S. v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 17-480V

(to be published)

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

E.S, *

* Filed: November 13, 2020

Petitioner, *

* Chief Special Master Corcoran

v. *

*

SECRETARY OF HEALTH AND * Human Papillomavirus Vaccine; Type

HUMAN SERVICES, * I Diabetes; Influenza Vaccine;

* Narcolepsy; Postural Orthostatic

* Tachycardia Syndrome;

Respondent. * Chronic Fatigue; Reliable Theory;

* Aggravation of Diabetes; Onset

*

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

Robert J. Krakow, Law Office of Robert J. Krakow, New York, NY, for Petitioner.

Sarah Duncan, U.S. Department of Justice, Washington, D.C., for Respondent.

DECISION 1

On April 4, 2017, E.S filed this action seeking compensation under the National

Vaccine Injury Compensation Program (the “Program”). 2 ECF No. 1; see also Amended Petition,

filed Apr. 4, 2017 (ECF No. 64-1). Petitioner alleges that she suffered autonomic dysfunction,

manifesting in a wide variety of conditions and symptoms (including headaches, chronic fatigue

syndrome (“CFS”), postural orthostatic tachycardia syndrome (“POTS”) and small fiber neuropathy

(“SFN”), after receipt of the human papillomavirus (“HPV”) and hepatitis A vaccines in July 2014,

with the same symptoms plus a cardiac condition and aggravation of preexisting diabetes mellitus

after receiving another HPV vaccine dose along with the influenza (“flu”) vaccine in August 2015.

1

This Decision will be posted on the United States Court of Federal Claims’ website in accordance with the E-

Government Act of 2002, 44 U.S.C. § 3501 (2012). This means the Decision will be available to anyone with access

to the internet. As provided by 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties may object to the published

Decision’s inclusion of certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party has

fourteen (14) days within which to request redaction “of any information furnished by that party: (1) that is a trade secret

or commercial or financial in substance and is privileged or confidential; or (2) that includes medical files or similar files,

the disclosure of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the

entire Decision will be available to the public in its current form. Id.

2

The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100

Stat. 3758, codified as amended, 42 U.S.C. §§ 300aa-10 through 34 (2012) [hereinafter “The Program” or “Program”].

Individual section references hereafter will be to Section 300aa of the Act.

Id. at 1. After the filing of multiple expert reports, I invited Respondent to request the claim’s

dismissal, and the matter is now fully briefed. Resp.’s Brief in Support of Dismissal, filed

Sept. 13, 2019 (ECF No. 103-1) (“Mot.”); Pet.’s Brief in Opposition of Dismissal, filed Dec.

2, 2019 (ECF No. 112) (“Opp.”); Resp.’s Reply Brief in Support of Dismissal, filed Feb. 4,

2020 (ECF No. 114-1)(“Reply”); Pet.’s Sur-Reply Brief in Opposition of Dismissal, filed Apr.

2, 2020 (ECF No. 118) (“Sur-Reply”).

Petitioner’s medical history establishes that she has experienced a variety of conditions and

symptoms, but many of her alleged injuries (in particular POTS and myocardial ischemia) are not

preponderantly established, nor are all related, as she seems to assume. In addition, those symptoms

she can establish having experienced appear attributable to her preexisting diabetes, or occurred too

long after vaccination to be deemed causal. And overall, Petitioner’s theories—that the HPV

vaccine or flu vaccine can either cause or aggravate (a) dysautonomia and/or POTS, (b) small fiber

neuropathies, (c) chronic fatigue syndrome, (d) narcolepsy, or (e) diabetes—reiterate contentions

that have rarely been successful in the Program, and are medically and scientifically unreliable

based upon the evidence offered in this case. I therefore find that Petitioner’s claim merits no further

consideration, and dismiss it on the basis of the existing filings.

I. Factual Background

A. Pre-Vaccination Health History

Ms. E.S. was born on January 2, 1996 (and was thus eighteen years old when she received

the first vaccines at issue in this case). Ex. 1 at 1. She was a strong student by her accounts, and an

accomplished athlete as well, who swam competitively and won top positions at regional swim

competitions during high school. Ex. 103; Ex. 43; Ex. 44. Ms. E.S. held summer employment

as a lifeguard and was reportedly considered for membership on college swim teams, although it is

unclear from the filed documentary evidence if she did in fact swim for the university she ultimately

attended (Villanova University). Ex. 103; Ex. 104 at 2.

The record, however, also reveals that Petitioner had her share of medical problems before

the relevant vaccinations, and some of these bear on her claim. In particular, Ms. E.S. was

diagnosed with type I diabetes mellitus (“DM-1”) when she was five years old (although she had

good control of it in the time before receiving the first vaccines alleged to have injured her). 3 Her

medical records also reflect problems with persistent lower back pain, intermittent hematuria,4 flank

pain, kidney stones, surgery for hemorrhagic right ovarian cyst, irregular menses, selective

3

See Mot. at 3 n.7 (“Petitioner’s DM-1 was under fair control prior to receiving the first HPV vaccine with a hemoglobin

A1c (“HbA1c”) typically in the range of 7-8% (ideal for a child being <7%) since 2008”) (citing Ex. 19 at 81–110).

4

Hematuria (or erythrocyturia) is blood (erythrocytes) in the urine. Dorland’s Illustrated Medical Dictionary 824 (33rd

ed. 2020) (hereinafter, “Dorland’s”).

2

immunoglobulin A deficiency, and rheumatoid arthritis. Ex. 19 at 50, 54, 66, 69; Ex. 4 at 152; Ex.

3 at 5, 8; Ex. 23 at 5.

Additionally, there are several documented instances from the record in which Ms. E.S.

sought emergency treatment for ambiguous complaints that did not result in any significant findings

or explanations. Thus, in July 2011, Petitioner visited the emergency room complaining of two days

of mid-sternal chest pain, weakness, and shortness of breath. Ex. 17 at 198–204. However, her vital

signs, chest x-ray, and EKG 5 were normal, her chest pain resolved, and she was discharged. Id. at

198–204, 207, 210. Later on, in the fall of 2012 (now about two years before her relevant

vaccinations), Ms. E.S. went two more times to the ER complaining of flank pain. Ex. 4 at 152–

196. At these visits she recounted similar episodes in the past and a prior history of kidney stones.

Id. at 152, 159. She also reported that blood in her urine was (at least at that time) a “chronic

problem.” Id.

Petitioner reported several health problems to her pediatrician in the months before her July

2014 receipt of the HPV and hepatitis A vaccines. She complained of recurring headaches and sore

throat in the fall of 2013. Ex. 3 at 16. A strep test came back negative and her treater diagnosed her

with adenopathy and acute pharyngitis. Id. She was directed to return if symptoms worsened. Id. In

March 2014, she visited her pediatrician, Dr. Rebekah Lipstein, for nausea and sore throat, and was

diagnosed with a viral infection. Ex. 3 at 13–15. She weighed 159 pounds at this visit. Id. Then, in

April 2014 she went to the ER again, this time complaining of blood in her urine, back and flank

pain, and hyperglycemia. Ex. 4 at 117–31. Her blood glucose was 349 (an extremely high level for

a diabetic6), she had glucose and ketones in her urine, and she now weighed 150 pounds. Id. at 118–

20.

B. July 15, 2014: Petitioner Receives HPV and Hepatitis A Vaccines

At a well visit with Dr. Lipstein on July 15, 2014, Ms. E.S. received the first vaccines at

issue—the HPV and hepatitis A vaccines. Ex. 3 at 8–12. She weighed 164 pounds at this visit, and

a urine dipstick test showed trace glucose (an indication of elevated serum glucose levels). Id. at

11. The record reveals no immediate vaccine reaction. In fact, as indicated below, there was a

subsequent, several-month gap before Petitioner again sought medical treatment. Thus, there is no

evidence from this period that she was experiencing symptoms of any kind.

Ms. E.S. began college in the fall of 2014. On September 2, 2014, she visited the student

health center for treatment of increased blood sugars that she had observed from her own self-

5

Electrocardiogram (“EKG” or ECG) is a graphic tracing of the variations in electrical potential caused by the excitation

of the heart muscle and detected at the body surface. Dorland’s at 593.

6

In children two years to adult, normal “casual” (meaning any time of day) blood glucose levels are ≤ 200 mg/dL or 11.1

mmol/L. Mosby’s Manual of Diagnostic and Laboratory Tests 253 (6th ed. 2018) (hereinafter, “Mosby’s”).

3

monitoring, and a sore throat. Ex. 14 at 88–90. Petitioner tested positive for group A streptococcus

and was prescribed antibiotics. Id. However, there is no evidence from this particular record that

any treater associated her strep infection or diabetes resurgence with her July vaccinations (which

had been administered nearly seven weeks before). Later that same month, from September 22–24,

2014, Ms. E.S. visited the health center multiple times for high glucose levels and a cough (later

diagnosed as bronchitis). Id. at 84–87. About ten days later, on October 2, 2014, she visited the

emergency room (“ER”) at Bryn Mawr Hospital for an abnormal glucose level of 338. Ex. 9 at 3–

12. She denied having previous similar symptoms (despite her history in the immediate weeks

prior), and although she complained of headache and sinus pressure, she did not identify the onset

of these symptoms occurring much before the ER visit. Id. Four days later, on October 6, 2014,

Petitioner visited her university health center for nausea and elevated blood sugars. Ex. 14 at 70.

Meanwhile, more than ten weeks had passed from the time in July when Petitioner received the

relevant vaccines.

No records have been filed establishing any additional visits by Ms. E.S. to medical

treaters in November 2014. Then, on December 5, 2014, Petitioner made a second visit to the Bryn

Mawr ER, now complaining of constant vomiting and diarrhea that she reported began about one

and a half weeks before her visit (late-November). Ex. 9 at 27–35. This was the first time in the

medical record Petitioner reported this combination of symptoms and based on her presentation she

was diagnosed with gastroenteritis. Id. Throughout December, Petitioner visited the Villanova

student health center multiple times for increased glucose levels, diarrhea, vomiting, and abdominal

pain. See, e.g., Ex. 14 at 68–69; Ex. 17 at 12–21, 102–05.

On December 11, 2014, Petitioner saw Dr. Keith Benkov, a gastroenterologist. Ex. 11 at 1–

2. She reported that in late September 2014 she had experienced several viral infections, high blood

sugars, and back pain. Id. She also told Dr. Benkov that in November 2014 she began vomiting

daily and having loose stools. Id. Dr. Benkov ordered labs, doubled Petitioner’s Protonix 7 dose,

considered performing an endoscopy, and took Petitioner’s weight (now 172 pounds). Id.

Petitioner’s celiac and thyroid profiles were negative, and she was also negative for thyroid

antibodies, FSH, testosterone, estradiol, and DHEAS. 8 Id. at 6. The records from this time reflect

some treater concerns that Petitioner may have suffered from a pancreatic condition, although this

was not confirmed. Id. at 10. Later that same December, Ms. E.S. was again hospitalized after

complaining of persistent headaches, and testing performed on her revealed elevated liver enzymes

plus some evidence of a possibly enlarged liver. Ex. 17 at 97, 99, 113. Dr. Benkov concluded that

7

Protonix is the trademark for preparations of pantoprazole sodium. Dorland’s at 1513. Pantoprazole sodium is a proton

pump inhibitor used in the treatment of erosive esophagitis associated with gastroesophageal reflux disease. Pantoprazole

Sodium, Dorland’s Online Medical Dictionary,

https://www.dorlandsonline.com/dorland/definition?id=36645&searchterm=pantoprazole+sodium (last visited Oct. 9,

2020).

8

Dehydroepiandrosterone sulfate (“DHEAS”) is a steroid secreted by the adrenal cortex, the major androgen precursor

in females; it is often present in excessive amounts in body fluids of patients with adrenal virilism. Dorland’s at 476.

4

Petitioner had poor diabetic control as well as poor gastric emptying, and a fatty liver. Id. at 105.

On January 6, 2015, Petitioner’s glycated hemoglobin (HbA1c) 9 level was 9.8% and 10.2%

on different readings taken that day—both highly elevated and evidence of ongoing diabetes. Ex.

19 at 114, 119. Later that month, on January 27, 2015, she visited Dr. Elizabeth Wallach, an

endocrinologist. Id. at 28–31. Petitioner’s mother was concerned about Ms. E.S. ’s increasing

HbA1c levels (9.8% that day) and increasing weight (12 pounds since she began college). She

privately discussed with Dr. Wallach that Petitioner was eating a lot and not always testing her

blood sugar. Id. at 29. Dr. Wallach felt Petitioner was doing well on her insulin pump, but discussed

the possibility of taking her off it (something Petitioner expressed a desire to do). Id. at 28.

C. Additional Vaccines Deemed Causal and Onset of Novel Symptoms

More than three months passed before Ms. E.S. again required medical treatment. On

May 1, 2015, Petitioner sought emergency room treatment at Bryn Mawr Hospital for the fourth

time, complaining of abrupt onset of right flank pain, nausea, and vomiting. Ex. 9 at 54. Petitioner’s

blood glucose at the point of care was 129 mg/dL, and urine glucose was 500 mg/dL. Id. at 70.

Three months passed before Petitioner’s next doctor visit which was for her annual pediatric exam

on August 19, 2015. Ex. 3 at 5–7. She now weighed 168 pounds, and a urine dipstick showed 3+

blood and no glucose.10 Id. During this exam, she received her second HPV vaccine dose, and a flu

vaccine. Id. Petitioner’s filed medical history reveals she had in the past repeatedly received the flu

vaccine with no complications. Ex 2; Ex. 17 at 185. There is no evidence of any immediate/close-

in-time reaction to these vaccinations.

Over the fall of 2015 and into early 2016, Ms. E.S. continued to seek emergency care on

a regular basis, with most treater visits seemingly oriented toward addressing diabetes-related issues

or complications. Approximately two months passed since the second set of vaccinations before

Petitioner had two ER visits. At the first visit (October 10, 2015), she complained of nausea,

vomiting, loose stools, and high blood sugar. Ex. 9 at 79, 81–82. However, she had a normal EKG,

and the discharge assessment was nausea and vomiting. Id. at 83. She was instructed to drink plenty

of fluids, avoid alcohol and certain over-the-counter pain relievers, and to adjust her insulin pump

9

In adults, about 98 percent of the hemoglobin in the red blood cell is hemoglobin A. About seven percent of hemoglobin

A consists of a type of hemoglobin (HbA1) that can combine strongly with glucose in a process called glycosylation. As

the red blood cell circulates, it combines its HbA1 with some of the glucose in the bloodstream to form glycohemoglobin

(GHb). The amount of GHb depends on the amount of glucose available in the bloodstream over the RBC’s 120-day life

span. Therefore, determination of the GHb value reflects the average blood sugar level for the 100- to 120-day period

before the test. The more glucose to which the RBC is exposed, the greater the percentage. Mosby’s at 266.

10

Urine reagent strips or dipsticks are used for the estimation of glucose, albumin, hemoglobin, and bile concentrations,

as well as urinary pH, specific gravity, protein, ketone bodies, nitrates, and leukocyte esterase. Mosby’s at 909. Dipstick

testing is considered preliminary or for screening. Id. Often more definitive and quantitative studies are necessary to

confirm the results. Id.

5

as directed by her diabetes physician. Id. Similarly, on her second ER visit (October 21, 2015) she

presented with high blood sugar and abdominal pain occurring since the prior visit. Ex. 12 at 1, 10,

75. A CT scan of the abdomen and pelvis was performed with no significant findings. Id.

Petitioner’s treater noted that her symptoms sounded like acid reflux and that she had a positive

response to such treatment. Id. at 36.

Vomiting and diarrhea prompted a third ER visit in early December 2015, and although

Petitioner’s blood sugar was now a bit lower, she was diagnosed with hypokalemia, 11 and instructed

to follow-up with her GI doctor about her visit and her potassium levels. Ex. 9 at 106, 108, 109.

Petitioner reported a similar constellation of symptoms at a January 10, 2016 visit. Ex. 7 at 5, 8–9.

None of the relevant treaters proposed that Petitioner’s receipt of the second HPV dose or flu

vaccine in August 2015 might have played a role in Petitioner’s illness, however, treaters did

consider her high blood sugar as causal. Ex. 12 at 39.

Petitioner again sought specialized treatment in early 2016. On February 16, 2016, she saw

Dr. David Lefkowitz, a cardiologist, for evaluation of chest pain. Ex. 5 at 1–4. She reported the pain

she was experiencing was “generally exertional” in nature, and that she also suffered from

occasional night sweats, decreased exercise tolerance, new onset migraines, and episodes of

tachycardia not experienced in the past. 12 Id. She also claimed that she had felt poorly since

receiving the HPV vaccine, two other vaccines, and a tuberculosis skin test. Id. at 1.

A physical exam performed by Dr. Lefkowitz showed regular heart rhythm, a mid-systolic

click, absent jugular venous pressure, normal carotid upstrokes and no lower extremity edema.13

Ex. 5 at 2. Pericardial 14 thickening was noted on Petitioner’s echocardiogram, and an EKG showed

“sinus rhythm, inferior and lateral repolarization abnormality compatible with pericarditis 15 versus

early repolarization.” Id. at 3–4, 13. A stress EKG revealed distal inferoseptal hypokinesis 16 at peak

stress, which (as Dr. Lefkowitz noted) might suggest a possible jeopardized myocardium,17

11

Hypokalemia is abnormally low potassium concentration in the blood resulting from excessive potassium loss by the

renal or the gastrointestinal route, from decreased intake, or from transcellular shifts. Dorland’s at 891.

Tachycardia is excessive rapidity in the action of the heart and is usually applied to a heart rate above 100 beats per

12

minute in an adult. Dorland’s at 1838.

13

Edema is the presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body, usually

referring to subcutaneous tissues, which may be localized. Dorland’s at 587.

