that Mr. Mager had not persuasively demonstrated that

autoimmune epilepsy was an appropriate diagnosis. Decision, issued July 29,

2021. Because this appeared to be a predicate showing, the decision found that

Mr. Mager was not entitled to compensation. The decision did not address whether

preponderant evidence supported a finding that Victoria suffered from JME. The

decision did not quote the portion of the June 16, 2021 status report in which Mr.

Mager maintained that “autoimmune epilepsy can present as milder epilepsy.”

Mr. Mager challenged this decision by filing a motion for review. In

relevant part, he argued that Broekelschen was distinguishable because the parties

agreed that Victoria suffered from epilepsy. Pet’r’s Mot. for Rev., filed Aug. 27,

2021, at 18.

The Secretary in turn, defended the July 29, 2021 decision. Citing

Broekelschen and Lombardi, the Secretary argued that Mr. Mager needed to show

the injury (autoimmune epilepsy) that he alleged the HPV vaccine aggravated.

Resp’t’s Resp. to Mot. for Rev., filed Sept. 24, 2021, at 6-7.

The Court granted the motion for review. The Court found that “JME and

autoimmune epilepsy are variants of the same disorder—i.e., a seizure disorder.”

Opinion and Order, at 20, 158 Fed. Cl. at 156. Because the “‘existence and nature

of the injury’ was not in dispute,” “the Special Master erred in failing to consider

whether the vaccine caused Ms. Mager’s injury under Althen and its progeny.” Id.

at 22, 158 Fed. Cl. at 158. In terms of direction, the Court indicated that “the

Special Master must perform the requisite causation analysis under Althen and its

progeny.” Id.

During the post-remand hearing, the parties continued to develop evidence

regarding the type of epilepsy Victoria suffered. Dr. Shafrir stated that Victoria

suffered from partial epilepsy with secondary generalizations. Tr. 296, 316; see

26

also id. at 548-49 (rebuttal testimony). He also explained why, in his opinion,

Victoria did not suffer from JME. Id. at 308-14. Dr. Kohrman had the opposite

point of view. 19 He stated that Victoria suffered from JME. Id. at 443-69. Dr.

Kohrman also discussed why autoimmune epilepsy (or epilepsy with an

autoimmune basis) is not an appropriate diagnosis for Victoria. Id. at 471-91.

After the hearing, Mr. Mager’s position matched the opinion offered by his

expert, Dr. Shafrir. Mr. Mager asserted “that as a result of the HPV vaccination

Victoria Mager developed epilepsy which is partial with secondary generalization

on an autoimmune basis.” Pet’r’s Posthear’g Br., filed Mar. 25, 2022, at 18.

2. Resolution

“Upon return of its mandate, the district court cannot give relief beyond the

scope of that mandate, but it may act on matters left open by the mandate.”

Laitram Corp. v. NEC Corp., 115 F.3d 947, 951 (Fed. Cir. 1997) (quoting Caldwell

v. Puget Sound Elec. Apprenticeship & Training Tr., 824 F.2d 765, 767 (9th Cir.

1987)) (internal quotation marks omitted). Furthermore, the doctrine of the law of

the case, which precludes relitigation of issues explicitly or implicitly decided on

appeal, sheds light on implicit appellate considerations of arguments. See

Travelers Ins. Co. v. United States, 72 Fed. Cl. 316, 325 (2006) (citing W.L. Gore

& Assocs., Inc. v. Garlock, Inc., 842 F.2d 1275, 1278 (Fed. Cir. 1988)) (“The

doctrine [of the law of the case], of course, does not constrain a trial court’s

consideration of an issue that has not been considered on appeal. But the doctrine

extends to issues that were implicitly addressed.”).

Through the parties’ briefs and oral argument, the Court understood their

competing positions. Reduced to its simple terms, Mr. Mager’s argument was that

evaluating whether Victoria suffered autoimmune epilepsy was irrelevant because

the parties agreed she had a seizure disorder and his theory for significant

aggravation was based on rechallenge. In contrast, the Secretary argued that an

Althen analysis is possible only after a determination of whether a vaccinee suffers

from a specific condition.

The Court found Victoria had a seizure disorder. Opinion and Order at 20,

158 Fed. Cl. at 156. The Court further ruled the precise type of seizure disorder

19

Dr. Fujinami also expressed the opinion that Victoria suffered from JME.

Tr. 393. However, because Dr. Fujinami is not a medical doctor, his opinion

regarding diagnosis merits less weight than the opinion of a neurologist, like Dr.

Shafrir or Dr. Kohrman.

27

did not matter because it found autoimmune epilepsy and juvenile myoclonic

epilepsy are on the same spectrum. Id. at 21-22, 158 Fed. Cl. at 157-58. The

Court did not remand with instructions to reevaluate whether Victoria suffered

from autoimmune epilepsy. The Court also did not remand with instructions to

determine, for the first time, whether Victoria suffered JME. The Court remanded

for a causation analysis.

Due to this procedural posture, any questions whether Victoria suffered from

autoimmune epilepsy, JME, or partial epilepsy with secondary generalizations are

not within the scope of remand. The parties agree with this assessment. See

Pet’r’s Posthear’g Br., filed Mar. 25, 2022, at 28-29; Resp’t’s Posthear’g Br., filed

Apr. 1, 2022, at 55-56. The Court has found the operative diagnosis is “seizure

disorder.” Thus, the remainder of this discussion uses this term, although another

appropriate term might be “epilepsy.”

B. Loving Prong One

The first Loving prong is to establish “the person’s condition prior to

administration of the vaccine.” Loving, 86 Fed. Cl. at 144. Here, restating the

vaccine at issue is critical.

The operative vaccine is the second dose, which was given on September 11,

2012. Mr. Mager cannot recover compensation based upon the first dose of HPV

vaccine, given on October 2, 2007, because Victoria experienced a seizure on

November 14, 2007. This November 14, 2007 seizure occurred more than 36

months before Mr. Mager filed his petition. See 42 U.S.C. § 300aa-16(a)(2); cf.

Pet’r’s Prehear’g Br. at 46 (“Petitioner concedes that he has not alleged injury from

the first HPV vaccine . . . .”). 20

Before this vaccine, Victoria had not suffered any seizures in nearly five

years. While Dr. Kohrman is correct that, as a matter of logic, Victoria could have

had a seizure that no one witnessed and about which Victoria herself was unaware,

Tr. 453-54, this argument does not rise to a level of preponderant proof. Victoria’s

parents appear to have brought her to doctors as needed. When the family saw a

doctor, they appeared to try to communicate information about behaviors possibly

consistent with a seizure. See Exhibit 6 at 20 (Dr. Koehn’s February 21, 2008

report); Exhibit 9 at 39 (Dr. Budde’s November 8, 2012 report). The lack of

20

Mr. Mager has not claimed the statute of limitations for a claim based

upon the October 2, 2007 vaccination should be equitably tolled.

28

medical records reporting seizures for approximately five years tends to show that

Victoria was not having seizures, at least at the more likely than not standard.

Although Victoria had not had any seizures in approximately five years

before the September 11, 2012 vaccination, five years earlier she did have seizures.

As explained above in section I.A, Victoria started having manifestations of her

seizure disorder before she received the first HPV vaccination. This finding is

based upon all the evidence, including the medical records, affidavits and the

reports and testimony of Dr. Shafrir and Dr. Kohrman. Because Victoria’s seizures

started before the October 2, 2007 HPV vaccination, the first HPV vaccination did

not cause the seizure disorder. Locane v. Sec’y of Health & Hum. Servs., 685 F.3d

1375, 1381 (Fed. Cir. 2012); accord Tr. 263. But, this finding carries little

consequence to Mr. Mager’s case for two reasons. First, as noted above, the

October 2, 2007 vaccination is not the basis for Mr. Mager’s claim. Second, as

discussed more extensively below, Ms. Mager has presented the alternative

argument that the first HPV vaccination made her seizure disorder worse. See Tr.

263-64. This worsening, according to Mr. Mager, constitutes a “challenge” event

that is one part of the challenge-rechallenge paradigm.

C. Loving Prong Two

The second Loving prong is to find “the person’s current condition (or the

condition following the vaccination if that is also pertinent).” Loving, 86 Fed. Cl.

at 144. After the September 11, 2012 HPV vaccination, Victoria suffered her first

seizure in approximately five years on October 10, 2012. Exhibit 7 at 9. She had

additional seizures on October 19, 2012 and November 7, 2012. Exhibit 9 at 6 (Dr.

Edgar), 39 (Dr. Budde). She was then placed on anti-seizure medications.

Roughly 15 months after the second dose of the vaccination, Victoria died.

Exhibit 1 (death certificate). The testifying neurologists agreed that Victoria’s

death was due to SUDEP. Exhibit 85 at 2; exhibit A at 13; Tr. 355, 533-34.

D. Loving Prong Three

The third Loving prong is to find “whether the person’s current condition

constitutes a ‘significant aggravation’ of the person's condition prior to

vaccination.” Loving, 86 Fed. Cl. at 144. A “significant aggravation” means “any

change for the worse in a preexisting condition which results in a markedly greater

disability, pain, or illness accompanied by substantial deterioration of health.” 42

U.S.C. § 300aa-33(4).

