Antoniades v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: May 5, 2026

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

ALEXANDRA ANTONIADES, *

*

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Petitioner, * No. 19-1244V

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v. * Special Master Young

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SECRETARY OF HEALTH *

AND HUMAN SERVICES, *

*

Respondent. *

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

Ronald Craig Homer, Conway, Homer, P.C., Boston, MA, for Petitioner.

Crystal Fialkowski, United States Department of Justice, Washington, DC, for Respondent.

DECISION ON ENTITLEMENT 1

On August 21, 2019, Nicholas and Brenda Antoniades filed a petition for compensation

under the National Vaccine Injury Compensation Program (“Vaccine Act” or “the Program”), 42

U.S.C. § 300aa-10 et seq. (2018), 2 on behalf of their then minor daughter, Alexandra Antoniades

(“Petitioner”). 3 Pet., ECF No. 1; Am. Pet., ECF No. 26. They alleged that Petitioner developed

autoimmune encephalomyelitis 4 as the result of a tetanus, diphtheria, acellular, and pertussis

(“Tdap”) vaccine she received on August 14, 2017. Id. at 1. Respondent argued against

compensation, asserting that Petitioner could not establish a causation-in-fact claim by a

preponderance of the evidence. Resp’t’s Rept. at 21, ECF No. 20.

1

Because this Decision contains a reasoned explanation for the action taken in this case, it must be made

publicly accessible and will be posted on the United States Court of Federal Claims’ website, and/or at

https://www.govinfo.gov/app/collection/uscourts/national/cofc, in accordance with the E-Government Act

of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic Government

Services). This means the Decision will be available to anyone with access to the internet. In accordance

with Vaccine Rule 18(b), Petitioner has 14 days to identify and move to redact medical or other information,

the disclosure of which would constitute an unwarranted invasion of privacy. If, upon review, I agree that

the identified material fits within this definition, I will redact such material from public access.

2

National Childhood Vaccine Injury Act of 1986, Pub L. No. 99-660, 100 Stat. 3755. Hereinafter, for

ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. §

300aa (2018).

3

On June 28, 2023, Petitioner’s parents filed a motion to change the case caption, as Petitioner had reached

the age of majority and wished to continue the case in her personal capacity. ECF No. 66. I granted this

motion on August 7, 2023. ECF No. 67.

4

Encephalomyelitis is “inflammation involving both the brain and the spinal cord. Encephalomyelitis,

DORLAND’S MED. DICTIONARY ONLINE,https://www.dorlandsonline.com/dorland/definition?id=16191&

searchterm=encephalomyelitis (hereinafter, “DORLAND’S”).

A careful analysis and weighing of all the evidence presented in this case in accordance

with the applicable legal standards 5 reveals that Petitioner has failed to provide preponderant

evidence that the Tdap vaccine she received on August 14, 2017, caused her to suffer from

autoimmune encephalomyelitis. Accordingly, Petitioner is not entitled to an award of

compensation.

I. Procedural History

Petitioner’s parents filed the petition on August 21, 2019. Pet. They then filed medical

records, an affidavit, and a statement of completion on September 3, 2019. Pet’r’s Exs. 1–5, ECF

No. 6; Pet’r’s Ex. 6, ECF No. 7; ECF No. 9. Petitioner’s parents filed additional medical records

on October 17, 2019, and on January 6, 2020, along with a statement of completion. Pet’r’s Exs.

7–8, ECF No. 11; Pet’r’s Exs. 9–11, ECF No. 17; ECF No. 19.

On February 21, 2020, Respondent filed his Rule 4(c) report. Resp’t’s Rept. On June 4,

2020, Petitioner’s parents filed an amended petition, additional medical literature, and another

affidavit. Am. Pet.; Pet’r’s Ex. 12, ECF No. 23; Pet’r’s Ex. 13, ECF No. 24. They then filed a

response to Respondent’s Rule 4(c) report on July 17, 2020, indicating they had filed the

outstanding medical records requested. ECF No. 28. On July 27, 2020, Petitioner’s parents filed

an expert report from Mahbubul Huq, M.B.B.S., Ph.D., his curriculum vitae (“CV”), and medical

literature. Pet’r’s Exs. 14–23, ECF No. 29; Pet’r’s Exs. 24–33, ECF No. 30; Pet’r’s Exs. 34–43,

ECF No. 31; Pet’r’s Exs. 44–53, ECF No. 32; Pet’r’s Exs. 54–56, ECF No. 33. Respondent then

filed an expert report from Eric Lancaster, M.D., Ph.D., his CV, and medical literature on

November 19, 2020. Resp’t’s Ex. A, Tabs 1–3, Resp’t’s Ex. B, ECF No. 38.

Petitioner’s parents filed additional medical records on March 17, 2021. Pet’r’s Exs. 58–

60, ECF No. 40. Additional medical literature and a supplemental report from Dr. Huq was filed

on June 14, 2021. Pet’rs Exs. 61–66, ECF No. 45. Respondent filed a supplemental report from

Dr. Lancaster on August 24, 2021. Resp’t’s Ex. C, ECF No. 47. More medical records were filed

on April 28, 2022. Pet’r’s Exs. 67–70, ECF No. 51.

On September 27, 2022, I held a Rule 5 conference between the parties. See Min. Entry,

docketed Sept. 27, 2022. Following the status conference, I ordered a supplemental expert report

clarifying the alleged diagnosis, medical theory of causation, and clarifying the relevance of

conversion disorder. ECF No. 56. On February 13, 2023, Petitioner’s parents filed a supplemental

report from Dr. Huq, as well as additional medical literature. Pet’r’s Exs. 72–87, ECF No. 60.

Respondent filed a supplemental report from Dr. Lancaster and supporting medical literature on

5

While I have reviewed all of the information filed in this case, only those filings and records that are

most relevant to the Ruling will be discussed. Moriarty v. Sec’y of Health & Hum. Servs., 844 F.3d 1322,

1328 (Fed. Cir. 2016) (“We generally presume that a special master considered the relevant record

evidence even though he does not explicitly reference such evidence in his decision.”) (citation omitted);

see also Paterek v. Sec’y of Health & Hum. Servs., 527 F. App’x 875, 884 (Fed. Cir. 2013) (“Finding

certain information not relevant does not lead to—and likely undermines—the conclusion that it was not

considered.”).

2

April 14, 2023. Resp’t’s Ex. D, Tabs 1–2, ECF No. 62. Additional medical records were filed on

May 16, 2023. Pet’r’s Ex. 88, ECF No. 63.

On June 28, 2023, Petitioner’s parents filed a motion to change the case caption, as

Petitioner had reached the age of majority and wished to continue the case in her personal capacity.

ECF No. 66. I granted this motion on August 7, 2023. ECF No. 67.

On April 1, 2024, I scheduled an entitlement hearing for this case to be held on December

5 and 6, 2024. ECF No. 68. Petitioner filed her pre-hearing brief on August 30, 2024. Pet’r’s Br.,

ECF No. 71. Respondent filed his pre-hearing brief on November 5, 2024. Resp’t’s Br., ECF No.

74. On November 13 and 14, 2024, the parties filed their pre-hearing submissions. ECF Nos. 75–

84. The entitlement hearing was held on December 5 and 6, 2024. See Min. Entry, docketed Dec.

6, 2024. No post-hearing briefs were filed.

This matter is now ripe for consideration.

II. Medical History

Petitioner was born on May 18, 2005. Pet’r’s Ex. 4 at 6. Her pre-vaccination medical

history was significant for an allergy to stinging insects, a history of febrile seizures, and

swimmer’s ear. Pet’r’s Ex. 2 at 6–11; Pet’r’s Ex. 5 at 101.

On August 14, 2017, Petitioner was 12 years old when she received the Tdap vaccine.

Pet’r’s Ex. 1 at 4. One month later, on September 15, 2017, Petitioner presented to Children’s

Primary Care Medical Group (“CPCMG”) with complaints of dizziness and paresthesias in her

legs. Pet’r’s Ex. 4 at 6. Her parents reported that two weeks prior she returned from a friend’s

house with a cold that subsided within two days. Id. Nine days before visiting CPCMG, Petitioner

began to experience episodes of dizziness and lightheadedness that lasted roughly one minute and

occurred about four times per day. Id. Her episodes would occur whether sitting or standing and

occasionally when running or playing tennis but would subside after sitting and resting. Id. Her

parents also reported that Petitioner had developed a new symptom of “stiff, heavy” legs and an

inability to stand four days ago, accompanied by pain in her ankles. Id. Petitioner’s attending

physician, pediatrician Ruey-Sjiuan Tsang, noted that Petitioner was experiencing one of these

episodes at the time of her examination. Id. Her parents also noted that Petitioner had headaches

before and after he leg episodes, and that Petitioner had been experiencing vision problems for

approximately six months. Id. Petitioner’s parents further reported that they delayed seeking

treatment because they initially believed Petitioner’s symptoms to be the result of overuse

following a tennis tournament. Id. at 7.

On examination, Dr. Tsang noted that Petitioner had experienced a fever two weeks ago at

the beginning of symptoms, but that the fever had since subsided. Pet’r’s Ex. 4 at 7. She also

recorded a “visual disturbance” in Petitioner’s eyes, as well as arthralgias, a gait problem,

dizziness, weakness, lightheadedness, and headaches. Id. Dr. Tsang wrote that Petitioner’s

symptoms “all [began] after acute viral [upper respiratory infection (“URI”)] just prior to onset of

these symptoms.” Id. at 10. Dr. Tsang also noted that aside from her vision problems, Petitioner’s

3

neurologic examination was otherwise normal. Id. She considered Guillain-Barré Syndrome 6

(“GBS”) due to Petitioner’s prior URI but noted that Petitioner’s symptoms were episodic. Id. Dr.

Tsang acknowledged that Petitioner had previously received the Tdap vaccine, “which is another

predisposition of [GBS].” Id. “She does not have fever or neck pain to suggest meningitis.” Id. Dr.

Tsang opined that Petitioner’s symptoms may also be a “post-strep phenomenon” due to her sore

throat at onset and scheduled Petitioner for a follow-up examination the next day. Id.

Petitioner returned to CPCMG on September 16, 2017, and was seen by Dr. George

Madany. Pet’r’s Ex. 4 at 14. In addition to the symptoms relayed to Dr. Tsang, Dr. Madany noted

that Petitioner was also experiencing pins and needles in her feet. Id. On examination, Dr. Madany

noted all neurological symptoms to be within normal limits and her deep tendon reflexes (“DTRs”)

registered as +2. Id. at 16. He considered GBS as a possible diagnosis but noted that this would be

more likely related to her prior URI than the Tdap vaccination. Id. at 17. Petitioner was instructed

to return if her symptoms worsened. Id.

Later that evening Petitioner presented to Dr. Jackson Vane at the Rady Children’s Hospital

(“RCH”) emergency department (“ED”) with complaints of leg pain and weakness. Pet’r’s Ex. 3

at 38. Her history section noted that she began to experience numbness and tingling over the top

of her legs that day, and that she had missed school last week due to her symptoms. Id. Petitioner

described the pain as “a hot tingling pain,” and Dr. Vane noted that there were “[n]o known

aggravating or alleviating factors.” Id. at 38–39. On examination Dr. Vane observed Petitioner was

experiencing back pain, joint swelling, myalgias, dizziness, lightheadedness, headaches, and

fatigue. Id. at 39. He also observed tenderness over her thighs and in the lumbar area with full

strength in both legs. Id. at 40. Dr. Vane’s differential diagnoses included nerve pain, dehydration,

and musculoskeletal pain, and he ordered a CK test to rule out rhabdomyolysis. Id. at 41. Petitioner

also underwent an electrocardiogram (“EKG”), which was normal. Id. Dr. Vane consulted with

neurology, who opined that no further testing was required. Id. She was advised to stop sports for

one week and was discharged home. Id.

Petitioner returned to Dr. Madany on September 22, 2017, with complaints of pain in her

legs and lower back. Pet’r’s Ex. 4 at 21. She reported that she was experiencing “random dizziness”

one to two times per day but did not feel like passing out and that “sitting down help[ed].” Id. She

had also developed carsickness. Id. at 22. On examination Petitioner’s neurologic systems were

within normal limits and her DTRs registered as +2. Id. at 23. Dr. Madany opined that her condition

appeared to be “like [post]-infectious myositis” and instructed her to return if her symptoms

worsened or failed to improve. Id. at 23. He also noted that Petitioner’s orthostasis appeared to be

an independent issue and would await a neurological evaluation. Id.

On October 7, 2017, Petitioner presented to ophthalmologist Mona Adams due to a failed

vision screening. Pet’r’s Ex. 3 at 87. Petitioner reported difficulty seeing the board at school and

that she “recently had a virus causing diplopia[7] and dizziness.” Id. She was prescribed glasses

and sent home. Id. at 91.

6

GBS is a “rapidly progressing ascending motor neuron paralysis of unknown etiology, frequently seen

after an enteric or respiratory infection.” Guillain-Barré Syndrome, DORLAND’S.

7

Diplopia, also called double vision, is “the perception of two images of a single object.” Diplopia,

DORLAND’S.

4

On October 13, 2017, at 2:36am, Petitioner presented to the RCH ED with complaints of

fatigue and an inability to stand. Pet’r’s Ex. 3 at 125. She reported that her leg pain began “[one]

month ago” and improved after 10 days, but “[i]n [the] last [four-to-five] days [the] pain got

worse.” Id. She described the pain as “heaviness, weakness, [and] throbbing” that lasted for about

five minutes and then returned again 10 minutes later. Id. She also had now developed “stiff,

tingling fingers,” double vision, and heavy eyelids, which last for about one minute and then

resolve. Id. Her attending physician, Dr. Matthew Kline, noted that she had an appointment with

neurology later that morning. Id. Her physical examination was unremarkable. Id. at 126. Dr. Kline

reported that her workup from her prior ED visit resulted in a normal EKG, CBC, CMP, and mildly

elevated lipase. Id. at 127. He further noted that neurology declined a workup given her impending

neurology appointment. Id. Dr. Kline’s differential diagnoses included myasthenia gravis, 8 GBS

(with a note of normal reflexes), post-viral myositis 9 (which he noted did not account for all of her

symptoms), multiple sclerosis 10 (“MS”), orthostatic hypotension, and somatic disorder, and she

was discharged home. Id. at 126–27.

Petitioner returned to RCH later that morning for her neurology appointment and was seen

by neurologist Anuja Jindal. Pet’r’s Ex. 3 at 167. Petitioner reported that her neurologic symptoms

began about four weeks ago and had now progressed to a “heavy” feeling in her legs where she

“feels like she cannot walk.” Id. The episodes occurred when she was both sitting and standing,

occasionally associated with dizziness, lightheadedness, and headaches. Id. She previously was

experiencing episodes three times per day, but two weeks ago she returned to normal until her

symptoms returned one week prior. Id. Now she had begun to experience dizziness, double vision,

and heavy eyelids while slumping over. Id. at 168. Petitioner reported that these episodes

occasionally included chest pain, shortness of breath, and paresthesias in her legs, though she

reported no loss of consciousness. Id. In her history, Dr. Jindal also took note of Petitioner’s URI

about one week before symptom onset. Id. She also noted that “[i]n late August [Petitioner received

the] Tdap booster [and f]elt ok after getting [the vaccine].” Id.

On examination Petitioner’s neurologic systems were all noted as normal aside from mildly

brisk DTRs in her right bicep. Pet’r’s Ex. 3 at 173. Dr. Jindal also reported that Petitioner began

to experience an episode of leg heaviness during the examination “and had some hesitation with

walking, but exam[ination] remained non-focal.” Id. Dr. Jindal ultimately opined that Petitioner’s

“exam[ination] and symptoms [did] not conform to a known neurological diagnosis. She likely

had post-viral myositis initially but this has likely resolved.” Id. She also noted that although

Petitioner experienced a URI prior to symptoms, she did not suspect GBS “given intact reflexes

and overall improving symptoms.” Id. Dr. Jindal also noted that Petitioner stated she had

experienced mild anxiety and that her symptoms “recurred when she was to return to school.” Id.

“There is a high likelihood that her symptoms are behavioral in nature, although conversion

8

Myasthenia gravis is “an autoimmune disease of neuromuscular function due to the presence of

antibodies to acetylcholine receptors at the neuromuscular junction.” Myasthenia Gravis, DORLAND’S.

9

Myositis is “inflammation of a voluntary muscle.” Myositis, DORLAND’S.

10

MS is “a disease in which there are foci of demyelination throughout the white matter of the central

nervous system.” Multiple Sclerosis, DORLAND’S.

5

disorder[11] is a diagnosis of exclusion.” Id. Dr. Jindal ordered labs for vitamin B12, vitamin D,

iron levels, and ordered neurologic imaging. Id.

Petitioner returned to CPCMG on October 18, 2017, with complaints of difficulty breathing

and a rapid heart rate. Pet’r’s Ex. 4 at 26. Petitioner reported her symptoms began while waiting

for a tutor at home and felt her heart rate increase and felt like she could not breathe, which lasted

for about one minute. Id. Another episode occurred 10 minutes later. Id. Petitioner reported that

she was feeling anxious about not seeing her friends and missing school. Id. Her provider noted

that her physical examination was normal but that Petitioner had “reproducible chest wall pain.”

Id. at 28. The provider opined that her difficulty breathing was “related to anxiety about

tachycardia.” Id. She was advised to keep a journal of her symptoms, referred for a Holter monitor,

and discharged. Id. Her Holter monitor was reported as normal on October 23, 2017. Id. at 240.

An October 31, 2017 magnetic resonance imaging (“MRI”) of her brain was also normal. Id. at

316.

On November 17, 2017, Petitioner returned to Dr. Madany with continued complaints of

difficulty walking and muscle weakness for two months. Pet’r’s Ex. 4 at 30. She reported that she

had experienced loss of consciousness, double vision, blurry vision, ringing in her ears, pain in her

legs, tingling in her fingers and toes, and chest pain. Id. at 30–31. Her physical examination was

normal, but Dr. Madany noted that she “struggle[d] to walk, need[ed] assistance.” Id. at 32. Dr.

Madany ordered an MRI of her spine and an electroencephalogram (“EEG”). Id. He also noted she

was not suffering from GBS and that her diagnosis was “[c]onversion per neuro[logy].” Id.