14

The pericardium is the fibroserous sac that surrounds the heart and the roots of the great vessels, comprising an external

layer of fibrous tissue and an inner serous layer. Dorland’s at 1391.

15

Pericarditis is inflammation of the pericardium. Dorland’s at 1391.

16

Hypokinesis or hypokinesia is abnormally decreased mobility/motor function or activity. Dorland’s at 891.

17

The myocardium is the middle and thickest layer of the heart wall, composed of cardiac muscle. Dorland’s at 1204.

6

although the stress test was cut short when Petitioner complained of chest pain. Id. at 2, 4, 15. The

positive stress test prompted the doctor to order cardiac CT angiography, 18 but that test produced

normal results. Id. at 16–18 (performed on March 3, 2016). There was no immediate follow-up with

Dr. Lefkowitz (moreover, Petitioner did not return to him for an entire year).

On February 17, 2016, Petitioner visited Dr. Benkov again (whom it does not appear from

the records she had seen for more than a year). Ex. 11 at 3. Although she reported experiencing less

severe gastrointestinal issues overall, she still had occasional episodes of nausea, diarrhea, and

vomiting. Id. Records from this visit establish that Petitioner’s mother now expressed the view that

Ms. E.S. ’s symptoms were associated with the second HPV dose she had received in August

2015. Id. The medical record, as discussed above, does not support this conclusion. However, it

does reveal that throughout this time period Ms. E.S. ’s diabetes was not under good control. Id.

Additionally, Petitioner reported that she continued to gain weight despite monitoring of her diet.

Id. Moreover, Petitioner’s mother informed Dr. Benkov that Petitioner’s sister seemed to have

gotten sick after receiving the HPV vaccine, 19 and that both sisters had developed pericarditis as a

result. Id.

In contrast to the mother’s statements, Dr. Benkov noted on exam that Petitioner “actually

looked pretty well off.” Ex. 11 at 3. However, she now weighed 177 pounds and her hemoglobulin

A1C was elevated (9.8%), and remained so even when tested again in early March. 20 Id. at 3, 7; Ex.

19 at 145. An abdominal ultrasound revealed two non-obstructing stones in Petitioner’s right renal

collecting system. Ex. 11 at 10. Dr. Benkov noted that Petitioner’s condition “could be some form

of pancreatitis” and suggested doubling her current dose of Protonix. Id. at 1, 2.

On May 12, 2016, Ms. E.S. visited Dr. Edith Schussler, a Clinical Fellow in the Division

of Allergy and Immunology at Icahn School of Medicine at Mount Sinai, for an immune

dysfunction consultation. Ex. 23 at 5–8. The records from this visit include a condensed medical

history, addressing her long-standing struggle with diabetes among other things. Id. at 5. The history

also stated that beginning in the summer of 2014, Petitioner had started to experience repeated throat

infections, cyclic vomiting (four times a day), diarrhea, racing heart, and fatigue. Id. During this

period, her athletic pursuits were curtailed, she experienced extreme weight gain and poor glucose

control, and she now claimed she had been diagnosed with a non-alcoholic fatty liver. Id.

Petitioner asserts she had improved the following summer, but then worsened after receiving

18

Angiography is the radiographic visualization of blood vessels following introduction of contrast material; used as a

diagnostic aid in such conditions as stroke syndrome and myocardial infarction. Dorland’s at 83.

19

See Opp. at 15.

20

Petitioner visited the ER on March 2, 2016 for non-radiating, waxing and waning abdominal pain that was aggravated

by menstruation diagnosed as a ruptured ovarian cyst. Ex. 14 at 13–14.

7

her second HPV vaccine in August 2015. She also reported “running in the 300-400 glucose range,”

but had better control after recently seeing her endocrinologist. Ex. 23 at 5. A physical examination

was mostly normal, although Dr. Schussler recommended that Petitioner not get the Rubella or

hepatitis B vaccines—the only two she needed at the time—while she was not feeling well. Id. at

7–8. 21 Dr. Schussler, based on HLA testing, 22 concluded that Petitioner did not appear to be a

vaccine “non-responder,” and that she should continue to be vaccinated in the future. Id. at 13.

At the end of May 2016, Petitioner visited Dr. John Wells for a neurologic evaluation. Ex. 24

at 6–7. She reported a number of medical problems within the last year. Id. at 6. Her primary

neurological complaint was a headache sensation, which had been persistent since starting college

and was characterized by constant pressure and “weird feelings in her head that come and go.” Id.

Ms. E.S. recounted the same general medical history post-2014 vaccinations, adding that she

had taken a leave of absence from school starting in March 2016. Id. Her neurological exam and

brain MRI/MRA were normal. Id. at 7 (MRI/MRA performed on June 27, 2016). Dr. Wells

concluded that Petitioner had persistent headaches despite a normal neurological exam and a normal

brain MRI/MRA, and suggested that she follow up with her cardiologist and endocrinologist and

try therapy for her anxiety. Id. at 7 (MRI/MRA performed on June 27, 2016).

In August 2016, Petitioner followed up with Dr. Wallach, her endocrinologist. Ex. 19 at 2–

3. She generally reported doing better, with an improved HbA1C level of 8.7%, down from more

than 9%, and some weight loss. Id. at 2. Dr. Wallach noted that Petitioner was ready to go back to

college after taking the prior semester off for health issues. Id. A treater thereafter (whom Petitioner

first saw that spring—and hence long after the vaccinations in question) recommended that

Petitioner not receive the flu vaccine again due to a “history of adverse reaction,” although (as

revealed by the record above) this assertion is not well-supported by either the bare medical record

or any informed treater opinion not solely reliant on Petitioner’s self-reported history. Ex. 15 at 1.

Petitioner obtained some mental health counseling in October 2016. Ex. 13 at 5–6. Later that

same month, Petitioner visited Dr. Sanjeev Kothare at NYU’s Langone Health System for

evaluation of possible seizures and sleep problems. Ex. 22 at 5. Although this is the first time such

symptoms are mentioned in Petitioner’s medical record, she now reported daytime sleepiness and

insomnia for the past two years (which would place onset in October 2014, or nearly three months

after the first vaccines in dispute), plus sleep paralysis, vivid/violent dreams, panic attacks, and

depressed mood—all of which she attributed to her receipt of the flu vaccine in 2015. Id. at 6;

21

Notes from that visit also briefly discussed Petitioner’s sister—who allegedly had her own reaction to the HPV vaccine

and has filed a petition in the Program. Ex. 23 at 8 (“[t]here is some confusion about what the sister had, and what

[Petitioner] has had: while racing heart was noted as ventricular tachycardia in the sister by a monitor, [Petitioner] who

has similar complaints has not had this. . . . The relationship between the reactions to Gard[a]sil [sic] in the sisters, if any

is also unclear”).

22

Human leukocyte antigen (HLA) testing is a blood test that identifies antigens on the surface of cells and tissues.

Mosby’s at 306–07. These antigens can identify patients who are allergic to certain medications or to confirm diagnosis

of certain diseases in which the antigens are present. Id. at 306.

8

Statement of Pet., filed Apr. 14, 2017 (ECF No. 7-1), at 3.

Dr. Kothare noted a history of snoring, dry mouth, mouth breathing, leg twitching, abnormal

arousals (sleep walking and confusional arousals), and daytime sleepiness were also present. Ex.

22 at 6. However, Petitioner had a normal neurological exam with no evidence of sensory deficits

in response to light touch, pin prick, position, and vibration. Id. at 8. It was also noted (at a follow-

up visit in December 2016) that there were no reported instances of cataplexy. 23 Id. at 11. As of the

initial visit, Dr. Kothare diagnosed Petitioner with narcolepsy type 2, non-REM parasomnia, and

REM sleep disorder. Id. at 9.

Petitioner underwent a nocturnal polysomnography test on November 21, 2016. Ex. 22 at 27.

The results were interpreted to reveal the existence of mild sleep apnea and “upper airway resistance

syndrome,” both of which were considered treatable. Id. Then, in January 2017, Ms. E.S. had

a multiple sleep latency test (“MSLT”). Ex. 36 at 33, 35. The results were deemed by Dr. Kothare

to reveal “evidence of excessive daytime sleepiness” which “could be consistent with narcolepsy

under the appropriate clinical circumstances,” leading him to propose follow-up clinical

confirmation. Id. at 35. Dr. Kothare noted mild obstructive sleep apnea but normal baseline

oxygenation, normal CO2, normal EKG, and no significant periodic leg movements. Id. at 24. Dr.

Kothare saw Petitioner again in March 2017, and after review of the MSLT results and another

exam, he again confirmed his earlier diagnosis of type 2 narcolepsy (i.e. without cataplexy). Ex. 36

at 46–50.

D. 2017 and Post-Filing Treatment

In January 2017, laboratory results from CellTrend and GmbH were sent to Petitioner’s

mother. Ex. 16 at 1. Ms. E.S. was found to be positive for anti α-1-adrenergic antibodies and

anti-muscarinic cholinergic receptor 4 antibodies. 24 Ex. 16 at 1. She was also “at risk” for anti-

muscarinic cholinergic receptor 3 antibodies. Id.

On February 23, 2017, Petitioner saw Dr. Lefkowitz again, who expressed the view that the

potentially cardiac-associated symptoms were not likely the product of coronary disease. Ex. 18 at

14 (“[s]he had a thorough workup which revealed ultimately that she had no evidence of coronary

artery disease on CT angiography”). Dr. Lefkowitz concluded that any cardiac risk factors that Ms.

E.S. faced were most credibly associated with her existing diabetes. Id. Petitioner still sought

treatment for her overall complaints, however, with some treaters allowing the possibility of a link

23

Cataplexy is a condition in which there are abrupt attacks of muscular weakness and hypotonia triggered by an

emotional stimulus such as mirth, anger, fear, or surprise and is often associated with narcolepsy. Dorland’s at 298.

24

Dr. Steinman (one of Petitioner’s experts) has referenced a recent study that associates certain autoantibodies, including

adrenergic receptor antibodies, with ME/CFS and fibromyalgia. Steinman Second Report, filed on Jan. 14, 2019 (ECF

No. 85-1), at 26. Dr. Steinman has also maintained that elevated muscarinic receptor antibodies are also associated with

ME/CFS, POTS, CRPS, and fibromyalgia. Id.

9

to the HPV vaccine. See, e.g., Ex. 19 at 3 (March 2017 visit to Dr. Wallach).

This case was subsequently initiated in April 2017, although the period thereafter continued

to be punctuated by urgent care or emergency treater visits, as Petitioner grappled with the same

overall constellation of symptoms that she had confronted since the fall of 2014. In May 2017, for

example, Petitioner visited the ER for chest pain—described as sharp, mild, ongoing, and

exacerbated by movement and palpitation. Ex. 33 at 57–71. An EKG showed possible left arterial

enlargement but no evidence of ischemia. Id. at 65. Ms. E.S. was diagnosed with non-specific

25

chest pain and hypoglycemia. Id. at 71.

Four days later, on May 24, 2017, Petitioner returned to the ER. Ex. 33 at 24. She stated that

“[s]he drank a lot and her insulin pump is going crazy.” Id. On intake, Petitioner reported a tingling

in her chest and chest pain for the last two days. Id. 24–25. Labs reported that Petitioner’s blood

alcohol level was 0.137, 26 and a urine screen was positive for cannabinoid. Id. at 17, 21, 40. An

EKG mostly was normal but did detect a prolonged QT. 27 Id. at 8, 23. Petitioner was discharged

and diagnosed with hypoglycemia and nausea. Id. at 11.

There is a lengthy records gap through January 2018, when Petitioner returned to the ER with

abdominal, rectal, and chest pain with nausea. Ex. 34 at 1. An EKG test was borderline but showed

normal sinus rhythm and a rightward axis. Id. at 72. A few months later, in April 2018, Petitioner

sought more treatment for her purported narcolepsy and sleep issues. Ex. 102 at 1. Dr. Rodriguez,

a board-certified sleep medicine specialist, noted that Petitioner had paralysis and hallucinations at

night. Id. He recommended 0.25-0.5 mg of Clonazepam, and Petitioner was advised to follow up in

three months. Id.

Then, in late June 2018, Ms. E.S. visited Dr. Susan Levine, a specialist in infectious

disease and internal medicine. Ex. 98 at 27. A subjective exam showed weakness, fatigue,

palpitations, upset GI, and numbness of lower extremities. Id. During an objective exam, Dr. Levine

noted that Petitioner had “[n]euro-diminished sensory over L4/L5 and L5/S1 deformities; 5/+5 good

motor strength in both lower extremities; [and] slightly diminished patellar reflexes bilaterally.” Id.

25

Hypoglycemia is an abnormally diminished concentration of glucose in the blood, which may lead to tremulousness,

cold sweat, piloerection, hypothermia, and headache; when chronic and severe it may cause central nervous system

manifestations that in rare cases can even be fatal. Dorland’s at 890.

26

A blood alcohol concentration (“BAC”) of 0.10-0.12 causes significant impairment of motor coordination, including

balance, speech, vision, and control, as well as loss of judgment. Stanford University, Office of Alcohol Policy and

Education, What is BAC?, https://alcohol.stanford.edu/alcohol-drug-info/buzz-buzz/what-bac (last visited Nov. 2, 2020).

A BAC of 0.13-0.15 causes gross impairment of motor control, blurred vision, and major loss of balance, as well as

dysphoria, which includes anxiety and restlessness. Id.

27

Long QT syndrome (“LQTS” or “prolonged QT”) is a heart rhythm condition that can potentially cause fast, chaotic

heartbeats. These rapid heartbeats might trigger you to suddenly faint. Mayo Clinic, Long QT syndrome,

https://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/symptoms-causes/syc-20352518 (last visited Nov.

10, 2020).

10

Relying on the above, but also on prior test results, Dr. Levine assessed Ms. E.S. with

28

inflammatory neuropathy, autonomic dysfunction, gastroparesis, and endometriosis. Id. Notably,

EMG and nerve conduction study tests performed on September 12, 2018 only supported a mild

radiculopathy rather than true neuropathy. Ex. 49 at 27. Not long after this visit, Dr. Levine prepared

the one-page report that Petitioner has submitted in support of her claim. Ex. 85.

Petitioner followed up with Dr. Levine in August 2018. Ex. 98 at 26. She now reported

continuing daily weakness, fatigue, palpitations, worsening ability to function, and increased panic.

Id. Dr. Levine assessed Petitioner with ME/CFS, 29 DM1, post-HPV vaccine onset of CFS symptoms,

dysautonomia, and POTS. 30 Id. However, the record does not include evidence of confirmatory

testing for the POTS diagnosis.

In the fall of 2018, Petitioner visited Dr. Russell Chin, a neurologist at Weill Cornell

medicine, for “suspected neuropathy” upon referral by Dr. Levine. Ex. 49 at 1; Ex. 48 at 1. Dr. Chin

ordered EMG testing and epidermal nerve fiber density testing via skin biopsy. Ex. 48 at 1; Ex. 49

at 27. Petitioner reported that since 2015, she had noticed some intermittent tingling sensations in

her mid-chest region, and since early 2018 tingling and “chilled” sensations to her scalp, neck, and

shoulders (complaints that, as the review of records to this date should reveal, are not especially

reflected in her overall history). Ex. 49 at 2. Although Petitioner has claimed that Dr. Chin

“suspected” she had progressing small fiber neuropathy in her body since 2015, Dr. Chin merely

expressed the view that her symptoms were possibly related to other dysautonomic/autoimmune

issues (such as her diabetes, inflammatory arthritis, or an IgA deficiency). Ex. 86 at 34–37.

However, he ultimately acknowledged that the “[e]tiology of these symptoms is unknown.” Ex. 49

at 7.

An EMG/nerve conduction study performed at this time suggested to Dr. Chin carpal tunnel

and ulnar entrapment of the right arm, a mild radiculopathy of the lower extremities, but no evidence

of neuropathy. Ex. 49 at 27–34. However, extensive laboratory tests for causes of neuropathy

yielded normal results with the exception of Petitioner’s known diabetes and elevated cholesterol

levels. Id. at 21–26. The two skin biopsies performed at this time showed reduced sweat gland nerve

fiber density and a reduced intra-epidermal nerve fiber density at one site. Ex. 48. A brain MRI

28

The autonomic nervous system is the portion of the nervous system concerned with regulation of the activity of cardiac

muscle, smooth muscle, and glandular epithelium; usually restricted to the two visceral efferent peripheral components,

the sympathetic nervous system, and the parasympathetic nervous system. Autonomic nervous system, Dorland’s

Medical Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=111779 (last visited Oct. 26, 2020).

29

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have overwhelming fatigue that is not

improved by rest. ME/CFS may get worse after any activity, whether it’s physical or mental. Other symptoms can include

problems with sleep, thinking and concentrating pain, and dizziness. Centers for Disease Control and Prevention, Myalgic

Encephalomyelitis/Chronic Fatigue Syndrome, What is ME/CFS? (last visited Nov. 10, 2020).

30

At a December 2018 follow-up Dr. Levine’s assessment was ME/CFS and dysautonomia. Ex. 98 at 26.

11

performed on Ms. E.S. on September 24, 2018 revealed “a 4 X 4 X 3 mm nonenhancing lesion

along the pituitary gland” and a “punctate focus of T2 hypointensity.” Ex. 49 at 20. The radiologist

who obtained the imaging deemed it to potentially “reflect the provided history of a pituitary

adenoma,”31 adding that no prior imaging was available to make any comparisons or further

assessments. Id. at 21. I am unaware of any additional documents filed in this case relating to any

subsequent exams or treatments conducted by Dr. Chin.

