Castaneda v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 15-1066V

Filed: May 18, 2020

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

*

KATHY CASTANEDA, on behalf of N.A.C., **

a minor child, *

* PUBLISHED

Petitioner, *

*

*

v. * Dismissal; Pentacel, MMR, Prevnar 13

* Vaccines; Pediatric Acute Onset

SECRETARY OF HEALTH AND * Neuropsychiatric Syndrome (PANS);

HUMAN SERVICES, *

* Insufficient Proof of Causation

*

Respondent. *

*

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

Andrew D. Downing, Van Cott & Talamante, PLLC, Phoenix, AZ, for Petitioner.

Daniel A. Principato, U.S. Department of Justice, Washington, DC, for Respondent.

DECISION DENYING ENTITLEMENT1

Oler, Special Master:

On September 25, 2015, Petitioner Kathy Castaneda, on behalf of her son, N.A.C., filed a

petition seeking compensation under the National Vaccine Injury Compensation Program (the

“Vaccine Program”). 2 Pet., ECF No. 1. Petitioner subsequently filed an amended petition on

November 29, 2016 alleging that N.A.C. suffered pediatric acute-onset neuropsychiatric syndrome

1

This decision will be posted on the United States Court of Federal Claims’ website, in accordance with

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

anyone with access to the internet. As provided in 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties

may object to the decision’s inclusion of certain kinds of confidential information. To do so, each party

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

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

or similar files, the disclosure of which would constitute a clearly unwarranted invasion of privacy.”

Vaccine Rule 18(b). Otherwise, this decision will be available to the public in its present form. Id.

2

The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L.

No. 99-660, 100 Stat. 3758, codified as amended at 42 U.S.C. §§ 300aa-10 through 34 (2012) (“Vaccine

Act” or “the Act”). Individual section references hereafter will be to § 300aa of the Act (but will omit that

statutory prefix).

1

(PANS), “an overlap of symptoms of OCD, Tourette’s syndrome, ADHD, and bipolar disorder,”

as a result of the Pentacel, MMR, Hepatitis A, 3 and Prevnar 13 vaccinations N.A.C. received on

September 26, 2012. Am. Pet., ECF No. 32.

Upon review of the evidence submitted in this case, I find that Petitioner has failed to carry

her burden showing that she is entitled to compensation under the Vaccine Act. Petitioner has

failed to show that the condition from which N.A.C. suffered was caused by his vaccinations. As

such, entitlement to compensation is denied and the petition is dismissed.

I. Procedural History

Petitioner filed her petition4 on September 25, 2015. ECF No. 1. She filed medical records

on November 20, 2015 (Exs. 1, 2, 3), December 9, 2015 (Exs. 4, 5), February 1, 2016 (Ex. 6),

February 17, 2016 (Ex. 7), March 14, 2016 (Ex. 8), and November 8, 2018 (Ex. 47).

Respondent filed a Rule 4(c) Report on May 31, 2016 presenting his analysis of Petitioner’s

claims and recommending that compensation be denied. Resp’t’s Rep., ECF No. 23-1. Petitioner

subsequently filed an amended petition on November 29, 2016. ECF No. 32.

On March 2, 2017, Petitioner filed Dr. Kiki Chang’s expert report along with his

curriculum vitae (“CV”). Exs. 14, 15; ECF Nos. 41-42. Petitioner filed all of the medical literature

cited by Dr. Chang on March 21, 2017. Exs. 16-34, ECF Nos. 44-45.

On June 14, 2017, Respondent filed an expert report by Dr. Donald Gilbert, his CV, and

all of the cited medical literature. Exs. A, A1-A11, B; ECF Nos. 47-48.

Petitioner filed an updated CV for Dr. Chang as well as additional medical literature on

September 5, 2018. Exs. 35-37, ECF Nos. 54-55. Petitioner filed her prehearing brief on

September 6, 2018. ECF No. 56. Respondent’s submission followed on September 23, 2018.

ECF No. 57.

Between September 25 and September 27, 2018, Petitioner filed additional medical and

school records. Exs. 38-40, ECF Nos. 61-63.

I held an entitlement hearing on October 4 and October 5, 2018. After the hearing,

Petitioner filed additional medical literature on October 26, 2018. Exs. 43-46, ECF No. 72. The

two volumes of the hearing transcript were entered on November 5, 2018. ECF Nos. 75-76. On

November 7, 2018, Respondent filed a compact disc containing videos that were played during the

entitlement hearing. Exs. D, E, F. Petitioner filed additional medical records on November 8,

2018. Ex. 47, ECF No. 78.

3

The vaccination record indicates that N.A.C. did not receive his Hepatitis A vaccine on September 26,

2012. See Ex. 1.

4

This case was initially assigned to now-retired Special Master Millman (ECF No. 4) and re-assigned to

my docket on January 16, 2018 (ECF No. 51).

2

On December 18, 2018, the parties filed a joint status report indicating that “the record is

complete.” ECF No. 79. I issued a scheduling order setting deadlines by which the parties were

to submit their respective post-hearing briefs. See Non-PDF Order of December 19, 2018.

Petitioner filed her brief on February 18, 2019 (ECF No. 80) and Respondent filed his brief on

May 17, 2019 (ECF No. 84).

On September 10, 2019, I issued an order asking each expert to answer several questions.

ECF No. 97. Petitioner filed a response from Dr. Chang on November 15, 2019. Ex. 49, ECF No.

99. Respondent filed a response from Dr. Gilbert on December 10, 2019. Ex. C, ECF No. 102.

Petitioner filed a response to Dr. Gilbert’s supplemental report on December 19, 2019. ECF No.

103. Respondent re-filed Petitioner’s Facebook page on February 26, 2020. Ex. G. This matter

is now ripe for a decision.

II. Medical Records

A. Petitioner’s Health Prior to the Allegedly Causal Vaccination

N.A.C. was born on October 9, 2007. He presented to the pediatrician for well-child visits

at two months (Ex. 47 at 18, 50), four months (Ex. 47 at 48), six months (Ex. 47 at 13, 60), 12

months (reference to this visit at Ex. 47 at 3), and 18 months (Ex. 47 at 65). No records of any

additional well-child visits were filed in this case.5

N.A.C. was treated for various complaints prior to his September 26, 2012 vaccinations.

See Ex. 4 at 122, 124, 131 (ER visit on July 3, 2010 at Washington County Hospital (“WCH”) for

fever, diagnosed with otitis media); id. at 112-13, 118 (ER visit on July 4, 2010 at WCH for rash);

Ex. 3 at 5-7 (visit at Martin General Hospital on July 5, 2010 for chickenpox); Ex. 4 at 102 (ER

visit at WCH February 5, 2011 for earache); id. at 93, 98 (ER visit at WCH on May 28, 2011 for

laceration on right foot sustained after a fall); id. at 83 (ER visit at WCH on February 22, 2012 for

cough, fever, and vomiting); id. at 73, 76 (ER visit at WCH on April 19, 2012 due to cutting finger

with a knife); id. at 61, 63 (N.A.C. burned his left hand (palm) by grabbing something plastic that

melted and subsequently went to the zoo and fell on his hand, he had an ER visit at WCH on May

29, 2012); Ex. 7 at 2, 3 (visit with primary care physician on May 31, 2012 that notes N.A.C.’s

5

I held a status conference with the parties on September 25, 2018 and requested that Petitioner file all of

N.A.C.’s well-child visits that pre-date his September 26, 2012 vaccinations. ECF No. 64. During the

hearing, when asked about well visits, Petitioner testified that the well visits are “from birth on up to like

maybe two, three. And that has all his baby checkups and birth weights, all of that from birth on up.” Tr.

at 87. At the hearing, I reiterated my request that Petitioner file medical records that specifically contain

these well visits, as none had been filed up to this point. Tr. at 417. Petitioner filed additional medical

records after the hearing (Ex. 47), but these records did not include any well visits after 18 months. In a

supplemental affidavit, Petitioner stated that “N.C. was a healthy child without any complaints, so I did not

take him in for either a 24-month or 36-months well-child checkup.” Ex. 48. Respondent’s expert, Dr.