Petitioner returned for a neurology follow-up with Dr. Jindal on December 5, 2017. Pet’r’s

Ex. 3 at 340. Dr. Jindal reported that she had had several phone calls with Petitioner’s parents since

her previous visit “for new and persistent symptoms of varying frequency,” including fainting

spells, leg paralysis, tingling in fingertips, tongue tingling, and jaw clenching. Id. at 341. Dr. Jindal

further noted that the family had not identified a trigger for any symptoms and that symptoms

never occurred during tutoring sessions. Id. Petitioner remained out of school and she had

experienced occasional fainting spells when spending time with friends. Id. Petitioner’s appetite

and physical activity had also decreased and she had gained about four-to-five pounds since her

last visit. Id. Dr. Jindal reported that Petitioner’s neurologic examination was “entirely nonfocal”

and that “[t]he etiology of [her] symptoms [was] still unclear. Her exam[ination] and symptoms

[did] not conform to a single known neurological diagnosis.” Id. at 344. Dr. Jindal agreed with Dr.

Madany’s order of a spinal MRI and discouraged a lumbar puncture at this time due to her normal

neurologic examination. Id. She also recommended Petitioner see a counselor as “the past few

months have been difficult for [Petitioner] emotionally.” Id. Dr. Jindal scheduled a follow-up for

February 2018 and told her family to call if her symptoms worsened. Id.

On December 13, 2017, Petitioner presented to cardiologist Matthew Williams for

evaluation of her syncope. Pet’r’s Ex. 3 at 406. Dr. Williams noted that Petitioner had begun

experiencing 10 to 15 syncopal episodes per day since September 2017. Id. He also noted that

Petitioner’s musculoskeletal symptoms did not have an “apparent association [with her syncope]

other than also starting in September.” Id. Petitioner’s parents also questioned whether the Tdap

11

Conversion disorder is “a mental disorder characterized by conversion symptoms . . . having no

demonstrable physiologic basis and whose psychological basis is suggested by [] exacerbation of

symptoms at times of psychological stress.” Conversion Disorder, DORLAND’S.

6

vaccination could have caused her symptoms. Id. Dr. Williams opined that the etiology of her

symptoms was inconsistent with arrhythmia and “not suggestive of a vasovagal etiology or any

abnormality in cardiac or vascular function.” Id. at 408. He also opined that conversion disorder

or another functional neurologic disorder was possible, though acknowledged this was outside his

realm of expertise. Id. He ultimately recommended Petitioner continue to pursue neurologic

evaluation and deferred to neurology for further recommendations. Id. Petitioner completed her

spinal MRI two days later on December 15, 2017, which was normal. Id. at 445.

Petitioner’s parents returned to Dr. Madany on January 3, 2018, to discuss the next steps

for diagnosing her condition. Pet’r’s Ex. 4 at 35. Her parents reported that she continued to

experience all symptoms and had begun to experience episodes where she could not ambulate. Id.

at 36. Dr. Madany informed her parents that he had reported Petitioner’s history to

GlaxoSmithKline (“GSK”), the vaccine manufacturer, and noted “[p]ossible [Vaccine Adverse

Event Reporting System (“VAERS”)].” Id. at 37. He also stated that GSK informed him that most

symptoms resolved within one month, and that there were no available studies beyond that

timeframe. Id. “Other[] situations may imply ?MS, autoimmune conditions being unmasked by

vaccine.” Id. Dr. Madany ordered an EEG to be completed on January 10, 2018, a repeat MRI to

screen for MS, prescribed vitamin D, and recommended a psychiatric consultation. Id.

On January 8, 2018, Petitioner presented to Dr. Susan Biffl at the RCH rehabilitation clinic

and relayed her history of symptoms. Pet’r’s Ex. 3 at 475. Dr. Biffl discussed conversion disorder

with Petitioner and her parents, explaining that “this was a disorder that is not under [Petitioner’s]

control and always has a neurologic finding that is generally not in an expected physiologic

distribution.” Id. Dr. Biffl recommended a continued neurologic workup to rule out other possible

causes and to start intervention for conversion disorder, as well as psychiatric intervention. Id.

Petitioner underwent continuous EEG monitoring from January 10, 2018, to January 11, 2018. Id.

at 537. Her “typical events of brief impaired consciousness were captured without a seizure

pattern,” and the family was informed these events were non-epileptic. Id. Petitioner and her

mother were advised to see a child psychologist for stress management. Id.

Also on January 10, 2018, Dr. Madany submitted a VAERS report for Petitioner. Pet’r’s

Ex. 10 at 2. The onset date of Petitioner’s symptoms was noted to be September 15, 2017, 32 days

after vaccination. Id. at 3. “The report[] considered the blurred vision, walking difficulty, increased

reflexes, myopia, creatine phosphokinase increased, paresthesia, numbness, myalgia of lower

extremities, lower extremities weakness . . . and dizziness to be possibl[y] related to [Tdap].” Id.

Petitioner presented for a rheumatology consultation with Dr. Robert Sheets on January

18, 2018. Pet’r’s Ex. 3 at 667. Dr. Sheets noted that Petitioner’s symptoms began on September 6,

2017, and that Petitioner was no longer experiencing headaches with her symptoms. Id. at 671. He

also reported that Petitioner did not feel anxious or depressed and that there was no family history

of depression. Id. at 672. Her parents reported that she received the Tdap vaccine about “[two-to-

three] weeks prior to this start of symptoms and . . . [felt] that this [was] the cause of these

symptoms.” Id. Dr. Sheets ultimately opined:

if this is not a conversion reaction and I would think that would be unlikely due to

the episodic nature of her symptoms and if this is not some form of seizure disorder

and she has seen neurology and they do not think that is the case given a normal 24

7

hour [EEG] then this could represent some form of inflammatory brain disease that

is autoantibody induced without personality changes. I don’t think that this could

represent [central nervous system (“CNS”)] vasculitis.

Id. at 674. Dr. Sheets recommended a CNS autoimmune antibody blood panel and requested to

see Petitioner again in two weeks. Id. Petitioner’s panel returned normal for CBC and differential,

CRP, DNA, DS antibody, Sjogren’s antibody, RNP antibody, and Smith antibody. Id. at 713. Her

ESR and C3 were borderline elevated and her ANA screen IFA was borderline positive. Id.

Petitioner followed up with Dr. Williams on January 25, 2018, for an EKG, which was normal. Id.

at 751. Dr. Williams did not feel any further cardiologic testing was warranted. Id. at 786.

Petitioner presented for a physical therapy evaluation on January 31, 2018, where her

parents again reported that she received the Tdap vaccine prior to the start of her symptoms. Pet’r’s

Ex. 3 at 819. Her physical therapist noted mild weakness in her hips, mild tightness in her quads

and hamstrings, and balance issues with both ankles. Id. at 821. Her therapist recommended

Petitioner return to regular exercise to return to baseline function and continue physical therapy

twice per week for six weeks. Id. Petitioner continued physical therapy through June 4, 2018, at

which point she had met all of her goals and was discharged to a home exercise program. Id. at

974, 1003, 1032, 1140, 1218, 1248, 1304, 1333, 1362, 1391, 1458.

The same day, Petitioner returned for a follow-up with Dr. Biffl, who noted Petitioner had

“consistently documented normal neurologic exam[inations] by multiple providers, normal [EKG]

and normal [EEG] with fainting episodes not associated with epileptiform activity.” Pet’r’s Ex. 3

at 891. Petitioner’s parents reported that she continued to have fainting episodes and stated that

“their [primary care provider (“PCP”)] listed [Tdap] as an allergy and [] called this a reaction

which they are pleased with.” Id. Dr. Biffl further noted that Petitioner’s parents “would like to

know if this is a reaction to an immunization [and] if they have seen the correct providers.” Id.

Petitioner’s physical examination was normal and Dr. Biffl recommended Petitioner continue

physical therapy, explore psychiatric options, and contact her school to develop a plan for her

return. Id. at 397.

The next day, on February 1, 2018, Petitioner returned to Dr. Sheets for a follow-up visit.

Pet’r’s Ex. 3 at 400. He noted that Petitioner’s testing thus far had been normal and that Petitioner’s

[d]ad is concerned that it is related to vaccines (but not anti-vaccine) and brings

[GSK] side effect profile about syncope and tonic clonic motions; although

symptoms occurred [two-to-three] weeks after the vaccine. PCP listed Tdap as an

allergy. Parents called company and verified that this has occurred but did not

clarify it would cause persistent symptoms.

Id. Dr. Sheets also noted that Petitioner’s parents were aware conversion disorder was a possibility.

Id. His ultimate impression was an “inflammatory brain disease that is autoantibody induced

without personality changes (and reiterated with parents that inflammatory brain disease is

unrelated to vaccines) or conversion reaction although unlikely due to episodic character.” Id. at

404. Dr. Sheets ordered a blood autoimmune antibody panel and stated he would follow up with

Petitioner’s parents once he had the results. Id. Dr. Sheets also had pediatrician Crystal Stephens

examine Petitioner and speak to her parents about whether the Tdap vaccine could have caused

8

Petitioner’s symptoms. Id. at 405. She explained that she had “never seen any reaction to

immunization create this set of symptoms” and that such a determination is best left to a specialist

in infectious diseases. Id. She also noted the possibility of immune mediated inflammatory brain

diseases, and that if testing for these were negative, to proceed with a lumbar puncture to check

for autoimmune encephalopathy. Id.

The following week, on February 8, 2018, Petitioner presented to infectious disease

specialist Mark Sawyer. Pet’r’s Ex. 3 at 940. Petitioner’s parents noted “the receipt of a Tdap

vaccine approximately [three] weeks prior to the first symptom onset.” Id. at 940–41. Her physical

examination was normal. Id. at 941. Dr. Sawyer noted that Petitioner’s symptoms “can not be

easily explained” given their intermittent nature, long duration, “lack of fever, and lack of

significant laboratory abnormalities,” which he noted make an infectious disease “very unlikely.”

Id. at 943. “The timing of onset . . . make a vaccine reaction unlikely in that the rare neurologic

events . . . usually appear within [one-to-two] days following vaccination. Further, if these

symptoms were a result of a post-vaccination . . . reaction [he] would have expected an abnormal

MRI.” Id. He also noted the only remaining helpful test would be a lumbar puncture, but did not

think it would be very revealing. Id.

With regard to the vaccine, Dr. Sawyer wrote the following:

I had a long discussion with the family about vaccine adverse events including the

fact that the adverse events listed in the vaccine package inserts are an accumulated

list of all reactions that occurred during clinical trials and not reflective of patterns

of symptoms occurring in single patients. I told them that [Petitioner’s] symptoms

were not anything I had heard of or read about as associated with a vaccine. I did

suggest that [Petitioner’s] symptoms be reported to the [VAERS] since that is the

only way rare reactions might be recognized. They agreed and will send me the

vaccine lot number information for her Tdap vaccination so I can file a VAERS

report. We discussed the fact that just because symptoms are reported in VAERS

does not mean they are caused by vaccines. I acknowledged that I could never

completely exclude the possibility that [Petitioner’s] symptoms were related to her

prior vaccination but encouraged them to consider the alternative diagnosis of a

conversion reaction.

Pet’r’s Ex. 3 at 943. Dr. Sawyer planned to search VAERS for any similar Tdap reactions, submit

the VAERS case report, and follow up with neurology and rheumatology to decide whether to

proceed with a lumbar puncture. Id.

On March 8, 2018, Petitioner presented to neurologist Mark Nespeca for a second opinion

following what Dr. Nespeca described as an “abnormal” antibody test. Pet’r’s Ex. 3 at 1061. He

also noted that Petitioner was scheduled to review the results with Dr. Sheets later that afternoon.

Id. Dr. Nespeca explained that Petitioner’s autoimmune encephalopathy panel was “indicative of

abnormal findings of a low range titer of 0.09 nmol/L (normal < 0.02 nmol/L)” for neuronal

ganglionic acetylcholine receptor antibody (“AChR”) antibody. Id. Dr. Sheets was interested in

Dr. Nespeca’s opinion because “that antibody has been associated with a variety of symptoms of

autonomic dysfunction, peripheral neuropathy and cognitive disorders especially in patients with

known carcinomas.” Id. Dr. Nespeca opined that Petitioner did not “seem to have a typical profile

9

of a child with psychosomatic disorder as she is truly bothered by the effect this has had on her

life and she is anxious to get back to school.” Id. at 1065. He observed that although she lacked

the features of “gastrointestinal dysmotility or sicca syndrome . . . many of her symptoms are quite

possibility related to autonomic . . . and peripheral neuropathy symptoms.” Id. He further noted

that Petitioner lacked the diagnostic criteria of postural orthostatic tachycardia syndrome

(“POTS”) 12 and did “not show statis exam[ination] features of a peripheral neuropathy” and her

reflexes were normal. Id. “Some patients with this antibody have substantial cognitive disturbance

or bad psychosis or depression none of which seem[ed] to be plagueing (sic) her now.” Id. Dr.

Nespeca expressed concern that a previous study “noted that several of the patients in [the] series

were found to have carcinomas who were not previously known to have a cancer,” and opined that

a workup to investigate renal, pancreatic, and thyroid cancers was reasonable. Id. He endorsed a

trial therapy of steroids, intravenous immunoglobulin (“IVIG”), or methotrexate to reduce

Petitioner’s titers and recommended another autoimmune encephalopathy panel to check her

levels. Id. He also told Petitioner’s parents that he had “not seen such symptoms occur in temporal

relation to her Tdap immunization she had a couple weeks before the symptoms began.” Id. He

ordered ultrasounds of her thyroid, kidneys, and abdomen to screen for cancer and planned to

discuss next steps with Dr. Sheets and Dr. Jindal. Id. at 1066.

Later the same day Petitioner presented to Dr. Sheets to follow up regarding “possible

autoimmune encephalomyelitis.” Pet’r’s Ex. 3 at 1103. Dr. Sheets noted that her labs showed

“positive anticholinesterase ganglioside antibody [that] can be associated with dysautonomia and

neuropathy according to case reports.” Id. He also noted that her spells were occurring less

frequently at once per day, but her spells lasted “a substantial amount of time.” Id. Dr. Sheets

opined that her positive antibody test made “autoimmune inflammatory brain disease more likely”

and recommended IVIG and prednisone treatment. Id. at 1107. He also repeated her

encephalopathy panel. Id.

Petitioner returned to Dr. Sheets on March 21, 2018, who noted that Petitioner’s symptoms

had not improved despite 40mg of prednisone daily, and that she had developed dizziness,

headaches, and epigastric pain. Pet’r’s Ex. 3 at 1170. Dr. Sheets reduced Petitioner’s prednisone

to 30mg and recommended IVIG if her symptoms still did not improve. Id. at 1174. Her repeat

encephalopathy panel showed her AChR ganglionic neuronal antibody remained elevated at .10.

Pet’r’s Ex. 7 at 23. Petitioner returned again to Dr. Sheets on May 9, 2018, and reported only one

syncopal episode since her last visit. Id. at 1421. She also had developed mild knee and ankle pain.

Id. Petitioner planned to return to school in the fall and Dr. Sheets planned a slow wean off her

prednisone. Id.

On July 25, 2018, Petitioner followed up with Dr. Sheets and noted that she had been off

prednisone for 10 days. Pet’r’s Ex. 3 at 1489. She had only one brief syncopal episode since her

last visit and experienced some fatigue and deceased appetite but denied headaches, rash,

numbness, weakness, and pain. Id. Dr. Sheets reported that she was “doing much better with

minimal symptoms that [he thought were] unrelated to her disease course and hopefully she will

not relapse.” Id. at 1492. He recommended only seeing Petitioner on an as-needed basis and noted

he would start her on prednisone again if her symptoms relapsed. Id.

Gastroparesis is “paralysis of the stomach, usually from damage to its nerve supply.” Gastroparesis,

12

DORLAND’S.

10

Petitioner returned for a follow-up visit with Dr. Nespeca on July 27, 2018. Pet’r’s Ex. 3

at 1524. Dr. Nespeca noted that Petitioner had declined his ultrasound recommendations and that

Petitioner planned to restart school and competitive tennis. Id. at 1524–25. His impression was

“[p]resumed autoimmune neurological disorder with wide array of peculiar symptoms . . . that

resolved on prednisone therapy . . . . Dad reported a theory that [Tdap] vaccine might be culprit in

producing elevation in this antibody titer.” Id. at 1525. Dr. Nespeca recommended a repeat of her

encephalopathy panel to check her antibody titers and proceed with next steps accordingly,

including the ultrasounds he previously recommended if her levels remained elevated. Id. Her

antibody panel came back on August 17, 2018, and revealed an elevated neuronal ganglionic

AChR antibody of 0.06. Pet’r’s Ex. 7 at 18.

On September 10, 2018, Petitioner returned to Dr. Sheets with complaints of several

episodes about one week after the start of school. Pet’r’s Ex. 3 at 1587. Her parents reported that

she experienced four-to-five episodes that day, including fatigue, dizziness, and a heavy feeling in

her arms and legs while sitting in the car on the way to school. Id. She also reported being “very

fatigued the last [two] weeks; she has also had some dizziness and nausea.” Id. Her spells had now

become daily and on September 9, 2018, Petitioner could not move her hands due to weakness. Id.

She also was now experiencing dizziness and shortness of breath while running in P.E. class, but

she had not experienced this problem while playing tennis. Id. Dr. Sheets ordered a repeat of her

encephalopathy panel and restarted her on 5mg of prednisone. Id. at 1590. He also noted

It is curious that she is flaring her symptoms with fatigue and dizziness as school

starts and now has spells that occur for minutes over a short period of time but that

she is not able to go to school because of this; the father still feels that this is due to

antibodies of the prior pertussis vaccine; I will see if she is still antibody positive

prior to starting very lose dose prednisone. I would however wonder if stress is the

trigger for these symptoms at this time.

Id.

Petitioner presented to Dr. Nespeca on October 1, 2018, for a second opinion of her new

occurrence of symptoms. Pet’r’s Ex. 3 at 1683. Dr. Nespeca noted her new symptoms included

hand, jaw, and eye paralysis. Id. at 1684. Her antibody titer had also increased to 0.11 nmol/L. Id.

“Her father remains convinced that the cause of the elevated antibody titer is that she received

immunizations [two-to-three] weeks before the initial symptom cluster began in mid[-]September

of 2017.” Id. “Today he specifically would like me to address his question of how we could remove

any intramuscular repository of the [Tdap] vaccine she had received since he perceives that as long

as that nidus remains present she will continue to make antibody producing her symptom cluster

(sic).” Id. Dr. Nespeca again recommended an ultrasound to screen for “disorders that have a more

compelling association with elevation of this antibody than do immunizations” and explained that

he did not know how to remove any residual component of the vaccine that remained. Id. at 1685.