On August 12, 2019, Petitioner saw Dr. David S. Younger, a neurologist, for additional

evaluation. Dr. Younger reviewed Petitioner’s medical history and past studies as well as performed

a physical examination. Ex. 105 at 3. The examination showed sensory loss, hyporeflexia, distal leg

weakness, Romberg sign, 32 and tandem imbalance. Id. Upon review of past studies, Dr. Younger

noted that a 2012 MRI showed degenerative changes. Id. Although, tests from 2016 appeared normal,

the 2018 pituitary MRI studies suggested a microadenoma. Id. at 2. Dr. Younger recommended

additional screening studies. Id. On November 7, 2019, Dr. Younger saw Petitioner for a follow-up

visit. Id. at 6. Dr. Younger now reported that skin changes suggested possible vasculopathy. Id.

Petitioner’s neck and shoulder pain and chest discomfort suggested combined cervicogenic and

autonomic disturbances. Id. Dr. Younger again recommended additional screening studies as well as

a psychiatric assessment. Id.

II. Expert Reports and Other Evidence

Thirteen expert reports have been filed in this matter, totaling more than 200 pages of opinion.

Hundreds, if not thousands, of pages in supporting medical research and literature have also been

offered. As of today, Petitioner has presented six reports from three different experts, and

Respondent has filed seven reports from four individual experts. Each expert, their credentials, and

opinions are considered in turn.

A. Petitioner’s Experts

1. Dr. Lawrence Steinman

Dr. Steinman prepared three reports in support of Petitioner’s claim. Report, dated Mar. 2,

2018, filed as Ex. 39 (ECF No. 47-1) (“First Steinman Rep.”); Report, dated Jan. 14, 2019, filed

as Ex. 86 (ECF No. 85-1) (“Second Steinman Rep.”); Report, dated Feb. 15, 2019, filed as Ex. 99

(ECF No. 90-1) (“Third Steinman Rep.”). Dr. Steinman inconsistently focuses on different aspects

31

A pituitary adenoma is a slow-expanding growth deemed benign in the vast majority of cases. Mayo Clinic, Pituitary

Tumors, https://www.mayoclinic.org/diseases-conditions/pituitary-tumors/symptoms-causes/syc-20350548 (last visited

Oct. 26, 2020).

32

Romberg sign/syndrome, or facial hemiatrophy, is a condition of unknown etiology, characterized by progressive

atrophy of the tissues of one side of the face, frequently with pigmentation disorders and alopecia. Sometimes it can

spread to involve both sides of the face or the ipsilateral trunk, viscera, or limbs.

12

of Petitioner’s case, depending on the date of his report and whether the report was reacting to the

assertions of one of Respondent’s experts.

Dr. Steinman currently serves as the chairman in immunology and professor in the

departments of neurology, pediatrics, and genetics at Stanford University. Steinman Curriculum

Vitae, filed as Ex. 40 (ECF No. 52-1) (“Steinman CV”) at 1. He obtained his bachelor’s degree

from Dartmouth College before earning his medical degree from Harvard University. Id. He then

completed his internship and residency in surgery, pediatrics, and pediatric and adult neurology at

Stanford University. Id. He has also completed several fellowships in the area of immunology. Id.

He is board certified in neurology, though much of his work in the field also involves

immunological concepts and theories. Id. at 2. However, he has no demonstrated expertise in

treating or diagnosing diabetes or conditions attributable to autonomic dysfunction.

a. First Steinman Report

In his first report, Dr. Steinman limited his opinion solely to whether the HPV vaccine doses

Petitioner received in 2014 and 2015 and/or the flu vaccine from 2015, could have caused the

narcolepsy and headaches Petitioner asserts she experienced. First Steinman Rep. at 1. He began by

considering when such symptoms likely first manifested. Dr. Steinman opined that onset of Ms.

E.S.’s headaches could be placed in early October 2014 (based on an ER note associated with

that visit). Ex. 9 at 3. Other medical records, however, reveal that Petitioner complained of

headaches well before her first HPV dose in July 2014. Id. at 30; Ex. 3 at 16 (headache listed among

chief complaints on September 19, 2013). Onset of narcolepsy, in contrast, was by Dr. Steinman’s

admission harder to pinpoint. Id. at 30–31. The first mention of any sleep issues appears in an

October 2016 record—where Petitioner reported that she had been experiencing such symptoms in

the two-plus years since receiving the flu vaccine. Id. at 31. This contention is not only

uncorroborated by the record but is partially in conflict with it (since Petitioner had received the flu

vaccine in August 2015—hence only 14 months prior). Ex. 22 at 5.

Dr. Steinman proposed that Petitioner’s narcolepsy could have been caused specifically by

the HPV vaccine. First Steinman Rep. at 6. He relied on molecular mimicry as the biologic

mechanism for how this occurred, basing this contention on what is known about how narcolepsy

likely occurs. Id. at 22. Dr. Steinman explained that decreased levels of hypocretin 33 and/or

abnormalities in hypocretin receptor 2 in the brain are scientifically understood to play a central

role in the occurrence of narcolepsy. Id. at 8 (citing Ex. 39, references 9 and 10). Aberrant immune

responses are thought to possibly explain such circumstances. First Steinman Rep. at 8 (discussing

33

Hypocretin, also known as orexin, is “either of two neuropeptides (orexin A ad orexin B) produced in the hypothalamus

and regulating behavior as well as the sleep-wake cycle.” Orexin, Dorland’s Medical Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=35458 (last visited Aug. 13, 2020).

13

references 11–17). Decreased hypocretin neurotransmission is thought to be due to autoimmune-

mediated destruction of hypocretin-containing neurons in the lateral hypothalamus. Ex. 39, Ref. 9,

at 39.

One possible way the immune response could create conditions for narcolepsy would be

where an antigen presenting to the immune system (whether from a wild virus or vaccine) might

mimic “various components of the hypocretin pathway, including hypocretin itself and the HCRT-

R2 receptor.” First Steinman Rep. at 9. Dr. Steinman estimated the HPV vaccine could accomplish

this—but to bulwark this contention he relied significantly on “BLAST” searches 34 he personally

performed, looking for homology between HPV vaccine components and hypocretin pathway

structures. Id. 35 In so doing, Dr. Steinman explained that his criteria for “a meaningful molecular

mimic” relied on evidence of five or more amino acids that were identical (although fewer could

also trigger a cross-reaction, and the amino acids did not in his view need to be identical in

sequence). Id. (citing Exhibit 39, references 18–20).

Based on electronic database research performed specifically for this case, Dr. Steinman

maintained that several proteins in the HPV vaccine had sufficient homology to hypocretin to have

the potential to induce an autoimmune cross-reaction that would trigger narcolepsy. First Steinman

Rep. at 11–22. For support, he referenced a study finding increased incidence of narcolepsy

following receipt of the HPV vaccination. Id. at 25 (citing L. Arnheim-Dahlstrom et al.,

Autoimmune, Neurological, and Venous Thromboembolic Adverse Events After Immunization of

Adolescent Girls with Quadrivalent Human Papillomavirus in Denmark and Sweden: Cohort Study,

British Med. J. 1, 1–11 (2013), filed as Ex. 39, Ref. 24 (ECF No. 50-4) (“Arnheim-Dahlstrom”)).

However, Arnheim-Dahlstrom found no supporting associations between exposure to the

quadrivalent HPV vaccine and autoimmune, neurological, or venous thromboembolic adverse

events. Although associations for three autoimmune events were initially observed, on further

assessment these associations proved weak, and not temporally related to vaccine exposure.

Arnheim-Dahlstrom at 1. Dr. Steinman acknowledged that this observed increase did not reach a

level of statistical significance—but proposed (based on his layman’s understanding of the legal

standards applicable to Vaccine Program cases) that it was sufficient to meet the preponderance test

relevant to fact determinations in this case. First Steinman Rep. at 27. 36

34

Basic Local Alignment Search Tool (“BLAST”) is a medical/scientific internet resource that assists researchers in

finding regions of similarity between biological sequences of amino acids. The program compares nucleotide or protein

sequences to sequence databases and calculates the statistical significance. BLAST, U.S. National Library of Medicine,

https://blast.ncbi.nlm.nih.gov/Blast.cgi (last visited Oct. 6, 2020).

35

In other cases, Dr. Steinman has characterized the research undertaken to identify such homology as an “in silica”

study—by which he means that he used a desktop or personal computer, and access to scientific databases, to identify

the comparable amino acid sequences that he references to establish homology. See, e.g., Blackburn v. Sec. of Health &

Hum. Servs., No. 10-410V, 2015 WL 425935, at *10 (Fed. Cl. Spec. Mstr. Jan. 9, 2015). This kind of research is clearly

case-oriented, and is not equivalent to lab or clinical research that an expert might perform and/or rely upon for an

opinion.

36

In his second report, Dr. Steinman went to great lengths to cast doubt on the lack of statistical significance he had

14

In addition, Dr. Steinman generally seemed to embrace a loose timeframe for narcolepsy

onset as medically acceptable—in effect suggesting that any onset “weeks to months” from the date

of vaccination to the time Petitioner obtained a formal sleep test confirmed narcolepsy diagnosis

was reasonable, since it was literally after the vaccines were administered in 2014 and 2015. Id. at

31. Dr. Steinman more specifically suggested that onset within eight months of vaccination would

be a generally reasonable timeframe for narcolepsy to first manifest (relying on studies about the

flu vaccine and narcolepsy). Id.

Further, Dr. Steinman opined that Petitioner’s headaches were attributable to the HPV

vaccine. First Steinman Rep. at 30. In support, he noted that the vaccine’s package insert lists

headaches as a frequent symptom (although it specifically envisions them as a transient response,

likely occurring close in time to vaccination, and does not identify headache as a chronic post-

vaccination concern). Id.; Gardasil [Package Insert]. Whitehouse Station, NJ: Merck & Co., Inc.;

2011, filed as Ex. 39, Ref. 7 (ECF No. 48-7) (“Gardasil Package Insert”).

Dr. Steinman also noted the existence of “strong evidence that calcitonin-gene-related-

peptide (CGRP) is involved in chronic headache, particularly migraine.” First Steinman Rep. at 28.

Based on sufficient evidence of homology between the antigenic components of the HPV vaccine

and CGRP, Dr. Steinman reasoned that the vaccine might plausibly trigger an autoimmune cross-

reaction sufficient to produce headaches. Id. at 28–29. The headaches could later become chronic,

due to the fact that the vaccine’s alum additive (used as an adjuvant, to cause a more robust immune

response) 37 has been demonstrated to persist for up to a year (albeit in animal studies). Id. at 30

(citing Z. Khan et al., Slow CCL2 Translocation of Biopersistent Particles from Muscle to Brain,

11 BMC Medicine (2013), filed Mar. 5, 2018 as Ex. 39, Ref. 27 (ECF No. 50-7)). This, plus the

fact that the immune response to HPV vaccine itself can be long-lasting, lent further support to his

conclusion that chronic headaches could be propagated by the vaccine. First Steinman Rep. at 30

(citing C. MacIntyre et al., Immunogenicity and Persistence of Immunity of a Quadrivalent Human

seemingly admitted in his first report about Arnheim-Dahlstrom’s conclusions, making arguments about the mathematic

guidelines used in evaluating whether a given statistical finding had significance that (by his own admission) exceeded

his expertise. Second Steinman Rep. at 22–23.

37

The argument that the alum adjuvant ingredient in a vaccine can remain in the body for extended periods of time post-

vaccination, and thereafter cause or contribute to immunologic harm, is perilously close to a discredited theory often

posed by unsuccessful petitioners, termed “ASIA,” or “autoimmune/inflammatory syndrome induced by adjuvants.” See,

e.g., Yalacki v. Sec’y of Health & Hum. Servs., No. 14-278V, 2019 WL 1061429, at *24 n.30 (Fed. Cl. Spec. Mstr. Jan.

31, 2019), mot. for review den’d, 146 Fed. Cl. 80 (2019) (noting several prior decisions in which special masters rejected

the ASIA theory as scientifically unreliable). The evidence that a vaccine’s adjuvants can act in this manner (as opposed

to merely increase the immunogenicity of the vaccine generally) is thin to none and has little acceptance in the medical

community otherwise as a reputable theory. See, e.g., Rowan v. Sec'y of Health & Hum. Servs., No. 10–272V, 2014 WL

7465661 (Fed. Cl. Spec. Mstr. Dec. 8, 2014); mot. for review den'd, 2015 WL 3562409 (Fed. Cl. 2015); D'Angiolini v.

Sec'y of Health & Hum. Servs., No 99–578V, 2014 WL 1678145 (Fed. Cl. Spec. Mstr. Mar. 27, 2014), mot. for review

den'd, 122 Fed. Cl. 86 (2015), aff'd, 645 F. App'x 1002 (Fed. Cir. 2016).

15

Papillomavirus (HPV) Vaccine in Immunocompromised Children, 34 Vaccine 4343, 4343–45

(2016), filed Mar. 5, 2018 as Ex. 39, Ref. 28 (ECF No. 50-8)).

b. Second Steinman Report

Dr. Steinman’s second report was of comparable length to his first, but largely aimed at

responding to counter-arguments (discussed in more detail below) that had been lodged by two of

Respondent’s experts. See generally Second Steinman Rep.

Dr. Steinman began by referencing some new research relevant to the biological processes

underlying narcolepsy (specifically pertaining to the hypocretin pathway) that he maintained was

additionally supportive of his previously-asserted opinion. Second Steinman Rep. at 1–4; D.

LaTorre et al., T cells in Patients with Narcolepsy Target Self-Antigens of Hypocretin Neurons,

Nature 1, 1–23 (2018), filed Jan. 14, 2019 as Ex. 87 (ECF No. 85-2) (“Latorre”). Latorre observed

the existence of “peptides that attacked orexin [another term for hypocretin] and were found in the

spinal fluid,” and that these amino acid sequences showed homology with HPV vaccine antigens

(based on Dr. Steinman’s BLAST searches). Second Steinman Rep. at 1–3; Latorre at 538. As a

result, Dr. Steinman concluded that “this degree of homology is sufficient to induce clinically

relevant neuroinflammation.” Second Steinman Rep. at 3. He later emphasized literature he felt

underscored the legitimacy of BLAST searches to establish potentially significant homologies (for

purposes of establishing the potentiality of pathologic autoimmune cross-reactions). Id. at 16–18.

Next, Dr. Steinman attempted to rebut arguments attacking various aspects of his theory. He

acknowledged that Petitioner did not have (and was never diagnosed with) type I narcolepsy—the

kind that is more definitively understood to have an autoimmune character. Thus, she was not

positive for the HLA molecules most associated with type I narcolepsy, and had otherwise not been

tested for hypocretin levels either. Second Steinman Rep. at 7. However, Dr. Steinman still

contended that type II narcolepsy could have an autoimmune character or etiology—although in

doing so he devoted many pages of his second report to a detailed defense of research he had

previously cited, or had been involved with, rather than citing evidence that more directly supported

his opinion. Id. at 5–15. At bottom, Dr. Steinman proposed that the rarity of a vaccine-induced

narcolepsy excused the need for more statistically-significant or robust evidence supporting his

argument. Id. at 14, 22.39

38

Page five of the Latorre article filed by Petitioner appears to be blank. Dr. Steinman, however, provides a copy of the

referenced table on page two of his second report.

39

Dr. Steinman similarly diminished the need for epidemiologic evidence linking the HPV vaccine to narcolepsy,

maintaining that it was “not the proper tool to decide whether, in a given individual with a given disease, the vaccine did

NOT trigger the disease in that individual.” Second Steinman Rep. at 18. This completely misstates the relevant

evidentiary burden (and underscores why Dr. Steinman should avoid commenting on the legal standards employed in

adjudicating Program claims). Although it is very true that petitioners are never compelled to present epidemiologic

evidence, and can thus prevail without it, it is a petitioner’s ultimate burden to establish preponderantly that a vaccine

caused an injury. The Respondent is not tasked with proving a negative (that the vaccine could not have caused the

16

Dr. Steinman reiterated prior arguments regarding the purported link between the HPV

vaccine and Petitioner’s chronic headaches. He emphasized that an association between the two

was not only established by the vaccine’s package insert, but also by VAERS 40 reports identifying

headache as a commonly reported adverse event. Second Steinman Rep. at 18–19. He elaborated

on how he proposed the headaches could become chronic, noting that the vaccine’s antigenic

particles would bind with alum contained in it, and thereby persist in the body for as long as the

alum did. Id. at 19–20. This argument seems to assume that because there is some limited evidence

that alum can persist, that the vaccine’s initial immune-stimulative impact would last for the same

timeframe; however, Dr. Steinman did not offer evidence showing this beyond items referenced in

his initial report suggesting that the vaccine had created long-lasting immunity against HPV (not

that its components would continuously stimulate the immune system in a pathologic manner, and

specifically cause chronic headaches in the process).

In addition to defending previously expressed opinions regarding Petitioner’s purported

narcolepsy and headaches, Dr. Steinman addressed some of the additional diagnoses she had

obtained after the case’s filing (including CFS and SFN). Second Steinman Rep. at 24. He noted

that testing performed on Ms. E.S. in the fall of 2016 (over a year from the time she received

the second HPV dose) and obtained in January 2017 established she possessed elevated levels of

muscarinic41 antibodies associated with CFS. Second Steinman Rep. at 24–25. He maintained that

these antibodies played a significant role in the pathogenesis of CFS. Id. In contrast, the literature

offered for this proposition was less certain. M. Loebel et al., Antibodies to β Adrenergic and

Muscarinic Cholinergic Receptors in Patients with Chronic Fatigue Syndrome, 52 Brain, Behavior,

and Immunity 32–39 (2016), filed Jan. 15, 2019 as Ex. 97 (ECF No. 42-4) (“Loebel”). Loebel, for

example, noted that there was evidence of elevated levels of these antibodies in only a “subset” of

CFS patients, and also that the function of the antibodies remained unclear (and thus could not

injury), but may offer evidence that undercuts the success of a claimant’s showing. As a result, reliable epidemiologic

studies can be evaluated—and can undermine a petitioner’s showing—even if they cannot preponderantly disprove the

possibility of causation by itself.