Gilbert describes the pre-vaccination evidence in this case as “a complete absence of standard medical

records from […] 2 year and 3 year well child visits.” Ex. C at 3. I agree with this assessment and note

that the absence of such records makes analysis of the issues in this case more difficult.

3

second degree burn on left hand); id. at 4-5 (visit with primary care physician on June 7, 2012 for

follow up regarding left hand burn).

B. Petitioner’s Health after the Allegedly Causal Vaccination

On September 26, 2012, N.A.C. received MMR, Prevnar 13, and Pentacel vaccinations. 6

See generally Ex. 1.

On October 9, 2012, N.A.C. was admitted to Vidant Medical Center with complaints of

behavioral problems, which included a twitch, stutter, and increased crying. Ex. 5 at 1, 2. The

“behavior problem” was described as new, starting “in the past few days.” Id. at 3. His mother

reported that N.A.C. “has always been an irritable child but has been worse over the past few

weeks. He has been fussy, crying more frequently, and misbehaving.” Id. at 2. He was reported

to be walking strangely by taking one or two steps and then shuffling. Id. His mother also reported

that N.A.C. had “been leaning his head right, then left, then saying ‘stop’” and had been doing so

repeatedly. Id. N.A.C. cried during his examination but stopped crying in order to answer

questions. Id. He denied pain and denied headache. Id. He did not have a fever. Id. at 3. His

physical examination was generally normal, however, during his psychiatric exam he was noted

to appear anxious and agitated. Id. at 4. The doctor indicated that N.A.C.’s behavior problems

“seem to be an exacerbation of some ongoing behavior problems” and noted his mother’s concerns

that N.A.C.’s symptoms may be tics. Id. N.A.C.’s head CT results were normal. Id. at 5. The

differential diagnoses were “ODD [Oppositional Defiant Disorder], tic/Tourettes, ongoing chronic

behavior problems, [and] intracranial process”. Id. at 4. The doctor provided Petitioner with the

contact information for child psychiatry. Id. at 5.

The medical record of N.A.C.’s October 11, 2012 visit notes that patient “complained of

unusual behavior.” Ex. 8 at 3. N.A.C.’s medical record reports that on October 12, 2012, N.A.C.

was seen for a follow up and that his “behavior seems to [be getting] worse.” Ex. 8 at 2. N.A.C.’s

temperature was listed as 97.9˚. Id.

On October 15, 2012, N.A.C. saw Dr. Ingrid Loma-Miller (a neurologist) for his abnormal

involuntary movements. Ex. 2 at 10. Petitioner informed the doctor that on September 27th, about

one or two days after his MMR vaccination, N.A.C. “started having episodes of abnormal

movements consisting of neck flexion, shoulder shrugging and throat clearing episodes.” Id.

While N.A.C. is aware of his episodes, he is unable to stop. Id. N.A.C. also had episodes “where

he would bang his head against the wall.” Id. His episodes were described to include obsessive

behaviors, which included repeating actions three times. Id. Petitioner expressed her concerns

that his episodes are “related to the vaccine that he got.” Id. During the examination, N.A.C. made

good eye contact but was noted to be uncooperative and refused to answer certain questions. Id.

at 11. He was able to name objects correctly when asked by Petitioner but only limitedly. Id.

6

Petitioner stated during testimony and in a letter to the Nursing Board (Ex. 39) that N.A.C. received four

vaccinations on the date in question. However, N.A.C.’s vaccination record shows that Petitioner received

only three vaccinations as listed above. Ex. 1. In the letter to the Nursing Board, Petitioner represented

that the record was incorrect and N.A.C. received a fourth vaccination (Varicella), that was deleted from

N.A.C.’s record.

4

Overall, his neurologic exam appeared to be normal. Id. Dr. Loma-Miller assessed N.A.C. with

“new-onset [of] abnormal movements, which appear to be tic-like in type.” Id. The record notes

that Dr. Loma-Miller “explained to the mother that [she] [does] not think that [N.A.C.’s] abnormal

movements are related to the vaccines” and that “[t]here [were] no specific data in the medical

literature to support such concerns.” Id. Regarding N.A.C.’s tics, Dr. Loma-Miller wondered if

N.A.C. had a tic disorder that could possibly be Tourette syndrome due to N.A.C.’s motor and

vocal tics. Id. She noted that N.A.C. had yet to meet the criteria for Tourette at such time due to

the fact symptoms had been occurring for less than one month. Id. Dr. Loma-Miller also explained

to Petitioner that OCD has been observed alongside tic disorders, and N.A.C. may exhibit

symptoms of OCD behavior along with his tic disorder. Id.

N.A.C. saw his primary care physician on October 18, 2012 and the record notes, “mother

states wants [sic] blood test.” Ex. 7 at 16. The record also indicates, “abn[ormal] behavior r/o

tic.” Id. at 17.

N.A.C. presented to Dr. Loma-Miller for a follow-up visit on November 9, 2012 in order

to discuss his EEG results. Ex. 2 at 8; see also Ex. 2 at 12. The record indicates that N.A.C.

continued to have episodes of abnormal movement since his previous visit. Ex. 2 at 8. Petitioner

reported to Dr. Loma-Miller that N.A.C. has also been getting very moody and aggressive. Id.

Dr. Loma-Miller noted that Petitioner had done research on Tourette syndrome and reported that

N.A.C. was exhibiting many of the symptoms, including “facial grimacing, shoulder shrugging,

sniffing, throat clearing and squeaking.” Id. Petitioner also reported that N.A.C. had been acting

impulsively and had several compulsions, such as “rechecking things over and over again, smelling

things, touching things…. He has to do 3 of everything.” Id. Petitioner told Dr. Loma-Miller that

the Tenex had not improved the tics and that his behavior was more concerning at that time, adding

that he was sleeping well. Id. Neurologic examination was normal, and N.A.C. was noted to have

good eye contact, but was fidgety and hyperactive. Id. at 9. His EEG was normal. Id. The doctor

also noted his blood work, which showed: ANA was negative; his lead was less than 5; his

“[c]omplete metabolic panel [was] normal except for mildly elevated AST of 39 and sodium 139”;

and his “CBC was significant for decreased hemoglobin and hematocrit of 12.4/35 with MCV low

at 78.” Id. Dr. Loma-Miller’s assessment noted that N.A.C. was neurologically stable and had

abnormal involuntary movements, “which appear to be more tic behavior and consistent with

Tourette syndrome.” Id. Dr. Loma-Miller directed that N.A.C. to stop taking Tenex7 and try

Clonidine8 for his behavioral issues. Id. Lastly, the doctor provided a referral for behavioral

therapy and psychology. Id.

7

Tenex is the trademark for a preparation of guanfacine hydrochloride. DORLAND’S ILLUSTRATED

MEDICAL DICTIONARY (33rd ed. 2020) at 1853 (hereinafter “Dorland’s”). Guanfacine hydrochloride is “an

α2-adrenergic agonist that stimulates the α2-adrenergic receptors of the central nervous system, resulting in

reduction of sympathetic overflow to the heart and peripheral vascular system, used as an antihypertensive,

administered orally.” Id. at 801.

8

Clonidine is “an α2-adrenergic agonist-antagonist … administered orally or transdermally as an

antihypertensive.” Dorland’s at 368. The clonidine was to be given at 0.1mg at night and could be scaled

up to 0.1mg twice per day if needed. Ex. 2 at 9.

5

N.A.C. saw Dr. Loma-Miller on March 11, 2013 for a follow-up visit regarding his tic

disorder. Ex. 2 at 7. Petitioner reported that Clonidine was helpful, but not consistently. Id.