He also advised Petitioner to continue her prednisone treatment. Id. Ultrasounds of Petitioner’s

kidney, bladder, and thyroid were completed on October 8, 2018, and did not reveal any

abnormalities. Id. at 1722. Petitioner presented again to Dr. Sheets on October 10, 2018, and noted

her symptoms had become less frequent since starting prednisone. Id. at 1772. He advised her to

continue home schooling and to decrease her prednisone as her symptoms improved. Id. Petitioner

11

also underwent an EEG at the order of Dr. Nespeca on November 5, 2018, which was normal. Id.

at 1872.

On December 12, 2018, Petitioner returned to Dr. Sheets for a follow-up. Pet’r’s Ex. 3 at

1880. She reported that her symptoms had resolved and she planned to return to school next

semester. Id. Dr. Sheets noted that “[t]iming of relapse with stress of school and improvement with

low dose prednisone does raise concern for somatic component of symptoms.” Id. He advised her

to continue low dose prednisone and plan for a taper in two-to-three months. Id. Dr. Sheets also

discussed the case with a social worker and the family and planned for a social worker to follow

up. Id.

Petitioner returned to Dr. Sheets on March 6, 2019, for a follow-up visit after her symptoms

began to flare again in the first week of January. Pet’r’s Ex. 8 at 12. Her parents reported that she

would have five spells in a row “lasting minutes with tremors and fainting and parallels.” Id. Her

parents reported that she was “very active” in December without any of these spells. Id. “[H]er

symptoms [were] more random with shaking tremors and [EEG] was normal but she would have

still random with weak or faint (sic). She has not been able to go to school.” Id. Dr. Sheets planned

to increase her prednisone to 10mg and repeat her encephalopathy panel. Id. at 15–16. He also

reported that she would be seeing a pediatric neurologist at Loma Linda University Children’s

Hospital. Id. at 16. Her panel revealed an elevated antibody titer of 0.11 nmol/L. Pet’r’s Ex. 7 at

10.

Petitioner then presented to Dr. Nespeca on March 9, 2019, where her father again repeated

his belief that her symptoms were related to the Tdap vaccine she received. Pet’r’s Ex. 8 at 21. Dr.

Nespeca ordered a cerebrospinal fluid (“CSF”) autoimmune panel and recommended Petitioner

see an encephalitis expert for a second opinion. Id. at 25. Petitioner’s CSF chemistry was normal

and a lumbar puncture performed on March 11, 2019, revealed no abnormalities. Id. at 29; Pet’r’s

Ex. 7 at 3.

On April 30, 2019, Petitioner presented to pediatric neurologist Gregory Aaen at Linda

Loma University Health. Pet’r’s Ex. 9 at 7. Petitioner’s parents repeated that Petitioner had

received the Tdap vaccine two weeks prior to the start of her symptoms. Id. at 10. Dr. Aaen also

noted that Petitioner’s “waxing and waning of symptoms may appear to correlate with antibody

titers.” Id. After her examination, Dr. Aaen noted that he was “unable to identify a unifying

neurological diagnosis for all of her myriad complaints.” Id. at 12. He also noted that the fact one

of her fainting episodes was “captured on video EEG and the EEG showed a normal awake

background means that that specific event was psychogenic in etiology.” Id. He also noted that he

felt “many of her complaints are psychogenic in nature.” Id. However, he did acknowledge that

her antibody titers were mediating some of her symptoms due to her improvement on steroids. Id.

He advised a trial dose of Cellcept and that Petitioner seek treatment for conversion disorder. Id.

at 13. Petitioner returned to Dr. Sheets on June 5, 2019, and reported feeling “much better over the

last [five] days with normal personality and no neurologic symptoms” after starting 500mg of

Cellcept one month prior. Pet’r’s Ex. 8 at 31. Dr. Sheets maintained her medication dosage and

requested to see her again in two months. Id. at 35.

Petitioner followed up with Dr. Nespeca on June 28, 2019, and reported having no

“attacks” since beginning Cellcept, though she did experience episodes of fatigue and dizziness.

12

Pet’r’s Ex. 8 at 39. Petitioner was homeschooled during this time but was planning to start high

school after the summer. Id. Petitioner’s father stated that he was “upset with Dr. Aaen when he

mentioned . . . the possibility of conversion disorder and said he never wanted to see that doctor

again.” Id. Dr. Nespeca also noted that the Mayo Clinic was unable to assay for the AChR antibody

in Petitioner’s CSF samples and that such a result would have greatly informed his diagnosis. Id.

at 41. He deferred to Dr. Sheets with regard to Petitioner’s continued course of medication. Id.

On July 25, 2019, Petitioner returned to Dr. Sheets for her two-month follow-up and

reported that she had not experienced any symptoms aside from mild dizziness. Pet’r’s Ex. 8 at 44.

Petitioner was due to start high school in two weeks and planned to resume tennis. Id. Dr. Sheets

noted that her June labs were normal and recommended she continue her prednisone and Cellcept,

and to call if the stress of school caused her symptoms to flare again. Id. at 47.

On September 12, 2019, Petitioner returned to Dr. Nespeca with complaints of new

episodes of symptoms over the past two weeks. Pet’r’s Ex. 8 at 52. Petitioner reported that she had

been doing “very well without relapse” until two weeks ago, when she began to experience “some

brief episodes of vertigo and nearly lost consciousness.” Id. She had not experienced any dizziness,

weakness, or parestheias, and her parents expressed a concern this was a side effect of the Cellcept.

Id. Dr. Nespeca noted her symptoms could be “related to her autoimmune encephalopathy or could

be anxiety related to the starting of school.” Id. at 56. He increased her dosage of Cellcept and

advised her to follow up in two months. Id.

Petitioner presented to Dr. Sheets again on November 7, 2019, with complaints of nausea

and new attacks that came as “jolts and altered state of consciousness episodes.” Pet’r’s Ex. 11 at

8. Petitioner had returned to homeschooling and “was much better for one week prior to about

[five] days ago.” Id. Dr. Sheets recommended stopping the Cellcept as he did not “think it [was]

helping and [] add[ed] Prilosec 20mg” due to the nausea associated with her prednisone. Id. at 11.

He also indicated he would speak to a neuroimmunologist at the Mayo Clinic “to see if they have

been getting reports of false positive antibody tests” and consult next steps. Id.

On November 18, 2019, Petitioner presented to Dr. Nespeca following a video EEG “to

capture what sounded like myoclonic jerks and collapsing episodes.” Pet’r’s Ex. 11 at 45. The

video EEG recorded two episodes of collapsing, one episode of jerks, and one episode of trembling

hands. Id. “None of these had any associated electroencephalographic seizure pattern. She

remained aware during the collapse events and recalled what people were saying though she could

not respond.” Id. at 45–46. A repeat encephalopathy panel showed slightly less elevated AChR

antibody levels of 0.06 nmol/L and high dose solumedrol and prednisone did not help. Id. at 46.

She now reported collapsing five times per day. Id. Dr. Nespeca also noted his reluctance to order

stronger treatment regimens due to the risk of side effects and that in his view it was “possible that

her symptoms may in the future disappear as [he has] seen happen in other autoimmune disorders

of neurological type even with no therapy.” Id. at 48. Dr. Nespeca ultimately concluded that further

EEG studies were unnecessary and agreed to stop both Cellcept and prednisone. Id. He also noted

that Petitioner’s HLA antibody test was negative and that she did not have the sleep stage

characteristics for narcolepsy. Id. He asked her parents to provide him with an update in two

months and to return to him in six months. Id. at 49.

13

Petitioner returned to Dr. Sheets on March 5, 2020, and reported doing well for a period of

weeks off medication “but then ha[d] short episodes lasting seconds off and on during the day but

[could] have no symptoms during the day.” Pet’r’s Ex. 59 at 55. Her symptoms included shaking

spells, eye fluttering, and alteration of consciousness, with up to 12 spells per day. Id. She reported

that Dr. Nespeca told her she could return to school if she could go three weeks without an episode,

but she had only been able to be asymptomatic for two weeks. Id. Dr. Sheets noted that the family

planned to have Petitioner see a psychotherapist for depression. Id. at 58. He also noted that the

neuroimmunologist at the Mayo Clinic agreed that a more aggressive treatment regimen was not

warranted and scheduled a follow-up for July. Id.

On April 20, 2020, Petitioner returned to Dr. Nespeca and reported that her symptoms had

been more frequent over the last two weeks. Pet’r’s Ex. 59 at 103. He noted that her “symptoms

of paralysis, burning sensation of knees and ankles, chest pain and breathing problems, and ‘jaw

locking up’” had resolved since her initial presentation in 2018, but she continued to experience

episodes of dizziness and loss of consciousness. Id. at 104. Petitioner’s father requested another

AChR antibody panel, but Dr. Nespeca declined until later in the fall. Id. Dr. Nespeca also

explained that he did not believe any further pharmacotherapy treatments would be helpful and

asked to reexamine Petitioner again in six months. Id. at 105.

Petitioner completed a behavioral health assessment on July 27, 2020, with Child Welfare

Services at Rady Central Clinic. Pet’r’s Ex. 58 at 7. The social worker reported that Petitioner was

“presenting with symptoms of depression and anxiety following exacerbated (sic) by a medical

condition. Specifically, at 12.5 years old, . . . [Petitioner] began experiencing physical symptoms

. . . consistent with Autoimmune Encephalomyelitis following Tdap vaccine, per client.” Id. at 8.

“Client reported feeling scared before diagnosis, but since then she feels sad and anxious all the

time . . . onset of depressive and anxious symptoms was 13.5 years old.” Id. The social worker

reported that Petitioner no longer had an interest in piano or tennis and had a “depressed mood on

most days, excessive worries and rumination about past and future events, and social isolation.”

Id. The social worker further reported that Petitioner’s “symptoms of depression and anxiety . . .

appear related to her medical condition, and will be addressed using cognitive-behavioral therapy

skills and mindfulness in treatment.” Id. at 15. Petitioner continued psychotherapy until her

discharge on September 17, 2020, where her therapist noted she was “engaging in pleasurable

activities with friends on a daily basis, and reporting minimal depressive and anxiety symptoms

that do not cause impairment in daily functioning.” Pet’r’s Ex. 70 at 47.

Petitioner returned to Dr. Sheets on August 12, 2020, and reported she was only able to go

a few days without an episode. Pet’r’s Ex. 59 at 146. Dr. Sheets suggested that Petitioner start

Rituxan to treat her symptoms and to follow up in four months. Id. at 149.

On November 4, 2020, Petitioner presented to ophthalmologist Henry O’Halloran with

complaints of headache and visual disturbance. Pet’r’s Ex. 59 at 194. She reported that she had

experienced dizziness, neck pain, and ear ringing for two weeks, as well as horizontal diplopia. Id.

Dr. O’Halloran ordered a computed tomography (“CT”) scan of her head to investigate. Id. at 196.

The next day, November 5, 2020, Petitioner followed up with Dr. Nespeca and reported

her diplopia and headaches, which occur “almost every day.” Pet’r’s Ex. 59 at 240. Dr. Nespeca

recommended Petitioner remove her braces so an MRI could be performed, as it would be “much

14

more likely to bear fruit than a head CT scan.” Id. at 242. He also ordered a repeat of Petitioner’s

encephalopathy panel, which showed a mildly elevated AChR level of 0.07 nmol/L. Id.; Pet’r’s

Ex. 60 at 3. Petitioner underwent an MRI of her brain on November 19, 2020, which was “within

normal limits, stable when compared to prior exam.” Pet’r’s Ex. 59 at 365.

Petitioner followed up with Dr. Sheets on December 2, 2020, who noted that “her

symptoms have continued without any significant change.” Pet’r’s Ex. 59 at 446. Dr. Sheets noted

his agreement with Dr. Nespeca to start IVIG treatment and noted a new pediatric inflammatory

brain disease clinic that may be helpful in Petitioner’s case. Id. at 450. The following day, on

December 3, 2020, Petitioner returned to Dr. Nespeca, who noted he had reviewed a “case of an

adult with very high titer antibody to nicotinic receptor who had a 20-year history of severe

hypotension, gastrointestinal dysmotility, sicca syndrome, and severe urinary and ejaculatory

dysfunction.” Id. at 496. He noted that other cases of autonomic failure had “similar but milder

symptoms.” Id. Petitioner was still attending online classes but still could only do limited exercise.

Id. Dr. Nespeca referred to Petitioner’s impression as a “mysterious disabling panoply of

symptoms . . . and which is associated with consistently elevated serum antibody to alpha 3

ganglionic nicotinic Acetylcholine receptor and mildly elevated sed rate.” Id. at 497. He noted her

working diagnosis to be “autoimmune neurologic disorder on broad spectrum of encephalomyelitis

(sic).” Dr. Nespeca noted that Petitioner did “not have typical symptoms or signs of autonomic

failure which [have] been associated with elevation of this antibody,” but still opined that “this

could be playing a role in her symptomatology now and in the past.” Id. at 498. He also expressed

his skepticism that “this is a psychosomatic problem for her since she has seemed to [him] over

the 2.5 years [he had] seen her to be a kid motivated to get back to normal life.” Id. He also noted

that she had “no features of any clear DMS V diagnosis” during an October 2019 psychiatric

consultation. Id. Dr. Nespeca ordered Petitioner to begin IVIG therapy and requested her to follow

up in three months. Id. Petitioner and her family declined to pursue IVIG therapy. Pet’r’s Ex. 88

at 6.

On August 25, 2021, Petitioner returned to Dr. Sheets and continued to describe daily

episodes of weakness and loss of consciousness. Pet’r’s Ex. 67 at 411. Petitioner’s father requested

she start plasmaphereses “with the idea that it would scrub the antibody associated with her

disease,” which he expressed was due to the Tdap vaccine. Id. Dr. Sheets explained the “significant

risks” of plasmaphereses and that there was “no evidence in literature it would help her disease

and would not necessarily be associated with a decrease in her antibody vs IVIG as a potential

therapy option.” Id. at 411–12. He instructed Petitioner to follow up with neurology and follow up

with himself as needed. Id. at 415.

Petitioner presented to Dr. Nespeca again on November 18, 2021, who noted that Petitioner

had declined to pursue IVIG therapy because she “hoped things would improve on its own.” Pet’r’s

Ex. 88 at 6. Petitioner reported she was experiencing episodes as frequently as twice per week and

also that “a friend told her that her doctors should include atonic seizures as a possible cause of

her episodes.” Id. at 7. However, Dr. Nespeca noted that there was no associated seizure pattern

on Petitioner’s video EEG. Id. Dr. Nespeca’s impression was that Petitioner had improved despite

a lack of treatment since her last visit 11 months ago and recommended she follow up as needed.

Id. at 9.

15

On April 6, 2023, Petitioner returned to Dr. Sheets with continued complaints of dizziness

and loss of consciousness episodes. Pet’r’s Ex. 88 at 31. Dr. Sheets opined that he “did not think

that her symptoms were consistent with a conversion reaction or other psychosomatic disease

given her course” and her antibody titers. Id. He also noted that inpatient psychiatry “did not feel

this had a emotional basis.” Id. Dr. Sheets noted that Petitioner had “gradually improved . . . but

did have several episodes last fall every other day for weeks” and was unable to drive due to the

spells.” Id. at 30–31. He noted that Petitioner now complained of redness in her cheeks and

“intermittent warm and cold hands” but that she had no other symptoms to suggest systemic lupus

erythematosus (“SLE”). Id. at 31. Dr. Sheets ordered labs to check for SLE and instructed

Petitioner to follow up with dermatology. Id. at 34. He also recommended Petitioner see

neuroimmunologist Jennifer Grave for another opinion. Id.

No other relevant medical records were filed.

III. Affidavit of Petitioner’s Mother, Brenda Antoniades

On June 4, 2020, Petitioner’s mother, Brenda Antoniades, filed a brief affidavit. Pet’r’s Ex.

13. Ms. Antoniades stated that prior to Petitioner’s August 2017 Tdap vaccination she was

“extremely active and healthy” and an active tennis player. Id. at ¶ 1. She also stated she was an

honors student who enjoyed school and was in the Girl Scouts. Id. at ¶¶ 3–4. Petitioner’s mother

stated that “[w]ithin a short time after receiving the Tdap vaccine, [Petitioner] began to complain

about unexplained pain in her legs and paresthesia.” Id. at ¶ 6. “Shortly thereafter [ Petitioner] was

unable to stand and walk on her own,” with the condition progressing to her “hands, fingers, face,

jaw, and mouth.” Id. Because of these symptoms, Ms. Antoniades stated Petitioner was unable to

attend school and placed on an independent study program. Id. at ¶ 7. She stated that in October

2017 Petitioner began to “lose consciousness and go limp” several times per day. Id. at ¶ 8. Due

to the frequency of her episodes, Ms. Antoniades reported that Petitioner was unable to attend

online classes with an attendance requirement, and instead had to use a more flexible schedule

program. Id. at ¶ 9. She stated that after several months Petitioner “was diagnosed with

autoimmune encephalomyelitis/encephalitis/encephalopathy based on Mayo Clinic testing

results.” Id. at ¶ 10. She noted that Petitioner was off of medication due to a lack of progress. Id.

at ¶ 11.

IV. Experts

A. Expert Qualifications

1. Petitioner’s Expert, Dr. Mahbubul Huq, M.B.B.S., Ph.D.

Dr. Huq is a board-certified pediatric neurologist and clinical geneticist at Children’s

Hospital of Michigan and a Professor of Pediatrics at Central Michigan University. Pet’r’s Ex. 14

at 1. He received his M.B.B.S. from Dhaka University Medical College in Bangladesh and his

Ph.D. in Philosophy from Tokushima University. Pet’r’s Ex. 15 at 1. He completed his internship

at Dhaka University and his residencies in pediatrics and neurology at Wayne State University. Id.

at 1–2. He also completed fellowships in medical genetics and pediatric neurology at Wayne State

University, Baylor College of Medicine, and the University of British Columbia. Id. at 1. Dr. Huq

16

has “treated many patients with autoimmune encephalitis in both inpatient and outpatient settings.”

Pet’r’s Ex. 14 at 1.