Whether any worsening is due to the natural course of Victoria’s underlying

seizure disorder is not part of this analysis. Sharpe v. Sec’y of Health & Hum.

29

Servs., 964 F.3d 1072 (Fed. Cir. 2020). Resolution of that issue is deferred to

section IV.H, below.

Here, in briefs filed after the hearing, the parties contested this issue

stridently. Mr. Mager maintained that before the second HPV vaccination,

Victoria “was able to live a normal life” and was “seizure-free for almost five

years.” Pet’r’s Posthear’g Br. at 60-61. Then, after the second vaccination, she

experienced seizures “in a greater quantity, frequency, and severity.” Id. at 61.

In contrast, the Secretary contended that Victoria “had mild epilepsy before

her September 11, 2012, vaccination, and she had mild epilepsy after her

September 11, 2012, vaccination.” Resp’t’s Posthear’g Br. at 16-17. The basis for

the Secretary’s argument regarding the “mildness” of Victoria’s epilepsy comes

from Dr. Shafrir’s testimony. Tr. 238, 344, 561. The Secretary further argued that

Victoria’s death was not due to any worsening of her epilepsy. Resp’t’s Posthear’g

Br. at 16.

Confronting the Secretary’s arguments, Mr. Mager replied more forcefully.

He answered: “going from seizure-free for five years, not requiring medication and

not being at risk for SUDEP (without seizures, you cannot have SUDEP), to

uncontrolled epilepsy, requiring medication, persistent and ongoing seizures, and

ultimately death, is a change for the worse in a preexisting condition.” Pet’r’s

Posthear’g Reply, filed Apr. 5, 2022, at 20. Mr. Mager pointed to the abnormal

EEG on January 14, 2013 as evidence that Victoria’s condition had deteriorated.

Id. at 20-21, citing exhibit 9 at 25.

The parties amplified their positions during oral argument. Spec. Mstr. Oral

Arg. Tr. 619-20, 627-30 (Mr. Mager), 621-26, 630-31 (the Secretary).

This issue is close. The Secretary’s argument that Victoria’s epilepsy was

mild before the September 11, 2012 vaccination and mild after the September 11,

2012 vaccination has merit. Following the vaccination, Victoria’s suffered three

seizures, but each seems mild. See exhibit 7 at 9; exhibit 9 at 39 (Dr. Budde’s

Nov. 8, 2012 report), 6. Then, she went for approximately eight months without

having more seizures when she was taking anti-seizure medications. Exhibit 9 at 3

(Dr. Edgar’s July 8, 2013 report).

Nevertheless, the evidence preponderates in favor of finding that Victoria’s

condition was worse than her condition before the vaccination. Before the

vaccination, Victoria had not had a seizure in approximately five years and was not

taking any anti-seizure medications. Afterwards, Victoria suffered three seizures

30

within about one month and began taking medications. This deterioration in health

constitutes a significant aggravation as defined in 42 U.S.C. § 300aa-33(4).

E. Loving Prong Six / Althen Prong Three

The resolution of the timing prong affects the remaining two prongs. See

Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1326 (Fed. Cir.

2006). Thus, this prong is addressed before an evaluation of the theory and logical

sequence prongs.

1. Standards for Adjudication

The third Althen prong, which corresponds to the sixth Loving prong,

requires the petitioner to show a “proximate temporal relationship” between the

vaccination and the alleged injury. Althen, 418 F.3d at 1281. The timing prong of

Althen contains two parts. A petitioner must establish the “timeframe for which it

is medically acceptable to infer causation” and show that the onset of the disease

occurred in this period. Shapiro, 101 Fed. Cl. at 542-43.

2. Parties’ Arguments

a) Events in Victoria’s Life

With respect to the question of when Victoria experienced observed

generalized tonic-clonic seizures after the vaccinations, the parties agree. Victoria

received her first HPV vaccination on October 2, 2007, and had her first tonic-

clonic seizure on November 14, 2007. Exhibit 3 (vaccination record); exhibit 11 at

13 (emergency department record). The period between these events is 43 days.

Tr. 249 (Dr. Shafrir); Pet’r’s Prehear’g Br., filed July 27, 2022, at 45. 21

21

One reason for finding that Victoria’s seizures started before the

vaccination was that a medical record created during her hospitalization for

November 14, 2007 generalized tonic-clonic seizure indicated that Victoria had

questionable events “2 month[s]” and “2 week[s]” earlier. Exhibit 11 at 30; see

also footnote 6 above. It seems that to be consistent, if the report of “2 months” is

credited, then the report of “2 weeks” also should be credited. And, if the report of

“2 weeks” is credited, then Victoria suffered a seizure on October 31, 2007, which

is 29 days after the October 2, 2007 vaccination. See exhibit 55 (Dr. Shafrir’s first

report) at 17 (stating that before the November 14, 2007 tonic-clonic seizure,

“there were suggestion[s] that the seizures were occurring earlier”).

However, neither party relied upon the report of “2 weeks.” Thus, the

undersigned will not rule upon an assertion that neither party has made. See Doles

31

For the second HPV vaccination, the latency is 29 days. Tr. 280 (Dr.

Shafrir). Victoria received the second dose on September 11, 2012. Exhibit 3.

She experienced a seizure for which she sought treatment at Theda Clark on

October 10, 2012. Exhibit 7 at 9.

b) Proximate Temporal Interval

While the parties agree about this chronology, the parties question the

appropriate temporal interval. Relying on the Slade post-marketing study (exhibit

59), Dr. Shafrir asserted that Victoria’s “seizure occurred within the risk period of

42 days defined by the study.” Exhibit 55 at 18.22 Dr. Shafrir also concluded

without elaboration: “The timeframe of the appearance of the seizure and

encephalopathy is within the range of other HPV vaccination reaction[s]. It

happened twice within the same time range.” Id. at 20.

Neither Dr. Kohrman nor Dr. Fujinami questioned the timing in their

responsive reports. See exhibits Z and AA. In his first report, Dr. Fujinami noted

that nearly 90 million doses of the HPV vaccine were administered in the United

States between June 2006 and March 2016. Exhibit I at 3. Among 90 million

doses administered, he stated that “there will be overlap with individuals who will

present with seizures following vaccination.” Id. Dr. Shafrir did not expand upon

his opinion regarding timing in his rebuttal report. See exhibit 85. Likewise, the

reports from Kohrman and Dr. Fujinami, which were submitted with briefs in

advance of adjudication, did not focus on timing. See exhibits BB and CC.

In his brief before remand, Mr. Mager relied on the Slade post-marketing

study of HPV vaccinations that showed that the median time between

immunization and onset of hypersensitivity reactions was 17 days, with a range of

8-49 days. Pet’r’s Prehear’g Br., filed Mar. 25, 2022, at 45, citing exhibit 59

(Barbara A. Slade et al., Postlicensure Safety Surveillance for Quadrivalent Human

Papillomavirus Recombinant Vaccine, Am. Med. Ass’n (2009)) at 754. He

emphasized that the Slade study described 4-42 days as “biologically plausible” for

onset of transverse myelitis and Guillain-Barré syndrome (“GBS”) following the

HPV vaccine. Id. Although Mr. Mager acknowledged that onset of autoimmune

v. Sec’y of Health & Hum. Servs., No. 17-642V, 2022 WL 1231434 (Fed. Cl. Apr.

1, 2022) (granting a motion for review when a special master accepted a theory

that petitioner did not assert).

22

Although Dr. Shafrir asserts that Victoria’s seizure occurred within 42

days, the seizure happened on the forty-third day after vaccination.

32

disorders normally occurs within 3 weeks following the first or second HPV

vaccination, he maintained that reports of a three-week onset are “not dispositive.”

Id.

Initially, the Secretary did not challenge whether 42 days (or 43 days) was

an appropriate temporal interval. Instead, the Secretary argued, “Even if the time

between Ms. Mager’s vaccination and the onset of her epilepsy were considered

‘medically acceptable to infer causation-in-fact,’ it is well established that temporal

proximity is insufficient to establish causation.” Resp’t’s Prehear’g Br., filed Apr.

1, 2022, at 23, citing Moberly, 592 F.3d at 1323 and Grant v. Sec’y of Health &

Hum. Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992).

On direct examination during the hearing, Dr. Shafrir’s testimony regarding

timing was relatively brief, spanning approximately three pages. Tr. 239-42.

Again, referencing the Slade post-marketing study, Dr. Shafrir opined that the

period of 4-42 days is considered biologically plausible. Id. at 240. Dr. Shafrir

added that the Secretary has associated some injuries that occur as long as 42 days

after vaccination in the Vaccine Injury Table. Id. at 240.

The Secretary’s cross-examination attempted to undermine Dr. Shafrir’s

opinion. Dr. Shafrir conceded that in his first report, he wrote that “the time

interval between the [first] vaccination and the seizure was longer than we

typically associate with vaccine side effects.” Tr. 250; exhibit 55 at 17. When

pressed to explain what immunologic process could be occurring 42 or 43 days

after a vaccination, Dr. Shafrir stated that he expected the adaptive immune system

(not the innate immune system) would be involved. Tr. 253, 259.