40

The Vaccine Adverse Event Reporting System (“VAERS”) is a national early warning system to detect possible safety

problems in U.S.-licensed vaccines. VAERS, https://vaers.hhs.gov/about.html (last visited Oct. 7, 2020). VAERS was

established in 1990 and is co-sponsored by the Centers for Disease Control and Prevention (CDC), and the Food and

Drug Administration (FDA), agencies of the U.S. Department of Health and Human Services (HHS). Id.

41

Muscarinic receptors are a type of cholinergic receptor that is stimulated by the alkaloid muscarine and blocked by

atropine; it is found on autonomic effector cells as well as central neurons in the thalamus and cerebral cortex. Muscarinic

Receptor, Dorland’s Medical Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=102569 (last

visited Oct. 7, 2020). Different types may be distinguished on the basis of pharmacologic specificity or molecular

structure; a number of differing nomenclatures have been applied to these types. Id. Cholinergic receptors are a type of

cell-surface receptor that binds the neurotransmitter acetylcholine and mediates its action on postjunctional cells.

Cholinergic Receptor, Dorland’s Medical Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=102541 (last visited Oct. 7, 2020). Types include

parasympathetic autonomic effector cells, sympathetic and parasympathetic autonomic ganglion cells, striated muscle,

and certain central neurons. Id.

17

definitely be said to contribute to CFS’s pathogenesis). Loebel at 38.

Dr. Steinman also proposed that these antibodies (that would potentially attack the same

neuroreceptors relevant to autonomic dysfunction that could in turn produce CFS, POTS, or other

similar conditions) could be produced as part of an autoimmune, cross-reactive process instigated

by the HPV vaccine, and cited literature purportedly to that effect. S. Ikeda et al., Autoantibodies

against Autonomic Nerve Receptors in Adolescent Japanese Girls after Immunization with Human

Papillomavirus Vaccine, 2 Annals of Arthritis and Clinical Rheumatology 1, 1–6 (2019), filed Nov.

24, 2019 as Ex. 107 (ECF No. 106-1) (“Ikeda”). Ikeda (in a case-control comparison of young girls

who received the HPV vaccine versus those who did not) did observe increased levels of these

autoantibodies directed against the relevant nerve receptors in those who had received the HPV

vaccine. Ikeda at 3. However, Ikeda’s authors also frankly admitted that “[t]here was no significant

association between the major symptoms including dysautonomic symptoms and the serum levels

of autoantibodies” (Id. at 4)—a lynchpin of the argument that these autoantibodies are pathogenic.42

Nevertheless, Dr. Steinman proposed that the antibodies associated with chronic fatigue were

also mimics of HPV antigens, similarly citing additional BLAST search evidence in support as with

prior representations about homology between HPV vaccine components and hypocretin pathway-

associated amino acid sequences. Second Steinman Rep. at 26–33. Thus, this could again establish

a mechanism by which the vaccine might promote this additional injury. Dr. Steinman also noted

that Petitioner’s visit to Dr. Chin in the fall of 2018 (after his first report was prepared and filed)

corroborated the chronic fatigue and small fiber neuropathy diagnoses with reliable testing (such as

a skin biopsy for the latter). Id. at 35–38.

c. Third Steinman Report

A month after his second report had been filed, Dr. Steinman prepared an additional, final

report solely to address the question of onset of Petitioner’s CFS or SFN. See generally Third

Steinman Rep. He asserted that the onset of these conditions (which were not even diagnosed until

three years after the second round of relevant vaccines administered in August 2015) was medically

acceptable, invoking his prior findings about post-vaccine headache onset (early October 2014,

hence two and one-half months after vaccination), and narcolepsy (in the fourteen months after

receipt of the flu vaccine in August 2015). Id. at 1–2.

To support the medical acceptability of onset for such varied conditions, Dr. Steinman

referenced an item of literature specific to the HPV vaccine. Third Steinman Rep. at 2; K. Ozawa

42

In addition, further undercutting the reliability of any determinations in Ikeda is the fact that its authors approvingly

cited to the ASIA theory discussed above to support the contention that vaccines can “occasionally trigger the

development of POTS, CRPS, and CFS.” Ikeda at 5 n.38 (referencing an article written by the creator of the ASIA theory,

Dr. Yehuda Shoenfeld). Dr. Shoenfeld is a frequent Program expert, and has offered the opinion that the HPV vaccine

can cause dysautonomic injuries like POTS or chronic fatigue—although not credibly. See, e.g., Johnson v. Sec’y of

Health & Hum. Servs., No. 14-254V, 2018 WL 2051760, at *22–23 (Fed. Cl. Spec. Mstr. March 23, 2018).

18

et al., Suspected Adverse Effects After Human Papillomavirus Vaccination: A Temporal

Relationship Between Vaccine Administration and the Appearance of Symptoms in Japan, 40 Drug

Safety 1, 1–11 (2017), filed Feb 15, 2019 as Ex. 100 (ECF No. 90-2) (“Ozawa”). Ozawa was an

observational study from Japan that considered the symptoms reported by 120 female subjects who

had received the HPV vaccine in the 2013-16 timeframe. Ozawa at 1. Ozawa observed that certain

symptoms (including fatigue, headaches, sleep disturbance, and autonomic dysfunction) manifested

on average within 360 days of vaccination—supporting a lengthy, post-vaccination timeframe.

Ozawa at 9. Ozawa itself, however, notes that the average time for onset observed was “very long

in comparison with the adverse effects of conventional vaccinations,” and attributed this in part to

the fact that “it is rather difficult to determine the exact time of onset” for the symptoms it

considered. Id. More importantly, the overall probative value of Ozawa’s findings was limited by

other deficiencies in the study readily acknowledged by its authors, including but not limited to (a)

a lack of an unvaccinated control group, (b) its generally small sample size, and (c) the self-selection

of studied subjects, all of whom specifically sought out the medical institution for which Ozawa’s

authors worked to report their concerns that the vaccine had caused their symptoms. Id. at 2, 9.

2. Dr. Sin Hang Lee

Dr. Lee, a pathologist, prepared two expert reports on Petitioner’s behalf, both of which

sought to establish that (a) her preexisting diabetes was exacerbated by the two HPV vaccine doses

she received in 2014 and 2015, and (b) she developed myocardial ischemia due to those same

vaccines. Report, dated Mar. 23, 2018, filed as Ex. 41 (ECF No. 55-1) (“First Lee Rep.”); Report,

dated Oct. 30, 2018, filed as Ex. 50 (ECF No. 78-1) (“Second Lee Rep.”).

Dr. Lee studied at Wuhan Medical College and Tongji University College of Medicine from

1951 to 1956. Sin Hang Lee Curriculum Vitae at 1, filed on Mar. 23, 2018 (ECF No. 61-1). In 1966,

he earned his F.R.C.P. (C) from the Royal College of Physicians and Surgeons of Canada. Id. He

participated in several post-graduate training programs and held several teaching positions in China,

Hong Kong, Canada, and the United States—several of which focused on pathology. Id. at 1–2. He

is licensed to practice medicine in Connecticut and is boarded in pathology. Id. at 2. Dr. Lee is

currently the director of Milford Molecular Diagnostics Laboratory, in Milford, Connecticut, which

performs DNA sequencing-based diagnostic testing to confirm conditions like Lyme disease. Id.;

Milford Molecular Diagnostics, http://www.dnalymetest.com/ (last visited Oct. 6, 2020). His first

report acknowledges that the opinions he has provided were based on a review of Petitioner’s

medical history and his own research into “the science available in the public domain,” (as opposed

to professional research or expertise pertaining to the issues in dispute). First Lee Rep. at 1.

a. First Lee Report

Dr. Lee described type 1 (or “insulin-dependent”) diabetes generally as an autoimmune-

19

induced condition, mediated by T cells and autoantibodies, in which insulin-producing beta cells

(responsible for regulating blood sugar) in the pancreas are destroyed, resulting in downstream

sequela attributable to the inability of the body in the absence of insulin to monitor and control

blood sugar levels. First Lee Rep. at 6; M. Cnop et al., Mechanisms of Pancreatic β-Cell Death in

Type 1 and Type 2 Diabetes: Many Differences, Few Similarities, 54 Diabetes S97, S97–S107

(2005), filed Mar. 23, 2018 as Ex. 41, Ref. 6 (ECF No. 56-6). Dr. Lee proposed that the HPV

vaccine had significantly exacerbated Petitioner’s DM-1, based on several independent points. First

Lee Rep. at 5.

First, Dr. Lee noted that federal safety disclosures relating to the HPV vaccine’s approval for

use revealed instances in which the vaccine may have been associated with new cases of diabetes—

although to reach this conclusion, Dr. Lee relied on tortuous math that is almost facially incorrect

from a scientific/epidemiologic standpoint. He cited to the fact that in the HPV vaccine’s clinical

trials, the same number of vaccinated individuals (two out of 10,706) reported new cases of type 1,

insulin-dependent diabetes (measured at fourteen days after each vaccine dose administration) as

the unvaccinated placebo group (two out of 9,412)—suggesting no statistically-significant greater

incidence of vaccine-associated cases (18.7 cases per 100,000 for vaccinated individuals, versus

21.2 for the control group). Id.; Gardasil [Package Insert]. Whitehouse Station, NJ: Merck & Co.,

Inc.; 2011, filed as Ex. 41, Ref. 4 at 8 (“Gardasil Package Insert”). This finding might seem not to

support Petitioner’s overall claim.

Dr. Lee, however, compared these rates to a “national statistics report” from 2016, which

showed an incidence of 19.9 cases of diabetes total per 100,000 unvaccinated individuals for the

entirety of 2005 (prior to the HPV vaccine’s approval). Although this earlier incidence rate exceeds

what was observed for even vaccinated individuals from the HPV vaccine trials, Dr. Lee maintained

(without demonstrating his methodology)43 that this figure “translates” into a far lower incidence

of .74 cases per 100,000 after two weeks—thus establishing a “25 fold” increase in the incidence

rate for vaccinated individuals as reflected in the safety study data. How this calculation can be

possibly reliable (since Dr. Lee has not shown that the 2005 data identifies diabetes onset as

reasonably occurring in the span of two weeks—and if so, based on what starting point, since it

does not measure time from a vaccination or placebo event) is not explained, although Dr. Lee’s

report rapidly moves on.

Next, Dr. Lee maintained that based upon what was understood about how the HPV vaccine

mechanistically “works” (coupled with some speculative points of his own about an inadvertent

byproduct of its manufacture), a reliable theory could be proposed for how the vaccine’s

components might worsen a preexisting case of DM-1. First Lee Rep. at 6–14. The relevant

formulation of the HPV vaccine, he contended, contains purified “virus-like particles,” or VLPs,

43

Presumably, Dr. Lee took the data for 2005, divided it by 365 (for the total days in a year), and then multiplied that

sum by 14—although doing so does not precisely produce the rate he cites in his report.

20

derived from the L1 capsid 44 for the HPV wild virus. Id. at 6; Gardasil Package Insert at 12. To

provoke an immune response to the presentation of these VLP antigens after vaccination, the HPV

vaccine includes alum as an adjuvant. First Lee Rep. at 7–9. Some vaccines have also begun to

incorporate toll-like receptor (“TLR”) agonists, a different kind of biologic adjuvant that helps

stimulate a greater immune response (although this distinct form of adjuvant has primarily been

used to date in anticancer therapies). Id. at 8–10. However, Dr. Lee admitted TLR agonists are not

an intentional component of the HPV vaccine’s formulation. Id. Nevertheless, Dr. Lee maintained

that the process by which HPV vaccine was manufactured likely resulted (inadvertently) in the

inclusion of some “viral DNA fragments” that would in effect “serve as potent long-acting TLR9

agonist”—and hence acting as “the actual functional adjuvant.” Id. at 12.

From the above, Dr. Lee attempted to explain how the HPV vaccine could aggravate type I

diabetes. Although much remains unknown about the pathogenesis of this form of diabetes, Dr. Lee

proposed that some new research establishes that TLR ligands (which can function like agonists)

play a “key role in initiation or aggravation of type 1 diabetes.” First Lee Rep. at 13 (citing A.

Limmer et al., Stimulation of Autoimmunity by Toll-like Receptor Ligands, 64 Annals Rheumatic

Diseases 15, 15–18 (2005), filed Mar. 23, 2018 as Ex. 41, Ref. 31 (ECF No. 59-1); S. Ferris et al.,

The Islet-Resident Macrophage is in an Inflammatory State and Senses Microbial Products in

Blood, 7;214(8) J. Experimental Med. 1, 1–17 (2017), filed Mar. 23, 2018 as Ex. 41, Ref. 32 (ECF

No. 59-2) (“Ferris”); J. Dowling & A. Mansell, Toll-like Receptors: The Swiss Army Knife of

Immunity and Vaccine Development, 5 Clinical Translational Immunology 1, 1–10 (2016), filed

Mar. 23, 2018 as Ex. 41, Ref. 33 (ECF No. 59-3)).

Of these cited articles, only Ferris addresses diabetes head-on. In Ferris, researchers

examined the transcriptional profiles of macrophages in diabetic mice. The mice demonstrated an

increased inflammatory signature, including elevated expression of chemokines 45 and chemokine

receptors and an oxidative response. Ferris at 1. Researchers concluded, among other things, that

macrophages have the capacity to sense blood-born stimuli. Id. at 10. Nevertheless, because type I

diabetes is believed to have an autoimmune component, activation of TLRs in such a person would

(in Dr. Lee’s view) occur by “augment[ing] production of all autoantibodies against self-antigens,”

including those autoantibodies thought to attack the insulin-producing beta cells—thus exacerbating

an existing case of diabetes. First Lee Rep. at 14.

Dr. Lee attempted to set his theory within the context of Ms. E.S.’s actual experience. First

Lee Rep. at 14–15. Relying on an overview of the medical history (Id. at 1–4), he observed that

44

Gardasil is the trade name for the Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant,

a non-infectious recombinant quadrivalent vaccine prepared from the purified virus-like particles (VLSs) of the major

capsid (L1) protein of HPV Types 6, 11, 16, and 18. The L1 proteins are produced by separate fermentations in

recombinant Saccharomysces cervisiae and self-assembled into VLPs. Gardasil Package Insert at 12.

45

Chemokines are regulators of the immune system and may also play a role in the circulatory and central nervous

systems. Dorland’s at 335.

21

Petitioner appeared to have fair control of her diabetes prior to her receipt of an initial HPV vaccine

dose. Id. at 1–2, 14. But, her diabetic-associated symptoms greatly worsened in the months thereafter,

as reflected in the many ER and doctor visits she had (at which time her glucose levels were

consistently determined to be high). Id. Then, after her second HPV vaccine dose in August 2015,

Petitioner started to develop chest pain and experienced additional worsening symptoms, including

vomiting. Id. at 14. He specifically deemed the timeframe between the second HPV dose

(administered August 19, 2015) and her October 10, 2015 ER visit—a more than seven-week

period—as medically acceptable, although (incongruously) in so doing he referenced his prior

arguments about the HPV clinical trials revealing post-vaccination onset as possible within two

weeks. Id.; Gardasil Package Insert at 14–21.

Besides exacerbation of type I diabetes, Dr. Lee’s first report included the opinion that the

HPV vaccine could outright trigger a myocardial ischemia due to low blood perfusion, and did so to

Petitioner. First Lee Rep. at 15. Dr. Lee explained that if and when immune cells are activated as a

result of receipt of the HPV vaccine, and then reach sufficient number in the myocardium, the

cytotoxic cytokines generated by these immune cells can cause myocardial depression with reduced

cardiac outputs and low blood profusion through the myocardium, leading to irreversible myocardial

damage in certain genetically and physically predisposed individuals. Id. at 16–17; See also Second

Lee Rep. at 7. He noted that (again referencing the HPV vaccine package insert) syncope (resulting

from insufficient blood flow to the brain attributable in turn to low blood pressure (hypotension) is

the most commonly-reported adverse reaction after receipt of the vaccine. Id; Gardasil Package Insert

at 27. He did not, however, specify the expected timeframe for such an adverse event (and syncope

itself is expected to occur very close-in-time, if at all, to vaccination—not months or years later).

Gardasil Package Insert at 1.

Syncope is a feature of orthostatic intolerance—a category that includes POTS, and that has

been associated with receipt of the HPV vaccine. However, by Dr. Lee’s admission this association

“has not received much attention of [sic] the medical community.” First Lee Rep. at 15. Dr. Lee cited

a post-licensure survey study observing (for a 2006 to 2008 timeframe) that out of 12,424 reported

adverse events, there were 32 deaths, six of which could be shown to have been cardiac-related. First

Lee Rep. at 15; B. Slade et al., Postlicensure Safety Surveillance for Quadrivalent Human

Papillomavirus Recombinant Vaccine, 302 JAMA 750–57 (2009), filed Mar. 23, 2018 as Ex. 41,

Ref. 36 (ECF No. 59-6) (“Slade”) (medical and autopsy reports on 20 of the 32 deaths confirmed

there were 4 unexplained deaths and 6 cardiac-related deaths). From this, Dr. Lee concluded that

vaccine-induced hypotension could in turn reduce blood flow to the heart, thereby incurring a

“jeopardized myocardium.” First Lee Rep. at 15.