2. Respondent’s Expert, Dr. Eric Lancaster, M.D., Ph.D.

Dr. Lancaster is an “academic neurologist with expertise in antibody-mediated neurologic

disorders” and is a board-certified neurologist. Resp’t’s Ex. B at 1. He received his M.D. and Ph.D.

in neuroscience from the University of Maryland. Id. He completed his internship, neurology

residency, and fellowships in neuromuscular research at the Hospital of the University of

Pennsylvania, where he currently serves as an Assistant Professor of Neurology. Id. Dr. Lancaster

has published several articles relating to antibody-mediated neurological disorders, to include

encephalitis and peripheral nerve hyperexcitability. Id. His lab work is “focused on detection of

neuronal autoantibodies, particularly in the context of autoimmune encephalitis and paraneoplastic

disorder.” Resp’t’s Ex. A at 1. His clinical practice is “focused on autoimmune neurological

diseases.” Id.

B. Expert Reports and Testimony

1. Dr. Huq’s Initial Report 13

Dr. Huq began his analysis by stating Petitioner suffered from “[Tdap] vaccination induced

autoimmune encephalopathy associated with elevated alpha 3 ganglionic nicotinic receptor

antibody leading to various sensory, autonomic and psychiatric symptoms as well as unexplained

spells.” Pet’r’s Ex. 14 at 2. He explained that autoimmune encephalopathies are “more complex

disorders characterized by subacute development in days to weeks . . . [and] may also present in

an atypical way with isolated features or variable symptoms.” Id. (citing Pet’r’s Ex. 33; 14 Pet’r’s

Ex. 34; 15 Pet’r’s Ex. 38; 16 Pet’r’s Ex. 52; 17 Pet’r’s Ex. 53). 18 Autoimmune encephalopathies may

be “associated with antibodies against cell surface proteins . . . [or] antibodies binding intracellular

antigens.” Id. He explained that such antibodies are “likely markers of a T-cell mediated process”

which are treated with immunosuppressant therapies. Id. at 2–3. He also opined that “[i]t is almost

certain that many other forms of autoimmune encephalopathy associated with other antibodies or

immune mechanisms remain to be identified.” Id. at 3.

Turning to Petitioner, Dr. Huq opined that her clinical course was “consistent with

autoimmune encephalopathy that has been described in patients with ganglionic [AChR]

13

Throughout both his reports and his testimony Dr. Huq uses the terms “autoimmune encephalopathy”

and “autoimmune encephalitis” interchangeably. Because these are distinct conditions and because I

cannot ascertain which Dr. Huq is intending to refer to at a given moment, I will refer to whichever

condition Dr. Huq has listed in a given instance.

14

Eoin P. Flanagan et al., Autoimmune Dementia and Encephalopathy, 133 HANDBOOK CLINICAL

NEUROLOGY 247 (2016).

15

F. Graus et al., Recommended Diagnostic Criteria for Paraneoplastic Neurological Syndromes, 75 J.

NEUROLOGY NEUROSURGERY PSYCHIATRY 1135 (2004).

16

Matthew S. Kayser et al., Psychiatric Manifestations of Paraneoplastic Disorders, 167 AM. J.

PSYCHIATRY 1039 2010).

17

Steven Vernino et al., Autoimmune Encephalopathies, 13 THE NEUROLOGIST 140 (2007).

18

Angela Vincent et al., The Growing Recognition of Immunotherapy-Responsive Seizure Disorders With

Autoantibodies to Specific Neuronal Proteins, 23 CURRENT OP. NEUROLOGY 144 (2010).

17

antibody.” Pet’r’s Ex. 14 at 3 (citing Pet’r’s Ex. 40). 19 McKeon et al. was a Mayo Clinic study

analyzing the presence of AChR antibodies as a potential marker for neurologic autoimmunity and

cancer. Pet’r’s Ex. 40 at 1. The authors explained that the ɑ3-AChR autoantibody “causes

autoimmune dysautonomia[20] that is either subacute or insidious in onset” and that a “direct

relationship between antibody titer and severity of dysautonomia occurs in both experimental

animals and patients.” Id. at 2. Patients with high levels of the ɑ3-AChR antibody (>1.0 nmol/L)

often developed “profound pandysautonomia,” while patients with lower levels of ɑ3-AChR

antibody developed limited dysautonomia, to include “[POTS] or gastroparesis.” The authors

analyzed 15,000 patients, with 1% testing seropositive for AChR antibodies. Id. at 1. Of the

positive results (greater than 0.02 nmol/L), the median result was 0.12 nmol/L and the median age

was 65 years. Id. Twelve patients had high antibody values (“ABV”) (>1.0 nmol/L), 85 patients

had medium ABV (0.10–0.99 nmol/L), and 58 patients had low ABV (0.03–0.09 nmol/L). Id. at

4–5. Eleven of the high ABV patients (92%) were considered to have a neurologic disorder with

an autoimmune pathogenesis and 10 (84%) had dysautonomia. Id. at 4.

Patients with medium ABV had a more diverse group of symptoms, with the predominant

presentation being peripheral neuropathy (36%). Pet’r’s Ex. 40 at 4. Other presentations included

dysautonomia (20%), limited dysautonomia (16%), coexisting sensorimotor neuropathy (7%), and

neurophysiological evidence of a distal small fiber neuropathy (6%). Eleven patients (13%) also

had “acute or subacute onset of cognitive and psychiatric symptoms and signs such as depression,

psychosis, executive dysfunction, personality change, and amnestic mild cognitive impairment.”

Id. Only one patient had inflammatory CFS markers, which improved following intravenous

steroids. Id. at 5. Ultimate diagnoses included non-immune-mediated neurological disorder (13%),

a nonneurological disorder (6%), MS (3.5%), and single cases of stiffman syndrome and

myasthenia gravis. Id. Patients with a low ABV had a median value of 0.06 nmol/L, and 54% had

either a non-immune-mediated neurological disorder or a nonneurological disorder. Id. Peripheral

neuropathy was the predominant neurological manifestation (22%), followed by dysautonomia

(10%). Id. Three patients were identified with subacute neuropsychiatric presentations, to include

a case of limbic encephalitis with coexisting ANNA-1 autoantibody and two with subacute

memory loss and depression. Id. With regard to objective testing and imaging, 63% of tested

patients had CSF abnormalities and only four out of 80 had abnormal MRI imaging. Id. Of the 16

patients who received immunotherapy, 12 showed improvement. Id.

McKeon et al. alsoobserved that “clinical suspicion for an autoimmune etiology as the basis

of the neurological presentation was directly proportional to the antibody titer.” Pet’r’s Ex. 40 at

7. Specifically, the authors highlighted that of patients with low ɑ3-AChR ABV values, “54% had

non-specific symptoms without a neurological diagnosis.” Id. They highlighted the presence of

dysautonomia amongst seropositive patients, noting that their laboratory had previously observed

14.6% of POTS patients registered low ɑ3-AChR ABV. Id. “Peripheral neuropathy was the most

common accompaniment of ɑ3-AChR [antibodies], document[ed] in 28% of patients.” Id. CNS

manifestations occurred in 20% of patients, with most of these patients experiencing

neuropsychiatric manifestations or extrapyramidal disorders. Id. Dr. Huq opined that these

findings were consistent with Petitioner’s presentation given her elevated ɑ3-AChR ABV. Pet’r’s

Ex. 14 at 3.

19

Andrew McKeon et al., Ganglionic Acetylcholine Receptor Autoantibody: Oncological, Neurological,

and Serological Accompaniments, 66 ARCHIVES NEUROLOGY 735 (2009).

20

Dysautonomia is the “malfunction of the autonomic nervous system.” Dysautonomia, DORLAND’S.

18

Dr. Huq also noted that Petitioner’s treating physicians, Dr. Sheets and Dr. Nespeca,

diagnosed her with autoimmune encephalopathy. Pet’r’s Ex. 14 at 3. “Although some of

[Petitioner’s] treating physicians have raised the possibility of a conversion disorder, it is important

to recognize that conversion or somatoform disorders are not malingering but are brain disorders

with unknown pathophysiology.” Id. (citing Pet’r’s Ex. 18; 21 Pet’r’s Ex. 19). 22 However, from his

review of Petitioner’s medical record, Dr. Huq “did not identify a psychosocial cause for her

symptoms.” Id. He also highlighted Dr. Nespeca’s note from Petitioner’s initial presentation to

him on March 8, 2018, where he opined that Petitioner did not seem to fit the “typical profile” of

a conversion disorder patient. Id. (citing Pet’r’s Ex. 3 at 1061). He further argued that Petitioner’s

lack of response to steroids was not indicative of conversion disorder, as Petitioner “initially

responded to prednisone,” and her later limited responses were “not unusual as not everyone with

autoimmune encephalopathy and elevated [ɑ3-AChR] responds to immunotherapy.” Id. (citing

Pet’r’s Ex. 40).

Dr. Huq then turned to describing ɑ3-AChR as “a neuronal nicotinic neurotransmitter

receptor subunit present in peripheral sympathetic ganglion and various brain regions.” Pet’r’s Ex.

14 at 3. He cited to Yeh et al., 23 which showed the presence of ɑ3-AChR in rat brains, and claimed

that other studies had found patients with elevated ɑ3-AChR presented with “autoimmune

ganglionopathy or neuropathy but an overrepresentation of psychiatric and sensory symptoms.”

Id. at 4 (citing Pet’r’s Ex. 56; Pet’r’s Ex. 40; Pet’r’s Ex. 42). 24 Given that patients with low ɑ3-

AChR ABV had more psychiatric and neurologic disorders than dysautonomia, Dr. Huq opined

that this could be due to the “[b]inding of the antibody to the brain regions important in conversion

or somatoform disorders or co-occurrence of other antibodies or autoimmune T-cells targeted

against antigens located in those regions.” Id. (citing Pet’r’s Ex. 16). 25 Baker et al. was a case study

reporting the case of a 47-year-old woman with an ɑ3-AChR ABV of 2060 pmol/L (2.06 nmol/L)

who presented with dysautonomia and later developed encephalitis visible via MRI, but had

normal cognition. Pet’r’s Ex. 16 at 1–3. The authors noted the “pathogenic” nature of ɑ3-AChR

antibodies that often reside in patients with subacute pan-autonomic failure, but could not

determine whether these antibodies were the cause of this patient’s encephalitis. Id. at 3.

Given the detection of antibody binding to both CNS ɑ4 and ɑ7 nAChR, it is

tempting to speculate that these may have precipitated the symptoms of brain stem

encephalitis. However, serum testing was performed on her initial sample and we

therefore cannot establish that these antibodies were present at the time of her

encephalopathy.

21

Markus Boeckle et al., Neural Correlates of Conversion Disorder: Overview and Meta-Analysis of

Neuroimaging Studies on Motor Conversion Disorder, 16 BMC PSYCHIATRY 195 (2016).

22

Marcus Boeckle et al., Neural Correlates of Somatoform Disorders From a Meta-Analytic Perspective

on Neuroimaging Studies, 11 NEUROIMAGE: CLINICAL 606 (2016).

23

Jenny Yeh et al., Neuronal Nicotinic Acetylcholine Receptor ɑ3 Subunit Protein in Rat Brain and

Sympathetic Ganglion Measured Using a Subunit-Specific Antibody: Regional and Ontogenic Expression,

77 J. NEUROCHEMISTRY 336 (2001).

24

Petitioner originally did not file an article for Exhibit 42 and instead filed a single page for this exhibit

which read “Petitioner has requested a copy of this article and will file upon receipt.” See Pet’r’s Ex. 42,

ECF No. 31-9. Petitioner later filed only the abstract of this article. See Pet’r’s Ex. 42, ECF No. 75.

25

S.K. Baker et al., Autoimmune Autonomic Ganglionopathy With Late-Onset Encephalopathy, 146

AUTONOMIC NEUROSCIENCE: BASIC & CLINICAL 29 (2009).

19

Id. The authors also noted the depletion of ɑ4 and ɑ7 nAChR in Alzheimer’s patients, “suggesting

that targeted autoimmunity against these receptors may impair neurocognitive function.” Id. Dr.

Huq further suggested that Petitioner’s ɑ3-AChR may instead be indicative of “autoimmunity

rather than having a direct pathogenic role in producing” all of her symptoms. Pet’r’s Ex. 14 at 4.

According to Dr. Huq, the Tdap vaccine “stands out as the only identified environmental

factor to trigger her autoimmune encephalopathy.” Pet’r’s Ex. 14 at 4. He acknowledged

Petitioner’s development of a febrile illness three weeks after vaccination, but stated that whether

such an infection “represents the onset of an autoimmune condition or represents a viral infection

is not known,” though infections have been linked to autoimmune encephalitis. Id. (citing Pet’r’s

Ex. 51). 26 However, he then stated that “[v]accines may trigger autoimmunity using similar

mechanisms and in fact, Tdap vaccine and a viral infection may have acted synergistically to

produce the autoimmune encephalopathy.” Id. “Although there is no previous report of association

of TdaP vaccine with autoimmune encephalopathy with elevated [ɑ3-AChR] antibody, TdaP has

been associated with other autoimmune conditions including immune mediated encephalitis.” Id.

Dr. Huq then proceeded to cite to examples of other vaccines causing unrelated autoimmune

diseases 27 and noted that Pellegrino et al. 28 found Tdap to be the fourth-most commonly associated

vaccine with the development of acute disseminated encephalomyelitis (“ADEM”) in the VAERS

database. Id. (citing Pet’r’s Ex. 45). He also cited to Hofmann et al., 29 a case report identifying the

development of anti-NMDA receptor encephalitis following Tdap vaccination. Id. at 5 (citing

Pet’r’s Ex. 36).

Turning to this theory of causation, Dr. Huq first noted the importance of genetic

predisposition in the development of autoimmune conditions. Pet’r’s Ex. 14 at 5. He then provided

seven potential mechanisms by which the Tdap vaccine could trigger autoimmunity: “cytokine

production, anti-idiotype network, expression of human HLA, molecular mimicry, bystander

action, epitope spreading and polyclonal activation of B cell.” Id. (citing Pet’r’s Ex. 30).30

However, of these mechanisms, he opined that “molecular mimicry between tetanus toxoid and

human beta-2glycoportein I is a likely mechanism, but . . . [a] variety of other mechanisms may

be involved.” Id. Dr. Huq then went on to explain the role of molecular mimicry in the development

of antiphospholipid syndrome (“APS”) following tetanus toxoid immunization in mice. Id. (citing

Pet’r’s Ex. 31). 31 Due to three-dimensional similarity and short-sequence homology to human beta

2-glycoprotein I and laminin proteins, “[t]his structural similarity favors the role of tetanus toxoid

26

Arun Venkatesan & David Benavides, Autoimmune Encephalitis and Its Relation to Infection, 15

CURRENT NEUROLOGY NEUROSCIENCE REP. 4 (2015).

27

These vaccines include those for yellow fever, swine flu, hepatitis B, hemophilus, flu, human papilloma

virus, and hepatitis A. Dr. Huq does not explain how these studies showing a potential association

between these vaccines and autoimmunity pertains to the development of autoimmune encephalopathy via

the Tdap vaccine.

28

Paolo Pellegrino et al., Acute Disseminated Encephalomyelitis Onset: Evaluation Based on Vaccine

Adverse Events Reporting Systems, 8 PLOS ONE 77766 (2013).

29

Caroline Hofmann et al., Anti-NMDA Receptor Encephalitis After TdaP-IPV Booster Vaccination:

Cause or Coincidence?, 258 J. Neurology 500 (2011).

30

M. De Martino et al., Vaccines and Autoimmunity, 26 INT’L J. IMMUNOPATHOLOGY &

PHARMACOLOGY 283 (2013).

31

L. Dimitrijevic et al., Vaccine Model of Antiphospholipid Syndrome Induced by Tetanus Vaccine, 21

LUPUS 195 (2012).

20

in autoimmunity, with molecular mimicry as the mechanism.” Id. (citing Pet’r’s Ex. 49). 32 He

explained that tetanus toxoid produced anti-beta 2-glycoprotein I antibodies, which “bind to the

central nervous system, suggesting it may have a direct role in [CNS] symptoms of [APS].” Id. He

then opined that this “may also be relevant in [Petitioner’s] case.” Id.

Turning to the logical sequence of cause and effect, Dr. Huq largely repeated verbatim his

opinion as to Petitioner’s diagnosis and his earlier opinions regarding potential causation. See

Pet’r’s Ex. 14 at 6. He added that while vaccines may trigger autoimmunity via similar mechanisms

as infections, the “timing ([three] weeks between Tdap and encephalopathy versus just days

between febrile illness and encephalopathy symptoms) favors vaccination as the trigger.” Id.

On the issue of timing specifically, Dr. Huq noted that Petitioner had no symptoms prior

to vaccination and that a study of the kinetics of the Tdap vaccination in women “showed that IgG

and IgA levels peaked by day 14.” Pet’r’s Ex. 14 at 6 (citing Pet’r’s Ex. 35). 33 Dr. Huq also

extrapolated a window of acceptable timing from other immune-mediated conditions following

infection and immunization, pointing to the onset of ADEM (“a few days to few weeks after an

infection or immunization”), GBS following influenza vaccination (“a few days to weeks after

vaccination”), and ADEM and multiple sclerosis following HPV vaccination (“within a month

after vaccination”). Id. (citing Pet’r’s Ex. 45; Pet’r’s Ex. 44; 34 Pet’r’s Ex. 20; 35 Pet’r’s Ex. 55).36

“Thus, the timing is consistent with an autoimmune encephalopathy triggered by Tdap

vaccination.” Id.

2. Dr. Lancaster’s Initial Report

Dr. Lancaster began his analysis by discussing the role of AChR antibodies and their

clinical associations. Resp’t’s Ex. A at 6. He explained that “[a]cetylcholine is a neurotransmitter

that is commonly present in the central and peripheral nervous systems” and is critical to the

connection between nerve and muscle tissue, as well as the regulation of the autonomic nervous

system. Id. He noted that there are multiple different types of AChRs throughout the nervous

system, “each with a particular localization and function.” Id. One of these receptors is the

ganglionic AChR (“gAChR”), which primarily uses the ɑ3-AChR subunit and controls blood

pressure, urination, heart rate, and other autonomic functions. Id. at 7.

Dr. Lancaster also noted that autoimmunity to other AChR receptors found in

neuromuscular junctions result in the development of myasthenia gravis. Resp’t’s Ex. A at 7. With

32

Marijana Stojanovic et al., The Context of Tetanus Toxoid Application Influences the Outcome of

Antigen-Specific and Self-Directed Humoral Immune Response, 53 MICROBIOLOGY IMMUNOLOGY 89

(2009).