The Secretary further probed Dr. Shafrir’s assertion that a 29-day interval

would be appropriate for a rechallenge event. Tr. 280-85. Dr. Shafrir had relied

upon a paper by Margaret Stanley that measured responses to the HPV

vaccinations. Exhibit 68 (Margaret Stanley, HPV – Immune Response to Infection

and Vaccination, 5 Infectious Agents and Cancer 19 (2010)). According to this

article, “Antigen challenge at 60 months post dose 1 with the quadrivalent vaccine

results in a rapid and robust anamnestic response with antibody levels rising within

3-5 days to levels greater than that achieved at peak in the initial immunisation

schedule[,] demonstrating the presence of reactive memory B cells.” Id. at 22.

When asked to explain why Victoria would develop seizures approximately three

and a half weeks after the antibodies peaked, Dr. Shafrir did not have a persuasive

answer. Tr. 282-84.

Dr. Shafrir fell back to relying upon the Slade study. Tr. 284. Dr. Shafrir

indicated that these authors “state that 4 to 42 days is [a] biologically plausible

33

time interval [for] the appearance of side effects of vaccination.” Id. at 285. When

pressed to say why the authors found 42 days plausible, Dr. Shafrir testified, “They

do not explain.” Id. When asked what his opinion is, Dr. Shafrir stated, “I don’t

have a strong opinion.” Id.

Upon redirect, Dr. Shafrir was asked no questions regarding timing. See Tr.

356-57.

The Secretary’s challenge to the appropriate temporal interval continued

through testimony from Dr. Fujinami. Tr. 400-03. Based upon the Stanley article,

Dr. Fujinami indicated that the antibody production in response to a booster dose

of the HPV vaccine “occurs within three to five days after that immunization.” Id.

at 402. Dr. Fujinami, then, reasoned that an anamnestic (or memory) response to a

booster dose should occur “within a week after receiving that HPV number 2.” Id.

at 402-03.

Dr. Fujinami reinforced his opinion by describing what he has observed in

his experiments in mice that are induced to develop inflammation within their

central nervous systems. In those experiments, the mice develop clinical signs of

inflammation about 7-14 days after the initial immunization and then have a

“markedly shortened” response after the booster. Tr. 400. Dr. Fujinami did not

cite any studies for this proposition.

In Dr. Fujinami’s view, the timing of what is predicted by the science does

not fit what happened to Victoria, especially for the second vaccination. The

interval between the second vaccination and the first seizure after the second

vaccination is 29 days. But, to Dr. Fujinami, this much time exceeds what should

happen in a rechallenge. Tr. 390. Thus, Victoria’s case does not fulfill the

challenge-rechallenge paradigm. Id. at 403.

In answering cross-examination questions and questions from the

undersigned, Dr. Fujinami defended his position that any rechallenge adverse event

would happen sooner than 29 days. Dr. Fujinami stated that literature discussing

how primates respond to immunizations shows that clinical disease becomes

apparent in 7-14 days. Tr. 418.23 Because the production of antibodies is one step

in the longer process through which antibodies might cross-react and cause

damage, the undersigned asked how long the complete process would take. Dr.

23

While Dr. Fujinami’s testimony is not entirely clear about how many

vaccinations the animals have received, it seems that Dr. Fujinami is discussing

how animals respond to the first (or “priming”) dose. Tr. 419.

34

Fujinami stated that in experimental models using mice, most mice become

paralyzed within 14 days. Id. at 420-23.

When asked whether vaccines can cause autoimmune conditions “40-plus

days out,” Dr. Fujinami acknowledged that some studies have used that window.

However, those studies were “very generous.” Tr. 419-20.

Dr. Fujinami’s opinion concurred with the opinion Dr. Kohrman offered

during his testimony. Dr. Kohrman stated that an injury mediated through

antibodies would occur within about 7-14 days. Tr. 471-72 (direct testimony), 535

(response to the undersigned’s question). He stated that an autoimmune reaction

past 40 days is possible, but not likely. Id. at 494 (testimony on cross-

examination).

During Dr. Shafrir’s rebuttal testimony, he was asked to address whether

Victoria’s rechallenge event should have occurred earlier. While Dr. Shafrir stated

that he “absolutely [did not] agree with” the opinions from the Secretary’s experts,

Dr. Shafrir did not provide a persuasive explanation. See Tr. 552-54. In this

approximately two-page answer, Dr. Shafrir generally maintained that the

vaccinations worsened Victoria’s seizures. At the end of this response, Dr. Shafrir

asserted “it could have happened in six weeks,” but did not give any basis for this

assertion. Id. at 554.

In their post-hearing briefs, the parties continued to dispute the medically

acceptable time. Mr. Mager stated that a petitioner is required to show a

“proximate temporal relationship between vaccination and injury.” Pet’r’s

Posthear’g Br. at 33. Citing Paluck v. Secretary of Health & Human Services, 786

F.3d 1373, 1383-84 (Fed. Cir. 2015), Mr. Mager further argued that deadlines

should not be “hard and fast.” Id.

Mr. Mager argued that Dr. Fujinami’s testimony that an immune-driven

reaction should take place within approximately two weeks was not persuasive for

several reasons. First, Dr. Fujinami did not disclose this opinion in reports before

the hearing. Second, Dr. Fujinami’s opinion is not consistent with other evidence.

The primary inconsistent evidence is the Slade post-marketing study. Pet’r’s

Posthear’g Br. at 34, 53. The only other article cited in connection with the timing

aspect is exhibit 70 (Britain Baker et al., The Safety of Human Papilloma Virus-

Blockers and the Risk of Triggering Autoimmune Diseases, 14 Expert Opinion on

Drug Safety 1387 (2015)). While this article states the manifestation of symptoms

of autoimmunity “normally occurred within the first 3 weeks and following the

first or second vaccine injections,” exhibit 70 (Baker) at 3, Mr. Mager argues that

this statement is “not dispositive.” Pet’r’s Posthear’g Br. at 34, 53. However, Mr.

35

Mager did not cite any evidence regarding an expert’s view of Baker and it appears

that no expert testified about Baker. See Resp’t’s Posthear’g Br. at 30. Although

Dr. Shafrir referenced the Vaccine Injury Table during his testimony (Tr. 295), Mr.

Mager did not cite it in his brief as being inconsistent with Dr. Fujinami’s opinion.

Mr. Mager’s third reason for not crediting Dr. Fujinami’s opinion is that his

opinion is based upon animal models, not people. Pet’r’s Posthear’g Br. at 35, 52.

In this context, Mr. Mager questions the usefulness of Dr. Fujinami’s opinion

because Dr. Fujinami is not a medical doctor. Id. at 35 n.8.

In contrast, the Secretary argued that Mr. Mager’s showing regarding timing

was not persuasive. Resp’t’s Posthear’g Br. at 27-37, 53-55. The Secretary

maintained that “the injuries and time frames set forth in the Vaccine Injury Table

have no bearing on this case.” Id. at 27. Later, the Secretary expanded this

argument by citing cases in which special masters have rejected the appropriate

temporal interval when the injury occurred around the forty-second day after

vaccination. Id. at 36-37. The Secretary further argued that the Slade post-

marketing study was not persuasive because, in part, “the authors did not explain

what made 4 to 42 days plausible for the onset of GBS or transverse myelitis.” Id.

at 28. In this regard, the Secretary emphasized that when asked why the Slade

authors selected this time, Dr. Shafrir did not “supply any basis for his conclusion

that 42 days is medically reasonable.” Id. at 29, citing Tr. 285. In addition, the

Secretary questioned the usefulness of exhibit 70 (Baker), noting that it evaluated a

variety of sources including the Vaccine Adverse Event Report System. Id. at 30.

Finally, the Secretary argued that Mr. Mager’s “exclusive reliance on challenge-

rechallenge, without providing any medical theory . . . renders Dr. Shafrir’s

testimony concerning timing both unreliable and unpersuasive.” Id. at 27.

Beyond attacking Dr. Shafrir’s opinion regarding timing, the Secretary also

defended Dr. Fujinami’s view. Procedurally, the Secretary maintained that he

could not disclose any opinion from Dr. Fujinami before the hearing because Dr.

Shafrir had not disclosed his opinion regarding timing before the hearing. Resp’t’s

Posthear’g Br. at 32-33. Substantively, the Secretary maintained that Dr.

Fujinami’s experience, including his hypothesis about molecular mimicry being

involved in autoimmune disease and work with animal models for epilepsy, made

him more qualified than Dr. Shafrir regarding the timeframe for an autoimmune

reaction. Id. at 33.

In his post-hearing reply, Mr. Mager again relied on the Slade study, stating

that the study establishes 4-42 days as an appropriate time interval between HPV

vaccination and onset of symptoms. Pet’r’s Posthear’g Br. at 11, citing Tr. 253;

exhibit 59 (Slade) at 754. Mr. Mager also reiterated his assertion that the

36

conclusion in the Baker article that the manifestation of symptoms typically occurs

within three weeks after HPV vaccination is “not dispositive.” Id. Mr. Mager

further stated that although he is not alleging a Table injury, the 2-42-day

timeframe contained in the Vaccine Injury Table helps establish a medically

acceptable time interval. Id. at 12 n.7. Mr. Mager again argued that appropriate

time intervals should not be “hard and fast,” and conceded that there “is no

definitive timeframe for onset” in this case. Id. at 13.