Petitioner was not only concerned with N.A.C.’s tic disorder but also his behavior, reporting that

he “gets very easily upset, moody, and angry.” Id. Petitioner recalled for Dr. Loma-Miller that

when N.A.C. “gets upset, he starts jumping. He also gets very upset and cries for no reason, very

defiant.” Id. Dr. Loma-Miller noted that N.A.C. had yet to visit psychology. Id. The record

further indicates that N.A.C. has “OCD where he has to have a certain pattern of doing things.”

Id. The record describes his pattern of closing the bathroom door and rotating store products to

face forward. Id. Petitioner reported that if N.A.C. is unable to conduct his same routine, he

becomes very upset. Id. Regarding N.A.C.’s development, Petitioner reported that he has been

learning new things and now knows his shapes. Id. Physical examination was normal, although

the doctor noted that N.A.C. was still shy and not making eye contact. Id. at 7. Neurological

examination was normal, although the doctor noted that N.A.C. was “very fidgety like before, very

hyperactive.” Id. Dr. Loma-Miller noted in his assessment that N.A.C. had a history of tic

disorder, and that he meets the criteria for Tourette syndrome. Id. Dr. Loma-Miller, again, referred

N.A.C. to psychology, and she explained to Petitioner the importance of scheduling this

appointment in order to assist N.A.C. with his behavioral problems. Id.

On August 27, 2013, N.A.C. saw Dr. Loma-Miller at Children’s Hospital’s neurology

office. Ex. 2 at 4. Petitioner reported that he “has been doing the same.” Id. She further reported

that “[f]ather did not want to go up on his dose … therefore he only takes clonidine, one tablet at

night.” Id. Petitioner stated that the Clonidine did not change N.A.C.’s tics and that he “still has

some eye blinking.” Id. N.A.C. was noted to be “constantly bothered.” Id. Petitioner denied

concerns for headaches, seizure activity, focal weakness, numbness or tingling. Id. Dr. Loma-

Miller noted that Petitioner expressed interest in having N.A.C. evaluated for autism. Id. N.A.C.

was uncooperative during physical examination and did not respond to any questions. Id. at 5. He

was able to follow “one-step commands” but had difficulty completing complex tasks. Id.

Neurologic examination was normal. Id. Dr. Loma-Miller’s assessment noted N.A.C.’s history

of Tourette syndrome and Dr. Loma-Miller “agree[d] with [N.A.C.’s] mom that he may be in the

spectrum of autism, but however, it is not clear cut….” Id. Dr. Loma-Miller referred N.A.C. to

Developmental Pediatrics for autism evaluation, directed that N.A.C. continue taking Clonidine,

and recommended that N.A.C. take Miralax for bowel incontinence and constipation. Id. Dr.

Loma-Miller again encouraged Petitioner to have N.A.C. follow up with psychology for behavioral

therapy and treatment. Id.

On August 30, 2013, N.A.C. saw his primary care physician for a kindergarten physical.

Ex. 7 at 14.

N.A.C. had an ER visit at WCH on January 16, 2014 for fever and cough. Ex. 4 at 34-35.

His history of Tourette syndrome was noted. Id. at 35. Lab results revealed that N.A.C. tested

positive for influenza A protein antigen. Id. at 38.

On May 7, 2014, N.A.C. had an ER visit at WCH for an itchy rash that he had on his

buttocks for the past three days. Ex. 4 at 22, 25. The medical record notes that he is taking

Clonidine. Id. at 23.

6

N.A.C. had an ER visit at WCH on June 2, 2014 for a splinter in his foot. Ex. 4 at 8-9. His

history of Tourette syndrome is also noted in the medical records. Id. at 12, 20.

On August 11, 2014, N.A.C. was seen at the Children’s Hospital of The King’s Daughters

(“Children’s Hospital”) pediatric neurology office by Dr. Matthew S. Warren. Ex. 2 at 2. The

record notes his routine visits with the office’s neurologist, Dr. Loma-Miller, as well as N.A.C.’s

history of vocal and motor tics and diagnosis of Tourette syndrome. Id. The record notes that

N.A.C.’s tics wax and wane. Id. The record indicates a concern that N.A.C. fits the autism

spectrum and notes his family history is positive for autism but that there are no psychiatric issues

in the family. Id. Physical and neurologic examinations were normal, however, the doctor noted

that N.A.C. is uncooperative during examination and that he refuses to walk on his toes; N.A.C.

had temper tantrums in the office. Id. at 3. The doctor’s impression remained Tourette syndrome

with comorbid ODD. The doctor noted Dr. Loma-Miller’s encouragement that N.A.C. see a

psychologist, which had yet to occur, however, according to Dr. Warren, N.A.C. “definitely needs

a psychological evaluation.” Id.

A medical record that reflects an admit date of September 18, 2014 reports N.A.C.’s

hematology results. Ex. 7 at 11. The record notes that N.A.C. has a history of “anemia – CBC”.

Id. at 12. The record also notes that N.A.C. had “ice cold” and “white (pale) color” hands for the

past two days as well as “dark colors under eyes.” Id. at 13.

A medical record dated May 29, 2015 notes “refer to psyc” and “clonidine”. Ex. 7 at 9.

N.A.C.’s history of Tourette syndrome, Attention-Deficit/Hyperactivity Disorder (“ADHD”),

Obsessive-Compulsive Disorder (“OCD”), and ODD is noted in the medical record. Id. at 10.

On July 2, 2015, N.A.C. saw his primary care physician for prescription refills. Ex. 7 at 7.

The record notes “tic”, “ADHD”, and “f/u psyc” as well as “clonidine”. Id. at 8.

N.A.C. visited Martin General Hospital on July 30, 2015 for left ear pain that began two

days prior to his visit. Ex. 3 at 1-2. The medical record notes a history of Tourette syndrome. Id.

at 2. N.A.C. was diagnosed with otitis externa. Id. at 3.

No other medical records filed were pertinent to the issues to be addressed in this case.

III. School Records

Petitioner filed records from evaluations N.A.C. received in a school setting. See Ex. 40.

Kimberly Page Reel, a licensed psychological associate at N.A.C.’s school, administered several

tests, which included the Childhood Autism Rating Scale (CARS-2) and the Gilliam Autism

Rating Scale (GARS-3). With respect to the GARS-3, both Petitioner and N.A.C.’s teacher

provided responses to questions indicating, in the opinion of the assessor that “it is very likely that

[N.A.C.] demonstrates behaviors consistent with an Autism Spectrum Disorder.” Ex. 40 at 55.

The results of the CARS-2 were not as pronounced; the general impression of N.A.C.’s teacher “is

that [N.A.C.] displays a mild degree of symptoms similar to a child with an Autism Spectrum

Disorder.” Id. at 54. In summary, Ms. Reel indicated that N.A.C. “may be autistic.” Id. at 55.

7

IV. Affidavits and Fact Testimony

A. Affidavits

Petitioner reported that “[i]n the days following” N.A.C.’s vaccinations, she “started

noticing odd things with N.A.C.”9 See Statement of Kathy Castaneda, Ex. 13 at 2. Petitioner

stated that N.A.C.’s odd actions became a daily occurrence, and she and her husband were unable

to determine what was going on; they attributed N.A.C.’s actions to “just being a kid, because kids

do weird things.” Id. Their concerns continued to grow as N.A.C. told them that he could not stop

his behavior, even though he got in trouble. Id.

On October 9, 2012, N.A.C. was admitted to Vidant Medical Center with complaints of

behavioral problems, which included a twitch, stutter, and increased crying. Ex. 5 at 1, 2.

Petitioner explained that about two or three days prior to his October 9, 2012 admission at Vidant

Medical Center, “N.A.C.’s symptoms had worsened.” Ex. 13 at 2. She stated that he began

“stuttering really badly to the point that he could barely say anything” and that he “started banging

his head into things…and would repeat the word ‘stop’ as he banged his head.” Id. N.A.C. would

continue banging his head until he cried, and he would inform Petitioner that he could not stop.

Id.