33

B.A. Halperin et al., Kinetics of the Antibody Response to a Tetanus-Diphtheria-Acellular Pertussis

Vaccine in Women of Childbearing Age and Postpartum Women, 53 CLINICAL INFECTIOUS DISEASES 885

(2011).

34

Yong-Shik Park et al., Clinical Features of Post-Vaccination Guillain-Barré Syndrome (GBS) in

Korea, 32 J. KOREAN MED. SCI. 1154 (2017).

35

R. Bomprezzi & B. Wildemann, Acute Disseminated Encephalomyelitis Following Vaccination Against

Human Papilloma Virus, 74 NEUROLOGY 864 (2010).

36

B. Wildemann et al., Acute Disseminated Encephalomyelitis Following Vaccination Against Human

Papilloma Virus, 72 NEUROLOGY 2132 (2009).

21

this in mind, Vernino & Lennon 37 developed an assay to detect gAChR antibodies and found that

approximately 50% of patients with subacute autoimmune autonomic neuropathy (“AAN”) tested

positive for gAChR binding antibodies. Id. (citing Resp’t’s Ex. A, Tab 1). The authors noted that

these antibodies were not found in healthy control subjects and that “[a]mong patients with

acquired dysautonomia, seropositivity is highly associated with the diagnosis of idiopathic or

paraneoplastic autonomic neuropathy.” Resp’t’s Ex. A, Tab 1 at 2. They also noted that while the

majority of patients expressed high ABV (>0.2 nmol/L), about 10% of patients with limited AAN

had levels between 0.05 and 0.20 nmol/L and presented with such as gastrointestinal dysmotility,

diabetic autonomic neuropathy, and POTS. Id. at 2–3. Dr. Lancaster also cited to McKeon et al.

and argued “results below 0.10 units are thought to generally not be significant, and could be found

in persons with diverse problems, most of which are not clearly autoimmune nor autonomic.”

Resp’t’s Ex. A at 7 (citing Pet’r’s Ex. 40). He then referenced the various symptoms discussed by

McKeon et al. and argued the paper supported the proposition that “the antibodies most likely do

not cause most of these problems.” Id. The antibodies, according to Dr. Lancaster, “do not target

the type of receptors expressed to a significant degree in the brain. Rather, this may reflect the

types of patients referred for paraneoplastic testing in general.” Id.

The antibodies themselves are only significant in the context of autonomic failure,

according to Dr. Lancaster, and are otherwise “not useful for diagnosing human disease.” Resp’t’s

Ex. A at 8. He argued that “low titer results do not have a clear diagnostic significance,” and that

any such association of non-autonomic symptoms with medium and low titer levels was “undercut

by the incredibly strong association of high titer antibodies with autonomic failure.” Id. He

explained that if such lower levels could cause encephalitis, he would expect to see encephalitis in

patients with higher titers, but instead these patients had fewer instances of encephalitis. Id. “The

McKeon [et al.] paper therefore strongly favors the idea that gAChR antibodies are associated with

AAN but that the test is imperfect and lower titer results or results associated with other phenotypes

should be regarded with suspicion. Id. In his private practice, Dr. Lancaster has treated about 20

patients with positive gAChR testing, which he claimed is “almost always a ‘junk’ result, a false

positive,” and typically below 1.00 nmol/L. Id. He asserted that these patients did not have

autonomic failure or evidence of autoimmune neurologic disorders, and thus “[l]ow titer results

should therefore be regarded with suspicion as a mechanism of disease in general, and especially

outside the context of autonomic failure.” Id.

In support of this assertion, Dr. Lancaster cited to Ebright et al., 38 which conducted a

review of the Mayo Clinic’s paraneoplastic autoantibody testing to determine the rate of false

positives, including those for gAChR. Resp’t’s Ex. A, Tab 3 at 1. The authors defined four

categories a test result could fall into: a true positive, a false positive, a true negative, and a false

negative. Id. at 2. A true positive was defined as any ABV higher than the normal range with no

other clinical explanation and the satisfaction of at least one of the following: “the syndrome is

known to be associated with the antibody, clinical improvement with immunosuppression or tumor

treatment, or a new malignancy was found.” Id. If none of the criteria were met or if another

explanation was found, the result was deemed a false positive. Id. To determine if the criteria were

met, the authors “performed detailed medical chart analysis” of each patient following their

37

Steven Vernino & Vanda Lennon, Neuronal Ganglionic Acetylcholine Receptor Autoimmunity, 998

ANN. N.Y. ACAD. SCI. 211 (2003).

38

Matthew Ebright et al., Unintended Consequences of Mayo Paraneoplastic Evaluations, 91

NEUROLOGY 2057 (2018).

22

antibody testing. Id. 500 panels were reviewed, and the gAChR antibody was the fourth most-

common positive result with 15 positive tests, 86% of which met the authors’ standard for a false

positive. Id. at 4. Specifically, the authors explained that gAChR “antibodies are frequently false

positive and have comparable positive rates in populations with neurologic symptoms, healthy

controls, and neurologically asymptomatic patients with cancer.” Id. at 8. They also noted the

decline in the specificity of neurological presentation was related to a similar decline in gAChR

titer level. Id. Using these results, Dr. Lancaster concluded that “[o]utside the context of a medium-

strong positive result in a patient with profound dysautonomia, [the gAChR ABV] is not useful

for diagnosing human disease.” Resp’t’s Ex A at 8. He also stated there was “no evidence that

vaccination causes gAChR antibodies.” Id.

On the issue of Petitioner’s diagnosis, Dr. Lancaster disagreed with Dr. Huq that Petitioner

suffered from autoimmune encephalopathy. Resp’t’s Ex. A at 8. He noted that “no physiological

cause” of her symptoms could be identified, evidenced by her normal neurological examinations,

cardiac examinations, and the recording of her episodes on video EEG without a seizure pattern.

Id. at 8–9. Instead, Dr. Lancaster believed conversion disorder to be the most likely diagnosis for

Petitioner, as expressed by several of her providers. Id. at 9. Dr. Lancaster specifically found it

“notable that [Petitioner’s] exacerbations seemed to correlate with starting (or resuming) school.”

Id. He noted that prior to her elevated ɑ3-AChR results, her providers believed Petitioner had a

psychological issue, but opined that “it is unlikely these symptoms had an organic etiology or any

connection to the gAChR antibody test.” Id. In addition to his argument regarding false positives,

Dr. Lancaster explained that these antibodies “target a synaptic receptor in autonomic ganglia,”

and that no signs of autonomic dysfunction, such as blood pressure regulation, heart rate, or

pupillary constriction, were present in Petitioner. Id. “The antibodies should not affect thinking

and cognition. The antibodies should not cause unexplained decreased responsiveness, numbness

of the extremities, attacks of unexplained paralysis of the limbs, or most of [Petitioner’s] main

symptoms.” Id.

Dr. Lancaster also argued that there was no evidence Petitioner suffered from autoimmune

encephalitis, as her symptoms would have produced abnormalities captured by the EEG if they

resulted from an encephalitis, in addition to “other objective findings”. Resp’t’s Ex. A at 9.

Because this diagnosis appeared to rest on Petitioner’s gAChR antibody tests, Dr. Lancaster

believed this diagnosis to be “in error,” and that Petitioner should have been treated for conversion

disorder instead of starting steroids. Id.

With regard to Dr. Huq’s report, Dr. Lancaster disagreed with several of his conclusions.

Resp’t’s Ex. A at 10. First, he opined that the link between gAChR antibodies and autoimmune

encephalitis was “very unlikely to be causal, but rather reflects the types of patients studied at the

Mayo clinic in their case series.” Id. He stated this was because patients “with encephalitis may

frequently have the panel sent, so patients with encephalitis will inevitably be represented among

the patients with false positive results.” Id. “If the Mayo [] panel were frequently sent on patients

with ingrown toenails there might have been an apparent association of gAChR antibodies with

that disorder.” Id. He argued that the primary antigen, ɑ3-AChR, resided on autonomic ganglia

and not the brain, “[s]o invoking gAChR antibodies as some kind of mechanism is not correct.”

Id. He also pointed to a quote from the McKeon et al. article, which read “it is unlikely that the

[ɑ3-AChR] subunit is the primary autoantibody target in all the neurologic presentations described

in this article.” Id.

23

Second, Dr. Lancaster disagreed with Dr. Huq’s theory that molecular mimicry between a

component of the Tdap vaccine and the gAChR antibodies caused Petitioner’s symptoms. Resp’t’s

Ex. A at 10. He argued that Dr. Huq had not presented any specific component of the Tdap vaccine

as a mimic and “was unable to provide any evidence that such mimicry occurs.” Id. He also noted

that Dr. Huq did not provide any evidence regarding his six other potential theories of causation.

Id. Further, Dr. Lancaster did not agree with Dr. Huq’s use of tetanus toxoid and human beta-2

glycoprotein I to cause APS as a proper mechanisms, as “this case has nothing to do with

autoantibodies to human beta-2 glycoprotein [I], so . . . it would not explain the gAChR antibodies

or [Petitioner’s] symptoms.” Id.

Third, Dr. Lancaster noted contradictions in Dr. Huq’s discussion of conversion disorder.

Resp’t’s Ex. A at 10. Specifically, he referred to Dr. Huq’s theory as “a paradoxical entity of

autoimmune conversion disorder.” Id. “Petitioner’s brief attacks of altered mentation with normal

EEG are not consistent with organic encephalitis.” Id. Dr. Lancaster also opined that there was no

scientific evidence to favor either the Tdap vaccine or her febrile illness as the cause of her

condition and that there were no reports of the Tdap vaccine causing gAChR antibodies to appear.

Id.

3. Dr. Huq’s Supplemental Reports

Dr. Huq began his first supplemental report by citing to Graus et al. 39 to provide a

diagnostic criteria for “autoimmune encephalopathy:” 40

1. Subacute onset (rapid progression of less than 3 months) of working memory

deficits (short-term memory loss), altered mental status, or psychiatric

symptoms

2. New focal CNS findings

3. Reasonable exclusion of alternative cause

Pet’r’s Ex. 61 at 1 (citing Pet’r’s Ex. 65). He noted that “not all cases of autoimmune

encephalopathy” will meet these criteria, but asserted that Petitioner’s presentation did. Id. He

argued that Petitioner’s dizziness and fainting were suggestive of dysautonomia and that

Petitioner’s other symptoms were “symptoms of encephalitis.” Id. at 2.

Dr. Huq repeated his assertion that Petitioner did not have conversion disorder and cited to

Dr. Nespeca’s comments doubting a conversion diagnosis. Pet’r’s Ex. 61 at 2 (citing Pet’r’s Ex. 3

at 1061; Pet’r’s Ex. 59 at 497). He also noted that Petitioner had multiple instances of an elevated

sed rate. Id. Dr. Huq argued it was possible that Petitioner’s EEG was normal because her

symptoms were arising from “abnormalities of subcortical structures in which EEG would be

normal.” Id. at 3.

39

Francesc Graus et al., A Clinical Approach to Diagnosis of Autoimmune Encephalitis, 15 NEUROLOGY

391 (2016). Dr. Lancaster is listed as one of the authors of this article.

40

Dr. Huq stated this is a criteria for “autoimmune encephalopathy” in his report; however, the article

discusses the diagnostic criteria of autoimmune encephalitis. See Pet’r’s Ex. 65.

24

In explaining his theory of causation, Dr. Huq commented that he was “not suggesting that

there is any known molecular mimicry between any component of [Tdap] and the ganglionic

nicotinic cholinergic receptor or that mimicry between tetanus toxoid and human beta-2

glycoprotein I is the mechanism in this case, but that evidence indicates that [Tdap] can produce

autoimmunity.” Pet’r’s Ex. 61 at 3. According to Dr. Huq, Petitioner’s febrile illness was a

symptom of her condition and not the cause, as “[o]ne would expect a few weeks delay between a

trigger and autoantibody production thus making an infection causing her febrile illness an unlikely

trigger in this case.” Id.

Turning to the presence of ɑ3-AChR antibodies in Petitioner, Dr. Huq contested Dr.

Lancaster’s assertion that these are only located in autonomic ganglia, citing to McKeon et al.,

which found ɑ3-AChR to also be present in “sensory dorsal root ganglia, trigeminal ganglia, and

in rat and mouse brains.” Pet’r’s Ex. 61 at 4 (citing Pet’r’s Ex. 40). He also cited to Whiteaker et

al., 41 which identified ɑ3-AChR in mouse brains. Id. (citing Pet’r’s Ex. 66). In rats, Yeh et al.

found ɑ3-AChR in the interpeduncular nucleus, pineal gland, habenula and superior colliculi, and

cerebral cortex, hippocampus, and cerebellum. Pet’r’s Ex. 56 at 1. Dr. Huq argued that ɑ3-AChR

could also bind to other AChR subunit receptors in the brain, and that “the antibody specificity in

different patients and different subgroups . . . [may explain] why neuropsychiatric symptoms rather

than profound dysautonomia were more prevalent in the low to medium titer group.” Id. at 5. He

acknowledged Dr. Lancaster’s argument and literature regarding the false positives associated with

the ɑ3-AChR ABV test but opined that “it appears . . . that McKeon et al. interpret their own data

differently,” citing to the reported 46% positive predictive value for an autoimmune neurological

diagnosis in the low titer group. Id. (citing Pet’r’s Ex. 40).

Dr. Huq used the majority of his second supplemental report to discuss Petitioner’s

alternative diagnosis of conversion disorder, questioning why her treaters would prescribe her

“potentially toxic immunotherapy if they “were certain, or even suspicious, about the diagnosis of

conversion disorder.” Pet’r’s Ex. 72 at 1. He also pointed to Petitioner’s psychiatric evaluation and

lack of a DSM V diagnosis as evidence against the diagnosis of conversion disorder. Id. Dr. Huq

also returned to his prior argument that conversion disorder was a brain disorder, noting that

dystonia, once thought to represent a conversion disorder, now has “a well understood brain

mechanism.” Id. (citing Pet’r’s Ex. 86). 42 He then presented a new argument that if Petitioner did

indeed have conversion disorder, it would have been caused by her Tdap vaccine. Id. at 2. He cited

to Ercoli et al. 43 as support, which was a case report identifying functional neurological disorder

(“FND”) following COVID-19 vaccination. Id. (citing Pet’r’s Ex. 76). Dr. Huq argued that

although the underlying pathogenesis of conversion disorder was unknown, it had been linked to

41

Paul Whiteaker et al., Involvement of the ɑ3 Subunit in Central Nicotinic Binding Populations, 22 J.

NEUROSCIENCE 2522 (2002).

42

Rachel Newby et al., A History of Dystonia: Ancient to Modern, 4 MOVEMENT DISORDERS CLINICAL

PRACTICE 478 (2017).

43

Tommaso Ercoli et al., Functional Neurological Disorder After COVID-19 Vaccination, 42

NEUROLOGICAL SCIENCES 3989 (2021).

25

low-grade inflammation and elevated CRP levels. Id. (citing Pet’r’s Ex. 77; 44 Pet’r’s Ex. 81). 45

“Thus, inflammation induced by TdaP vaccination could have predisposed [Petitioner] to develop

conversion disorder.” Id.

In describing how the Tdap vaccine could cause this kind of inflammatory response, Dr.

Huq explained that inflammation is “essential” after vaccination for the adaptive immune system

to work properly, but a vaccine may “also produce local and systemic inflammation that may vary

depending on individual susceptibility.” Pet’r’s Ex. 72 at 2. He also argued that there was evidence

that cytokines were produced both at the local injection site and in “distant organs” following

vaccination. Id. (citing Pet’r’s Ex. 87). 46 Regarding how this could affect brain function, Dr. Huq

stated the following:

Peripheral inflammation can affect brain function. Peripherally induced

inflammation can access brain (sic) and influence neuronal and glial physiology.

Inflammation can disrupt blood brain barrier (sic), cytokines can access the brain

through leaky regions of brain (sic) such as circumventricular regions. Cytokines

can bind to cytokine specific transport molecules expressed on brain endothelium.

Even low levels of circulating cytokines have been postulated to affect brain

function. . . . Inflammation induced by vaccination may be transmitted to the brain

and produce or aggravate a proinflammatory state and trigger sickness behavior or

even conversion disorder in a susceptible individual. . . . Thus, even if we think that

[Petitioner] had conversion disorder, TdaP vaccination induced inflammation could

have been a significant contributory factor.

Id. at 2–3.

Turning to diagnosis, in addition to his previously discussed arguments, Dr. Huq asserted

that Petitioner’s “laboratory evidence of systemic inflammation (elevated CRP and ESR)” was

evidence she suffered from autoimmune encephalopathy. Pet’r’s Ex. 72 at 3. Elevated CSF “may

be seen in autoimmune encephalitis but are not uniformly present.” Id. (citing Pet’r’s Ex. 74; 47

Pet’r’s Ex. 78). 48 He also noted that “over half of patients with autoimmune encephalitis” will have

normal brain and spinal MRIs. Id. at 4. (citing Pet’r’s Ex. 65; Pet’r’s Ex. 74; Pet’r’s Ex. 78).

Accordingly, he opined the lack of these findings in Petitioner’s case did not preclude a diagnosis

of “autoimmune encephalitis.” Id. Addressing his theory of molecular mimicry, Dr. Huq reiterated

that “[i]t is not clear if molecular mimicry is the mechanism of autoantibody production against

[ɑ3-AChR], and again mentioned six other potential causative mechanisms. Id. at 5.

44

Christina van der Feltz-Cornelis et al., Assessment of Cytokines, MicroRNA and Patient Related

Outcome Measures in Conversion Disorder/Functional Neurological Disorder (CD/FND): The CANDO

Clinical Feasibility Study, 13 BRAIN, BEHAVIOR, & IMMUNITY – HEALTH 100228 (2021).

45

Kasia Kozlowksa et al., Blood CRP Levels Are Elevated in Children and Adolescents With Functional

Neurological Symptom Disorder, 28 EUR. CHILD & ADOLESCENT PSYCHIATRY 491 (2019).

46

Weihong Pan et al., Cytokine Signaling Modulates Blood-Brain Barrier Function, 17 CURRENT

PHARMACEUTICAL DESIGN 3729 (2011).

47

Tania Cellucci et al., Clinical Approach to the Diagnosis of Autoimmune Encephalitis in the Pediatric

Patient, 7 NEUROLOGY NEUROIMMUNOLOGY NEUROINFLAMMATION 663 (2020).