3. Resolution

Mr. Mager has met his burden. He has persuasively shown that two

questions should be answered in his favor. The first (and less important) question

is whether 43 days is an appropriate inference for which to infer the first HPV

vaccination in 2007 worsened Victoria’s preexisting seizure disorder. 24 The

second question is whether 29 days is an appropriate interval to infer the 2012

vaccination significantly aggravated a quiescent seizure disorder. On these similar

questions, persuasive evidence comes from Slade. When Slade and colleagues

were attempting to discover whether the HPV vaccination caused any adverse

effects, they used the period of 4 to 42 days as biologically plausible. Exhibit 59 at

754.

While the Slade study, by itself, justifies crediting Dr. Shafrir’s opinion

regarding timing, some additional support comes from the Vaccine Injury Table.

In recommending an association between the flu vaccine and GBS, a peripheral

nerve disease, the Secretary “propose[d] an onset interval of 3-42 days.” National

Vaccine Injury Compensation Program: Revisions to the Vaccine Injury Table, 80

Fed. Reg. 45,132, 45,146 (proposed July 29, 2015) (codified at 42 C.F.R. pt.

100.3). Special masters have relied upon the Secretary’s acceptance of 42 days for

flu vaccine-GBS to find an appropriate temporal relationship in other

circumstances in some cases. See Mason v. Sec’y of Health & Hum. Servs., No.

17-1383V, 2022 WL 600415, at *25 (Fed. Cl. Spec. Mstr. Feb. 4, 2022) (“[T]he

fact that Table claims reflect the Government’s reasoned interpretation of

persuasive medical science thinking on a causation theory means they can at least

be considered in deciding non-Table claims.”); Randolph v. Sec’y of Health &

Hum. Servs., No. 15-146V, 2021 WL 5816271, at *20 (Fed. Cl. Spec. Mstr. Nov.

12, 2021) (“[T]he GBS ‘template’ is useful in evaluating Petitioner’s success in

meeting this Althen prong.”). In doing so, special masters have not violated the

24

Whether 43 days after the first HPV vaccination is an appropriate

temporal interval is less important because Mr. Mager’s claim is not based upon

the first HPV vaccination.

37

Federal Circuit’s direction that “[s]imple similarity to conditions or time periods

listed in the Table is not sufficient evidence of causation; evidence in the form of

scientific studies or expert medical testimony is necessary to demonstrate causation

for such a petitioner.” Grant, 956 F.2d at 1148, cited in Resp’t’s Posthear’g Br. at

27. Here, Mr. Mager has advanced “scientific studies” (the Slade study) and

“expert medical testimony” from Dr. Shafrir.

On the other hand, as the Secretary argues, special masters have not

universally and uncritically transferred times listed on the Table to cases involving

off-Table injuries. See Resp’t’s Posthear’g Br. at 36, citing Greene v. Sec’y of

Health & Hum. Servs., 146 Fed. Cl. 655, 661 (2020) (denying a motion for review

of a decision in which the special master found that 41 days was not a medically

reasonable interval); Nussman v. Sec’y of Health & Hum. Servs., 83 Fed. Cl. 111,

123 (2008) (denying motion for review of a decision in which the special master

found that an appropriate time for the hepatitis B vaccine to cause seizures was 30

days). Those cases undermine, but do not eliminate, the value of the Vaccine

Injury Table as supporting Dr. Shafrir’s opinion.

From Slade’s recognition of 4 to 42 days as biologically plausible, it is a

short step of just one additional day to 43 days, which is the amount of time

between Victoria’s first HPV vaccination and her first generalized tonic-clonic

seizure. The Federal Circuit has admonished special masters not to set “hard and

fast deadlines.” Paluck, 786 F.3d at 1383-84. Thus, the amount of time from

Slade may be reasonably expanded to 43 days.

Dr. Fujinami’s opinions regarding timing are not credited. First, Dr.

Fujinami did not indicate that timing was a problem in his reports. Exhibit I, X,

AA, CC.25 Likewise, the Secretary did not warn that he disputed the timing. See

Resp’t’s Prehear’g Br., filed Feb. 10, 2021, at 22-23.26 This lack of disclosure is

25

At best, in response to the (now withdrawn) report from Dr. Mikovits and

Dr. Ruscetti, Dr. Fujinami addressed the amount of time for a reaction involving

histidine. Exhibit I at 4. But, Dr. Shafrir has not put forward a theory based upon

histidine.

26

The Secretary’s excuses regarding the nondisclosure of Dr. Fujinami’s

opinions are not persuasive. First, the Secretary stated that until Dr. Shafrir

testified, Dr. Fujinami did not know when Dr. Shafrir believed Victoria’s first

seizure occurred. Resp’t’s Posthear’g Br. at 32. However, Dr. Shafrir linked the

first HPV vaccination to Victoria’s generalized tonic-clonic seizure on November

14, 2007. See exhibit 55 at 3, 16-17. Second, the Secretary stated that he did not

know that Mr. Mager was putting forward 4 to 42 days as a medically reasonable

38

inconsistent with how the Vaccine Program usually operates. If Mr. Mager had

objected to Dr. Fujinami’s testimony that an adverse reaction would have occurred

within about two weeks, the undersigned most likely would have sustained the

objection and struck Dr. Fujinami’s testimony. See Simanski v. Sec’y of Health &

Hum. Servs., 671 F.3d 1368, 1382 (Fed. Cir. 2012).

Apart from the lack of disclosure, Dr. Fujinami’s testimony suffers because

he did not present literature supporting his position. Although literature is not

required, Althen, 418 F.3d at 1280-81, “a scientific theory that lacks any empirical

support will have limited persuasive force.” Caves v. Sec’y of Health & Hum.

Servs., 100 Fed. Cl. 119, 134 (2011), aff’d without opinion, 463 F. App’x 932

(Fed. Cir. 2012). Similarly, the Federal Circuit has recommended that petitioners

support expert opinions with medical literature. LaLonde v. Sec’y of Health &

Hum. Servs., 746 F.3d 1334, 1341 (Fed. Cir. 2014). This same principle should

govern the analysis of opinions that respondent presents. 27

The Secretary’s argument that establishing an appropriate temporal interval

requires a medical theory has support from case law. See Bazan v. Sec’y of Health

& Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008) (stating that the petitioner

must offer a medically acceptable timeframe that coincides with the medical theory

of causation under Althen prong one); see also Shapiro, 101 Fed. Cl. at 542. As

discussed in section IV.F below, Mr. Mager’s medical theory for causation is based

on challenge-rechallenge. Since Mr. Mager has established that Victoria’s

time until Mr. Mager presented exhibits 59 and 70 in his prehearing brief. Resp’t’s

Posthear’g Br. at 33. This point is accepted. But, the Secretary did have a chance

to respond to the materials presented in Mr. Mager’s prehearing brief. With this

opportunity, the Secretary presented another report from Dr. Fujinami that did not

address timing. See exhibit CC.

27

On the other hand, in future cases the undersigned might find a properly

disclosed and well-supported opinion from Dr. Fujinami persuasive. In

determining whether an amount of time is medically appropriate for an inference

of causation, the undersigned has considered animal models that attempt to

replicate disorders in a person's central nervous system. Contreras v. Sec’y of

Health & Human Servs., No. 05-626V, 2012 WL 1441315, at *9-13 (Fed. Cl.

Spec. Mstr. Apr. 5, 2012) (lengthy discussion of the time for molecular mimicry),

mot. for rev. denied in relevant part after intervening proceedings, 121 Fed. Cl.

230, 246-47 (2015), vacated on other grounds and remanded, 844 F.3d 1363 (Fed.

Cir. 2017).

39

challenge event and rechallenge event occurred within a medically acceptable

timeframe, the timing is supported by the medical theory.

Accordingly, for these reasons, Mr. Mager has met his burden of proof

regarding Loving prong six. Victoria experienced an aggravation of her

preexisting seizure disorder for which she was not taking medications within an

appropriate time after the second dose of the HPV vaccination. She also

experienced a worsening of her epilepsy after the first dose of the HPV vaccination

within a medically appropriate time.

F. Loving Prong Four / Althen Prong One

1. Standards for Adjudication

The first Althen prong requires the petitioner to provide a “sound and

reliable” medical theory demonstrating that the vaccine can cause the alleged

injury. Boatmon v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1359 (Fed.

Cir. 2019) (quoting Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548

(Fed. Cir. 1994)). The petitioner must also offer “a reputable or scientific

explanation that pertains specifically to [his] case.” Moberly, 592 F.3d at 1322.

The petitioner “need not produce medical literature or epidemiologic evidence” to

support his theory. Andreu, 596 F.3d 1367, 1379. A petitioner satisfies his burden

under prong one when his expert “present[s] a ‘biologically plausible’ theory.”

See id. at 1375; see also J. v. Sec’y of Health & Hum. Servs., 155 Fed. Cl. 20, 42-

43 (2021).

2. Procedural History and Parties’ Arguments

In Dr. Shafrir’s first report, he opined that the first HPV vaccination can

produce an immune-mediated response, resulting in the development of

autoimmune epilepsy. See exhibit 55 at 18, 20. Dr. Shafrir further explained that

the second dose leads to an enhanced immune response. See id. at 20. Because

Victoria experienced seizures after the first and second doses of the HPV vaccine

(and no seizures for nearly five years between vaccinations), Dr. Shafrir opined

Victoria’s case qualifies as an example of challenge-rechallenge. Id. at 17.