Petitioner noted that while at Vidant Medical Center she asked the doctor whether vaccines

could be the cause of N.A.C.’s problems, and that “[t]he doctor told us that the vaccines could

have possibly caused this.” Ex. 13 at 3. The medical record does not reflect this conversation.

See generally Ex. 5.

On October 11, 2012, Petitioner took N.A.C. to see Dr. Myung Kil Jeon, at Plymouth

Primary Care. Ex. 13 at 3. The doctor said that N.A.C. was having tics and involuntary body

movements. Id. Petitioner wrote that she asked if the vaccines could have caused this, and

according to Petitioner, the doctor said yes. Id. The medical record does not reflect this

conversation. See generally Ex. 8.

On October 15, 2012, Petitioner and her husband took N.A.C. to a neurology appointment.

Ex. 13 at 3. According to Petitioner, the neurologist informed her that Tourette syndrome could

9

Petitioner provided the following examples:

…when he walked, he would walk a couple of steps, stop suddenly, and then repeat this

process. He would move his head to his shoulder so that the side of his head touched his

shoulder two or three times. His head would go down and his shoulder would shrug up to

meet his head, and then he would quickly do the same thing on the opposite side….[he]

also started spitting on his shoulder….[he] began to copy what [her] husband and [she]

would say….[he] started doing things in threes; for example, he would pick up or set down

his cup three times (same with his toys, eating utensils, crayons, or anything he could pick

up). He would flush the toilet three times, turn lights on and off three times, and had to go

through any doorway three times.

Ex. 13 at 2.

8

not be diagnosed until February 2013. Id. at 3-4. When Petitioner asked if the vaccines could

have caused N.A.C.’s condition, the doctor “was quick to say no” because “the government frowns

on doctors who say injuries occur from vaccines.” Id. at 4.

Petitioner also stated that she did not take N.A.C. to either a 24-month or 36-month well-

child checkup because he was a “healthy child”. Ex. 48 at 1.

B. Fact Testimony

Petitioner testified at the October 4, 2018 hearing. She described N.A.C. as a playful little

boy who loved being outdoors. Tr. at 10. Petitioner also testified that N.A.C. met all of his

milestones and experienced no obsessive-compulsive tendencies or tics prior to the allegedly

causal vaccinations. Id. at 10, 12. Petitioner stated that on September 26, 2012, N.A.C. was

supposed to receive a total of five vaccinations but had gotten chicken pox from his brother’s live

virus varicella vaccination in 2009 and didn’t need the varicella vaccination, therefore N.A.C. only

received four vaccinations. Id. at 14-15.

Petitioner stated that on the next day, approximately 30 hours after vaccination, she was

holding hands with N.A.C. and he abruptly stopped walking, stepped in place three or four times,

continued walking a few steps, and stepped in place again. This cycle repeated. Tr. at 15-16.

N.A.C. would also move his head from shoulder to shoulder repeatedly. Id. at 16. Another tic that

N.A.C. developed was spitting on his own shoulder, covering his shirt with saliva. Id. Petitioner

recalled an incident where N.A.C.’s father reprimanded N.A.C. for spitting on his shirt and on the

couch and told N.A.C. to stop spitting. Id. N.A.C. said he could not stop spitting and began crying

and telling himself to stop. Id. at 16-17.

Petitioner described other changes in N.A.C., which included N.A.C. having aggressive

fits. Tr. at 17. N.A.C. would throw toys or small objects and would kick, bruising his parents and

siblings. Id. at 17, 36, 45-46. N.A.C. would also flush the toilet three times, pick up and set things

down multiple times, flip the light switch on and off, and jump in the same place repeatedly. Id.

at 18, 47. Petitioner bought N.A.C. a trampoline because N.A.C. wanted to jump on a springy

surface and ruined their couch by his jumping. Id. at 47-48. Petitioner also noted that N.A.C.

became less social and got angry at himself for not being able to stop his tics. Id. at 18, 42-43.

N.A.C. would frequently bang his head against various surfaces. Id. at 18, 24.

Petitioner testified that neither N.A.C.’s sibling nor half-siblings have any neuropsychiatric

behavioral issues. Tr. at 60. None of N.A.C.’s extended family members have Tourette syndrome

or tic-based behaviors, though Petitioner’s brother, N.A.C.’s uncle, has ADHD. Id. at 69-70.

V. Expert Opinions

A. Dr. Kiki Chang

Petitioner filed one expert report and one supplemental report from Dr. Kiki Chang; Dr.

Chang also testified at the hearing. See Expert Report, filed as Ex. 14, hereinafter “Chang Rep.”

and Supplemental Expert Report, filed as Ex. 49, hereinafter “Chang Supplemental Rep.”.

9

1. Qualifications

Dr. Chang attended Princeton University and graduated in 1988 with a degree in molecular

biology. See Chang CV at 1, filed as Ex. 15 (ECF No. 42) (“Chang CV”). He then attended Tufts

Medical School, graduating in 1993. Id. Dr. Chang completed his residency at the University of

Cincinnati in general psychiatry. Id. After his general residency, Dr. Chang completed a three-

year combined research and clinical fellowship in child and adolescent psychiatry at Stanford

University. Id. In 1999, Dr. Chang was appointed as an assistant professor of psychiatry and

behavioral sciences at Stanford University. Tr. at 99. During his time at Stanford, Dr. Chang was

on the faculty at Stanford University Hospital and Stanford’s Children’s Hospital. Id. at 100. He

is currently licensed in California. Chang CV at 1.

After approximately 18 years at Stanford, Dr. Chang opened his own practice. Tr. at 98-

99. He currently sees patients two to three days per week. Id. at 99. Dr. Chang treats children,

adolescents, and adults with complex psychiatric and neuropsychiatric illnesses. Id. He treats

patients with bipolar disorder, serious mood disorders, anxiety disorders, pediatric autoimmune

neuropsychiatric disorder associated with streptococcal infection (“PANDAS”), and PANS. Id.

Dr. Chang spends approximately 70% of his time in clinical practice. Id. at 97. Approximately

30% of his time is devoted to consultations and speaking about various psychiatric illnesses. Id.

Dr. Chang is a member of the American Association of Child and Adolescent Psychiatry and the

American College of Neuropsychopharmacology. Chang CV at 1. Dr. Chang has published

numerous medical journal articles and has participated as a journal referee, peer-reviewing journal

articles. Tr. at 100. I recognized Dr. Chang as an expert in the areas of Pediatric and Adolescent

Psychiatry, and Neuropsychiatric Illness. Id. at 106.

2. Expert Testimony

In his report and at the hearing, Dr. Chang opined that N.A.C. developed PANS as a result

of the vaccinations he received on September 26, 2012. Chang Rep. at 4; Tr. at 197.

In 2012, Dr. Chang formed Stanford University’s PANS clinic. Tr. at 103. In 2013, Dr.

Chang organized the expert consensus meeting for researchers on PANS and PANDAS at Stanford

University. Id. at 102. At that meeting, experts clarified the clinical criteria for a diagnosis of

PANS. Id. Dr. Chang estimated that he has seen anywhere from 100 to 200 patients diagnosed

with PANS. Id. at 104.

Dr. Chang went on to explain that in the 1990s, Dr. Susan Swedo at the National Institutes

of Health proposed PANDAS as a diagnosis. Tr. at 106. Dr. Chang explained that this disorder

involves an acute onset of OCD along with accompanying symptoms such as “motor tics,

behavioral problems, changes in … handwriting, changes in … focus and concentration, extreme

aggressiveness, irritability, depression, [and] extreme separation anxiety” that occur after strep

infection. Id. at 107.

PANS was then established as a diagnosis to address the fact that some children displayed

acute onset of various symptoms without clear-cut streptococcal infection. Tr. at 109. Dr. Chang

10

explained that with respect to acuity of onset, it was agreed at the 2013 meeting that for PANS,

onset of comorbid symptoms is between 48 and 72 hours. Id. at 111. Dr. Chang further clarified

that “what that means is that it had to be going from not noticing any symptoms to noticing

significant symptoms within that time as well as the associated symptoms starting to emerge.” Id.