Dr. Lee offered a causation theory for how the HPV vaccine might initiate such a process,

which paralleled or relied on his theory addressing aggravation of diabetes. He reiterated his prior

contention that the vaccine likely contained “a set of ready-made instant DNA immune ‘mediators’”

(in the form of the purported TLR agonist attributable solely to the vaccine’s manufacture, rather

22

than an actual ingredient), which enabled the innate immune system’s macrophages to transport

vaccine antigens throughout the body—including across the blood-brain barrier. First Lee Rep. at

16. He offered a case report as evidence of the latter. F. DiMario et al., A 16-year-old Girl with

Bilateral Visual Loss and Left Hemiparesis Following an Immunization Against Human

Papillomavirus, 25 J. Child Neurology 321–27 (2010), filed Mar. 23, 2018 as Ex. 41, Ref. 39 (ECF

No. 59-9) (“DiMario”). However, DiMario is factually distinct in that it involved localized

encephalomyelitis and a biopsy-confirmed tumefactive demyelinating lesion. In addition, Dr. Lee

referenced a Program case in which it was purportedly established that the HPV vaccine caused a

child’s death from a silent myocardial infarction (however, the facts and circumstances of that case

are readily distinguishable). First Lee Rep. at 18; Gomez v. Sec’y of Health & Hum. Servs., No. 15-

160V, 2016 WL 6072391 (Fed. Cl. Spec. Mstr. Sept. 21, 2016). 46

Dr. Lee proposed that the stimulation of TLRs induced by vaccination could equally promote

upregulation of a variety of proinflammatory cytokines, some of which (like tumor necrosis factor

alpha (TNF-α or Il-1β)) are “recognized myocardial depressants” which can cause damage to the

myocardium in physically predisposed individuals. First Lee Rep. at 16–17; J. Parrillo et al., A

Circulating Myocardial Depressant Substance in Humans with Septic Shock: Septic Shock Patients

with Reduced Ejection Fraction have a Circulating Factor that Depresses in Vitro Myocardial Cell

Performance, 76 J. Clinical Investigation 1539–53 (1985), filed Mar. 23, 2018 as Ex. 41, Ref. 40

(ECF No. 59-10). A sufficient number of these “cytotoxic cytokines” would be capable of causing

myocardial depression and low blood perfusion, resulting in “irreversible myocardial damage.”

First Lee Rep. at 16–17.

Dr. Lee supported his theory pertaining to Petitioner’s purported heart issues with the medical

record. As before, he deemed significant the before/after vaccination distinction in Ms. E.S.’s

health, focusing particularly on the growing evidence that she might have a cardiac disorder after

the August 2015 second HPV vaccine dose. First Lee Rep. at 17. He took particular note of the

cardiac consultation Petitioner received from Dr. Lefkowitz in the winter of 2016 (six months from

receipt of the second dose), at which time a stress EKG revealed the possibility of a jeopardized

myocardium. Id; Ex. 5 at 3. However, Dr. Lee acknowledged that this determination was not

conclusively made at this time. Id. Nevertheless, Dr. Lee maintained that literature supported an

association of the kind of abnormality observed at this time with moderate ischemia. First Lee Rep.

at 17; L. Shaw et al., Comparative Definitions for Moderate-Severe Ischemia in Stress Nuclear,

Echocardiography, and Magnetic Resonance Imaging, 7 JACC Cardiovascular Imaging 593–604

(2014), filed Mar. 23, 2018 as Ex. 41, Ref. 50 (ECF No. 60-7). In addition, Dr. Lee drew attention

to the fact that as of March 2016, Petitioner’s serologic testing revealed heightened levels of white

blood cells, which he deemed “indicative of an augmented immune reaction . . . probably with

associated increased discharge” of the cytokines he previously maintained were known myocardial

46

In Gomez (a matter in which Dr. Lee also offered an expert report), a 14-year old male died a day after receipt of a

second dose of HPV vaccine—a far cry from the present facts. Moreover, that case settled, and therefore no reasoned

causal determination was issued that could shed light on this matter’s disposition. Gomez, 2016 WL 6072391, at *1.

23

depressants. First Lee Rep. at 18.

To support the timing for an association between the August 2015 second HPV dose and the

February 2016 diagnostic evidence as proof of Petitioner’s vaccine-caused cardiac issues, Dr. Lee

noted again the post-licensure studies, like Slade. First Lee Rep. at 18; Slade at 750. Of the 32 post-

HPV vaccine deaths observed (approximately .26 percent of the 12,424 reported adverse events),

the timeframes for fatality were from 2 to 405 days. Slade at 755. As a result (although without any

showing specific to the cardiac-associated deaths), Dr. Lee concluded that a six-month lag in this

case was medically acceptable.

b. Second Lee Report

In reaction to arguments lodged by Respondent’s experts in opposition to his theories, Dr.

Lee prepared a second report even lengthier than his first (although it was padded with large sections

featuring wholesale reproduction of other articles, portions of websites, or similar authorities). See

generally Second Lee Rep. 47

Much of the supplemental report addresses Dr. Lee’s prior contentions that Petitioner’s

alleged cardiac injuries were caused by the HPV vaccine. Second Lee Rep. at 1–16. He strenuously

defended his conclusion that Petitioner had in fact experienced an “untoward cardiac event,”

referencing the February 2016 stress test cited in his first report, and noting that Dr. LaRue

(Respondent’s cardiologist expert) had acknowledged that some “ST segment elevation” was

observed from the stress test, which could “represent acute ischemia.” Id. at 1–2. Dr. Lee (who lacks

comparable cardiac expertise) fiercely attacked Dr. LaRue’s diminishment of the importance of

these findings as medically incorrect. Id. at 2–5; A. Ali et al., Early Repolarization Syndrome: A

Cause of Sudden Cardiac Death, 7 World J. Cardiology 466, 466–75 (2015), filed Nov. 16, 2018

as Ex. 51 (ECF No. 79-1). He also observed that Petitioner had additional abnormal EKG results

after her ER visits in May 2017 and January 2018, thus corroborating the proposed diagnosis.

Second Lee Rep. at 4; Ex. 33 at 8; Ex. 34 at 72. Ultimately, he accused Respondent’s expert of

relying on “half-truth and twisted science” in rejecting the conclusion that Petitioner had

experienced myocardia ischemia. Second Lee Rep. at 7. And he went to great lengths to defend his

conclusion that the test results set forth in the record were a sufficient basis for his diagnostic

opinion. Id. at 7–10.

To bulwark his prior contentions that Petitioner’s purported myocardial ischemia occurred in

a medically acceptable timeframe, Dr. Lee noted that the two cytokines even Respondent’s experts

admitted were associated with it (TNF-α and Il-1β) had been established to persist even six months

47

Indeed, Dr. Lee attempted to rebut some of the criticisms and questions that Respondent’s experts lodged against his

first report mainly by repeating verbatim the arguments he had already set forth (rather than by homing in on how the

objections were unreasonable or wrong). See, e.g., Second Lee Rep. at 41 (“I have copied and pasted below the most

relevant part” of prior report), 42–49 (reproducing five pages of the first report in the second).

24

from the date of vaccination. Second Lee Rep. at 14; Report, dated July 2, 2018, filed as Ex. A

(ECF No. 68-1), at 6, 8; D. Herrin et al., Comparison of Adaptive and Innate Immune Responses

Induced by Licensed Vaccines for Human Papillomavirus, 10 Hum. Vaccines Immunotherapies

3446–54 (2014), filed Mar. 23, 2018 as Ex. 41, Ref. 29 (ECF No. 58-9) (“Herrin”). In Herrin,

however, blood plasma was analyzed for ten circulating cytokines and chemokines, including TNf,

at pre-vaccination and post-first and third vaccination at days 1, 2, 5, 14 and 28 and at month seven,

but no statistically significant trends were observed that would corroborate the conclusion that these

two particular cytokines were likely to persist for as long as Dr. Lee assumed. Herrin at 3449–50.

Dr. Lee expanded on his causation theory, offering additional support for his general assertion

that “aluminum adjuvant-laden macrophages” travel in the body (and thus transport the adjuvant

away from the site of vaccine administration) but also could conceivably cluster in the myocardium,

causing a sufficiently-harmful concentration of the cytokines specific to myocardial ischemia to

propagate the condition. Second Lee Rep. at 16; M. Mold et al., Insight into the Cellular Fate and

Toxicity of Aluminium Adjuvants Used in Clinically Approved Human Vaccinations, Nature:

Science Reports 1, 1–13 (2016), filed Mar. 23, 2018 as Ex. 41, Ref. 34 (ECF No. 59-4) (“Mold”).

In Mold, a comparative study was undertaken to monitor the particle size distributions of aluminum

adjuvants through the process of vaccine formulation using dynamic light scattering. Id. at 1.

Results suggested that the particle size distributions may be important for its immunological

recognition and subsequent clearance from the injection site. Id. Dr. Lee deemed this

“straightforward science.” Second Lee Rep. at 16.

In addition, Dr. Lee maintained his contentions (relating type I diabetes to the HPV vaccine)

in the face of Respondent’s experts’ criticisms. First, he strenuously argued that his treatment of the

HPV vaccine licensing data (which he had cited as proof that the vaccine was associated with an

increased incidence of diabetes) was legitimate (despite the obvious mistakes in his reading of this

data that Respondent’s experts readily pointed out). Second Lee Rep. at 17–18, 20–21. He attacked

other epidemiologic studies referenced by Respondent which credibly undercut the HPV vaccine-

diabetes association as biased or merely “observational” and thus not worthy of significant weight.

Id. at 18–20; C. Chao et al., Surveillance of Autoimmune Conditions Following Routine Use of

Quadrivalent Human Papillomavirus Vaccine, 271 J. Internal Med. 193–203 (2012), filed July 27,

2018 as Ex. C, Tab 18 (ECF No. 70-9) (“Chao”). At the same time, he referenced again Arnheim-

Dahlstrom as bulwarking his argument (even though in comparison it dealt with a drastically

smaller sample size of only 23 individuals). Second Lee Rep. at 18–20; Arnheim-Dahlstrom at 4.

Second, Dr. Lee reiterated his argument about the mechanism by which the HPV vaccine

would theoretically cause injury, explaining the extent to which his theory was adjuvant-based. He

repeated arguments contained in his first report about how a “proprietary aluminum salt” used in

HPV vaccine’s manufacture could only act as an adjuvant in concert with a TLR agonist—

something purportedly found in the vaccine due to the presence of “gene DNA fragments” left over

in the process of manufacture. Second Lee Rep. at 49. He referenced two items of literature he had

25

himself authored to support this argument. S. Lee, Detection of Human Papillomavirus (HPV) L1

Gene DNA Possibly Bound to Particulate Aluminum Adjuvant in the HPV Vaccine Gardasil, 117

J. Inorganic Biochemistry 85, 85–92 (2012), filed Nov. 16, 2018 as Ex. 66 (ECF No. 80-6); S. Lee,

Guidelines for the Use of Molecular Tests for the Detection and Genotyping of Human

Papillomavirus from Clinical Specimens, 903 Methods Molecular Biology 65–101 (2012), filed

Nov. 16, 2018 as Ex. 67 (ECF No. 80-7); Second Lee Rep. at 49–52. As indirect support for these

overall contentions, Dr. Lee referenced Nobel prize-winning research into the role that TLRs play

“as the sensors of innate immunity.” Second Lee Rep. at 52; Press Release, The Nobel Assembly at

Karolinksa Institutet, The Nobel Prize in Physiology or Medicine 2011 (Oct. 3, 2011),

https://www.nobelprize.org/prizes/medicine/2011/press-release/ (last visited Oct. 13, 2020).

Moreover, Dr. Lee revisited different elements of the medical record to defend his opinion.

He argued, for example, that the flank pain Ms. E.S. frequently reported was reflective of

hyperglycemia related to her diabetes—and thus spikes in glycated hemoglobin levels caused (in

his view) by the HPV vaccine would explain such symptoms. Second Lee Rep. at 24. He rejected

attributing the worsening of Petitioner’s diabetes to adolescence, arguing that she lacked other

important risk factors linked to worsening such as an eating disorder, treatment-associated insulin

restriction, or other disruptions in medical monitoring that might occur when a young person goes

to college. Id. at 25–27. He maintained that evidence of inflammation taken from testing performed

on Petitioner in March 2016, at which time she had been diagnosed with a ruptured ovarian cyst,

was independent of the cyst (since the type of inflammation associated with such a cyst was

absent 48) and instead attributable to “autoimmune reaction” begun by the vaccines received no

earlier than seven months before (the time of the second HPV vaccine dose). Id. at 29–33.

Besides defending his own conclusions, Dr. Lee endeavored to rebut the suggestions of

Respondent’s experts that the general picture of Petitioner’s overall post-vaccination worsening

(evidenced in her repeated returns to the ER beginning in the fall of 2014) could be explained by a

“selective IgA [antibody] deficiency,” thereby producing more frequent viral infections that could

in turn trigger loss of control of blood glucose. Second Lee Rep. at 36, 37. Dr. Lee countered by

pointing out the limited number of pre- versus post-vaccination ER visits (Id. at 37), and also that

48

Specifically, Dr. Lee opined that in cases of what he termed “acute abdomen,” an afflicted individual would display

high levels of neutrophils in the blood and site of infection/injury, but normal to below-normal lymphocytes in blood

tests. Second Lee Rep. at 28–30. Petitioner’s CBC differential from March 6, 2016 showed the opposite, in his reading.

Id. at 31–32. However, the article Dr. Lee cited for this proposition (although never filed into the record) related to

abdominal pain generally rather than a burst cyst. Id. at 30; J. Deibener-Kaminsky, Leukocyte Differential for Acute

Abdominal Pain in Adults, 17 Lab Hematology 1, 1–5 (2011). Moreover, one of Respondent’s experts, Dr. MacGinnitie,

observed that a CBC count performed just two days before the cyst incident showed no lymphocyte increase, consistent

with an earlier blood test in November 2015—and thus totally rebutting Dr. Lee’s supposition that the CBC reading he

called attention to reflected some ongoing and chronic condition consistent with his theory. Ex. 19 at 142. Dr. Lee

explained away these contrary results, arguing that lymphocyte levels could naturally fluctuate, and adding that the

evidence he had previously offered establishing that the HPV vaccine generally caused sustained levels of inflammatory

cytokines ultimately supported his contentions (disregarding the fact that the two other blood tests referenced by Dr.

MacGinnitie were inconsistent with the idea that the HPV vaccine would lead to persistently-elevated inflammation due

to the cytokines it encouraged). Second Lee Rep. at 33–36.

26

some of the support for Respondent’s argument was derived from a case control study with a

distinguishable study sample group (males considerably older than Petitioner). Id. at 38–39. He

emphasized that the GI symptoms Petitioner often experienced were common by-products of

uncontrolled diabetes, further limiting the likelihood that they reflected something else (although

not making it more likely that the vaccine itself was to blame for the diabetes-related flares). Id. at

39–40.

Regarding onset, Dr. Lee acknowledged (in effect) that type I diabetes would not literally

“begin” within two weeks of vaccination, but clarified that he meant to argue that its impact on a

person’s insulin-producing pancreatic beta cells could be discerned in such a short timeframe.

Second Lee Rep. at 21. He also disputed the contention of Respondent’s experts that glycated

hemoglobin levels were themselves a strong biomarker for destruction of such beta cells, proposing

instead that these levels were only proof of a “general trend” and not a predictor independent from

the impact of vaccination. Id. at 23–24. He nevertheless attempted to link record instances in which

testing exposed a spike in these levels to prior receipt of the HPV vaccine, maintaining that the

process would “take a few months to express.” Id. at 24.

Finally, Dr. Lee attempted to defend his opinion that the HPV vaccine could cause orthostatic

intolerance (manifesting in different ways, like syncope or POTS) by arguing that it could occur on

a transient basis, and thus the record (which does not establish persistent instances of POTS close

in time to vaccination, or regular events comparable to it) supported his contention. Second Lee

Rep. at 13–14. He again referenced VAERS reporting of such instances, along with the vaccine’s

package insert. Second Lee Rep. at 28.

3. Dr. Susan Levine

Dr. Levine, a board-certified specialist in infectious diseases, and one of Petitioner’s more

recent treaters, offered a one-page letter in support of Petitioner’s claim. Letter, dated September

28, 2020, filed as Ex. 47 (ECF No. 75-1). The letter was derived from Dr. Levine’s treatment of

Ms. E.S. well after the filing of this case. Dr. Levine opined that Petitioner suffers from CFS,

orthostatic intolerance, “brain fog,” and migraine headaches, all of which interfere with her ability

to “function in a predictable and consistent manner.” Letter at 1. The bases for Dr. Levine’s opinion

seem to be derived from a review of Petitioner’s medical history. Ex. 98 at 27. Dr. Levine has not

provided any substantiation for these diagnoses outside of her record review, nor does her one-page

letter propose that Petitioner’s illnesses are attributable to the HPV or flu vaccines.

B. Respondent’s Experts

1. Dr. Shane LaRue

Dr. LaRue is a cardiologist by training and teaches at the Washington University School of

27

Medicine. He prepared two reports in support of Respondent’s position in this case. See generally

Report, dated July 2, 2018, filed as Ex. A (ECF No. 68-1) (“First LaRue Rep.”); Report, dated May

3, 2019, filed as Ex. G (ECF No. 94-1) (“Second LaRue Rep.”). Dr LaRue maintains that Ms.

E.S. does not suffer from myocardial ischemia, and denies that any of the relevant vaccines she

received could cause it.

Dr. LaRue studied at the University of Wisconsin-Madison where he obtained his bachelor’s

degree in biochemistry before earning his medical degree from the Medical College of Wisconsin.

LaRue Curriculum Vitae at 1, filed on July 27, 2018 (ECF No. 68-9). He then obtained a master’s

degree in population health sciences from Washington University School of Medicine. Id.

Currently, Dr. LaRue is Assistant Professor of Medicine, Section of Heart Failure and Cardiac

Transplantation, in the Cardiovascular Division at Washington University School of Medicine. Id.

He is board certified by the American Board of Internal Medicine in Advanced Heart Failure and

Transplant Cardiology. Id. at 2. And has authored numerous peer-reviewed manuscripts concerning

various aspects of cardiology. Id. at 5–11.