Dr. Shafrir also put forward “[m]echanisms by which Gardasil can produce

an autoimmune disease.” Exhibit 55 at 19. The most developed mechanism was

molecular mimicry, although Dr. Shafrir listed epitope spreading, bystander

activation, and polyclonal activation. Id.; see also id. at 20 (“The mechanism is

likely based on molecular mimicry . . . .”).

40

The response to Dr. Shafrir’s theory came from Dr. Fujinami.28 In response

to Dr. Shafrir’s opinion that the HPV vaccine can cause brain inflammation, Dr.

Fujinami relied on a study of mice that were injected with peptides, which showed

that the “injection of peptides from HPV could actually protect from autoimmune

neuroinflammation.” Exhibit AA at 3-4, citing exhibit AA, tab 5 (Ruiz).

In addition, in Dr. Fujinami’s report that preceded Dr. Shafrir’s first report,

Dr. Fujinami cited studies about the safety of the HPV vaccine. Dr. Fujinami

referenced an article from the Centers for Disease Control and Prevention, which

discusses studies from 2012 and 2014. Exhibit I, citing exhibit V (Ctrs. for

Disease Control & Prevention, HPV Vaccine Is Safe – (Gardasil) (2016)) at 2.

Both studies found that women and girls who received the HPV vaccine “were not

more likely to develop autoimmune disorders than those who were unvaccinated.”

Exhibit V at 2. Dr. Fujinami discussed the studies at the hearing, testifying that

“they found no autoimmune signal or . . . association with autoimmune disease.”

Tr. 375. He added, “there was no indication that there’s an increase in seizures in

the individuals who were vaccinated with HPV.” Id.

Dr. Fujinami also relied on a study that found “no safety signals with respect

to autoimmune, neurological, and venous thromboembolic events” among about

one million HPV vaccine recipients between ages 10 and 17. Exhibit K (Lisen

Arnheim-Dahlstrom et al., Autoimmune, Neurological, and Venous

Thromboembolic Adverse Events After Immunisation of Adolescent Girls with

Quadrivalent Human Papillomavirus Vaccine in Denmark and Sweden, 347 BMJ

5906 (2013)) at 5.

Dr. Shafrir’s second report was similar to his first report. He emphasized the

“importance of challenge/rechallenge.” Exhibit 85 at 1. Dr. Shafrir referenced a

study of autoimmune encephalitis in children, which reported that out of 48

patients with autoimmune encephalitis, three patients received a recent HPV

vaccination. Id. at 4, citing exhibit 95 (Yael Hacohen et al., Paediatric

Autoimmune Encephalopathies, 84 J. Neurology, Neurosurgery, & Psychiatry 748

(2012)). He also cited a series of articles in which the authors reported people

developed autoimmune diseases after a HPV vaccination. Id. at 4-5.

Another study that examined patients with encephalopathy following the

HPV vaccination concluded that the patients’ responsiveness to immunotherapy

suggested an autoimmune mechanism. See exhibit 105 (M. Ando & N. Belonguel,

Dr. Kohrman’s report did not meaningfully address the theory by which

28

the HPV vaccine can cause or aggravate seizures. See exhibit Z.

41

Autoimmune Disorders, 381 J. Neurological Sci. 530 (2017)). However, the

authors acknowledged that they could not establish a “direct relationship” between

the neurological symptoms and the HPV vaccine. Id.

In conjunction with Dr. Shafrir’s second report, Mr. Mager presented written

arguments. As a prong-one causation theory, Mr. Mager advanced challenge-

rechallenge. See Pet’r’s Prehear’g Br. at 19, 23-24; see also exhibit 55 at 17, 20;

exhibit 85 at 1. Mr. Mager heavily relied on literature by the World Health

Organization (“WHO”), which “defines the relationship between challenge-

rechallenge as an adverse reaction to a vaccine as one of certain causality.” Pet’r’s

Prehear’g Br. at 24, citing exhibit 57 (World Health Org., Pharmacovigilance

Guidelines) at 4.

Mr. Mager argued that “epilepsy can have an immunological mechanism.”

Pet’r’s Prehear’g Br. at 21. To support this theory, Mr. Mager noted that “epilepsy

is more common in patients with systemic lupus erythematosus (SLE) who have

antiphospholipid antibodies, and it is possible that these antibodies can lead to

immune-mediated cortical damage.” Id., citing exhibit 64 (Antonio Greco et al.,

Autoimmune Epilepsy, 15 Autoimmunity Revs. 221 (2016)). He added that

“autoimmune antibodies are detected in 9-14% of patients with epilepsy.” Id.,

citing exhibit 64 at 2 and exhibit 88 (Jehan Suleiman et al., Autoantibodies to

Neuronal Antigens in Children with New-Onset Seizures, 54 Epilepsia 2091

(2013)).

Mr. Mager relied on the Slade post-marketing study of the HPV vaccine.

See Pet’r’s Prehear’g Br. at 23, 26, citing exhibit 59 (Slade). The study reports that

convulsions made up 8.8% of the serious reported side effects on VAERS reports

from June 2001 through December 2008. Exhibit 59 at 752.

Mr. Mager claimed that molecular mimicry was the most probable biological

mechanism by which the HPV vaccine can cause epilepsy that is autoimmune in

nature. See Pet’r’s Prehear’g Br. at 21; Pet’r’s Prehear’g Reply at 31. Mr. Mager

explained that molecular mimicry “is the cross-reactivity between a foreign-

antigen . . . and self-antigens, which induces a break in self-tolerance of the amino

acids of the human cells and leads to the immune system attacking its owner’s

body.” Pet’r’s Prehear’g Br. at 21, citing exhibit 74 (Nancy Agmon-Levin et al.,

Vaccines and Autoimmunity, 5 Rheumatology 648 (2009)) at 3. Mr. Mager

elaborated that the HPV vaccine “contains viral sequences in L1 protein that are

similar to several human proteins integral in regulating immune and neurological

function, which set off an autoimmune action triggering [Victoria’s] epileptic

seizures.” Id. at 23.

42

To support the theory of molecular mimicry, Mr. Mager relied on articles

that discuss risks of cross-reactivity with the HPV vaccine. See Pet’r’s Prehear’g

Br. at 23, citing exhibit 72 (Darja Kanduc, Quantifying the Possible Cross-

Reactivity Risk of an HPV16 Vaccine, 8 J. Experimental Therapeutics & Oncology

65 (2009)) and exhibit 73 (Darja Kanduc & Yehuda Shoenfeld, From HBV to

HPV: Designing Vaccines for Extensive and Intensive Vaccination Campaigns

Worldwide, 11 Autoimmunity Revs. 1054 (2016)). Mr. Mager argued that the

articles support the theory of molecular mimicry “by demonstrating six and seven

amino acid homologies between the L1 capsid protein of the different strains of

HPV included in the Gardasil [vaccine] and human proteins.” Id. Mr. Mager

added that “the authors identified homologies of the viral vaccine protein and 2

human proteins, the dysfunction of which can cause seizures – calcium sensing

reception (CASRO) and perforin (PERF).” Id. Additionally, Mr. Mager argued

that this theory is further supported by challenge-rechallenge. See id.

Mr. Mager also referenced a study documenting autoimmune neuromyotonia

following the HPV vaccination. See Pet’r’s Prehear’g Br. at 20, 43, citing exhibit

107 (Chiara Cerami et al., Autoimmune Neuromyotonia Following Human

Papillomavirus Vaccination, Muscle & Nerve, Mar. 2013). Mr. Mager asserted

that this study shows that the HPV vaccine can cause brain inflammation and

autoimmune neurological conditions. Pet’r’s Prehear’g Br. at 20.

With a second chance to address to Dr. Shafrir’s theory, Dr. Fujinami

responded more directly. He disagreed with Mr. Mager’s challenge-rechallenge

theory, stating that “there is no clear information linking the occurrence of seizures

to [the] HPV vaccination, let alone an enhanced immune response occurring

against the second HPV vaccination due to immunological memory present after

the first vaccination with HPV.” Exhibit CC at 1. Dr. Fujinami also pointed out

that Dr. Shafrir had not addressed the study (Ruiz) “where mimicking

immunologic epitopes presented in alum [were] reported to protect against

neuroinflammation.” Id. As to the series of articles that Dr. Shafrir cited, Dr.

Fujinami asserted that exhibits 96-108 “are a compilation of case reports . . . and

do not relate to seizures/epilepsy let alone autoimmune epilepsy.” Id. at 2.

With evidence from Dr. Fujinami, the Secretary disputed Mr. Mager’s

theory that the HPV vaccine can cause an autoimmune disease. See Resp’t’s

Prehear’g Br. at 19. Citing Dr. Fujinami’s report, the Secretary asserted, “There is

no evidence that HPV DNA fragments lead to an immune-mediated response and

that aluminum at the injection site can cause an autoimmune syndrome.” Resp’t’s

Prehear’g Br. at 19, citing exhibit I at 3.

43

The July 29, 2021 Decision did not address any theory by which a HPV

vaccine can cause or aggravate autoimmune epilepsy because it found that Mr.