He stated that “it couldn’t be something that may have developed gradually over a month or two

months or a year.” Id. Dr. Chang explained the reason for the necessity of acute onset is “to

distinguish it between other more typical neuropsychiatric illnesses like OCD and Tourette that

tend to have a more gradual onset.” Id.

Dr. Chang stated that the criteria for PANS differed from PANDAS. Tr at 113. He

explained that unlike PANDAS, where the primary criterion is OCD or tics, in PANS the primary

criterion must be OCD or an eating restriction. Id. Concurrent with that, Dr. Chang stated that a

PANS patient must also have at least two of the following symptoms comorbidly: general anxiety,

separation anxiety, emotional lability and/or depression, irritability, aggression, oppositional

behavior, or behavioral developmental regression, deterioration in school performance, inability

to concentrate, becoming hyperactive, hand writing changes, working memory executive function

changes, sensory motor abnormalities including motor and vocal tics, and somatic signs and

symptoms. Id. at 114-15.

Dr. Chang went on to discuss mechanisms for the development of PANDAS and PANS.

Tr. at 116. He explained that in both PANDAS and PANS, there is a triggering event, “which is

either known or unknown, and because of the triggering event there is an inflammatory reaction

that for some reason targets the basal ganglia.” Id. Dr. Chang stated that the basal ganglia “fine

tunes many, if not all, of the brain functions.” Id. Dr. Chang explained that in both Parkinson’s

and Tourette syndrome, abnormalities in the basal ganglia have been noted. Id. at 117. He stated

that several “functional and structural studies done [on] the brain suggest that this area is related

to OCD, as well as tics, as well as ADHD symptoms.” Id. at 118.

Dr. Chang explained that based on his experience, there are two major mechanisms through

which PANDAS and PANS may develop. Tr. at 118. The first is an autoimmune mechanism

known as molecular mimicry, in which antibodies created against a particular antigen cross-react

with brain tissue, including basal ganglia tissue. Id. at 119. In other words, parts of an antigen

look enough like host brain tissue that the host would make antibodies against it, thinking that

might be a defense mechanism, and start attacking its own brain tissue. Id. Dr. Chang stated

“[s]omehow they would get past the blood-brain barrier, bind to the areas of the brain and trigger

inflammatory cascades that would then lead to inflammation and disruption of the area leading to

[PANS] symptoms.” Id.

The second mechanism Dr. Chang described is a general inflammatory reaction driven by

cytokine production. Tr. at 120. He explained that such reactions then lead to inflammatory

mediators crossing the blood-brain barrier and selectively attacking the basal ganglia. Id. Dr.

Chang emphasized that he does not know why it would attack the basal ganglia, but that “it’s sort

of a ripe area due to where it is located in the vasculature.” Id. Dr. Chang believes that this

mechanism is probably “more relevant” for this case. Id. He explained that there is some trigger

that causes an immune reaction to an inflammatory cascade that selectively hits the basal ganglia

and leads to PANS. Id. at 121. Dr. Chang stated that this mechanism can be triggered by infection,

11

by autoimmune conditions, or “it can be triggered by anything that can really cause an

inflammatory state, including a vaccination.” Id. at 122.

Dr. Chang discussed the Parker-Athill article (Parker Athill et al., Cytokine Correlations

in Youth with Tic Disorders, JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY, Vol.

25, No. 1, pp. 86-92 (2015), filed as Ex. 25 (hereinafter “Parker-Athill”)) as standing for the

proposition that inflammatory cytokine production was responsible for tic exacerbation in children

with Tourette syndrome or a chronic tic disorder. Tr. at 122-23. He testified that the same pro-

inflammatory cytokine tumor necrosis factor alpha is expressed following vaccination. Id. at 123.

When asked whether the model of cytokine involvement with neuropsychiatric disease is the same

for an infection and vaccination, Dr. Chang replied, “it very well could be.” Id. at 124.

When asked about timing of onset following a known trigger, Dr. Chang stated that onset

of symptoms is “usually fairly quick,” “within days” of the initial event, “at the most a week.” Tr.

at 124. Dr. Chang testified that OCD typically has a more gradual onset. Id. at 125. He highlighted

an article that stated “[a]ll participants exhibited an abrupt onset of OCD and associated

neuropsychiatric symptoms in contrast to the gradual onset experienced by children with non-

PANS OCD.” Tanya K. Murphy et al., Characterization of the Pediatric Acute-Onset

Neuropsychiatric Syndrome Phenotype, JOURNAL OF CHILD AND ADOLESCENT

PSYCHOPHARMACOLOGY, Vol. 25, No. 1, pp. 14-25 (2015), filed as Ex. 31.

Dr. Chang went on to compare Ms. Castaneda’s testimony regarding her son’s symptoms

with the clinical criteria for PANS. Under Roman Numeral I, Dr. Chang stated that N.A.C.

exhibited both OCD and eating restrictions. Tr. at 130. With respect to Roman Numeral II, Dr.

Chang described what he considered to be anxiety, emotional lability,

irritability/aggression/oppositional behaviors, behavioral regression, deterioration in school

performance, sensory motor abnormalities, and somatic signs and symptoms, all of which he stated

N.A.C. exhibited. Id. at 132-38. Although the PANS criteria only require at least two symptoms

under Roman Numeral II, in his opinion N.A.C. exhibited all seven symptoms. Id. at 138. Dr.

Chang concluded his analysis by testifying that, as required by Roman Numeral III of the criteria,

no other diagnosis better explains N.A.C.’s symptoms. Id. at 141.

Dr. Chang testified that Tourette syndrome typically does not present with the comorbidity

of symptoms and acuity of onset that was seen in N.A.C.’s condition. Tr. at 141. He stated that

Tourette syndrome has a more gradual development from motor tics to vocal tics, followed by

comorbidity of OCD and ADHD. Id. Dr. Chang testified that Tourette syndrome does not have

the same underlying mechanism as PANS. Id. When I asked him to clarify, he stated that Tourette

syndrome is more commonly associated with a genetic disorder or predisposition. Id. at 142.

Dr. Chang went on to discuss the Calaprice article (Calaprice et al., A Survey of Pediatric

Acute-Onset Neuropsychiatric Syndrome Characteristics and Course, JOURNAL OF CHILD AND

ADOLESCENT PSYCHOPHARMACOLOGY, pp. 1-12 (2017) (filed as Exhibit 16) (This article was

double filed as Ex. 16 and Ex. 37). Tr. at 144–47. He explained that this article related to a survey

of approximately 700 patients that had been clinically diagnosed with PANS. Id. Dr. Chang

testified that in this survey, “a significant portion…reported triggering events that have to do with

inflammation.” Id. at 145. About 300 of those surveyed, provided information about events

12

following vaccination. Id. at 146. Dr. Chang testified that of the 300, approximately half reported

“that vaccines appeared to precipitate a flare of PANS symptoms.” Id. In response to my question

about whether the article discussed timing between vaccination and flare, Dr. Chang clarified that

timing was not indicated. Id. at 148.

The final article that Dr. Chang discussed on direct examination was Exhibit 36. Tr. at

150. Douglas L. Leslie, et al., Temporal Association of Certain Neuropsychiatric Disorders

Following Vaccination of Children and Adolescents: A Pilot Case-Control Study, FRONTIERS IN

PSYCHIATRY (2017), filed as Ex. 36 (hereinafter “Leslie”). He testified that this article involved

children who presented with neuropsychiatric disorders. Id. Using a control group of children

with injuries including broken bones and open wounds, the researchers set out to determine what,

if any, connection prior vaccinations had to those children with neuropsychiatric disorder. Id. at

151. Dr. Chang stated that the study revealed an increased incidence of vaccination three, six, and

12 months prior to a new diagnosis of anorexia nervosa. Id. at 152. He stated that anorexia nervosa

is often a misdiagnosed food restriction under Roman Numeral I of the PANS criteria. Id. Dr.