48

Yael Hacohen et al., Paediatric Autoimmune Encephalopathies: Clinical Features, Laboratory

Investigations and Outcomes in Patients With or Without Antibodies to Known Central Nervous System

Autoantigens, 0 J. NEUROLOGY NEUROSURGERY PSYCHIATRY 1 (2012).

26

4. Dr. Lancaster’s Supplemental Reports

Dr. Lancaster began his first supplemental report by critiquing Dr. Huq’s use of the Graus

et al. criteria to support the contention that Petitioner suffered from autoimmune encephalitis.

Resp’t’s Ex. C at 1. “As an author on this paper . . . [i]t was definitely not the intent . . . to imply

that meeting these criteria made the diagnosis certain but rather merely possible.” Id. Dr. Lancaster

stressed the importance of the third criterion regarding alternative causation, as this “would not

prevent the diagnosis of autoimmune encephalitis from being rejected if there were an alternative

cause found later.” Id. He also critiqued Dr. Huq for “overlooking the lack of clear new focal

neurologic findings” in Petitioner’s case. Id. This would include “objective evidence of focal

organic injury to the [CNS],” which Dr. Lancaster argued was not present. Id. Dr. Lancaster also

argued that conversion disorder was a more likely diagnosis than autoimmune encephalitis,

therefore not satisfying the third criterion. Id. In cases with a potential autoimmune encephalitis

diagnosis, Dr. Lancaster explained he would want to see clinical symptoms of encephalitis and

“some kind of supporting objective evidence,” to include clinical signs, MRI findings, or positive

CSF inflammation. Id. He also disagreed that Petitioner suffered from dysautonomia, as

“[e]pisodes of passing out in a patient with documented non-epileptic events would not be reliable

evidence of autonomic failure.” Id. at 2.

Dr. Lancaster next reiterated his belief that Petitioner suffered from conversion disorder

and discarded Dr. Huq’s theory that conversion disorder could be mechanically caused by a

vaccine. Resp’t’s Ex. C at 2. He also argued that “Dr. Huq’s alternative proposal that [Petitioner]

had some unspecified subcortical disorder as an explanation for the normal EEG studies during

her events is highly unlikely to be correct and not supported by the overall medical literature.” Id.

He noted that Dr. Huq had failed to identify a disease process or consistent diagnosis and had not

“provided any literature explaining what this disease is and why it is the correct diagnosis.” Id.

Turning to the issue of ɑ3-AChR antibodies, Dr. Lancaster stated that Dr. Huq had failed

to provide evidence that the Tdap vaccine could cause these antibodies, and discounted the medical

literature relied on by Dr. Huq as irrelevant to the present case. Resp’t’s Ex. C at 2. ADEM, APS,

and anti-NMDAR encephalitis are not analogous conditions to Petitioner’s alleged ɑ3-AChR

autoimmune encephalitis, and Dr. Lancaster noted that Dr. Huq had not “specified any particular

mechanism or provided any basis to conclude that such a mechanism is likely to be applicable or

have occurred here.” Id.

Dr. Lancaster next addressed the McKeon et al. paper and Dr. Huq’s characterization of

Petitioner’s injury, stating that although “a small fraction of patients with [] median titer antibodies

had the symptom of encephalopathy[, e]ncephalopathy is not encephalitis.” Resp’t’s Ex. C at 3.

“Encephalopathy is [] a general term for any disease in which the function of the brain is affected

by a substance or condition,” and has “thousands of causes.” Id. “Very few cases of

encephalopathy have anything to do with encephalitis, which is a specific term for brain

inflammation.” Id. He also explained that the singular patient from the McKeon et al. study with

encephalitis had co-existing ANNA1 antibodies, which are associated with encephalitis, and thus

the ɑ3-AChR positive result “was probably incidental.” Id. Dr. Lancaster did acknowledge the

authors speculation that “some patients could have autoantibodies to other types of AChR

receptors including those in the brain,” but argued they failed to provide follow-up research to this

27

point. Id. He also conceded the presence of ɑ3-AChR in the brain, but noted it was “much lower

than in autonomic structures.” Id.

In Dr. Lancaster’s second supplemental report, he contested Dr. Huq’s theory that vaccines

could cause conversion disorder through a biomechanical mechanism. Resp’t’s Ex. D at 2. He

explained that conversion disorder was a “subconscious reaction to stress” and that “[t]he idea that

conversion disorder is actually a previously unrecognized inflammatory brain disease is not

supported by the medical literature and well outside the mainstream medical thinking on the

condition.” Id. at 2–3. He continued by noting that the very name of the condition came from the

“‘conversion’ of underlying emotional distress into physical (neurologic) findings.” Id. at 3. (citing

Resp’t’s Ex. D, Tab 1). 49 He critiqued the studies relied on by Dr. Huq, calling the inflammatory

abnormalities “minor” and CRP “a non-specific marker of inflammation that could be elevated

under many conditions.” Id. He also found it notable that none of these patients had autoimmune

encephalitis. Id. He argued that the mechanism of conversion disorder induced via inflammatory

cytokines from the Tdap vaccine would not explain the months-long course of conversion disorder

given the brief and self-limited cytokine response to a vaccine. Id.

5. Dr. Huq’s Testimony

At the entitlement hearing Dr. Huq characterized Petitioner’s presentation as a “POTS-like

condition” and speculated whether Petitioner’s fainting spells were “brain fog,” a symptom

associated with POTS. 50 Tr. 29. He explained that he did not believe Petitioner had conversion

disorder because of Dr. Nespeca’s recorded doubt regarding the diagnosis and Petitioner’s

presentation. Tr. 39. He explained that a patient needed to show two criteria to meet a conversion

diagnosis: inconsistency, where “each time you present you see a different kind of symptom” or

an internal inconsistency, such as a seizure recorded on EEG without a seizure pattern; and

incongruence, which is when the patient’s symptoms do not line up with a known neurological or

psychiatric condition. Tr. 39–42. Dr. Huq opined that Petitioner showed no incongruence because

“her symptoms are consistent with [] what . . . might happen from a postural autonomic failure,

like condition like POTS.” Tr. 42. He noted a lack of bullying, abuse, or traumatic life event that

may have precipitated her conversion disorder, though he acknowledged that such disorders may

come from avoidance, such as “want[ing] to avoid going to school.” Tr. 43.

On cross examination, Dr. Huq was asked whether Petitioner’s normal Holter monitoring

and EEG would be examples of inconsistency, and he explained that the level of inconsistency

allowed before a conversion diagnosis “varies person to person [and] varies with the doctor.” Tr.

206. He also pointed to the overall lack of understanding of Petitioner’s diagnosis from her treating

physicians, stating that “nobody really understood very well. Everybody is saying that variety of

symptoms, difficult to explain, and that means that people . . . didn’t have a conviction in any

diagnosis.” Tr. 207. He did explain that Petitioner’s presentation was consistent with POTS, but

that Petitioner’s cardiologist “didn’t evaluate for dysautonomia the way it needs to be done.” Tr.

208, 212. He recognized that seven of Petitioner’s treating physicians across a variety of specialties

49

Anthony Feinstein, Conversion Disorder: Advances in Our Understanding, 185 CANADIAN MED.

ASS’N J. 915 (2011).

50

Dr. Huq acknowledged that none of Petitioner’s treating physicians considered POTS as a potential

diagnosis. See Tr. 29–30.

28

considered a diagnosis of conversion disorder, but maintained that the opinions of Dr. Sheets and

Dr. Nespeca regarding autoimmune encephalopathy were correct. Tr. 235.

Dr. Huq acknowledged Petitioner did not meet all the criteria for POTS, and thus he

characterized her presentation as POTS-like. Tr. 45. “[S]he has sort of symptoms of postural

autonomic failure, and this is coming from a relatively new autoantibody, . . . and so it is a type of

autoimmune encephalitis where you don’t have seizure, where you don’t have . . . a severe

depression of your awareness or altered mental consciousness.” Tr. 46. He also explained that

because the AChR receptors make up less than 1% of the brain, he would not expect to see

abnormal CSF or MRI findings because the “autoimmunity is targeted towards a very [small]

group of cells, but those cells are important.” Tr. 47. He also recognized that Dr. Nespeca

performed the active stand test for POTS, which was normal, but opined that a normal finding on

this test would not exclude a diagnosis of POTS in the same way a tilt-table test would. Tr. 47–48.

He later testified that Vernino & Lennon supported the association of low-titer ɑ3-AChR and

partial autonomic dysfunction. Tr. 63 (citing Resp’t’s Ex. A, Tab 1).

Dr. Huq testified that he believed Petitioner’s May 18, 2019 dermatology visit was

significant due to her report of facial flushing and cold hands and feet, and opined these symptoms

were supportive of partial autonomic failure. Tr. 74. He opined that the episodic nature of

Petitioner’s symptoms was also supportive of postural autonomic failure “because the symptoms

are kicking in when you are trying to do something or trying to stand [] which are basically the

definition of orthostatic intolerance.” Tr. 77. He also found it significant that Petitioner was

prescribed a beta-blocker, as this is typically prescribed for POTS. Tr. 83.

Turning to McKeon et al., Dr. Huq testified that autonomic nerve failure was a form of

peripheral neuropathy, and thus Petitioner’s symptoms would align with the findings of the authors

for medium and low titer groups. Tr. 83. He also stated it was possible that more common AChR

antibodies found in the brain, such as ɑ4 and ɑ7, may be binding to the ɑ3-AChR receptor because

the test is a “radioimmunoassay that just measure the binding of the antibody . . . so we really don’t

know which antibody – which molecule the body started.” Tr. 89. He speculated that the binding

of these other antibodies to the ɑ3-AChR could cause a POTS-like phenotype, but “we don’t

know.” Tr. 90–91. Dr. Huq also argued that Vernino & Lennon 51 supported a POTS-like

presentation was consistent with the symptoms associated with elevated ɑ3-AChR. Tr. 86. He also

disagreed with Dr. Lancaster’s argument that Petitioner’s results could have been false positives.

Tr. 93.

Dr. Huq also opined that a peripheral neuropathy could not be ruled out in Petitioner’s case

because an EMG, nerve conduction study, and skin biopsy had not been performed. Tr. 94. On

cross examination he testified that Petitioner may have had a small-fiber neuropathy because it

“can present like POTS.” Tr. 168. When asked whether Petitioner could have had ɑ3-AChR

antibodies prior to the onset of symptoms, Dr. Huq noted there was no other reasonable explanation

of her symptoms and thus concluded the antibodies must be pathogenic. Tr. 94–95. However, he

did acknowledge that he could not “100 percent rule [] out the possibility that maybe she had this

antibody” prior to vaccination. Tr. 95. Even if Petitioner had the antibody prior to vaccination, Dr.

Huq still opined the vaccine caused her symptoms through inflammation which caused “blood-

51

The transcript occasionally refers to Vernino et al. as “Bernina,” however, Petitioner cites to both

references as Respondent’s Ex. A, Tab 1, which is the filed Vernino et al. article. See Tr. 96.

29

brain barrier disruption,” allowing the antibody to enter the brain. Id. He clarified his ultimate

diagnosis of Petitioner to be “autoimmune encephalopathy due to autoantibody, [ɑ3-AChR], and

her condition mostly presented as a POTS-like postural autonomic failure or dysregulation.” Id.

He then referred to Petitioner’s diagnosis as “autoimmune encephalitis with a POTS-like

phenotype.” Tr. 96.

Turning to the Graus et al. criteria, Dr. Huq testified why he believed Petitioner met each

of the three criteria for an autoimmune encephalitis diagnosis. Tr. 106. For the first criterion, he

noted Petitioner’s subacute onset within three months, and for the second, he pointed to

Petitioner’s headaches, tremors, and “unusual movements” as evidence of focal neurologic

findings. Id. Dr. Huq could only think of Petitioner’s prior “viral infection-type symptoms” as a

reasonable alternative cause of her symptoms, but he opined this was “the prodromal symptoms

of autoimmune encephalopathy” because one day was not enough time for a viral infection to

cause her symptoms. Tr. 107.

Dr. Huq also testified that although conversion disorder is a DSM V diagnosis, he believed

it to be a neurologic disorder because “all psychiatric conditions come from the brain” and

diagnosis of conversion disorder often requires a neurologist. Tr. 118. “In order to make the

diagnosis, you have to do an EEG and show that the event you are evaluating is not a seizure.” Id.

However, for more complicated phenotypes, such as Petitioner’s, Dr. Huq acknowledged a

psychiatrist would be needed to rule out conversion disorder, which he argued was the case here.

Tr. 119. He also argued that even if Petitioner did have conversion disorder, it came from “the

psychoanalytic theory of inner conflict, stress [] getting converted into physical symptoms . . .

there is no evidence for that.” Tr. 120. Instead, Dr. Huq stated that “cytokines and inflammation

[have] at least some relation, because conversion disorder has some similarity to that sickness

behavior.” Id. He discussed Boeckle et al. and the contention that infection had a relation to

conversion disorder, explaining “infection produces sickness behavior, which is [an]

evolutionarily adaptive response for our survival, and so the thinking is that those part of the brain

[responsible for conversion disorder] . . . that would be affected by the cytokine or inflammation,

and peripheral inflammation can be just limited to the brain.” Tr. 123. Dr. Huq also compared

these findings to the symptoms of long COVID after both COVID vaccination and infection, which

he stated “has a lot of similarity to POTS-like symptoms.” Tr. 124. However, on cross examination

Dr. Huq admitted that his theory of causation would be weaker if Petitioner did in fact have

conversion disorder and that he was not familiar enough with conversion disorder to say with

preponderant confidence that there was a biological mechanism connecting cytokine regulation to

conversion disorder. Tr. 240.

Next, Dr. Huq discussed Herve et al. 52 and the reactogenicity of vaccines, which he

described as “fever, headache, lethargy, [and] malaise,” caused in this case by local inflammation

from the vaccine site. Tr. 128. He explained that cytokines and other chemicals released from this

inflammation go to the brain, where “some areas [do not] have the blood-brain barrier, so it can

directly reach it there.” Id. “There are several cell adhesion molecules that can bind activated

immune cells . . . so you end up creating a [] mirror type of inflammation in the brain.” Tr. 129.

He opined that this mechanism, combined with the articles he provided regarding anti-NDMA

receptor encephalitis and ADEM following Tdap vaccination, was sufficient to conclude that

Petitioner’s Tdap vaccine could have caused her to develop autoimmune encephalitis. Tr. 135–39.

52

Caroline Herve et al., The How’s and What’s of Vaccine Reactogenicity, 4 NPJ VACCINES 39 (2019).

30

Evidence of ADEM following the Tdap vaccine supports Dr. Huq’s mechanical theory of

causation because ADEM following Tdap vaccination is caused by “molecular mimicry or

cytokine.” Tr. 145. In Petitioner’s case, the “targets are different, and the why it is different, it’s

probably most individual susceptibility.” Id. Dr. Huq continued, opining that the Tdap vaccine

“can produce [] alpha-3 autoimmunity . . . by molecular mimicry to other antigen [and] can also

lead to the production of [] unlinked or unassociated molecules, and so it give[s] me more

confidence that . . . autoimmune encephalitis tied to the link to the alpha-3 molecule can happen

after Tdap.” Tr. 145–46. He also argued that the genetic makeup of an individual determined the

ultimate mechanism of the cause of encephalitis, to include polyclonal activation and cytokine

activation, and opined they may also have been the cause of Petitioner’s symptoms. Tr. 157.

When asked to explain the logical sequence of cause and effect connecting his theory to

Petitioner’s injury, Dr. Huq provided the following testimony:

So she received the vaccines, then [a] few weeks later, she initially had [] prodromal

symptoms, . . . [a]nd then she had a set of symptoms that I feel represent partial

autonomic failure, which is internally very consistent with the alpha-3 antibody

production, and how she made this antibody . . . that inflammation from the local

site can just mutate to a distant place, like a brain, and it can disrupt that brain

barrier and create inflammation in the brain, and that can allow . . . this antibody is

produced in the periphery. We don’t know whether alpha-3 antibody was produced

in the spleen, in the bone marrow, [] or it was inside the brain, which then came out

because of blood-brain barrier disruption. . . . [T]here are a variety of ways this

antibody can be produced. It could be by . . . molecular mimicry of tetanus toxoid

with MOG protein, with beta-2 glycoprotein. So it can produce some autoimmunity

and some low-level inflammation in the brain and then allow the immune cell to

see that molecule, . . . and that way one can produce cytokines, and in our body, we

have auto-reactive T-lymphocytes that are probably in more frequency than

autoimmune disease patient. We just have them suppress variability of T cells, and

that can be activated by cytokine inflammation. That can be another way that alpha-

3 molecules are produced.

Tr. 160–61. He also opined that if Petitioner’s febrile illness was the result of an infection and not

prodromal symptoms of an autoimmune condition, then “both are substantially and probably

important in a perfect storm situation . . . and because I’m thinking this is the perfect storm

situation, if you miss one of those, it would not have happened.” Tr. 163. When asked if there was

any difference between postinfectious and post-vaccine autoimmune encephalitis, Dr. Huq

testified, “I don’t think there is any difference.” Tr. 139. Dr. Huq compared the timing of

Petitioner’s symptoms to the timing reported to be associated with the development of ADEM and

other forms of autoimmune encephalitis, and concluded that the three-week onset following Tdap

vaccination was appropriate. Tr. 164. On cross examination, Dr. Huq clarified that there was no

direct relation between molecular mimicry of anti-beta-2 glycoprotein 1 antibodies from tetanus

toxoid and the development of ɑ3-AChR antibodies, and that his suggestion to this point was

theoretical based upon the development of other forms of encephalitis following Tdap vaccination.

Tr. 237, 242–43.

31

Also on cross examination, Dr. Huq testified that he believed Petitioner had autoimmune

encephalopathy 53 and did not have POTS, but had a POTS-like phenotype. Tr. 168. When asked

to then clarify his biomechanical theory (that relied on inflammation), he explained that

Petitioner’s inflammation could have been on a molecular level, which would not have been seen

by an MRI. Tr. 181. Dr. Huq admitted there was no objective evidence of inflammation from

Petitioner’s clinical course but stated that “[t]he evidence of inflammation is through the

mechanistic aspect [of] it . . . how a vaccination can produce inflammation, it can go to the brain.

So it is coming from my [] theoretical understanding, not from the patient’s clinical info.” Tr. 184,

187. He also agreed that his theory was “based upon indirect evidence using other vaccines and

other autoimmune diseases.” Tr. 239.