Mager had not established that Victoria suffered from autoimmune epilepsy.

In light of the lack of discussion of a theory or mechanism connecting a

HPV vaccine to seizures, the parties’ briefs supporting and opposing Mr. Mager’s

motion for review did not discuss this aspect of the case in any detail. Mr. Mager

contended that his “predominant argument was that Victoria experienced

challenge/rechallenge.” Pet’r’s Mot. for Rev., filed Aug. 27, 2021, at 21. He

further argued, “Rechallenge is not dependent on a finding that Victoria suffered

from autoimmune epilepsy.” Id.

The Secretary disagreed with this proposition. Shortly after quoting this

portion of Mr. Mager’s brief, the Secretary argued that “it was necessary and

legally correct for the Special Master to undertake a preliminary inquiry regarding

whether petitioner met his burden in proving that Ms. Mager suffered from

autoimmune epilepsy.” Resp’t’s Resp. to Mot. for Rev., filed Sept. 24, 2021, at 17.

The Court ruled that the approach in the July 27, 2021 Decision was flawed.

The “Special Master did not consider petitioner’s primary argument; i.e., an

autoimmune reaction to the HPV vaccine triggered recurrence and aggravation of

Ms. Mager’s epilepsy disorder.” Opinion and Order at 19, 158 Fed. Cl. at 155.

The Court required the special master to “perform the requisite causation analysis

under Althen and its progeny.” Id. at 22, 158 Fed. Cl. at 158.

In the hearing, Dr. Shafrir and Dr. Fujinami largely testified in accord with

the reports they authored. Dr. Shafrir emphasized challenge-rechallenge. He

discussed the WHO guidelines, stating that Victoria “clearly meets the criteria for

certain side effects caused by the vaccine.” Tr. 216. He also reviewed the events

in Victoria’s life in an attempt to show her history fits the challenge-rechallenge

paradigm. Id. at 214-19. Dr. Shafrir also explained that the five-year period of

seizure freedom between vaccinations qualifies as a “dechallenge” event, further

evidence supporting challenge-rechallenge. Tr. 216-17, 273. On cross-

examination, the Secretary questioned whether Dr. Shafrir possessed enough

information about Victoria to fulfill the WHO guidelines. These guidelines

indicate that an adverse event must take place within a “plausible time.” Exhibit

57 at 4; accord Tr. 244, 259. But, by the intimations in his attorney’s questions,

the Secretary seemed to suggest that the time of events in Victoria’s case was not

appropriate. See Tr. 259.

When asked about potential biologic mechanisms by which the HPV vaccine

can cause or aggravate seizures, Dr. Shafrir stated that molecular mimicry is one

44

potential mechanism. Tr. 223. He repeated this point on cross-examination,

stating that his opinion regarding molecular mimicry is “not a definite

certainty . . . . I suggest this is possible, molecular mimicry.” Id. at 247. He added

other potential mechanisms included a cytokine-driven response, an innocent

bystander in the brain’s immune system, and “epitope spread.” Id. at 247-49.

Among these possible theories, the evidence for molecular mimicry “is a little bit

stronger than for the other mechanisms.” Id. at 249.

Dr. Fujinami’s testimony addressed Dr. Shafrir’s testimony. Dr. Fujinami

explained how repeat vaccinations can enhance the immune response. Tr. 400.

However, the challenge-rechallenge paradigm requires appropriate timing. Id. at

403. In this case, Victoria’s seizures occurred too long after the vaccinations to be

caused by the vaccinations. Id.

Dr. Fujinami also opined that the HPV vaccine has not been shown to

increase the incidence of different autoimmune diseases. For example, Dr.

Fujinami discussed a short publication from the WHO (exhibit U) that reviewed

studies with hundreds of thousands or million participants. These studies did not

detect an increase in autoimmune diseases generally and, in some investigations,

the authors did not find an increased incidence in seizures specifically. Tr. 371-75.

These studies, to Dr. Fujinami, undermined Dr. Shafrir’s opinion because if the

HPV vaccination could cause a dysregulated immune response, some evidence of

that dysregulated immune response would have shown up in these large studies.

Id. at 372.

With respect to the possible mechanisms, Dr. Fujinami stated that he did not

agree with Dr. Shafrir. For example, on molecular mimicry, Dr. Fujinami pointed

out that Dr. Shafrir had not identified what portion of the HPV vaccine would

cross-react with a body part leading to epilepsy. Tr. 367. Dr. Fujinami elaborated

on his written report’s discussion of the Ruiz article to maintain that that the use of

a weak adjuvant, like alum, protects against developing an autoimmune reaction.

Id. at 367-71, 377-78.

Dr. Fujinami also explained why other potential mechanisms, such as a

cytokine-driven reaction, epitope spreading, or bystander activation were not

likely. Tr. 365-66, 388-91. His direct testimony concluded with a statement that

there is “no connection” between the HPV vaccination and epilepsy. Id. at 403.

After the evidence was completed, Mr. Mager argued his case. He

recognized that Althen requires a petitioner to provide “a medical theory

connecting the vaccination to the injury.” Pet’r’s Posthear’g Br., filed Mar. 25,

2022, at 30. However, this “medical theory” differs from a biologic mechanism,

45

which is not an element of petitioner’s case. Id., citing Knudsen, 35 F.3d at 549

and Simanski, 671 F.3d at 1384.

Mr. Mager further argued that establishing challenge-rechallenge satisfies

petitioner’s obligation to provide a medical theory. Pet’r’s Posthear’g Br. at 31-32;

Pet’r’s Posthear’g Reply, filed Apr. 5, 2022, at 3. A large portion of Mr. Mager’s

argument under the “Althen prong 1” header consists of contending that Victoria

fulfills the challenge-rechallenge paradigm. See Pet’r’s Posthear’g Br. at 37-44.

Beyond challenge-rechallenge, Mr. Mager repeated some of his arguments

from his prehearing brief. He again asserted, “Molecular mimicry is the most

likely mechanism by which Victoria suffered seizures.” Pet’r’s Posthear’g Br. at

45. Mr. Mager did not raise a theory based on cytokines, epitope spreading, or

bystander activation in this brief.

The Secretary disagreed with Mr. Mager’s arguments regarding Loving

prong four / Althen prong one. On the question of whether invoking the challenge-

rechallenge paradigm fulfills the requirement to present a medical theory, the

Secretary asserted that Mr. Mager “has not cited any authority in the Vaccine

Program that has held that asserting challenge-rechallenge obviates a petitioner’s

burden to offer reliable evidence of a scientific theory causally connecting the

vaccination and the injury.” Resp’t’s Posthear’g Br., filed Apr. 1, 2022, at 17-18.

The Secretary also argued that evidence for Victoria experiencing challenge-

rechallenge was lacking, primarily due to the problems with timing. See id. at 20-

21, 27-34.

As to the potential theories, the Secretary commented that Mr. Mager “made

clear his intent to rely exclusively on the challenge-rechallenge paradigm, and

elected not to advance any other medical theories of causation.” Resp’t’s

Posthear’g Br. at 22, citing Pet’r’s Posthear’g Br. at 32-33; accord id. at 21 (Mr.

Mager “has declined to endorse any causal theory beyond the challenge-

rechallenge paradigm.”). 29 The Secretary, thus, made “a truncated response” to

questions regarding the plausibility of the different theories Dr. Shafrir mentioned.

Id. at 24-25. In conjunction with this response, the Secretary argued, “Several

epidemiological studies have demonstrated the absence of increased risk of

seizures or epilepsy following HPV vaccination.” Id. at 25.

29

The Secretary did not address Mr. Mager’s attempt to distinguish a theory

from a mechanism.

46

3. Resolution

Mr. Mager appears to attempt to satisfy Loving prong four in two respects.

First, he offers the challenge-rechallenge paradigm. Second, he offers a

hodgepodge of theories, such as molecular mimicry. The former is persuasive and

the latter is not.

a) Challenge-Rechallenge

Whether invoking the challenge-rechallenge paradigm constitutes a “theory”

depends, at least in part, on the meaning of the phrase “a medical theory causally

connecting the vaccination and the injury” from Althen, 418 F.3d at 1278. The

interpretation of a case is a question of law, which appellate authorities review de

novo. Alcon Research Ltd. v. Barr Laboratories, Inc., 745 F.3d 1180, 1190 (Fed.

Cir. 2014); Toro Co. v. White Consolidated Industries, Inc., 383 F.3d 1326, 1330

(Fed. Cir. 2004).

Here, there appears to be no controlling precedent that answered the specific

question of whether challenge-rechallenge constitutes a theory. However, the

appellate authorities seem inclined to accept challenge-rechallenge as a theory.

In assessing challenge-rechallenge, a starting point is Capizzano. In the

special master’s underlying decision, he found that the hepatitis B vaccine can

cause rheumatoid arthritis. Thus, he effectively found that the petitioner had met

her burden regarding the first Althen prong. Capizzano, 440 F.3d at 1325. Thus,

as the Secretary argues, the Federal Circuit “did not discuss whether the challenge-

rechallenge paradigm is sufficient by itself to satisfy Althen prong 1.” Resp’t’s

Posthear’g Br. at 18. 30 For the issue that the Federal Circuit did confront, whether

the petitioner had met her burden of proof on prong two, the Federal Circuit

recognized that challenge-rechallenge evidence could be probative of causation.