Chang made it clear that this temporal study does not establish causation. Id. at 153.

Dr. Chang concluded his direct examination by stating that in his opinion NAC’s

September 26, 2012 vaccinations triggered his neuropsychiatric disease. Tr. at 154–55. He stated

that “it’s possible if he never received that vaccination or any vaccinations, it’s possible that he

never would have developed this.” Id. at 156–57.

On cross examination, Dr. Chang stated that there is some data, currently not published, to

suggest a correlation between PANS and HLA–B5 genotype. Tr. at 158. Dr. Chang is, however,

unaware whether N.A.C. possesses HLA–B5. Id. at 159. He stated that he is speculating that

N.A.C. has some sort of genetic predisposition for PANS. Id. Dr. Chang testified that he is not

familiar with the exact level of cytokine production following vaccinations. Id. at 160. He also

testified that he is not aware of any evidence of the permeability of the blood-brain barrier in

N.A.C.’s case. Id. at 161. Dr. Chang went on to clarify that there is “[n]o way of

definitively…seeing if that was actually inflammation going on” in N.A.C.’s case. Id. at 162.

Dr. Chang was unable to explain why N.A.C. did not have similar adverse reactions to all

of the previous routine vaccinations he had received up until September 2012. Tr. at 165. When

asked how one can rule out a diagnosis of autism, Dr. Chang explained that the acuity of onset and

the comorbidity of symptoms in N.A.C.’s case do not support what is typically seen in autism. Id.

at 177.

Following the entitlement hearing, Petitioner filed a supplemental report from Dr. Chang.

In this report, Dr. Chang stated that the video of N.A.C. in Exhibit E does not present as a motor

tic. Chang Supplemental Rep. at 1. More pronounced or repetitive movements would be more

indicative of a motor tic. Id. This video did not change Dr. Chang’s opinion of N.A.C.’s condition.

Id. Even if N.A.C. had motor tics, Dr. Chang stated that he has seen patients with “brief periods

of motor tics that then resolve, happening years before the onset of PANS.” Id. at 1-2.

B. Dr. Donald Gilbert

13

Respondent filed one expert report and one supplemental report authored by Dr. Donald

Gilbert; Ex. A, (hereinafter “Gilbert Rep.”) and Ex. C (hereinafter “Gilbert Supplemental Rep.”).

Dr. Gilbert also provided live testimony at the entitlement hearing.

1. Qualifications

Dr. Gilbert is currently a practicing physician and professor of pediatrics and neurology.

Tr. at 205. He graduated cum laude in 1987 from Princeton University with an undergraduate

degree in philosophy. Id. Dr. Gilbert taught high school before attending the University of

Michigan for medical school. Id. at 205-06. During medical school, he received a Howard Hughes

Medical Institute Scholarship to go to the National Institutes of Health to complete an additional

year, researching identification of genes involved in the process of HIV infection of brain cells

and the cytokines produced by the viruses when exposed to brain cells. Id. at 206.

After medical school, Dr. Gilbert completed his residency at Johns Hopkins University in

pediatrics and clinical child neurology. Tr. at 207. He holds a board certification in neurology,

with a special competence in child neurology. Id. After residency, Dr. Gilbert began in his current

position as a child neurologist at Cincinnati Children’s Hospital Medical Center. Id. Hired as an

assistant professor, Dr. Gilbert is now a full professor and treats patients with movement disorders.

Id. at 207-08. More specifically, Dr. Gilbert’s practice centers around patients with movement

disorders and neuropsychiatric symptoms arising from possible basal ganglia and cerebellar

dysfunction. Id. at 208. Dr. Gilbert also earned a master’s degree in statistics and clinical research

design. Id. at 207. Additionally, Dr. Gilbert founded the Tourette Syndrome and Movement

Disorders Clinic and serves as the director of the Movement Disorder Program. Id. at 209.

Outside of his regular practice, Dr. Gilbert has served on several boards and committees,

to include the Tourette Syndrome Association Medical Advisory Board, the Tourette Syndrome

Association Science Advisory Board, the Child Neurology Society Executive Committee, and the

neurology section of the American Academy of Pediatrics. Tr. at 211.

In 2002, Dr. Gilbert was approached to assist in two NIH funded PANDAS research

studies. Tr. at 212. He was involved in publications related to those two epidemiologic studies

and studies exploring the immune expression profiles of children with Tourette syndrome. Id. To

date, Dr. Gilbert estimated that he has written about 100 publications. Id. at 213.

Dr. Gilbert’s most recent publication relating to PANDAS or PANS was an article

published in the Journal of Pediatrics in August 2018. Tr. at 213. The same month, he presented

grand rounds at his institution on PANDAS and PANS. Id. at 214. Dr. Gilbert receives referrals

for PANDAS and PANS on a regular basis. Id. In total, Dr. Gilbert estimated that he treats about

six patients per month where a PANDAS or PANS diagnosis has been considered by the referring

physician or the parent. Id. at 215.

I recognized Dr. Gilbert as an expert in pediatric neurology and movement disorders. Tr.

at 215-16.

2. What is PANS?

14

Dr. Gilbert testified regarding the history of PANDAS and the emergence of PANS. Tr.

at 216. He agreed with Dr. Chang that PANS developed from PANDAS. Id. Dr. Gilbert testified,

however, that the studies conducted originally by Dr. Swedo, exploring whether strep infections

could cause tics or OCD, were flawed in their design and did not definitively answer the question.

Id. Dr. Gilbert stated that, on the contrary, the studies performed by Dr. James Leckman and Dr.

Roger Kurlan better identified and addressed the questions regarding PANDAS at that time: 1)

whether an exacerbation of tics or OCD followed identifiable infections, and 2) whether children

with PANDAS are different than those with Tourette syndrome or OCD, apart from the waxing

and waning of symptoms. Id. at 216-17. Dr. Gilbert stated that the studies determined that the

onset of exacerbated symptoms did not usually follow a recognizable infection or involvement of

the immune system and that there was no clear distinction between children with PANDAS and

those with Tourette syndrome. Id. at 217-18.

Dr. Gilbert testified that it was the lack of positive results from these studies that led to the

formation of PANS, in an effort to capture the children who presented with a “thunderclap onset

of severe symptoms” not caused by strep. Tr. at 218. Dr. Gilbert testified, however, that PANS

was and still is a working hypothesis regarding this presentation of symptoms. Id. at 219. He

stated that in his opinion, no autoimmune or inflammatory mechanism had yet been identified as

the cause of PANS. Id. Furthermore, he testified that the distinguishing factor between PANS

patients and OCD or anorexia nervosa patients was the acute onset of the symptoms, but

emphasized that no biological way of distinguishing the two had been identified. Id.

Dr. Gilbert testified that it was not clear that PANS was a distinct disorder or that PANS

could be caused by immune activation. Tr. at 219. Unlike the development of research relating

to NMDAR encephalitis, PANS research had not yet identified mechanisms of causation. Id. at

220. Dr. Gilbert added that gene identification in Tourette syndrome and autism research had

revealed that the identified genes dealt with nerve cell function rather than immune cell function.

Id. Dr. Gilbert testified that there are no clinical trials showing that the recommended immune-

modulating therapy is effective in the treatment of PANS. Id. Furthermore, Dr. Gilbert testified

that when correctly interpreted, the Parker-Athill study referenced by Dr. Chang illustrates that

only one of seven cytokines measured was found to have a marginally significant increase in

expression following an onset of symptoms in tic disorder or OCD patients. Id. at 224-27.

Dr. Gilbert stated that the assumption of investigators that PANS results from an immune

reaction ignores numerous other mechanisms commonly seen in neurologic disorders. Tr. at 220.

Dr. Gilbert testified that genetic, mitochondrial, and vascular conditions can also have abrupt

onsets, such that an acute onset neurologic condition develops. Id. at 232-33.