On redirect examination, Dr. Huq was asked to clarify his mechanism for causation, and

he provided the following explanation:

[S]omehow this Tdap vaccination produced the antibody, the alpha-3 nicotinic

receptor antibody, the production of this antibody. So [my] theory mostly talks

about [] how that could be possible, and so the [] autoantibody could be produced

via molecular mimicry. It can be produced via, for example, activation of the

autoreactive T cells that we have all in our system. It can be via polyclonal B cell

activation, for example, and there are several other mechanisms, or another

common way would be if there is exposure of immune cells to this molecule. And

the way I think some of these things might have happened, that we have some

example of molecular mimicry, like Tdap, tetanus toxoid as similar or proven

molecular mimicry, beta-2 glycoprotein, which is also a model of – which is the

antibody that cause a condition called antiphospholipid syndrome. And in

antiphospholipid syndrome, which [] we have submitted two articles . . . those

articles shows that you can have antiphospholipid syndrome, you can have a variety

of neurological symptoms, and it is not clear, was it all happening from the blood

clot? And so those others there, they wondered whether the presence of beta-2

glycoprotein in the brain can also produce some symptoms. . . . [S]o that’s not, of

course, the alpha-3 antibody, but if . . . this molecular mimicry could potentially

allow the immune cells to see other molecules in the brain, which include different

alpha subunit.

Tr. 391–92. He also used MOG proteins as an example of molecular mimicry, which would allow

“immune cells to enter the brain tissue and then see the alpha-3 antibody and produce antibody

against the alpha-3.” Tr. 394. Noting however, that he was not implicating MOG or beta-2

glycoproteins in this case, but rather he was “saying that how they can potentially lead to the

production of alpha-3 and nicotinic receptor antibody.” Tr. 395–96.

6. Dr. Lancaster’s Testimony

53

Dr. Huq frequently used the terms autoimmune encephalopathy and autoimmune encephalitis

interchangeably throughout his reports and testimony. On cross examination he clarified that he was

intending to refer to autoimmune encephalopathy, and much time was spent clarifying this issue. Tr. 169–

215.

32

Dr. Lancaster began his testimony with a brief explanation of the difference between

encephalopathy and encephalitis, stating that “encephalopathy is a term for a failure of brain

function or a failure of cognition,” while encephalitis “implies that there was some brain

inflammation.” Tr. 282. He then turned to his disagreement with Dr. Huq’s characterization of

Petitioner’s symptoms as POTS, explaining “POTS involves primarily dysautonomia . . . [t]his is

not generally thought to be due to encephalitis or involve primarily the brain.” Tr. 285. He

continued that the antibodies involved in this case are “primarily occurring at autonomic ganglia,

outside the central nervous system and not part of the brain.” Id. He then contextualized Graus et

al., noting that in addition to the criteria, “we would also want something to think it’s not simply

a psychiatric disorder, an intoxication, or some other cause of brain failure.” Tr. 288. This would

include “focal, new central nervous system findings,” such as paralysis, MRI or CSF

abnormalities, or seizures. Tr. 288–89. It was the lack of these findings in Petitioner, in addition

to the potential for conversion disorder, that led Dr. Lancaster to believe Petitioner did not have

autoimmune encephalitis. Tr. 289–90. Dr. Lancaster also noted three years in which Petitioner’s

symptoms would worsen around the beginning of the school year, improve when Petitioner was

pulled out of school, and then relapse shortly or soon before returning to school. Tr. 331–36.

Dr. Lancaster later explained that it was unlikely Petitioner’s symptoms, including her

fainting, was a result of autonomic failure. Tr. 314. The only way this could occur would be

through a decline in blood pressure, and he “would expect some abnormalities to be detected on a

cardiovascular examination and . . . on the Holter monitor.” Id. He also disagreed that

dysautonomia would not be detectable on an EEG, because passing out would alter a person’s

brain waves and be detectable. Tr. 316. In particular, Dr. Lancaster disagreed with Dr. Huq’s

argument that Petitioner did not have a sufficient autonomic workup. Id. Instead, he asserted that

her treating physicians did not have significant concern for POTS given her cardiac, neurologic,

and autonomic testing results, and that if such a concern existed it would have been noted. Tr. 317.

Dr. Lancaster also explained why he believed Petitioner suffered from conversion disorder

despite a lack of a formal diagnosis of depression or anxiety. Tr. 330. “It’s quite common for

people with conversion disorder to not necessarily have severe depression or anxiety. . . . Many of

them just have the conversion process and not those other disorders.” Id. He continued that

“[c]onversion disorder is primarily a psychiatric disorder where people are having, we believe, an

aberrant response to stress and other factors.” Tr. 343. He noted that while a prior history of abuse

was a major risk factor, “many patients have no clear history of abuse or trauma, and yet they still

have this process.” Tr. 331. In Petitioner’s case, Dr. Lancaster referred to the correlation of the

start of her symptoms and the return to school and opined that this could have been a trigger,

because school can be a stressor for children. Tr. 332.

Turning to the issue of ɑ3-AChR antibodies, Dr. Lancaster explained that Vernino et al.

showed “very clearly and elegantly that if you have an autoimmune disease with a true, bona fide

immune response to this receptor, that it can disrupt these signals,” resulting in severe autonomic

failure. Tr. 298. “This is not in any way an encephalitis or an encephalopathy. It is an autoimmune

disease of a part of the peripheral nervous system, particularly the autonomic part of the peripheral

nervous system.” Tr. 299. He stated that he would not use the ɑ3-AChR antibody test to diagnosis

encephalitis or encephalopathy in patients and that he would ultimately prefer if this test was not

included in an autoimmune encephalopathy panel. Tr. 303. In the 20 patients Dr. Lancaster had

seen personally with positive tests for ɑ3-AChR, he testified that only one suffered from

33

dysautonomia with a level of 13.0 nmol/L and none had any autoimmune disorder. Tr. 304. He

also opined that it was “doubtful it can cause even peripheral neuropathy, because there are no

ganglia on peripheral sensory motor nerves.” Tr. 308.

Addressing Dr. Huq’s theory of molecular mimicry, Dr. Lancaster stated that “[h]e did not

provide any evidence that such mimicry actually occurs or any plausible reason to believe it would

occur.” Tr. 338. He also argued that Dr. Huq had not specified a component of the Tdap vaccine

that could cause the molecular mimicry, what the mimicked substance in the human body was, or

“why there would be any structural resemblance between anything in the vaccine that could cause

immune cross-reactivity to any substance in the human body.” Tr. 338–39. He testified that Dr.

Huq’s cytokine theory did not make sense because “just the fact that cytokines are activated by

many processes doesn’t mean that those processes cause each other to happen. Otherwise, a

vaccination would cause everything that activates or associates with the activation of cytokines.”

Tr. 340–41. He also contested Dr. Huq’s theory that the Tdap vaccine could cause conversion

disorder stating, “[t]he idea that a vaccination would somehow change the brain in such a precise

way as to reset our thoughts and our perceptions of our own illness is implausible and not

reasonable.” Tr. 343. He ultimately opined that while he did not believe Petitioner suffered from

autoimmune encephalitis, if she did, her febrile illness in early September 2017 was a more likely

cause than the vaccine. Tr. 346. On cross examination Dr. Lancaster was asked what evidence he

believed was required to show an association between the Tdap vaccine and “the type of

autoimmune encephalopathy alleged in this case,” and he provided three criteria: “a very clear idea

we’re dealing with an autoimmune disease, some idea of how it’s triggered, and some reasonable

basis to believe that the vaccination can trigger that immune response to occur.” Tr. 359–60.

V. Applicable Legal Standards

To receive compensation under the Vaccine Act, a petitioner must demonstrate either that:

(1) the petitioner suffered a “Table injury” by receiving a covered vaccine and subsequently

developing a listed injury within the time frame prescribed by the Vaccine Injury Table set forth

at 42 U.S.C. § 300aa-14, as modified by 42 C.F.R. § 100.3; or (2) that the petitioner suffered an

“off-Table injury,” one not listed on the Table, as a result of her receiving a covered vaccine. See

§ 300aa-11(c)(1)(C); 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, 1319–20 (Fed. Cir. 2006). In

this case, Petitioner does not allege a Table injury, and thus Petitioner must prove by preponderant

evidence that her injury was caused-in-fact by a Table vaccine.

A. Factual Issues

A petitioner must prove, by a preponderance of the evidence, the factual circumstances

surrounding her claim. § 13(a)(1)(A). To resolve factual issues, the special master must weigh the

evidence presented, which may include contemporaneous medical records and testimony. See

Burns v. Sec’y of Health & Hum. Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (explaining that a special

master must decide what weight to give evidence including oral testimony and contemporaneous

medical records). Contemporaneous medical records, “in general, warrant consideration as

trustworthy evidence.” Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir.

1993); but see Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d 1378, 1382 (Fed. Cir. 2021)

(rejection the presumption that “medical records are accurate and complete as to all the patient’s

physical conditions”); Shapiro v. Sec’y of Health & Hum. Servs., 101 Fed. Cl. 532, 538 (2001)

34

(“[T]he absence of a reference to a condition or circumstance is much less significant than a

reference which negates the existence of the condition or circumstance”).

There are situations in which compelling testimony may be more persuasive than written

records, such as where records are deemed to be incomplete or inaccurate. Campbell v. Sec’y of

Health & Hum. Servs., 69 Fed. Cl. 775, 779 (2006) (“[L]ike any norm based upon common sense

and experience, this rule should not be treated as an absolute and must yield where the factual

predicates for its application are weak or lacking.”); Lowrie v. Sec’y of Health & Hum. Servs., No.

03-1585V, 2005 WL 6117475, at *19 (Fed. Cl. Spec. Mstr. Dec. 12, 2005) (“[W]ritten records

which are, themselves, inconsistent, should be accorded less deference than those which are

internally consistent.” (quoting Murphy v. Sec’y of the Dep’t of Health & Hum. Servs., 23 Cl. Ct.

726, 733 (Fed. Cl. 1991)). Ultimately, a determination regarding a witness’ credibility is needed

when determining the weight that such testimony should be afforded. Andreu v. Sec’y of Health &

Hum. Servs., 569 F.3d 1367, 1379 (Fed. Cir. 2009); Bradley v. Sec’y of Dep’t of Health & Hum.

Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

Despite the weight afforded medical records, special masters are not bound rigidly by those

records in determining onset of a petitioner’s symptoms. Valenzuela v. Sec’y of Health & Hum.

Servs., No. 90-1002V, 1991 WL 182241, at *3 (Fed. Cl. Spec. Mstr. Aug. 30, 1991); see also Eng.

v. Sec’y of Health & Hum. Servs., No. 90-1754V, 1994 WL 67704, at *3 (Fed. Cl. Spec. Mstr. Feb.

18, 1994) (Section 13(b)(2) “must be construed so as to give effect also to § 13(b)(1) which directs

the special master or court to consider the medical records (reports, diagnosis, conclusions,

medical judgment, test reports, etc.), but does not require the special master or court to be bound

by them.”).

B. Causation-In-Fact

To establish causation-in-fact, a petitioner must demonstrate by a preponderance of the

evidence that the vaccine was the cause of the injury. § 300aa-13(a)(1)(A). A petitioner is required

to prove that the vaccine was “not only a but-for cause of the injury but also a substantial factor in

bringing about the injury.” Moberly, 592 F.3d at 1321–22 (quoting Shyface v. Sec’y of Health &

Hum. Servs., 165 F.3d 1344, 1352–53 (Fed. Cir. 1999).

In the seminal case of Althen v. Sec’y of Health & Hum. Servs., the Federal Circuit set forth

a three-pronged test used to determine whether a petitioner has established a causal link between

a vaccine and the claimed injury. See 418 F.3d 1274, 1278–79 (Fed. Cir. 2005). The Althen test

requires petitioners to set forth: “(1) a medical theory causally connecting the vaccination and the

injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for

the injury; and (3) a showing of a proximate temporal relationship between vaccination and

injury.” Id. at 1278. To establish entitlement to compensation under the Program, a petitioner is

required to establish each of the three prongs of Althen by a preponderance of the evidence. Id.

“[C]lose calls regarding causation are resolved in favor of injured claimants.” Id. at 1280. Further,

evidence used to satisfy one prong of the test may overlap to satisfy another prong. Capizzano,

440 F.3d at 1326.

Under the first prong of Althen, a petitioner must offer a scientific or medical theory that

answers in the affirmative the question: “can the vaccine[] at issue cause the type of injury

alleged?” See Pafford v. Sec’y of Health & Hum. Servs., No. 01-0165V, 2004 WL 1717359, at *4

(Fed. Cl. Spec. Mstr. July 16, 2004), mot. for rev. den’d, 64 Fed. Cl. 19 (2005), aff’d, 451 F.3d

35

1352 (Fed. Cir. 2006). To satisfy this prong, a petitioner’s theory must be based on a “sound and

reliable medical or scientific explanation.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d

543, 548 (Fed. Cir. 1994). Such theory must only be “legally probable, not medically or

scientifically certain.” Id. at 548–49. Petitioners are not required to identify “specific biological

mechanisms” to establish causation, nor are they required to present “epidemiologic studies,

rechallenge[] the presence of pathological markers or genetic disposition, or general acceptance in

the scientific or medical communities.” Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at

1280). Scientific and “objective confirmation” of the medical theory with additional medical

documentation is unnecessary. Althen, 418 F.3d at 1278–81; see also Moberly, 592 F.3d at 1322.

However, as the Federal Circuit has made clear, “simply identifying a ‘plausible’ theory of

causation is insufficient for a petitioner to meet her burden of proof.” LaLonde v. Sec’y of Health

& Hum. Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014) (citing Moberly, 592 F.3d at 1322). Indeed,

the Federal Circuit has “consistently rejected theories that the vaccine only ‘likely caused’ the

injury and reiterated that a ‘plausible’ or ‘possible’ causal theory does not satisfy the standard.”

Boatmon v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1360 (Fed. Cir. 2019) (citing Moberly,

592 F.3d at 1322; LaLonde, 746 F.3d at 1339). Rather, “[a] petitioner must provide a reputable

medical or scientific explanation that pertains specifically to the petitioner’s case.” Moberly, 592

F.3d at 1322. In general, “the statutory standard of preponderance of the evidence requires a

petitioner to demonstrate that the vaccine more likely than not caused the condition alleged.”

LaLonde, 746 F.3d at 1339.

Furthermore, establishing a sound and reliable medical theory connecting the vaccine to

the injury often requires a petitioner to present expert testimony in support of her claim. Lampe v.

Sec’y of Health & Hum. Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s

opinion in Daubert v. Merrell Dow Pharmaceuticals, Inc. requires that courts determine the

reliability of an expert opinion before it may be considered as evidence. 509 U.S. 579 (1993).

However, in the Vaccine Program, the Daubert factors are used in the weighing of the reliability

of scientific evidence proffered. Davis v. Sec’y of Health & Hum. Servs., 94 Fed. Cl. 53, 66–67

(2010) (“[U]niquely in this Circuit, the Daubert factors have been employed also as an acceptable

evidentiary-gauging tool with respect to the persuasiveness of expert testimony already

admitted.”); see also Cedillo v. Sec’y of health & Hum. Servs., 617 F.3d 1328, 1339 (Fed. Cir.

2010) (citing Terran v. Sec’y of Health & Hum. Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999)).

Under Daubert, the

Factors for analyzing the reliability of testimony are: (1) whether a theory or

technique can be (and has been) tested; (2) whether the theory or technique has

been subjected to peer review and publication; (3) whether there is a known or

potential rate of error and whether there are standards for controlling the error; and

(4) whether the theory or technique enjoys general acceptance within a relevant

scientific community.

Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592–95).

The Daubert factors are “meant to be helpful, not definitive.” Kumho Tire Co. v.

Carmichael, 526 U.S. 137, 151 (1999). The factors do not “constitute a ‘definitive checklist or

test’” and may be applied differently depending on the facts of a particular case. Id. at 150 (quoting

Daubert, 509 U.S. at 593).

36

“In short, the requirement that an expert’s testimony pertain to ‘scientific knowledge’

establish a standard of evidentiary reliability.” Daubert, 509 U.S. at 590 (citation omitted). Thus,

for Vaccine Act claims, a “special master is entitled to require some indicia of reliability to support

the assertion of the expert witness.” Moberly, 592 F.3d at 1324. Nothing requires the acceptance

of an expert’s conclusion “connected to existing data only by the ipse dixit of the expert,”

especially if “there is simply too great an analytical gap between the data and the opinion

proffered.” Synder v. Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 743 (2009) (quoting Gen.

Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)); see also D’Tiole v. Sec’y of Health & Hum. Servs.,

No. 15-085V, 2016 WL 7664475, at *24 (Fed. Cl. Spec. Mstr. Nov. 28, 2016) (stating that the

Vaccine Act “require[s] a chain of reliable propositions supporting [a] petitioner’s theory”).

Under the second prong of Althen, a petitioner must prove that the vaccine actually did

cause the alleged injury in a particular case. See Pafford, 2004 WL 1717359, at *4; Althen, 418

F.3d at 1279. The second Althen prong requires proof of a logical sequence of cause and effect,

usually supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278;

Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Hum. Servs., 956 F.2d 1144, 1148 (Fed.

Cir. 1992). A petitioner does not meet this obligation by showing only a temporal association

between the vaccination and the injury; instead, the petitioner “must explain how and why the

injury occurred.” Pafford, 2004 WL 1717359, at *4 (emphasis in original). The special master in

Pafford noted petitioners “must prove [] both that her vaccinations were a substantial factor in

causing the illness . . . and that the harm would not have occurred in the absence of the

vaccination.” 2004 WL 1717359, at *4 (citing Shyface, 165 F.3d at 1352). A reputable medical or

scientific explanation must support this logical sequence of cause and effect. Hodges v. Sec’y of

Health & Hum. Servs., 9 F.3d 958, 961 (Fed. Cir. 1993) (citation omitted). Nevertheless,

“[r]equiring epidemiologic studies . . . or general acceptance in the scientific or medical

communities . . . impermissibly raises a claimant’s burden under the Vaccine Act and hinders the

system created by Congress . . . .” Capizzano, 440 F.3d at 1325–26. “[C]lose calls regarding

causation are resolved in favor of injured claimants.” Althen 418 F.3d at 1280.

In Program cases, contemporaneous medical records and the opinions of treating

physicians are favored. Capizzano, 440 F.3d at 1326 (citing Althen, 418 F.3d at 1280). Indeed,

when reviewing the record, a special master must consider the opinions of treating physicians.