Capizzano, 440 F.3d at 1327.

Subsequently, in evaluating whether reasonable basis supported the claims

set forth in a petition, the Federal Circuit stated that “the occurrence of a challenge-

rechallenge event . . . has been recognized as a basis for establishing causation.”

James-Cornelius v. Sec’y of Health & Hum. Servs., 984 F.3d 1374, 1381 (Fed. Cir.

2021) (citing Capizzano, 440 F.3d at 1322). While the sentence in James-

30

This lack of analysis from the Federal Circuit on prong one, in turn,

allowed for a different finding on prong one based upon different evidence. See

Bean-Sasser v. Sec’y of Health & Hum. Servs., 127 Fed. Cl. 161, 167-68 (2016).

47

Cornelius does not specify whether the challenge-rechallenge occurrence is part of

Althen prong one or Althen prong two, that analytic structure does not matter.

Althen prong two has been likened to asking whether the vaccine did cause

the injury. Evidence that a vaccine did cause an injury must imply that the vaccine

can cause the injury. “When a treating physician concludes that an injury or illness

was caused by a vaccine, that conclusion is circumstantial evidence that the

vaccine did in fact cause that injury or illness.” Caves, 100 Fed. Cl. at 136.

Thus, the undersigned holds that persuasive proof that a vaccinee

experienced challenge-rechallenge satisfies a petitioner’s burden to present a

theory causally connecting a vaccine to an injury. See Waterman v. Sec’y of

Health & Hum. Servs., No. 13-44V, 2016 WL 761173, at *7-8 (Fed. Cl. Spec.

Mstr. Feb. 5, 2016) (ruling finding entitlement to compensation based, in part, on

the special master’s finding that the petitioner demonstrated challenge-

rechallenge).

The ensuing question, then, is whether Mr. Mager has shown with

preponderant evidence that Victoria experienced challenge-rechallenge. The short

answer is yes.

The Secretary’s argument against challenge-rechallenge is that the timing

does not fit. See Resp’t’s Posthear’g Br. at 19-22; Spec. Mstr. Oral Arg. Tr. 660.

However, for reasons explained in section IV.E, above, Mr. Mager has met his

burden regarding timing.

The basic chronology shows how Victoria experienced worse seizures

within an appropriate amount of time after the vaccinations to conclude that she

experienced challenge-rechallenge.

Date Event

Approximate onset of tongue biting, which is evidence of a

9/14/2007 seizure. In addition, by this time, Victoria was having episodes

of bedwetting.

10/2/2007 First HPV vaccination.

11/14/2007 First generalized tonic-clonic seizure.

A nearly five-year period in which no seizures are reported,

consistent with Dr. Shafrir’s opinion on dechallenge.

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9/11/2012 Second HPV vaccination.

The first of three seizures, leading to a prescription for anti-

10/12/2012

seizure medication.

Accordingly, Mr. Mager has met his burden on Loving prong four (Althen

prong one) due to the preponderant proof of challenge-rechallenge.

b) Other Theories

As noted previously, whether a demonstration of challenge-rechallenge

satisfies an obligation to present a medical theory causally connecting the vaccine

with the injury has not been directly addressed by an appellate authority. To avoid

the need for a potential remand, the undersigned discusses Mr. Mager’s alternative

methods for establishing Loving prong four.

Mr. Mager’s evidence as to how the HPV vaccine can aggravate a

preexisting seizure disorder is not persuasive. Among the different theories Mr.

Mager advanced, Mr. Mager identified molecular mimicry as “most likely.”

Pet’r’s Posthear’g Br. at 45. However, Mr. Mager has not shown that Dr. Shafrir’s

opinion how the HPV vaccine can cause (or aggravate) seizures is reliable.

Mr. Mager has shown that the HPV vaccine prompts human beings to

produce an immune response, including the production of antibodies. Exhibit 68.

Mr. Mager has also shown that portions of a vaccine might resemble (or mimic)

portions of human tissue. See exhibit 74.

But, Mr. Mager has not persuasively linked the production of antibodies to

the development of epilepsy. While Dr. Shafrir stated that antibodies are “known”

to cause autoimmune epilepsy, Tr. 224, Dr. Shafrir later retreated from this

statement. The presence of antibodies in patients with epilepsy was not

statistically different from the presence of antibodies in controls. Id. at 305-07

(discussion of exhibit 88 (Suleiman)). Furthermore, while Mr. Mager cites to a

series of articles, Pet’r’s Posthear’g Br. at 46, he elicited no significant testimony

about those articles. The lack of testimony is not surprising as those articles

discuss conditions other than epilepsy. See exhibit CC (Dr. Fujinami’s report) at

1-2. While the undersigned has considered those articles, Mr. Mager has not

persuasively shown how they are relevant to the theory.

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On cross-examination, Dr. Shafrir testified “molecular mimicry is a

possibility.” Tr. 245.31 This description is apt. A theory that is “possible” does

not meet a petitioner’s burden of proof. Moberly, 592 F.3d at 1322.

As for the remaining theories, Mr. Mager has done even less to support

them. For example, although the Secretary elicited testimony from Dr. Shafrir

about cytokines, bystander activation, and epitope spreading, Tr. 247-49, Mr.

Mager did not advance those theories. Neither “cytokine” nor “bystander” nor

“epitope spreading” appears in Mr. Mager’s post-hearing brief. In any event, Dr.

Fujinami easily and persuasively demonstrated weaknesses in Dr. Shafrir’s

testimony. Id. at 365-71, 386-98.

In conjunction with this testimony, Dr. Fujinami discussed epidemiological

studies, which his earlier reports had cited. Tr. 365-77. These studies did not

detect any increase in various diseases after HPV vaccination. 32 For a lengthy

discussion of the value of epidemiologic studies in the Vaccine Program, see Tullio

v. Sec’y of Health & Human Servs., No. 15-51V, 2019 WL 7580149, at *5-8 (Fed.

Cl. Spec. Mstr. Dec. 19, 2019), mot. for rev. denied, 149 Fed. Cl. 448, 475 (2020).

Consequently, if challenge-rechallenge were not a way to satisfy the

requirement to present a theory, then Mr. Mager would not have met his burden of

proof regarding Loving prong four (corresponding to Althen prong one).

31

The transcript may contain an error at this point. The entire sentence as

transcribed reads: “Differently molecular mimicry is a possibility.” Dr. Shafrir

may have actually stated “Definitely molecular mimicry is a possibility.”

Regardless of the first word, Dr. Shafrir said “molecular mimicry is a possibility.”

32

Studies included exhibit U (World Health Org., 89 Weekly

Epidemiological Record 53 (2014)); exhibit M (C. Chao et al., Surveillance of

Autoimmune Conditions Following Routine Use of Quadrivalent Human

Papillomavirus Vaccine, 271 J. Internal Med. 193 (2011)); exhibit V (Ctrs. for

Disease Control & Prevention, HPV Vaccine Is Safe – (Gardasil) (2016)); exhibit

AA, tab 5 (Pedro J. Ruiz et al., Microbial Epitopes Act as Altered Peptide Ligands

to Prevent Experimental Autoimmune Encephalomyelitis, 189 J. Experimental

Med. 1275 (1999)).

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G. Loving Prong Five / Althen Prong Two

1. Standards for Adjudication

The second Althen prong requires a petitioner to show a logical sequence of

cause and effect usually supported by the medical records. Althen, 418 F.3d at

1278; Capizzano, 440 F.3d at 1326. The Federal Circuit has instructed special

masters to consider carefully the views of a treating doctor, “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.’”

Capizzano, 440 F.3d at 1326.

2. Parties’ Arguments

In briefing before remand, Mr. Mager argued that Victoria experienced

challenge-rechallenge, meaning she experienced seizures following both HPV

vaccinations. Pet’r’s Prehear’g Br. at 44. Mr. Mager further explained that she

experienced a five-year period of seizure freedom in between in her first and

second HPV vaccinations. Id. Mr. Mager argued that challenge-rechallenge

supports a logical sequence of cause and effect. See id. Dr. Shafrir wrote in his

first report, “Victoria’s immune system ha[d] been primed and then reactivated for

[a] more pronounced immune reaction to the vaccine.” Exhibit 55 at 20.

Additionally, with respect to prong two, Dr. Shafrir opined in his

supplemental report that the subpial gliosis found in Victoria’s autopsy suggests

chronic brain inflammation. Exhibit 85 at 4. This is consistent with Dr. Shafrir’s

testimony during the hearing. Tr. 287.

Dr. Shafrir opined in his supplemental report that the finding of subpial

gliosis in Victoria’s autopsy indicated that she likely had chronic

neuroinflammation. Exhibit 85 at 4. Dr. Shafrir reiterated this opinion at the

hearing. Tr. 287. He elaborated that neuroinflammation can cause gliosis. Id. at

289.

Conversely, the Secretary argued that the record does not support a logical

sequence of cause and effect because there is “no indication ‘of autoimmune

indicators being present.’” Resp’t’s Prehear’g Br. at 21, citing exhibit AA at 3.