3. Could Vaccines Have Caused N.A.C.’s Acute Neurologic Disorder?

Dr. Gilbert testified that it is unlikely that N.A.C.’s vaccinations could have triggered a

severe cytokine response within 24 hours and caused his acute symptom expression. Tr. at 367.

Dr. Gilbert clarified that for Dr. Chang’s theory to be possible, the influx of cytokines would have

to cross the blood-brain barrier and bypass all other structures of the brain in order to target the

basal ganglia within 24 hours. Id. at 227-28.

15

As an initial matter, Dr. Gilbert testified that the theory of the PANS mechanism was

atypical when compared to other autoimmune encephalitis conditions. Tr. at 229. He stated that

generally autoimmune encephalitis presents with additional symptoms, such as seizures or

generalized movement disorders, and not just specific, targeted dysfunction of certain structures

within the basal ganglia resulting in only tics and/or OCD. Id. at 366. As an example, Dr. Gilbert

noted that dysfunction of the basal ganglia, such as with Sydenham’s chorea (“SC”) 10, results in a

presentation of other movement disorders, such as dystonia or chorea. Id. at 229-30. It would be

unlikely, Dr. Gilbert explained, for basal ganglia dysfunction to be specifically restricted to tics

and OCD as a result of an inflammatory response. Id. at 366. Dr. Gilbert asserted that this signaled

a gap in the understanding of what is actually occurring in a PANS patient. Id. at 230.

Dr. Gilbert testified that an abrupt onset of tics or OCD is not atypical. Tr. at 231-32. He

stated that neurologic conditions could present acutely without a clear indication of any triggering

event. Id. at 233-34.

Dr. Gilbert provided a supplemental post-hearing expert report as well. Dr. Gilbert stated

that it is difficult to determine if N.A.C. has a motor tic in Ex. E. Id. at 1. However, Dr. Gilbert

does point out that N.A.C. misuses the pronoun “you,” which is a characteristic in children with

Autism Spectrum Disorder (“ASD”). Id. Dr. Gilbert further stated that the video seems to indicate

that “N.A.C. had early signs of ASD that were missed.” Id. at 1. In addition to the pronoun misuse,

N.A.C. “becomes quickly agitated and frustrated, his gait appears somewhat uncoordinated and

hypotonic.” Id. at 1-2. N.A.C. had a history of screaming spells during infancy, and coupled with

his agitation in the video, Dr. Gilbert stated that it is possible N.A.C. has sensory hypersensitivity,

which is “often seen in children with ASD.” Id. at 2. Regarding how pre-existing tics would

change his opinion, Dr. Gilbert stated that the diagnostic criteria for PANS is “controversial and

unsubstantiated,” and “it is irrelevant whether tics occurred prior to the vaccination.” Id. Dr.

Gilbert stated that the primary symptoms in a PANS diagnosis are OCD and anorexia, not tics,

thus, it is “not highly relevant whether tics occurred prior to vaccination because they are not a

core feature of PANS.” Id. at 2-3. Due to the lack of information of N.A.C.’s neuropsychiatric

and developmental status prior to vaccination, Dr. Gilbert does not believe that N.A.C. has PANS

but has “an inadequately treated autism spectrum disorder.” Id. at 3-4.

VI. Applicable Law

A. Petitioner’s Overall Burden in Vaccine Program Cases

Under the Vaccine Act, a petitioner may prevail in one of two ways. First, a petitioner may

demonstrate that she suffered a “Table” injury—i.e., an injury listed on the Vaccine Injury Table

that occurred within the time period provided in the Table. § 11(c)(1)(C)(i). “In such a case,

causation is presumed.” Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed.

10

Dr. Gilbert discussed Sydenham’s chorea briefly at the hearing. First, Dr. Gilbert testified that SC results

from a strep infection. The streptococcal bacteria, Dr. Gilbert explained, has numerous proteins on its

surface that are similar to those present in the human body, allowing for antibodies to misidentify the foreign

agent. SC, therefore, results from the targeted misidentification and destruction of basal ganglia cells

following molecular mimicry.

16

Cir. 2006); see § 13(a)(1)(B). Second, where the alleged injury is not listed in the Vaccine Injury

Table, a petitioner may demonstrate that he suffered an “off-Table” injury. § 11(c)(1)(C)(ii).

For both Table and non-Table claims, Vaccine Program petitioners bear a “preponderance

of the evidence” burden of proof. § 13(1)(a). That is, a petitioner must offer evidence that leads

the “trier of fact to believe that the existence of a fact is more probable than its nonexistence before

[she] may find in favor of the party who has the burden to persuade the judge of the fact’s

existence.” Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1324 (Fed. Cir. 2010);

see also Snowbank Enter. v. United States, 6 Cl. Ct. 476, 486 (1984) (mere conjecture or

speculation is insufficient under a preponderance standard). Proof of medical certainty is not

required. Bunting v. Sec’y of Health & Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In

particular, a petitioner must demonstrate that the vaccine was “not only [the] but-for cause of the

injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321

(quoting Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999));

Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). A petitioner

may not receive a Vaccine Program award based solely on her assertions; rather, the petition must

be supported by either medical records or by the opinion of a competent physician. Section

13(a)(1).

In attempting to establish entitlement to a Vaccine Program award of compensation for a

non-Table claim, a petitioner must satisfy all three of the elements established by the Federal

Circuit in Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274 (Fed. Cir. 2005). Althen

requires that petitioner establish by preponderant evidence that the vaccination he received caused

his injury “by providing: (1) a medical theory causally connecting the vaccination and the injury;

(2) a logical sequence of cause and effect showing that the vaccination was the reason for the

injury; and (3) a showing of a proximate temporal relationship between vaccination and injury.”

Id. at 1278.

Under Althen prong one, petitioners must provide a “reputable medical theory,”

demonstrating that the vaccine received can cause the type of injury alleged. Pafford, 451 F.3d at

1355-56 (citations omitted). 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 & Human Servs., 35

F.3d 543, 548 (Fed. Cir. 1994). Proof that a vaccine likely caused an injury or that the proffered

medical theory is reasonable, plausible, or possible does not satisfy a petitioner’s burden. Boatmon

v. Sec’y of Health & Human Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019).

Petitioners may satisfy the first Althen prong without resort to medical literature,

epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical

theory. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1378-79 (Fed. Cir. 2009)

(citing Capizzano, 440 F.3d at 1325-26). However, special masters are “entitled to require some

indicia of reliability to support the assertion of the expert witness.” Boatmon, 941 F.3d at 1360,

quoting Moberly, 592 F.3d at 1324. Special Masters, despite their expertise, are not empowered

by statute to conclusively resolve what are complex scientific and medical questions, and thus

scientific evidence offered to establish Althen prong one is viewed “not through the lens of the

laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant evidence

standard.” Id. at 1380. Accordingly, special masters must take care not to increase the burden

17

placed on petitioners in offering a scientific theory linking vaccine to injury. Contreras v. Sec’y

of Health & Human Servs., 121 Fed. Cl. 230, 245 (2015).

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; Andreu,

569 F.3d at 1375-77; Capizzano, 440 F.3d at 1326 (“medical records and medical opinion

testimony are favored in vaccine cases, as treating physicians are likely to be in the best position

to determine whether a ‘logical sequence of cause and effect show[s] that the vaccination was the

reason for the injury’”) (quoting Althen, 418 F.3d at 1280). Medical records are generally viewed

as particularly trustworthy evidence, since they are created contemporaneously with the treatment

of the patient. Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).

However, medical records and/or statements of a treating physician’s views do not per se

bind the special master to adopt the conclusions of such an individual, even if they must be

considered and carefully evaluated. Section 13(b)(1) (providing that “[a]ny such diagnosis,

conclusion, judgment, test result, report, or summary shall not be binding on the special master or

court”); Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (“there is

nothing … that mandates that the testimony of a treating physician is sacrosanct -- that it must be

accepted in its entirety and cannot be rebutted”). As with expert testimony offered to establish a

theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the

reasonableness of their suppositions or bases. The views of treating physicians should also be

weighed against other, contrary evidence also present in the record -- including conflicting

opinions among such individuals. Hibbard v. Sec’y of Health & Human Servs., 100 Fed. Cl. 742,

749 (2011) (not arbitrary or capricious for special master to weigh competing treating physicians’

conclusions against each other), aff’d, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec’y of Health &

Human Servs., No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011), mot.

for review den’d, 100 Fed. Cl. 344, 356 (2011), aff’d without opinion, 475 Fed. App’x 765 (Fed.