Dr. LaRue’s first report began with consideration of some of the instances of cardiac-oriented

treatment documented in Petitioner’s medical records. He noted the July 2011 instance (three years

prior to the first HPV dose) when Ms. E.S. first appeared to complain of chest pain and

associated symptoms, and at that time received some degree of medical work-up (including an

EKG). First LaRue Rep.at 2; Ex. 17 at 198. Not only did treaters identify no underlying explanation

for her complaints, but the EKG was deemed normal. At most, it included evidence of “early

repolarization”—a benign finding that is common in young people (especially those who are

athletic like Petitioner), even though the shape of the relevant wave recorded on the EKG looks

similar to the pathologic wave elevation that can be seen during acute myocardial infarction or

pericarditis. Id; Second LaRue Rep. at 1; Ex. 17 at 198; A. Goldberger, et al., Electrocardiogram

in the Diagnosis of Myocardial Ischemia and Infarction, uptodate.com 36 (2019), Ex. G1, filed on

May 7, 2019 (ECF No. 94-2). This early EKG was also in Dr. LaRue’s view consistent with

Petitioner’s two later EKGs. Second LaRue Rep. at 1.

Thereafter, the record revealed that Petitioner next obtained treatment for possibly heart-

related symptoms in February 2016, when she saw Dr. Lefkowitz. Ex. 5 at 2. However, Dr. LaRue’s

detailed evaluation of the records from this treatment event (as well as testing performed in its wake)

suggested to him no evidence of anything significant from a cardiac standpoint, let alone myocardial

ischemia. In particular, he highlighted the fact that Petitioner’s pain was initially considered

“exertional in nature,” and thus had not appeared spontaneously, and also that her initial physical

exam was normal. First LaRue Rep. at 2; Ex. 5 at 2. Dr. LaRue admitted that the 2016 EKG did

reveal the possibility of an abnormality, but opined that (comparing this one to the 2011 EKG and

one other Petitioner received in October 2015—both of which were deemed normal) it also included

wave shapes consistent with the (normal) “early repolarization” he saw in all three EKGs. First

28

LaRue Rep. at 2–3, 6–7. 49

Dr. LaRue conceded that Petitioner also received a positive EKG stress test 50, but emphasized

his view that it only supported the “possible” existence of a jeopardized myocardium, adding that

the stress test generally only serves as a screening device that should prompt additional testing and

analysis. First LaRue Rep. at 4; see also Second LaRue Rep. at 4 (“positive findings of a wall

motion abnormality on a stress [EKG] may not be the result of ischemia”). Its sensitivity was

correlated to the general incidence for coronary issues in the relevant population—and here,

Petitioner’s youth made it unlikely that the result would have much predictive value. Id. Moreover,

as a result of the positive stress test result (and consistent with its very purpose), Petitioner was

subsequently referred for a cardiac CT angiography 51—which in Dr. LaRue’s reading revealed no

evidence at all of “significant coronary artery disease,” myocardial ischemia, or a “jeopardized”

49

In response to Dr. Lee’s argument that the “early polarization” justification for all three EKGs’ reported normal findings

did not hold up (because Petitioner was no longer a college athlete as of 2016), Dr. LaRue maintained that (a) she had

been a consistent athlete when the 2011 EKG was performed, and (b) the repolarization pattern was far more prevalent

than the incidence of observable EKG abnormalities, thus allowing for the conclusion that the possible abnormality

suggested by the repolarization pattern was only an “incidental [EKG] finding with no clinical implications.” Second

LaRue Rep. at 3. He also proposed that the finding in 2016 was not new in light of the two earlier EKGs, further reducing

its overall significance. Id. at 2.

I need not decide the evidentiary significance or meaning of this aspect of the EKG performed on Petitioner in 2016. It

cannot be disputed that the EKG resulted in a subsequent positive stress test, followed by a negative CT angiography,

and that treating cardiologists like Dr. Lefkowitz did not (after consideration of all of the above) ultimately diagnose

Petitioner with myocardial ischemia, or any other significant cardiac condition. The weight of the evidence is thus against

the Petitioner on this aspect of her claim no matter which expert is more “right” about the significance of repolarization

patterns specifically (although Dr. LaRue’s demonstrated greater expertise in the field gives his opinions on these subjects

additional heft).

50

Dr. LaRue also speculated that the stress test constituted a false positive, noting that the low likelihood of obstructive

coronary disease in a woman in her early twenties, even with type I diabetes, and the fact that prior studies have noted a

false-positive rate of approximately 30% for stress echocardiography. First LaRue Rep. at 4. Dr. Lee termed this argument

a straw man, reflective of an effort by Dr. LaRue to distract from the real issue under discussion while admitting that

Petitioner did show inferior ST elevation. But (just like my evaluation of the purported early polarization evidence from

the EKG) because my analysis turns on test results collectively and what on-the-ground treaters determined, the accuracy

of the stress test in that process (which unquestionably led Dr. Lefkowitz to order follow-up testing) need not be

evaluated, but instead can be presumed to support only the possibility of a cardiac problem—as in fact it was read.

51

As noted above, Dr. Lee contested whether the testing Petitioner received constituted the best means of evaluating the

presence of myocardial ischemia, noting (as Dr. LaRue acknowledged) that a different diagnostic test—coronary

angiography—was the true “gold standard.” First LaRue Rep. at 5. But Dr. LaRue went on to explain why a CT

angiography was still a perfectly valid test when (as here) the likelihood of coronary disease was not high to begin with,

and that this kind of test was generally sufficiently sensitive to identify the presence (or absence) of a more serious

coronary problem. Id. Dr. LaRue also noted that Ms. E.S. would not have been a proper recipient for a more accurate

but invasive test, and also that her treaters (who could have ordered any testing they thought appropriate) did not pursue

additional testing. Second LaRue Rep. at 6.

I find that Dr. LaRue persuasively established the legitimacy of the CT angiography test that Petitioner received, and its

reliable scientific value under the circumstances (especially given the lack of other evidence corroborating Petitioner’s

assertions in this regard).

29

myocardium. Id. at 2, 3, 5; Ex. 5 at 18. (“[a]ll coronaries are patent without evident atherosclerotic

plaque”). Indeed, based on such results, Dr. Lefkowitz made no negative diagnostic finding close,

in any respect, to what Petitioner alleges. Id. at 5; Second LaRue Rep. at 2, 5–6. 52 Thus, Dr. LaRue

considered Petitioner’s 2016 stress test result a false positive. First LaRue Rep. at 6.

Moving beyond Dr. Lefkowitz’s 2016 exam, Dr. LaRue saw little from the subsequent

records that would support the conclusion that Petitioner ever suffered from any meaningful form

of cardiac issue, vaccine-caused or not. At the first of Petitioner’s May 2017 ER visits (when she

complained of chest pain, among other things), for example, she received a largely normal EKG

result (except for the possibility of left atrial enlargement), First LaRue Rep. at 3. Her second May

2017 visit (facially prompted by an incident of drinking that caused her insulin pump to overreact)

also resulted in an EKG result deemed normal, with no findings of cardiac-related problems upon

discharge. Id.; Ex. 33 at 23. 53 Her January 2017 ER visit was comparable, with a similar nonspecific

EKG (beyond the same evidence of early polarization that Dr. LaRue observed in Petitioner’s prior

EKGs). Id. at 4. And he discounted the probative value of a January 2018 EKG that was at the time

interpreted as “borderline-abnormal” (Ex. 34 at 72), noting that his reading of the results did not

convince him that it was in fact properly understood in this manner, and that her primary symptoms

as of the date of this EKG pertained to abdominal pain ultimately attributable to a ruptured cyst.

First LaRue Rep. at 6; Second LaRue Rep. at 4. Petitioner otherwise never displayed other objective

evidence of ischemia, such as “elevated serum cardiac biomarkers or an abnormality seen on cardiac

CT or cardiac MRI.” Second LaRue Rep. at 3, 5.

Dr. LaRue commented on the persuasiveness of Dr. Lee’s arguments that the HPV vaccine

could be associated with myocardial ischemia (although he admitted in so doing that immunologic

issues were in fact outside of his primary expertise). Second LaRue Rep. at 10. He agreed that

cytokines like TNF-α and IL-1β did play a role in myocardial depression, but questioned whether

they would remain sufficiently elevated months after vaccination to effect such injury (adding that

the record did not establish that Petitioner had experienced other impacts of cytokine-driven

inflammation that would be expected to exist under such circumstances, like low cardiac output or

damage). First LaRue Rep. at 6, 8. He also disputed that the record supported the conclusion that

these cytokines were in fact elevated as of March 2016. Id. at 8–9.

52

Indeed—as Dr. LaRue observed, Petitioner was not even complaining of symptoms of ischemia at the time of her

March 2016 exam, when Dr. Lee maintains the ischemia diagnosis was confirmed by EKG and other testing. Second

LaRue Rep. at 2.

53

In discussing the May 24, 2017 EKG, Dr. LaRue noted (as he did when discussing the February 2016 EKG) another

reason to doubt that it evidenced any potential problems. In Dr. LaRue’s experience, an “auto-generated [EKG] machine”

can produce unreliable results—in particular when the machine itself (via its computer programming) deems a result

suggestive of injury, independent of a human treater’s read of the findings. Second LaRue Rep. at 2, 5; M.E. Guglin et

al., Common errors in computer electrocardiogram interpretation, 106 Int. J. Cardiol. 232–37 (2006). Thus, the first

evidence of a problem from the February 2016 EKG was derived from the “computer generated reading” from the EKG

machine (which itself included the heading “UNCONFIRMED INTERPRETATION”) rather than Dr. Lefkowitz. Second

LaRue Rep. at 2; Ex. 5 at 5. The same was true, in Dr. LaRue’s review, of the subsequent May 2017 EKG report. Second

LaRue Rep. at 4.

30

Besides opining on causal allegations specific to Petitioner’s alleged cardiac injury, Dr.

LaRue reviewed some of her other claimed vaccine-caused harms. For example, his review of the

record did not lead him to conclude that Petitioner ever experienced persistent or significant

hypotension. First LaRue Rep. at 6. He agreed hypotension could be a transient post-vaccination

concern, but challenged that a valid and reliable mechanism existed for explaining how the HPV

vaccine could produce circumstances in which it would be “transiently” experienced six to nineteen

months post-vaccination. Second LaRue Rep. at 9. He also noted that Ms. E.S. ’s blood pressure

was measured in connection with Petitioner’s March 2016 stress test, but that her readings even

after the stress of exercise never measured below normal such that an orthostatic hypotension

diagnosis could be supported. Id. Nor could the condition of cardiac ischemia be deemed to be

caused by hypotension (although hypotension could result from “cardiac abnormalities”). Id. at 10.

2. Dr. Andrew MacGinnitie

Dr. MacGinnitie, a pediatrician and immunologist/allergist, prepared two reports for

Respondent. Report, dated May 1, 2018, filed as Ex. C (ECF No. 69-1) (“First MacGinnitie Rep.”);

Report, dated May 3, 2019 filed as Ex. H (ECF No. 95-1) (“Second MacGinnitie Rep.”). Dr.

MacGinnitie’s opinions mostly focused on Petitioner’s alleged narcolepsy, POTS, and headaches,

and whether the HPV vaccine could cause any of the above, nevertheless he did also address some

of Dr. Lee’s contentions specific to cardiac issues or mechanisms for vaccine causation.

Dr. MacGinnitie is currently an attending physician as well as Clinical Director for the

Division of Immunology at Boston’s Children’s Hospital, where he oversees clinical operations for

Allergy/Immunology, Rheumatology, and Dermatology. First MacGinnitie Rep. at 1. He obtained

his medical degree and Ph.D. in Pathology from the University of Chicago Pritzker School of

Medicine. Id. Dr. MacGinnitie is board certified in both Allergy/Immunology and Pediatrics and

maintains an active clinical practice seeing more than 1,600 patients annually. Id. at 2. He also

performs research and has published numerous articles in areas relating to Allergy/Immunology,

including vaccine reactions. Id.

a. MacGinnitie First Report

After a brief overview of Petitioner’s medical history, Dr. MacGinnitie endeavored to rebut

Dr. Steinman’s narcolepsy theory. First MacGinnitie Rep. at 4. He noted a diagnostic issue that

undermined Dr. Steinman’s causation theory as presented in this case. Dr. MacGinnitie conceded

that at least a “plausible case” existed for the contention that a specific formulation of the flu vaccine

(one that is adjuvanted—a form rarely administered in the U.S., and not received by Ms. E.S.

in this case) could trigger narcolepsy with cataplexy, or “type 1” narcolepsy, 54 via an autoimmune

54

Type 1 narcolepsy is caused by extensive loss of hypothalamic neurons that produce the neuropeptides orexin-A and -

B (also referred to as hypocretin-1 and -2). Narcolepsy type 2 includes most of the same symptoms, but its cause is

31

process in which antibodies triggered by vaccine antigen presentation cross-react with the

hypocretin pathway. 55 Id. However, Ms. E.S. had at best been diagnosed only with type 2

narcolepsy56—a less severe form not accompanied by cataplexy, and not also believed to be

autoimmune-driven. Id. at 4–5, 7; T. Scammell, Narcolepsy, 373 New Eng. J. Med. 2654–62

(2015), filed July 27, 2018 as Ex. C, Tab 1 (ECF No. 69-2). As a result, Dr. Steinman’s entire

causal explanation was inapplicable to the facts of this case.

In addition, Dr. MacGinnitie questioned whether (independent of the version of narcolepsy

Petitioner allegedly had experienced) Dr. Steinman had even established that narcolepsy could be

driven by an autoimmune process that was vaccine-triggered. First MacGinnitie Rep. at 5–6. Thus,

he pointed out that many of the individual items of literature Dr. Steinman had cited did not

demonstrate that persons with narcolepsy possessed sufficient amounts of the purportedly

hypocretin-oriented autoantibodies for a cross-reaction, while individuals without narcolepsy had

comparable quantities of the antibodies. Id. at 6; S. Ahmed et al., Antibodies to Influenza

Nucleoprotein Cross-React with Human Hypocretin Receptor 2, 7 Sci. Translational Med. 1, 1–15

(2015), filed July 27, 2018 as Ex. C, Tab 3 (ECF No. 69-4). Dr. MacGinnitie deemed this to cast

“considerable doubt on the importance of these antibodies.” First MacGinnitie Rep. at 6.

Dr. MacGinnitie raised several other technical objections to the reliability of the causation

theory that vaccination could provoke an autoimmune response sufficient to interfere with

hypocretin pathways and thereby cause narcolepsy. First MacGinnitie Rep. at 6–9. But in his view

a more fundamental flaw in the theory arose from the fact that such evidence, reliable or not,

involved an adjuvanted flu vaccine—not the HPV vaccine. Regarding the latter, Dr. MacGinnitie

noted that Dr. Steinman’s argument relied heavily on the contention that mimicry existed between

HPV vaccine amino acid sequences (the building-blocks of proteins) sufficient to interfere with

hypocretin pathways, but without reliable evidence (in the form of experimentation or other

research) showing this actually could occur. Instead, Dr. Steinman relied on animal studies relevant

to autoimmune-driven demyelination generally, a disease pathogenesis wholly distinguishable from

unknown, and it does not feature cataplexy. T.E. Scammell, Narcolepsy, 373 N. Engl. J. Med. 2654-62 (2015), filed July

27, 2018 as Ex. C, Tab 1 (ECF No. 69-2).

55

In his second report, Dr. MacGinnitie devoted greater attention to the argument that the flu vaccine could be credibly

associated with any form of narcolepsy, offering two 2018 articles that he proposed diminished the significance of prior

research linking certain formulations of the H1N1 fly vaccine to type 1 narcolepsy. Second MacGinnitie Rep. at 5–8

(references omitted). But because Petitioner did not receive the form of flu vaccine even arguably associated with

narcolepsy, and based on my prior reasoned determinations (mentioned below) that the non-adjuvanted flu vaccine

commonly administered in the U.S. is highly unlikely to cause the condition, I do not herein devote extensive discussion

to these issues. Of the theories advanced in this case, the contention that type II narcolepsy can be caused by the flu or

HPV vaccines was among the least well-substantiated—no matter how robust the association between type I narcolepsy

and some versions of the flu vaccine might be.

56

People with type 2 narcolepsy do not have cataplexy and have normal orexin-A levels. Scammell, at 4. Type 2

narcolepsy may be caused by less extensive injury to orexin-A and -B transmitters, but data on the disease process are

quite limited. Id.

32

the receptor blocking at issue in narcolepsy. Id. at 9–10. Dr. MacGinnitie also pointed out that there

were in nature numerous examples of possible molecular mimicry between amino acid sequences

and self-structures (“this level of overlap in protein sequence is common”), yet autoimmune

diseases were not regular occurrences (thus suggesting that homology between sequences alone was

no guarantee of an autoimmune/pathologic reaction). Id. at 10.

More significantly, Dr. MacGinnitie observed that several large epidemiologic studies (one

of which Dr. Steinman himself cited in his own report) did not demonstrate any significant

incidence of narcolepsy after receipt of the HPV vaccine. First MacGinnitie Rep. at 11; Arnheim-

Dahlstrom at 1. Chao—a study referenced by Dr. Lee, and in Dr. MacGinnitie’s report (and which

has been offered in many other Program decisions)—reached a similar conclusion. Chao at 193.

Chao was a peer-reviewed observational study analyzing a database comprised of the medical

histories of approximately 189,000 women in California to determine whether the studied

population had developed a variety of autoimmune conditions after receiving the HPV vaccine.

Chao at 194.