Capizzano, 440 F.3d at 1326. This is because “treating physicians are likely to be in the best

position to determine whether ‘a logical sequence of cause and effect show[s] that the vaccination

was the reason for the injury.’” Id. In addition, “[m]edical records, in general, warrant

consideration as trustworthy evidence. The records contain information supplied to or by health

professionals to facilitate diagnosis and treatment of medical conditions. With proper treatment

hanging in the balance, accuracy has an extra premium. These records are also generally

contemporaneous to the medical events.” Cucuras, 993 F.2d at 1528. However, there is no

“presumption that medical records are accurate and complete as to all of the patient’s physical

conditions.” Kirby, 997 F.3d at 1383 (finding that a special master must consider the context of a

medical encounter before concluding that it constitutes evidence regarding the absence of a

condition). While a special master must consider these opinions and records, they are not “binding

on the special master or court.” § 300aa-13(b)(1). Rather, when “evaluating the weight to be

afforded to any such . . . [evidence], the special master . . . shall consider the entire record . . . .”

Id.

In determining the accuracy and completeness of medical records, special masters will

consider various explanations for inconsistencies between contemporaneously created medical

37

records and later given testimony. The Court of Federal Claims has identified four such

explanations for explaining inconsistencies: (1) a person’s failure to recount to the medical

professional everything that happened during the relevant time period; (2) the medical

professional’s failure to document everything reported to her or him; (3) a person’s faulty

recollection of the events when presenting with testimony; or (4) a person’s purposeful recounting

of symptoms that did not exist. LaLonde v. Sec’y of health & Hum. Servs., 110 Fed. Cl. 184, 203

(2013), aff’d, 746 F.3d 1334 (Fed. Cir. 2014).

To satisfy the third Althen prong, a petitioner must establish a “proximate temporal

relationship” between the vaccination and the alleged injury. Althen, 418 F.3d at 1281. This

“requires preponderant proof that the onset of symptoms occurred within a timeframe for which,

given the medical understanding of the disorder’s etiology, it is medically acceptable to finger

causation-in-fact.” de Bazan v. Sec’y of health & Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir.

2008). Typically, “a petitioner’s failure to satisfy the proximate temporal relationship prong is due

to the fact that onset was too late after the administration of a vaccine for the vaccine to be the

cause.” Id. However, “cases in which onset is too soon” also fail this prong; “in either case, the

temporal relationship is not such that it is medically acceptable to conclude that the vaccination

and the injury are causally linked.” Id.; see also Locane v. Sec’y of Health & Hum. Servs., 685

F.3d 1375, 1381 (Fed. Cir. 2012) (“[If] the illness was present before the vaccine was administered,

logically, the vaccine could not have caused the illness.”).

Although a temporal association alone is insufficient to establish causation, under the third

prong of Althen, a petitioner must show that the timing of the injury fits with the causal theory.

See Althen, 418 F.3d at 1278. The special master cannot infer causation from temporal proximity

alone. See Thibaudeau v. Sec’y of health & Hum. Servs., 24 Cl. Ct. 400, 403–04 (1991); see also

Grant, 956 F.2d at 1148 (“[T]he inoculation is not the cause of every event that occurs within the

ten[-]day period . . . [w]ithout more, this proximate temporal relationship will not support a finding

of causation.” (quoting Hasler v. United States, 718 F.2d 202, 205 (6th Cir. 1983))).

A petitioner who satisfies all three prongs of the Althen test has established a prima facie

showing of causation. Hammitt v. Sec’y of health & Hum. Servs., 98 Fed. Cl. 719, 726 (2011). A

petitioner who demonstrates by a preponderance of the evidence that she suffered an injury caused

by vaccination is entitled to compensation unless the respondent can demonstrate by a

preponderance of the evidence that the injury was caused by factors unrelated to the vaccination.

See Althen, 418 F.3d at 1278; Knudsen, 35 F.3d at 547. In such a case, the government must not

merely prove the existence of an alternative cause, but that such an alternative actually caused the

injury. Kundsen, 35 F.3d at 549. Consequently, when and if the petitioner establishes a prima facie

case, the burden the shifts to the government to prove that an alternative cause, unrelated to the

administration of the vaccine, was the “sole substantial factor” in causing the alleged injury. See

de Bazan, 539 F.3d at 1354; see also Hammitt, 98 Fed. Cl. at 726 (explaining that respondent’s

burden is to show that the “factor unrelated” was the “sole substantial factor” in causing the injury).

Additionally, a factor unrelated “may not include ‘any idiopathic, unexplained, unknown,

hypothetical, or undocumentable cause, factor, injury, illness or condition.’” § 300aa-13(a)(2); see

also Doe v. Sec’y of Health & Hum. Servs., 601 F.3d 1349 (Fed. Cir. 2010) (stating that an

idiopathic diagnosis cannot be a “factor unrelated,” as it is idiopathic).

VI. Analysis

A. Diagnosis

38

In cases where the diagnosis is contested, “special masters may find whether a

preponderance of evidence supports any proposed diagnosis before evaluating whether a vaccine

caused that illness.” Hibbard v. Sec’y of Health & Hum. Servs., No. 07-446V, 2011 WL 1766033,

at *6 (Fed. Cl. Spec. Mstr. Apr. 12, 2011) (citing Broekelschen v. Sec’y of Health & Hum. Servs.,

618 F.3d 1339, 1345–46 (Fed. Cir. 2010)). In this case, diagnosis is in dispute, so it is appropriate

to address it first.

Throughout the litigation of her claim, Petitioner and her expert have referred to her

condition in a variety of ways: in Petitioner’s amended petition and pre-hearing brief, she claims

an injury of autoimmune encephalomyelitis; throughout Dr. Huq’s reports and testimony, he refers

to Petitioner’s injury as an autoimmune encephalopathy, an autoimmune encephalitis, an “alpha-

3 nicotinic receptor antibody disease with partial autonomic failure,” a “POTS-like postural

autonomic failure or dysregulation,” a peripheral neuropathy, and a small-fiber neuropathy. 54 See

Am. Pet. at 1; Pet’r’s Br. at 1; Tr. 94–95, 387; see generally Pet’r’s Ex. 14; Pet’r’s Ex. 72.

Conversely, Respondent contends that Petitioner suffers from conversion disorder, as speculated

by several of her treating physicians.

First, it is important to note that the terms Petitioner uses to refer to her injury throughout

her claim are distinct diagnoses. According to Dorland’s Medical Dictionary, encephalopathy is

“any degenerative disease of the brain.” Encephalopathy, DORLAND’S. Encephalitis is a different,

though related, condition defined as “inflammation of the brain.” Encephalitis, DORLAND’S.

Further distinct from these, encephalomyelitis is defined as “inflammation involving both the brain

and the spinal cord.” Encephalomyelitis, DORLAND’S. Though these three conditions all involve

the brain, each is more specific than the last. These distinctions provide an important framework

for analyzing Petitioner’s arguments regarding diagnosis in this case.

Next, a point of clarification. The fact Dr. Huq used the terms encephalopathy and

encephalitis interchangeably was a significant point of confusion during the entitlement hearing.

See Tr. 169–215. Dr. Huq ultimately testified that he believed Petitioner had “alpha-3 nicotinic

receptor antibody disease with partial autonomic failure,” which he stated was an encephalopathy

and not an encephalitis. See Tr. 95. However, a substantial amount of the medical literature he

relied on throughout his reports referred to various forms of encephalitis, including the Graus et

al. criteria Dr. Huq used to diagnose Petitioner. See Tr. 95; see also Pet’r’s Ex. 36 (discussing anti-

NDMA receptor encephalitis following Tdap vaccination); Pet’r’s Ex. 54 (discussing Anti-NMDA

receptor encephalitis); Pet’r’s Ex. 55 (discussing encephalomyelitis following HPV vaccination);

Pet’r’s Ex. 62 (discussing antibody-mediated encephalitis); Pet’r’s Ex. 65 (providing diagnostic

criteria for autoimmune encephalitis); Pet’r’s Ex. 74 (discussing the diagnosis of autoimmune

encephalitis). He also frequently argued about the presence of undetectable inflammation in

Petitioner’s brain despite claiming that Petitioner’s injury was not an encephalitis. See Tr. 160.

And notably, despite the abundant variation in how Dr. Huq characterized Petitioner’s injury, he

never referred to or discussed Petitioner’s injury as encephalomyelitis, which is the injury claimed

in Petitioner’s actual petition.

54

Because Petitioner never claims a peripheral nerve injury and because Dr. Huq does not spend a

significant amount of time discussing whether Petitioner suffered from a peripheral nerve injury, I will

not discuss whether Petitioner suffered from a small-fiber neuropathy or other peripheral neuropathy.

39

Petitioner’s treating physicians also varied in their diagnosis of Petitioner. At the outset of

her presentation, the majority of her physicians suspected conversion disorder or a psychosomatic

process as being responsible for her symptoms. See Pet’r’s Ex. 3 at 173 (neurologist Dr. Jindal

suspecting conversion disorder), 406 (cardiologist Dr. Williams suspecting conversion disorder),

475 (rehabilitation specialist Dr. Biffl suspecting conversion disorder), 940 (infectious disease

specialist Dr. Sawyer suspecting conversion disorder); Pet’r’s Ex. 4 at 35 (PCP Dr. Madany

recommending Petitioner seek a psychiatric consultation); Pet’r’s Ex. 9 at 13 (neurologist Dr. Aaen

suspecting conversion disorder). Only rheumatologist Dr. Sheets and neurologist Dr. Nespeca

expressed their doubts as to the diagnosis of conversion disorder and both considered a possible

diagnosis of encephalomyelitis, though neither could articulate a definitive diagnosis. Following

Petitioner’s positive ɑ3-AChR testing, Dr. Nespeca opined the results may be associated with her

disease process, due to case reports associating “a variety of symptoms of autonomic dysfunction,

peripheral neuropathy, and cognitive disorders” with the presence of the antibody. Pet’r’s Ex. 3 at

1061. In the immediate aftermath of these results, both Dr. Nespeca and Dr. Sheets characterized

Petitioner’s injury as a possible diagnosis of autoimmune encephalomyelitis. However, as her

treatment continued, their diagnosis became less specific, with both practitioners most commonly

referring to Petitioner’s condition as a “presumed autoimmune neurological disorder.” Id. at 1525.

Two years into her treatment with Dr. Nespeca, he noted that Petitioner’s symptoms were not

consistent with the autonomic failure associated with elevated ɑ3-AChR and specifically ruled out

POTS as a diagnosis. Pet’r’s Ex. 59 at 498. This is particularly notable given that McKeon et al.

found 54% of patients with low-titer elevated ɑ3-AChR had either a non-immune-mediated

neurological disorder or a nonneurological disorder. Petitioner also points to a reference of

autoimmune encephalomyelitis in the report of a social worker from July 2020 following a visit

with Petitioner; however, the reference specifically refers to Petitioner’s diagnosis as

“Autoimmune Encephalomyelitis following Tdap vaccine, per client,” and thus is not an actual

diagnosis from a treating physician. Pet’r’s Ex. 58 at 8 (emphasis added).

Further, it is notable that Petitioner’s elevated ɑ3-AChR appeared to be the only objective

indicator of a potential brain injury. Multiple MRIs revealed no abnormalities and video EEGs

which captured her episodes did not reveal an electroencephalographic seizure pattern. Petitioner’s

CSF testing also did not show signs of inflammation. Petitioner had a very limited response to

steroids, to the point that Dr. Sheets became worried about restarting her on higher dosages or

pursuing more aggressive therapies at the suggestion of her family. It was also at this point that

Dr. Sheets began to speculate whether stress was a trigger for her symptoms because “she [was]

flaring her symptoms . . . as school starts and . . . she [was] not able to go to school because of

this.” Pet’r’s Ex. 3 at 1590.

Even assuming arguendo that Petitioner intended to claim encephalitis and not

encephalomyelitis as her injury, Dr. Huq’s application of the Graus et al. criteria to Petitioner’s

history is flawed. The paper itself notes that the “[e]xisting diagnostic criteria for autoimmune

encephalitis [is] too reliant on antibody testing and response to immunotherapy” due to the varied

meaning of antibody presence and the variation in response to immunotherapy. Pet’r’s Ex. 65 at

1. The first criterion, subacute onset of working memory deficits, altered mental status, or

psychiatric symptoms, is met in this case. See id. at 3. However, where Dr. Huq’s analysis begins

to fray is in the second and third criteria.

The second criterion, according to the authors, is for the presence of at least one of the

following: new focal CNS findings, seizures not explained by a previously known seizure disorder,

CSF pleocytosis, or MRI features suggestive of encephalitis. Pet’r’s Ex. 65 at 3. Here, Petitioner

40

does not have seizures as shown by multiple EEGs, her CSF was normal, and her MRIs revealed

no abnormalities. Rather, Dr. Huq relies on the presence of new focal CNS findings to argue

Petitioner has met this criterion, pointing to instances of headaches, tremors, and “unusual

movements.” Tr. 106. However, these symptoms were described as “entirely nonfocal” by

Petitioner’s treating physicians, and they could not identify a neurologic diagnosis. Pet’r’s Ex. 3

at 344. I find it persuasive that Dr. Lancaster, an author of this paper, disagrees with Dr. Huq’s

application of it. He notes the overall lack of objective findings outside the presence of ɑ3-AChR

antibodies and that Petitioner’s presentation does not constitute the kind of focal CNS deficits

referred to in the paper. I also find it notable that Petitioner’s neurologic exams were consistently

normal, even when she experienced episodes during visits with her providers.

Assuming these symptoms could constitute sufficient focal CNS findings to satisfy the

second criterion, Dr. Huq’s analysis of the third criterion also falls short. His analysis to this point

consists of ruling out a potential viral infection, instead characterizing her febrile illness as

“prodromal symptoms” of an autoimmune encephalitis. Tr. 107. Though he does not directly

address conversion disorder in the context of an alternate cause for the Graus et al. criteria, he does

argue she does not have conversion disorder largely based on the opinions of Dr. Sheets and Dr.

Nespeca. What Dr. Huq does not address is the consistent flaring of Petitioner’s symptoms around

her scheduled returns to school, something noted by several of her providers, including Dr. Sheets.

Dr. Huq also argues that Petitioner had no history of abuse and that a psychiatrist did not diagnosis

Petitioner with a DSM V diagnosis, meaning that Petitioner cannot have conversion disorder

because that is a DSM V diagnosis. However, I find Dr. Lancaster’s explanation of this point in

the entitlement hearing to be persuasive, especially given that Petitioner’s symptoms consistently

flared around the time she would be scheduled to return to school, and could be a potential stressor,

triggering a conversion reaction.

This leaves the presence of ɑ3-AChR antibodies as the sole objective evidence of a

potential autoimmune injury, however, I do not find this alone to be a sufficient indicator of such

an injury in Petitioner’s case. Petitioner’s ɑ3-AChR varied between 0.06 nmol/L at its lowest to

0.11 nmol/L at its highest, which would fall into the low-titer and lower portion of the medium-

titer levels identified by McKeon et al., respectively. Pet’r’s Ex. 40 at 5. It was in these ranges

where the authors identified a majority of the low-titer presentations as non-immune-mediated

neurological disease or non-neurologic diseases entirely. Id. The authors also explicitly stated that

“[i]t is unlikely that the AChR ɑ3-subunit is the primary autoantibody target in all neurological

presentations described in this article.” Id. at 7. Further, Ebright et al. provides a useful analysis of

the potential for false positives from this test, noting that in the case of ɑ3-AChR ABV there was

a false-positive rate of 86%. Resp’t’s Ex. A, Tab 3 at 6. Dr. Huq argues that McKeon et al.

“interpret their own data differently,” however, this figure would seem to align with the rate of

non-neurologic disease and the disclaimer provided by the authors, providing caution against using

the presence of low-titer antibodies as a diagnostic tool for encephalitis, encephalopathy, or

encephalomyelitis. Pet’r’s Ex. 61 at 5. Dr. Nespeca’s comments that Petitioner’s presentation was

inconsistent with reports of elevated ɑ3-AChR is also persuasive to this point.

In sum, although some of her providers suspected an autoimmune encephalomyelitis as the

cause of Petitioner’s symptoms, her overall course of progression appear to detail these providers

continuing to return to the possibility of conversion disorder, despite their own notations regarding

the potential pathogenic presence of ɑ3-AChR antibodies. Because I do not find that the presence

of these antibodies at the levels demonstrated in Petitioner’s case to be sufficient evidence of

autoimmune encephalomyelitis on their own, and because no other objective findings showed

41

evidence of autoimmune encephalomyelitis, Petitioner has failed to provide preponderant evidence

that she suffered from autoimmune encephalomyelitis. Instead, I find the record preponderantly

reflects that Petitioner suffered from conversion disorder.

B. Althen Prong One

Under Althen prong one, Petitioner must set forth a medical theory explaining how the

received vaccine could have caused or sustained injury. Andreu, 569 F.3d at 1375; Pafford, 451

F.3d at 1355–56. Petitioner’s theory of causation need not be medically or scientifically certain,

but it must be informed by a “sound and reliable” medical or scientific explanation. Boatmon, 941

F.3d at 1359; see also Knudsen, 35 F.3c at 548; Veryzer v. Sec’y of Health & Hum. Servs., 98 Fed.

Cl. 214, 223 (2011) (noting that special masters are bound by both § 13(b)(1) and Vaccine Rule

8(b)(1) to consider only evidence that is both “relevant” and “reliable”), aff’d 475 F. App’x 765

(Fed. Cir. 2012). If Petitioner relies upon a medical opinion to support her theory, the basis for the

opinion and the reliability of that basis must be considered in the determination of how much

weight to afford the offered opinion. See Broekelschen, 618 F.3d at 1347 (“The special master’s

decision oftentimes is based on the credibility of the experts and the relative persuasiveness of

their competing theories”); Perriera v. Sec’y of Health & Hum. Servs., 33 F.3d 1375, 1377 n.6

(Fed. Cir. 1994) (stating that an “expert opinion is no better than the soundness of the reasons

supporting it” (citing Fehrs v. United States, 620 F.2d 255 (Ct. Cl. 1980))). Importantly, as the

Federal Circuit has made clear, “simply identifying a ‘plausible’ theory of causation is insufficient

for a petitioner to meet her burden of proof.” LaLonde, 746 F.3d at 1339. Instead, Petitioner must

show it was more likely than not that the vacc

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