Both Dr. Fujinami and Dr. Kohrman addressed Dr. Shafrir’s opinion regarding

subpial gliosis and chronic brain inflammation in their reports. See exhibit A at

14; exhibit AA at 4. Dr. Fujinami stated that “just the act of having seizures can

cause gliosis.” Exhibit AA at 4. He added, “One does not have to hypothesize that

[the] HPV vaccination causes gliosis when individuals with epilepsy already have

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gliosis.” Id. Dr. Fujinami reiterated his opinion that seizures can cause gliosis

during the hearing. Tr. 394.

Dr. Kohrman opined that the finding of gliosis in Victoria’s temporal lobe

was caused by her seizures. Exhibit A at 14. He stated, “There was no evidence of

acute or chronic inflammation documented at the time of autopsy.” Id. He noted

that Victoria’s lab work on May 30, 2012, showed a normal white blood cell count

and “the eosinophils and basophils were only slightly [above] the upper limits of

normal.” Id.; see also exhibit 9 at 21-22. Dr. Kohrman asserted that these results

do not suggest inflammation in the central nervous system. Exhibit A at 14. He

added that Victoria’s MRI after her first seizure was normal and did not show any

flair changes, which would have been indicative of inflammation. Id. at 12. This

was consistent with Dr. Kohrman’s testimony at the hearing.

Dr. Kohrman also disputed Dr. Shafrir’s theory regarding brain

inflammation. In his first report, Dr. Kohrman stated that Victoria’s “MRI shortly

after [her] first seizure was normal with no evidence of changes on flair studies.

Flair changes are sensitive to blood brain barrier breakdown that can be associated

with brain inflammation.” Exhibit A at 12. Similarly, at the hearing, Dr. Kohrman

testified, “I would expect [Victoria’s] MRI to have shown [flair] and T2 changes,

none of which were present.” Tr. 482. He characterized flair and T2 changes as

“the hallmark of inflammation.” Id. During his rebuttal testimony, Dr. Shafrir

agreed with Dr. Kohrman that if Victoria’s seizures were caused by

neuroinflammation, her MRI would have shown flair and T2 changes. Id. at 562-

63.

Dr. Fujinami also argued that Victoria’s seizures were more likely the result

of poor compliance with her anti-seizure medication. Exhibit CC at 1. Dr.

Fujinami referenced an article about JME, which states that JME patients can

control their seizures with “relatively low doses of appropriate anticonvulsants.”

Id., citing exhibit 86 (James Selph, Juvenile Myoclonic Epilepsy, Medscape (June

24, 2016)) at 3.

3. Resolution

Here, there is no dispute that challenge-rechallenge can show that a vaccine

harmed a person and then, on re-exposure, harmed the person again. Capizzano,

440 F.3d at 1322. As explained in the previous section, Mr. Mager has shown this

sequence of events for Victoria. Thus, an inference of causation is appropriate.

Capizzano also teaches that the views of treating doctors merit

consideration. 440 F.3d at 1326. Here, the most direct statement from a treating

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doctor came from Dr. Koehn in July 2008. In an exchange of telephone messages

with Victoria’s stepmother, Dr. Koehn communicated that the HPV vaccination

was not related to the seizure. Exhibit 6 at 19 (call log). This statement, however,

does not dictate a finding against Mr. Mager because any statement from a treating

doctor does not bind a special master. 42 U.S.C. § 300aa-13(b)(1); see also Snyder

v. Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 745 n.67 (2009). Dr. Koehn’s

July 2008 statement carries less weight because Dr. Koehn expressed this opinion

before Victoria received her second HPV vaccination. Thus, in a way, Dr.

Koehn’s opinion was based upon incomplete information.

Accordingly, Mr. Mager has met his burden of proof for Loving prong five.

H. Natural Course of Underlying Disorder

Mr. Mager has demonstrated a prima facie case that the 2012 vaccination

significantly aggravated Victoria’s preexisting epilepsy. He is entitled to

compensation unless the Secretary can show some other factor caused Victoria’s

injury. 42 U.S.C. § 300aa-13(a)(1)(B). For a significant aggravation case, the

Secretary bears the burden of showing that the vaccinee’s post-vaccination

condition was consistent with the natural course of the vaccinee’s preexisting

problem.

Here, the Secretary has not carried his burden. The Secretary’s argument

seems premised, at least in part, on an assertion that Victoria suffered from

juvenile myoclonic epilepsy. See Resp’t’s Prehear’g Br. at 25; Resp’t’s Posthear’g

Br. at 60; Spec. Mstr. Oral Arg. Tr. 688-89. This argument is difficult to credit

after the Court determined that the relevant condition is simply epilepsy. See

Resp’t’s Posthear’g Br. at 55-56.

The parties did not extensively discuss the natural course of generic epilepsy

in their briefs and the evidence on this point seems paltry. Through Dr. Kohrman,

the Secretary persuasively showed that a person with JME and who is not taking

anti-seizure medication may have years without seizures and then redevelop

seizures. Tr. 456, discussing exhibit BB-2 (Iris E. Martinez-Juarez et al., Juvenile

Myoclonic Epilepsy Subsyndromes: Family Studies and Long-Term Follow-Up,

129 Brain 1269 (2006)), 466, 489-90. Thus, the Secretary possessed a good-faith

basis for arguing that Victoria’s course was coincident to, and not aggravated by,

the two HPV vaccinations. This argument, however, is outweighed by the value of

challenge-rechallenge.

A secondary argument from the Secretary is that Victoria’s death was due to

the natural course of her epilepsy. See Resp’t’s Posthear’g Br. at 15-17. Several

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points underlie this argument. First, as found in section I.A above, Victoria

suffered from seizures before the initial dose of the HPV vaccination. Thus, the

HPV vaccination did not cause her epilepsy. Second, people whose epilepsies are

controlled without medication can redevelop seizures unpredictably. See exhibit F

(Julia Hofler et al., Seizure Outcome in 175 Patients with Juvenile Myoclonic

Epilepsy – A Long-Term Observational Study, 108 Epilepsy Rsch. 1817 (2014)) at

1820 (observing that 16 out of 175 JME patients experienced two years of seizure

freedom without taking antiepileptic medications); see also Tr. 492 (Dr.

Kohrman’s testimony that periods of seizure freedom are common in patients with

JME). Third, Victoria had “reluctance to remain on Depakote (an effective

treatment for her generalized seizures)” and she “lack[ed] compliance with Keppra

(a less effective treatment for generalized seizures).” Resp’t’s Posthear’g Br. at 16.

To this list, the Secretary added testimony from Dr. Shafrir. Dr. Shafrir

stated that risk factors for sudden unexplained death in epilepsy (“SUDEP”)

include nocturnal seizures, generalized seizures, poorly controlled seizures, and

poor compliance. Tr. 331-32. But, regardless of risk factors, “SUDEP could have

occurred after a few months with epilepsy, could have occurred after 20 years of

epilepsy.” Id. at 355. To Dr. Shafrir, Victoria’s “SUDEP is not correlated to the

vaccine or anything else.” Tr. 355. The Secretary emphasizes Dr. Shafrir’s “not

correlated” comment. Resp’t’s Posthear’g Br. at 16-17.

Mr. Mager’s response is to cite Dr. Kohrman’s testimony that before

Victoria’s death, her epilepsy was “uncontrolled.” Pet’r’s Posthear’g Reply at 19,

citing Tr. 534. However, characterizing Victoria’s epilepsy in the months before

her death in January 2014 as “uncontrolled” does not mean that the vaccination

approximately one year earlier made the seizures uncontrolled. Dr. Shafrir

testified that Victoria’s “death may have not happened if she was able to get better

treatment.” Tr. 355. A relevant factor is that Victoria may have had poor

compliance with her medication. See exhibit 13 at 2 (witness report that Victoria

had been missing doses of her medication prior to her death). However, according

to a toxicology report, Victoria had therapeutic levels of Keppra in her blood at the

time of her death. Id. at 11; Tr. 302 (Dr. Shafrir), 467 (Dr. Kohrman).

Mr. Mager further maintained that although Dr. Shafrir did not correlate

Victoria’s death with the HPV vaccination, he correlated her death with epilepsy.

Spec. Mstr. Oral Arg. Tr. 647. Mr. Mager argued, SUDEP “is directly related to

[Victoria’s] seizures,” and her seizures were “directly related to the vaccine.” Id.

He added that Victoria’s epilepsy was uncontrolled after her second HPV

vaccination, and her resulting condition cannot be separated from her subsequent

death. Id. at 672-74.

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This issue, too, is close. A potentially useful piece of information would

have been how often people with mild epilepsy experience SUDEP. This evidence

could have informed an assessment of how Victoria’s epilepsy, unaggravated by

the second HPV vaccination, might have progressed.

Without this evidence, the claim that Victoria’s death is the natural result of

her epilepsy seems possible. But, the Secretary has not established this argument

by a preponderance of the evidence.

V. Conclusion

Accordingly, Mr. Mager has established that the September 11, 2012 HPV

vaccination significantly aggravated Victoria’s epilepsy and caused her death.

Therefore, he is entitled to compensation under the Vaccine Act. Pursuant to

Vaccine Rule 28.1(a), the Clerk is directed to notify the Court of this decision.

An order regarding damages will be issued shortly.

IT IS SO ORDERED.

s/Christian J. Moran

Christian J. Moran

Special Master

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