Next, Dr. MacGinnitie evaluated the strength of Dr. Steinman’s arguments that Petitioner’s

reported headaches could be associated with the HPV vaccine. He noted that the record did not offer

substantiation for a migraine headache diagnosis for Petitioner, and also that the vaccine package

inserts (which Dr. Steinman purported established headache as an expected post-vaccination

adverse event) described “almost certainly acute events occurring immediately after vaccination,”

rather than a chronic occurrence manifesting long after. First MacGinnitie Rep. at 11. Dr.

MacGinnitie expressed doubt about the proposed mechanism for the headaches, arguing that the

likelihood of the small amount of presenting antigen in the vaccine could travel into the central

nervous system (the “CNS”) to bind with or activate receptors there associated with headache was

low, and that other evidence cited by Dr. Steinman to substantiate persistence of effect over time

(whether due to the alum included in the vaccine as an adjuvant, or evidence that the immunity

effect of the vaccine could last) did not amount to a showing that the “vaccine proteins themselves”

(which constituted tiny amounts of the vaccine) would remain in the body for the same period. Id.

at 12; Second MacGinnitie Rep. at 12.

Besides his review of Dr. Steinman’s opinion, Dr. MacGinnitie critiqued elements of Dr.

Lee’s arguments about the association between the HPV vaccine and worsening of diabetes or heart

damage. He deemed the former to suffer from “a number of glaring weaknesses,” including but not

limited to the following:

• The table referenced from the HPV vaccine safety trials did not establish an increased,

post-vaccination incidence of new-onset type 1 diabetes, and also used as a control group

subjects who received a placebo (as opposed to the general population) (First

MacGinnitie Rep. at 13);

33

• Epidemiologic studies like Chao or Arnheim-Dahlstrom showed no association between

the HPV vaccine and type 1 diabetes (Id. at 13-14 (citing Chao at 201; Arnheim-

Dahlstrom at 5)); and

• Dr. Lee’s incidence calculation was not only mathematically erroneous, but proposed an

unlikely, drastically high level that “if it were accurate, we would be observing an

epidemic of [type 1 diabetes] in adolescent boys and girls” (First MacGinnitie Rep. at

14).

In addition, Dr. MacGinnitie offered to show, via the filed medical records, that in fact

Petitioner’s “worsened control” of her diabetes was not likely vaccine-related. First MacGinnitie

Rep. at 14. As he observed, Ms. E.S. had one of her highest glycated hemoglobin readings in

early July 2014—before receipt of the first HPV vaccine dose. Id.; see also Second MacGinnitie

Rep. at 3 (“her control was worsening prior [to] receiving her fist HPV vaccine”). In contrast, one

of her best readings came in December 2016, by which time she had received both doses at issue,

undercutting Dr. Lee’s contention that her levels would be expected to be persistently high due to

vaccination. Id. at 14–15. Dr. MacGinnitie felt the onset of Petitioner’s late adolescence, with the

attendant “life changes” that might make monitoring more difficult, or other unhealthy behaviors”

that occur at the college level (pointing specifically to the instance in which a drinking bout resulted

in an ER visit), better explained her experiences. Id. at 15; Second MacGinnitie Rep. at 4. 57

Regarding Petitioner’s purported myocardial ischemia, Dr. MacGinnitie echoed Dr. LaRue,

maintaining that the medical record (and more specifically EKG and CT testing Petitioner had

received) did not establish either evidence of decreased blood flow or a jeopardized myocardium,

nor had any treaters ultimately found otherwise. First MacGinnitie Rep. at 16-17. He disputed Dr.

Lee’s effort to link such problems to syncope or POTS, noting that (a) at most, the vaccine was

associated with acute (one-time) episodes of post-vaccination syncope rather than chronic blood

flow issues, and (b) the HPV vaccine was only linked to POTS by a single four-patient case study.

First MacGinnitie Rep. at 16. Dr. Lee offered little to no other evidence reliably establishing the

vaccine could injure the heart. Id. And the record did not suggest that Ms. E.S. had experienced

heightened levels of inflammation around the time of her March 2016 cardiac consultation, with

some testing done before this time revealing no abnormalities, and any higher levels revealed in

57

As an alternative explanation for Ms. E.S. ’s diabetes-related post-vaccination symptoms and associated ER visits,

Dr. MacGinnitie proposed “selective IgA deficiency”—a deficiency in an immunoglobulin protective against infection

that Petitioner was diagnosed with as a younger child. First MacGinnitie Rep. at 15. Dr. Lee argued in response that

selective IgA deficiency could not be the cause because Ms. E.S. ’s relevant ER visits were post-vaccination and not

throughout her childhood. Second Lee Rep. at 37. Further, Ms. E.S ’s chronic tonsillitis was a health care issue only

after vaccination and obviously unrelated to her SIgAD. Id. at .38. Both sides make reasonable points about the

significance of the levels of this particular antibody, but my decision does not turn on who is “more” correct on this issue,

since (as discussed in detail throughout) I ultimately do not find that any vaccine Petitioner received likely caused the

exacerbation of her type I diabetes.

34

March 2016 likely attributable to the ruptured cyst she had experienced. Id. at 16–17. 58

b. MacGinnitie Second Report

Dr. MacGinnitie’s second report contained some more detailed evaluations of theories

presented by Petitioner’s experts. First, he questioned Dr. Lee’s contention that the HPV vaccine

doses Petitioner received in 2014 and 2015 could later cause elevated cytokine levels persisting into

the winter of 2016. He highlighted the fact that articles, like Herrin, explicitly stated that they did

not find that the specific proinflammatory cytokines (identified by Dr. Lee) became elevated over

long periods of time after receipt of the HPV vaccine. Second MacGinnitie Rep. at 1–2; Herrin at

3449–50.

Dr. MacGinnitie also noted that the mere production of proinflammatory cytokines by

macrophages was not a “controversial” point, but it did not mean that vaccines encouraged this

process or could cause it to persist. In so arguing, Dr. MacGinnitie specifically challenged Dr. Lee’s

assertion that macrophages bearing alum would likely travel into the CNS, noting that the literature

cited for this concept by Dr. Lee was speculative rather than supported with “actual data.” Second

MacGinnitie Rep. at 3. And he distinguished literature establishing that the HPV vaccine could

promote a subsequent increased T-cell/immune response to the vaccine’s proteins (the very purpose

of vaccination) from a demonstration that the “immune system in general shows increased activity

after vaccination,” and that this increase would persist for long periods of time. Id. at 4 (emphasis

in original).

In addition, Dr. MacGinnitie attempted to address head-on Dr. Lee’s contentions about DNA

matter persisting in the HPV vaccine formulation—a condition for Dr. Lee’s overall causal theory

that a “silent” adjuvant (the TLR agonist) found its way into the vaccine and would thereafter

amplify its pathologic impact. He noted that this element of Dr. Lee’s opinion was only supported

by two articles Dr. Lee himself authored plus his own experiment, adding that the technique used

to sense the presence of this DNA was so sensitive that it would pick up the presence of “miniscule”

amounts, thereby producing false positives. Second MacGinnitie Rep. at 4–5. And in any event, Dr.

Lee had offered “no evidence that the amount [of cell-free DNA] in the HPV vaccine is sufficient

to stimulate a significant immune response,” as his theory posited. Id. at 5. 59

58

Inflammation is a localized protective response elicited by injury or destruction of tissue. Dorland’s at 935.

Inflammation can be acute, usually of sudden onset and predominated by vascular and exudative processes. Id. When

chronic and slow in its progression, it is marked chiefly by the formation of new connective tissue; it may be a

continuation of an acute form or a prolonged low-grade form, and usually causes permanent tissue damage. Id. Dr.

MacGinnitie later partially granted Dr. Lee’s contention that the ruptured cyst might exhibit different kinds of

inflammatory immune cells, but insisted nonetheless that there was overall little evidence of “persistent inflammation.”

Second MacGinnitie Rep. at 4.

59

Dr. MacGinnitie added that as a general matter, “trace amounts” of DNA in a vaccine were simply unlikely to be

harmful, noting that humans already are exposed to similar DNA from bacteria and micro-organisms without aberrant

impacts, and the blood itself also contains cell-free DNA. Second MacGinnitie Rep. at 5. And vaccine development

35

Because chronic fatigue had not been alleged as an additional vaccine injury at the time of

his first report, Dr. MacGinnitie only addressed it in the second report, emphasizing that the

diagnosis post-dated the vaccinations at issue by three to four years. Second MacGinnitie Rep. at

12. Also, he noted that Dr. Steinman’s support for the association between the HPV vaccine and

chronic fatigue came from a four-person case study, contrasting the embrace of such limited

evidence (since case studies at bottom only demonstrated a temporal relationship) with Dr.

Steinman’s arguments that large-scale epidemiologic studies were not sufficiently powered to

suggest the absence of an association. Id. at 13. Dr. MacGinnitie cited additional epidemiologic

evidence undercutting a relationship between the HPV vaccine and chronic fatigue. Id.; J. Skufca

et al., The Association of Adverse Events With Bivalent Human Papillomavirus Vaccination: A

Nationwide Register-Based Cohort Study in Finland, 36 Vaccine 5226–33 (2018), filed May 7,

2019 as Ex. H, Tab 17 (ECF No. 96-8) (“Skufca”). Skufca (evaluating a different formulation of

the HPV vaccine) considered the evidence of adverse outcomes for more than 240,000 females in

Finland aged 11-15 who received the vaccine, finding no statistically-significant increased

incidence rate for CRPS or POTS; while a slight increase was observed for chronic fatigue, it was

consistent with what boy subjects experienced. Skufca at 3. Dr. MacGinnitie otherwise disputed

that chronic fatigue could even be understood as an autoimmune condition in the first place. Second

MacGinnitie Rep. at 13–14.

3. Dr. David Raizen

A neurologist and medical professor with specific training and expertise in sleep medicine

issues, Dr. Raizen offered two written reports. Report, dated May 24, 2018, filed as Ex. E (ECF No.

72-1) (“First Raizen Rep.”); Report, dated May 4, 2019, filed as Ex. I (ECF No. 97-1) (“Second

Raizen Rep.”). Dr. Raizen mainly addressed Dr. Steinman’s contentions pertaining to narcolepsy,

although he expanded his focus to include Petitioner’s allegations of chronic fatigue in his second

report.

Dr. Raizen is an associate professor at the Perelman School of Medicine for the University

of Pennsylvania, and a practicing neurologist with a sub-specialty in sleep medicine. First Raizen

Rep. at 1. He is board certified in psychiatry and neurology as well board certified in sleep medicine.

Id. Dr. Raizen has been treating patients with sleep disorders for the past fourteen years and

currently follows approximately 50 patients with narcolepsy in an outpatient clinic. Id. In addition,

he directs a research group aimed at understanding the fundamental mechanisms regulating sleep

and wake. Id. at 2. Dr. Raizen’s reports were based on consideration of the reports offered from

Drs. Steinman and Lee, his review of the medical record, and a variety of medical and scientific

articles bearing on the diagnoses in question and what is known about the pathogenesis of each.

First Raizen Rep. at 2–3; Second Raizen Rep. at 1.

efforts that seek to rely on the stimulative, adjuvant-like effect of this DNA employ amounts far in excess of the trace

levels that would be found in the HPV vaccine. Id.

36

a. Raizen First Report

In discussing narcolepsy, Dr. Raizen noted that the “presence of cataplexy” (which he defined

as “the sudden loss of muscle tone during wakefulness”) was the main distinguishing feature

between types 1 and 2. First Raizen Rep. at 4. Diagnosing narcolepsy requires consideration of

medical history, a physical exam, and then the combination of a polysomnography test and a MSLT.

Id. A sleep latency of eight minutes or less, plus proof of two or more sleep onset REM periods, is

supportive of a narcolepsy diagnosis. Id. From a pathophysiologic perspective, Dr. Raizen

emphasized that more was known scientifically about type 1 narcolepsy, and his explanation for it

(loss of brain neurons that produce hypocretin, plus association with HLA antigen) was consistent

with what Drs. MacGinnitie and Steinman agreed upon—as was his admission that evidence existed

associating an adjuvanted form of the flu vaccine that was only administered in Europe (Pandemrix)

with an increased incidence of type 1 narcolepsy. Id. at 5–6.

In this case, Dr. Raizen disputed the legitimacy the MSLT Ms. E.S. underwent in January

2017, arguing that critical protocols needed to ensure the accuracy of results did not occur. First

Raizen Rep. at 5. In particular,

• performance of the polysomnography the night before the MSLT (“to ensure that proper

sleep amount was achieved” before the MSLT) did not occur—instead, the two were

performed two months apart;

• sleep logs were not obtained for the week before the MSLT;

• a urine drug screening (for medications that might impact sleep) was not performed; and

• the sleep apnea diagnosis Petitioner had previously obtained provided an alternative

explanation for daytime sleepiness that undercut the MSLT findings.

Id. at 6–7. Thus, he disputed that the MSLT test, coupled with other exam and testing results

considered by Ms. E.S.’s treaters, in fact supported the narcolepsy diagnosis she received.

Moreover, assuming the diagnosis was substantively supported, Dr. Raizen pointed out

(consistent with Dr. MacGinnitie) that the distinction between types 1 and 2 narcolepsy was harmful

to Petitioner’s causation theory. He noted that there was “essentially no evidence for autoimmunity

in the pathogenesis of type 2 narcolepsy,” and therefore, what was believed plausible about the

pathogenesis of type 1 narcolepsy had no relevance in explaining Petitioner’s case. First Raizen

Rep. at 7, 8. And (referencing Arnheim-Dahlstrom) he denied that reliable evidence connecting the

HPV vaccine to any form of narcolepsy existed, noting that “the ratio of narcolepsy incidence

between those vaccinated and those unvaccinated has a mean that is less (and not more) than 1.” Id.

37

at 8 (emphasis in original); Arnheim-Dahlstrom at 5. 60

b. Raizen Second Report

Dr. Raizen’s second report focused on Ms. E.S.’s chronic fatigue diagnosis and its

purported causal association with the HPV vaccine. He observed that the diagnosis (which came

from Dr. Levine’s treatment of Ms. E.S. in 2018) often featured “unrefreshing sleep” as a

symptom. Second Raizen Rep. at 1–2. But he disputed that there was any overlap between this feature

of chronic fatigue and narcolepsy, noting that those diagnosed with the latter often reported feeling

refreshed after the instances in which they slept normally, with ever-present sleepiness more the

problem they faced. Id. at 2; C. Baumann et al., Challenges in Diagnosing Narcolepsy without

Cataplexy: A Consensus Statement, 37 Sleep 1035–42 (2014), filed July 27, 2018 as Ex. E, Tab 12

(ECF No. 73-3). As a result, he rejected the contention that chronic fatigue sleep-related symptoms

would corroborate a narcolepsy diagnosis (and in fact maintained that Dr. Levine’s findings further

undercut the accuracy of Petitioner’s earlier narcolepsy diagnosis). Id. at 2.

Dr. Raizen otherwise (consistent with his arguments about the narcolepsy-HPV vaccine

causal relationship) contested Petitioner’s allegations that the HPV vaccine was associated with

chronic fatigue. He noted that science still did not fully understand the pathogenesis of chronic

fatigue. Second Raizen Rep. at 5. As a result, he rejected Petitioner’s argument that it was more likely

than not an autoimmune condition. In addition, he noted that reliable studies from Europe did not

observe an association between the HPV vaccine and an increased risk of chronic fatigue. Id; B.

Feiring et al., HPV Vaccination and Risk of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis:

A Nationwide Register-Based Study from Norway, 35 Vaccine 4203–12 (2017), filed May 7, 2019

as Ex. I, Tab 5 (ECF No. 97-6); K. Donegan et al., Bivalent Human Papillomavirus Vaccine and the

Risk of Fatigue Syndromes in Girls in the UK, 31 Vaccine 4961–67 (2013), filed May 7, 2019 as Ex.

I, Tab 6 (ECF No. 97-7).

4. Dr. Christopher Gibbons

Dr. Gibbons, a board-certified neurologist with specific expertise in both diabetes and small

fiber neuropathies, prepared a single report. Report, dated May 3, 2019, filed as Ex. J (ECF No. 98-

1) (“Gibbons Rep.”). In it, he set forth his dim view of Dr. Steinman’s contention that Ms. E.S.’s

purported small fiber neuropathy was caused by the HPV vaccine.

Dr. Gibbons is an Associate Professor of Neurology at Harvard Medical School. Gibbons

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In his second report, Dr. Raizen revisited Arnheim-Dahlstrom in light of arguments Dr. Steinman had made about his

interpretation of its findings (in particular criticisms he leveled at how the raw data was adjusted). Second Steinman Rep.

at 21–22. Dr. Raizen admitted his lack of expertise in statistics or epidemiology (which Dr. Steinman shares), but deemed

the adjusted figures (which he placed more faith in) to be common in reliable epidemiologic studies, and otherwise argued

the results that supported his contentions were scientifically reasonable. Second Raizen Rep. at 3–4.

38

Rep. at 1. He completed neurological training at Johns Hopkins Hospital and subspecialty training

in Clinical Neurophysiology at Harvard Medical School and Beth Israel Deaconess Medical Center.

Id. Dr. Gibbons has previously served as the Chair of the Autonomic Section of the American

Academy of Neurology and Chair of the Clinical Affairs Committee of the American Autonomic

Society. Id. He is currently the Director of the Beth Israel Deaconess Medical Center

Neurocutaneous Laboratory—the diagnostic laboratory for small fiber neuropathy—and has treated

thousands of patients with small fiber neuropathy and reviewed tens of thousands of skin biopsy

slides for evaluation of small fiber neuropathy. Id. at 2. Of particular note, Dr. Gibbons reports that

he personally published the “seminal articles” on both small fiber neuropathy as well as the use of

skin biopsies as a diagnostic tool, and that he has over the years treated thousands of individuals

suffering from small fiber neuropathy. Id. at 1–2; C. Gibbons et al., Quantification of Sudomotor

Innervation: a Comparison of Three Methods, 42 Muscle Nerve 112–119 (2009), filed May 7, 2019

as Ex. J, Tab 4 (ECF No. 98-5); C. Gibbons, et al., Quantification of Sweat Gland Innervation: a

Clinical-Pathologic Correlation, 72 Neurology 1479–86 (2009), filed May 7, 2019 as Ex. J, Tab 5

(ECF No. 98-6).

Like the other experts before him, Dr. Gibbons initiated his report with an overview of

Petitioner’s medical history, noting in particular that (a) Ms. E.S. had struggled controlling her

diabetes, and (b) her small fiber neuropathy diagnosis came from the time period when she began

seeing Dr. Chin in September 2018 (three-plus years after the last vaccinations at issue) and was

based on two skin biopsies performed at that time. Gibbons Rep. at 3; Ex. 48. He challenged the

diagnosis, arguing (despite the fact that the test results themselves were in the abnormal range (Ex.

48 at 2)) that the underlying records for the actual results had not been provided, making it

impossible for him to evaluate the accuracy of the diagnosis in light of the proper reading of the

results. Gibbons Rep. at 4.

More so, Dr. Gibbons maintained that Petitioner had received normal neurologic exams from

2016 until her visits with Dr. Chin, that there was no filed record establishing follow-up with Dr.

Chin that would confirm the accuracy of the diagnosis, and that overall the record lacked sufficient

clinical proof to corroborate the small fiber neuropathy diagnosis. Gibbons Rep. at 5. In addition,

Dr. Gibbons maintained that the diagnosis could not be based solely on biopsy results, which could

constitute a false positive. Id.; B. Callaghan et al., Better Diagnostic Accuracy of Neuropathy in

Obesity: A New Challenge for Neurologists, 129 Clinical Neurophysiology: Official J. of the Int’l

Federation of Clinical Neurophysiology 654–62 (2018), filed May 7, 2019 as Ex. J, Tab 5 (ECF

No. 98-6).

Dr. Gibbons highlighted the significance of Petitioner’s preexisting type 1 diabetes.

Neuropathies are well-known to be highly associated with diabetes (as well as other risk factors

Petitioner possessed, such as an elevated body mass index and hypercholesterolemia 61). Gibbons

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Hypercholesterolemia is excessive cholesterol in the blood. Dorland’s at 876.

39

Rep. at 6. Indeed, the association between diabetes and any form of neuropathy was far better

established by medical science than a link to the HPV vaccine. Id. Dr. Gibbons therefore opined

that assuming the small fiver neuropathy diagnosis was correct, it was still far more likely that it

was explained by her diabetes than her receipt of the HPV vaccine. Id.

Regarding Petitioner’s causal theory, Dr. Gibbons rejected the contention that the HPV

vaccine was associated with small fiber neuropathy. He noted that (based on his own research) there

were exceedingly few publicly available articles involving the topic, no research evaluating how

the vaccine would cause such a form of neuropathy, and no case reports. Gibbons Rep. at 4. At

most, Petitioner had referenced “a case series from Japan with an enormous array of symptoms”

from a pool of individuals who received the vaccine. T. Kinoshita et al., Peripheral Sympathetic

Nerve Dysfunction in Adolescent Japanese Girls Following Immunization with the Human

Papillomavirus Vaccine, 53 Internal Med. 2185–2200 (2014), filed May 7, 2019 as Ex. J, Tab 1

(ECF No. 98-2) (“Kinoshita”). But, Dr. Gibbons opined that Kinoshita may not even have identified

actual incidents of small fiber neuropathy (conflating them with biopsy evidence of purported

“nerve” damage that in his reading was merely proof of damage to nerve myelin), adding that its

findings otherwise had been cast in doubt. Id.; S. Hanley et al., Peripheral Sympathetic Nerve

Dysfunction in Adolescent Japanese Girls Following Immunization with the Human Papillomavirus

Vaccine, 54 Internal Med. 1953 (2015), filed May 7, 2019 as Ex. J, Tab 2 (ECF No. 98-3) (letter

criticizing Kinoshita as not “demonstrat[ing] any relationship between vaccination and adverse

events, which are [in Kinoshita] poorly-defined and include an eclectic range of symptoms”).

Dr. Gibbons also proposed that the reasonableness of the timeframe in which Petitioner’s

onset occurred had not been established. The earliest evidence of a diagnosis of small fiber

neuropathy was from 2018—three years after the last HPV dose Petitioner received. Moreover (and

contrary to the history provided to Dr. Chin), the record for the intervening period of 2015 to 2018

showed numerous instances in which Ms. E.S. received normal neurologic exams. As a result,

the period from last HPV dose to when Dr. Gibbons speculated Petitioner might have developed a

small fiber neuropathy was too lengthy to be medically acceptable. Gibbons Rep. at 6–7.

C. Other Scientific or Medical Evidence Pertaining to Petitioner’s Case

Petitioner filed some additional items of literature (15 in all) in the course of briefing

Respondent’s dismissal motion. Only a small few, however, plowed new ground, and therefore

merit discussion.62 One such article was only published in the late summer of 2019, and purports to

62

Illustrative of the misguided, “more heat than light” nature of Petitioner’s overall showing in this case, the Sur-Reply

was filed with seven additional items of literature—most of which could have been offered far earlier in the matter’s life,

since all but one were published before 2018, and did not otherwise reflect new scientific findings. One of the newly-

filed items, Exhibit 117, was a nearly nine-hundred-page excerpt from the Institute of Medicine’s treatise Adverse Effects

of Vaccines: Evidence and Causality—essentially the entirety of the work. The filing of whole texts into the record of a

Vaccine Act case is not a practice reflective of careful lawyering aimed at persuading the special master through focused

reference to helpful evidence.

40

support Petitioner’s contentions about the autoimmune character of POTS. See, e.g., W. Gunning

et al., Postural Orthostatic Tachycardia Syndrome is Associated with Elevated G-Protein Coupled

Receptor Autoantibodies, 8 J. Am. Heart Assoc. 1–10 (2019), filed Nov. 24, 2019 as Ex. 109 (ECF

No. 107-1) (“Gunning”). Gunning observed the presence of elevated G-protein coupled adrenergic

autoantibodies or muscarinic autoantibodies in the majority of a group of 55 patients. Gunning at

5–6. However, its authors conceded that the significance of its findings remained “unknown” (Id.

at 7), and although Gunning purported that an association between vaccination and POTS was

“well-documented,” it based this proposition on articles written by some of the same individuals

that have been found unpersuasive in past cases. Id. at 8 fn. 47–50 (citing an article written by Dr.

Shoenfeld). 63 Gunning otherwise is not strong evidence for the conclusion that all cases of POTS

are autoimmune in origin or nature—let alone a subset.

Respondent similarly filed some additional articles bearing on the resolution of the case. First,

he filed a 2019 statement from the American Autonomic Society (the “AAS”), written by certain

individuals deemed leaders in the field, 64 finding specifically that “there are no data [at this time]

to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and [POTS]

to other forms of dysautonomia.” A. Barboi et al., Human Papillomavirus (HPV) Vaccine and

Autonomic Disorders: A Position Statement from the American Autonomic Society, Clinical

Autonomic Res. 1, 1–6 (2019), filed Feb. 4, 2020 as Ex. M (ECF No. 115-2) (the “AAS Statement”),

at 1. The AAS Statement references L. Brinth et al., Orthostatic Intolerance and postural

tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus,

33 Vaccine 2602–05 (“Brinth”).

Second, Respondent filed a response to the AAS Statement written by a medical expert whose

work has been favorably cited by Petitioner in this case as supportive of the relationship between

the HPV vaccine and POTS. S. Blitshteyn, Human Papillomavirus (HPV) Vaccine Safety

Concerning POTS, CRPS and Related Conditions, Clinical Autonomic Res. (2019), filed Feb. 4,

2020 as Ex. N (ECF No. 115-3) (“Blitshteyn”). Dr. Blitshteyn’s article proposes that vaccine-

triggered, immune-mediated autonomic dysfunction could possibly lead to the development of de

novo post-HPV vaccination syndrome in genetically susceptible individuals. Blitshetyn, et al.,

Autonomic dysfunction and HPV immunization: an overview, Immunologic Res., filed as Ex. 96 on

January 15, 2019 (ECF No. 88-1). But in her letter, (and while maintaining that the concept of

dysautonomia induced by the HPV vaccine should be taken seriously and be made the subject of

63

Once again, reference is made to an article on the propensity of vaccination to cause autoimmune disease written by

Dr. Shoenfeld—the same expert who (a) came up with the discredited ASIA theory discussed in footnote 56 above, and

(b) has repeatedly, but unpersuasively, testified that the HPV vaccine can cause POTS and other purportedly autoimmune

conditions. See Gunning at 8.

64

The AAS Statement’s 22 authors include one of Respondent’s experts, Dr. Gibbons, as well as Dr. Philip Low, a

nationally-recognized expert on the autonomic nervous system who has testified previously in the Program for

Respondent in cases involving POTS as a claimed vaccine injury. See, e.g. Yalacki, 2019 WL 1061429, at *18.

41

further research), Dr. Blitshteyn acknowledged the accuracy of the AAS’s conclusions. Blitshteyn

Letter at 1 (noting that Dr. Blitshteyn “agree[s] with [the AAS’s] conclusion that given the existing

evidence to date, a causal relationship has not been supported”) (the “Blitshteyn Letter”).

Finally, Respondent offered a 2018 statistical analysis from Japan (source of articles like

Ozawa and Kinoshita) of approximately 30,000 female recipients of the HPV vaccine and 24 kinds

of post-vaccination symptoms commonly reported in studies claiming an association between the

vaccine and the kinds of injuries claimed in this case. S. Suzuki et al., No Association Between HPV

Vaccine and Reported Post-Vaccination Symptoms in Japanese Young Women: Results of the

Nagoya Study, 5 Papillomavirus Res. 96–103 (2018), filed Feb. 4, 2020 as Ex. L (ECF No. 115-1)

(“Suzuki”). The sample group in Suzuki is far larger than the number of individuals considered in

Ozawa, Kinoshita, or even Brinth. Suzuki’s authors only noted statistically relevant increases in

complaints of headache or hospitalization due to menstrual bleeding, but not the kind of symptoms

that might be deemed autonomic in character (e.g., fatigue, dizziness, weakness, brain fog, etc.).

Suzuki at 98–100.

III. Procedural History

The Petition was initiated in April 2017. By September of that year, after the filing of medical

records and a substitution of counsel, Respondent filed his Rule 4(c) Report opposing an entitlement

award. ECF No. 27. For nearly two years thereafter, the parties filed back-and-forth expert reports

as discussed above. By May 2019, however, I had determined (given misgivings I had regarding

some aspects of the case) that certain elements of the matter might be amenable to disposition via

ruling on the record. To that end, I set up an initial schedule for briefing the matter. Docket Entry

Order, dated May 15, 2019. The parties completed briefing the matter with the filing of Petitioner’s

Sur-Reply in April 2020, and the matter is fully ripe for resolution.

IV. Parties’ Respective Arguments

Respondent’s Motion attacks both the adequacy of evidence establishing certain of

Petitioner’s claimed injuries, as well as her success in demonstrating that the HPV and/or flu

vaccines could cause them in the first place. He disputes that the record supports Petitioner’s claim

of chronic headaches, noting a lack of such a diagnosis (Mot. at 18), and also similarly contests that

the record establishes that Ms. E.S. experienced myocardial ischemia. Mot. at 28–30. He also

maintains that Petitioner’s type 2 narcolepsy diagnosis was based on incomplete testing (Mot. at

33–34), adding that preponderant evidence does not establish that this form of narcolepsy (which

cannot be assumed to be autoimmune, in comparison to the first form) has not reliably been

associated with the HPV or flu vaccine. Id. at 34–36.

In addition, Respondent similarly observes that Petitioner’s purported diagnoses for chronic

42

fatigue, small fiber neuropathy, and POTS were all obtained long after the vaccinations at issue

(calling into question how they could be reasonably associated with vaccines), and that the evidence

offered to support each either lacks corroboration in the record or reflects an incomplete

determination. Mot. at 37–42. And Respondent challenges Petitioner’s ability to show that her DM1

could be significantly aggravated by either relevant vaccine, arguing that (a) no Program decision

has ever held that diabetes can be caused or aggravated by any vaccine, (b) Petitioner’s course did

not necessarily reveal consistent worsening, but instead was characterized by numerous ups and

downs (as reflected in varying blood sugar testing results in the timeframe after vaccination), and

(c) Dr. Lee’s causation theory is not credible or reliable, and comes from an individual lacking the

expertise to so opine. Id. at 21–28.

In reaction, Petitioner opposes dismissal, arguing instead that ample matters have been

presented warranting a hearing. She consistently takes note of the difference in her health overall

pre- versus post-vaccination. Opp. at 3–4, 5–6. After a lengthy review of her medical history, she

emphasizes the diagnostic support for autonomic-related injuries from Dr. Levine in 2018, followed

by Drs. Chin and Younger. Id. at 17–23. The narcolepsy diagnosis, she maintains, similarly finds

support in Dr. Kothare’s evaluation, and she proposes that the testing evidence (that she possesses

the autoantibodies that are key to her theory for how these injuries came about) is sound. Id. at 23–

24, 29. She makes a similar argument to vouch for the skin biopsy findings of small fiber

neuropathy, over the objections of Dr. Gibbons. Id. at 34. These injuries are all related and are in

Petitioner’s view bulwarked by reliable recent literature underscoring the significance of anti-

adrenergic antibodies in causing autonomic harm, such as Ikeda. Opp. at 27–28.

Ms. E.S. also maintains that her myocardial ischemia and DM1 significant aggravation

claims are supported by the record and reliable science and medical evidence, including the

testimony of Dr. Lee. To do so, she relies on inclusion of large block-quoted sections from Dr.

Lee’s reports. Opp. at 36–40. And as further support for her significant aggravation of diabetes

claim, Petitioner revisits again her argument that her health took a noticeable turn for the worse

post-vaccination, and emphasizes Dr. Lee’s assertion (logically questioned by Respondent’s

experts, as noted above) that there was a “25-fold increase” in the incidence of diabetes after

administration of the HPV vaccine. Id. at 40–42.

Respondent filed a succinct reply. It emphasized my authority to resolve this matter without

a hearing, noting that none of the “new” articles or more recent treatment records Petitioner filed

established persuasive grounds for a hearing. Reply at 2–3. Respondent made specific comment

about the unpersuasive or unreliable character of articles filed in conjunction with the Opposition

Brief, like Kinoshita and Gunning, while highlighting his own newly-filed articles, such as the AAS

Statement or Suzuki. Id. at 4–5.

Given the opportunity to offer a sur-reply, Petitioner prepared and filed a brief twice as long

as the Reply, but which largely repeated arguments already lodged in opposing Respondent’s initial

43

dismissal motion. Petitioner admitted that the evidence for a POTS diagnosis might not be

preponderant (Sur-Reply at 3 (“Dr. Younger’s medical record and testing points in the direction of

a POTS diagnosis”) (emphasis added)), but claimed the evidence suggestive of that diagnosis had

to be considered in light of the other record evidence supportive of some kind of dysautonomia,

which was likely related to Petitioner’s receipt of the HPV vaccine. Id. at 3–4. The “newly emerged”

evidence associating the two marshaled in favor of a hearing. Id. at 4. She reiterated her arguments

about a decline in health post-vaccination (Id. at 5–9). She also raised two somewhat new injury

complaints that she had not emphasized before: (1) that she had showed “[s]ymptoms of ovarian

failure” after vaccination—a condition she maintained is associated with the HPV vaccine; 65 and

(2) that 2018 MRI results revealed a pituitary lesion that could be associated with HPV infection.

Id. at 9–11.

V. Applicable Law

A. Petitioner’s Overall Burden in Vaccine Program Cases

To receive compensation in the Vaccine Program, a petitioner must prove either: (1) that he

suffered a “Table Injury”—i.e., an injury falling within the Vaccine Injury Table—corresponding to

one of the vaccinations in question within a statutorily prescribed period of time or, in the alternative,

(2) that his illnesses were actually caused by a vaccine (a “Non-Table Injury”). See Sections

13(a)(1)(A), 11(c)(1), and 14(a), as amended by 42 C.F.R. § 100.3; § 11(c)(1)(C)(ii)(I); see also

Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec’y

of Health & Hum. Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006). 66 In this case, Petitioner does not

assert a Table claim.

For both Table and Non-Table claims, Vaccine Program petitioners bear a “preponderance of

the evidence” burden of proof. Section 13(1)(a). That is, a petitioner must offer evidence that leads

the “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, 592 F.3d at 1322 n.2; see also Snowbank Enter. v. United States, 6 Cl. Ct. 476, 486 (1984)

(mere conjecture or speculation is insufficient under a preponderance standard). Proof of medical

certainty is not required. Bunting v. Sec’y of Health & Hum. Servs., 931 F.2d 867, 873 (Fed. Cir.

1991). In particular, a petitioner must demonstrate that the vaccine was “not only [the] but-for cause

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In fact, claims of post-HPV vaccine ovarian failure have been litigated several times in the Program—never to success.

See, e.g. Wright v. Sec. of Health & Hum. Servs., No. 15-851V, 2017 WL 8218937 (Fed. Cl. Spec. Mstr. Dec. 28, 2017);

Culligan v. Sec. of Health & Hum. Servs., No. 14-318V, 2016 WL 3101981 (Fed. Cl. Spec. Mstr. June 2, 2016); Laughlin

v. Sec. of Health & Hum. Servs., No. 13-289V, 2016 WL 3101977 (Fed. Cl. Spec. Mstr. June 2, 2016).

66

Decisions of special masters (some of which I reference in this ruling) constitute p

This text is long and has been trimmed here. Open the source document for the complete record.