Cir. 2012).

The third Althen prong requires establishing a “proximate temporal relationship” between

the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to

the phrase “medically-acceptable temporal relationship.” Id. A petitioner must offer

“preponderant proof that the onset of symptoms occurred within a timeframe which, given the

medical understanding of the disorder’s etiology, it is medically acceptable to infer causation.” de

Bazan v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation

for what is a medically acceptable timeframe must also coincide with the theory of how the relevant

vaccine can cause an injury (Althen prong one’s requirement). Id. at 1352; Shapiro v. Sec’y of

Health & Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand, 105 Fed. Cl.

353 (2012), aff’d mem., 503 F. App’x 952 (Fed. Cir. 2013); Koehn v. Sec’y of Health & Human

Servs., No. 11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review

den’d (Fed. Cl. Dec. 3, 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014).

B. Law Governing Analysis of Fact Evidence

The process for making factual determinations in Vaccine Program cases begins with

analyzing the medical records, which are required to be filed with the petition. Section 11(c)(2).

18

The special master is required to consider “all [] relevant medical and scientific evidence contained

in the record,” including “any diagnosis, conclusion, medical judgment, or autopsy or coroner’s

report which is contained in the record regarding the nature, causation, and aggravation of the

petitioner’s illness, disability, injury, condition, or death,” as well as the “results of any diagnostic

or evaluative test which are contained in the record and the summaries and conclusions.” Section

13(b)(1)(A). The special master is then required to weigh the evidence presented, including

contemporaneous medical records and testimony. See Burns v. Sec’y of Health & Human Servs.,

3 F.3d 413, 417 (Fed. Cir. 1993) (it is within the special master’s discretion to determine whether

to afford greater weight to contemporaneous medical records than to other evidence, such as oral

testimony surrounding the events in question that was given at a later date, provided that such

determination is evidenced by a rational determination).

Medical records created contemporaneously with the events they describe are presumed to

be accurate and “complete” such that they present all relevant information on a patient’s health

problems. Cucuras, 993 F.2d at 1528; Doe/70 v. Sec’y of Health & Human Servs., 95 Fed. Cl.

598, 608 (2010) (“[g]iven the inconsistencies between petitioner’s testimony and his

contemporaneous medical records, the special master’s decision to rely on petitioner’s medical

records was rational and consistent with applicable law”), aff’d, Rickett v. Sec’y of Health &

Human Servs., 468 F. App’x 952 (Fed. Cir. 2011) (non-precedential opinion). This presumption

is based on the linked propositions that (i) sick people visit medical professionals; (ii) sick people

honestly report their health problems to those professionals; and (iii) medical professionals record

what they are told or observe when examining their patients in as accurate a manner as possible,

so that they are aware of enough relevant facts to make appropriate treatment decisions. Sanchez

v. Sec’y of Health & Human Servs., No. 11-685V, 2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr.

Apr. 10, 2013), mot. for review den’d (Fed. Cl. Feb. 11, 2019), appeal docketed, No. 19-1753 (Fed.

Cir. 2019); Cucuras v. Sec’y of Health & Human Servs., 26 Cl. Ct. 537, 543 (1992), aff’d, 993

F.2d at 1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would fail to

accurately report the onset of their daughter’s symptoms.”).

Accordingly, if the medical records are clear, consistent, and complete, then they should

be afforded substantial weight. Lowrie v. Sec’y of Health & Human Servs., No. 03-1585V, 2005

WL 6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed, contemporaneous medical

records are generally found to be deserving of greater evidentiary weight than oral testimony --

especially where such testimony conflicts with the record evidence. Cucuras, 993 F.2d at 1528;

see also Murphy v. Sec’y of Health & Human Servs., 23 Cl. Ct. 726, 733 (1991), aff’d per curiam,

968 F.2d 1226 (Fed. Cir. 1992), (citing United States v. U.S. Gypsum Co., 333 U.S. 364, 396

(1947) (“[i]t has generally been held that oral testimony which is in conflict with contemporaneous

documents is entitled to little evidentiary weight.”)).

However, there are situations in which compelling oral 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 & Human Servs., 69 Fed. Cl. 775, 779 (2006) (“like 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, 2005 WL 6117475, at *19

(“[w]ritten records which are, themselves, inconsistent, should be accorded less deference than

those which are internally consistent”) (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a

19

determination regarding a witness’s credibility is needed when determining the weight that such

testimony should be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec’y of Health & Human

Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

When witness testimony is offered to overcome the presumption of accuracy afforded to

contemporaneous medical records, such testimony must be “consistent, clear, cogent and

compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec’y of Health & Human

Servs., No. 90-2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)). In

determining the accuracy and completeness of medical records, the Court of Federal Claims has

listed four possible explanations for inconsistencies between contemporaneously created medical

records and later testimony: (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

testimony; or (4) a person’s purposeful recounting of symptoms that did not exist. LaLonde v.

Sec’y of Health & Human Servs., 110 Fed. Cl. 184, 203-04 (2013), aff’d, 746 F.3d 1334 (Fed. Cir.

2014). In making a determination regarding whether to afford greater weight to contemporaneous

medical records or other evidence, such as testimony at hearing, there must be evidence that this

decision was the result of a rational determination. Burns, 3 F.3d at 417.

C. Analysis of Expert Testimony

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

& Human Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is

usually evaluated according to the factors for analyzing scientific reliability set forth in Daubert

v. Merrell Dow Pharm., Inc., 509 U.S. 579, 594-96 (1993). See Cedillo v. Sec’y of Health &

Human Servs., 617 F.3d 1328, 1339 (Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Human

Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999). “The Daubert 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 play a slightly different role in Vaccine Program cases than they do

when applied in other federal judicial fora. Daubert factors are employed by judges to exclude

evidence that is unreliable and potentially confusing to a jury. In Vaccine Program cases, these

factors are used in the weighing of the reliability of scientific evidence. Davis v. Sec’y of Health

& Human Servs., 94 Fed. Cl. 53, 66-67 (2010) (“uniquely in this Circuit, the Daubert factors have

been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of

expert testimony already admitted”). The flexible use of the Daubert factors to evaluate

persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g., Snyder, 88

Fed. Cl. at 743. In this matter, (as in numerous other Vaccine Program cases), Daubert has not

been employed at the threshold to determine what evidence should be admitted, but instead to

determine whether expert testimony offered is reliable and/or persuasive.

20

Respondent frequently offers one or more experts of his own in order to rebut a petitioner’s

case. Where both sides offer expert testimony, a special master’s decision may be “based on the

credibility of the experts and the relative persuasiveness of their competing theories.”

Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing

Lampe, 219 F.3d at 1362). However, 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.” Snyder, 88 Fed. Cl. at 743

(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)). 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. Weighing the relative persuasiveness of competing expert testimony, based on a

particular expert’s credibility, is part of the overall reliability analysis to which special masters

must subject expert testimony in Vaccine Program cases. Id. at 1325-26 (“[a]ssessments as to the

reliability of expert testimony often turn on credibility determinations”); see also Porter v. Sec’y

of Health & Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this court has unambiguously

explained that special masters are expected to consider the credibility of expert witnesses in

evaluating petitions for compensation under the Vaccine Act”).

D. Consideration of Medical Literature

Although this decision discusses some but not all of the medical literature in detail, I

reviewed and considered all of the medical records and literature submitted in this matter. See

Moriarty v. Sec’y of Health & Human Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally

presume that a special master considered the relevant record evidence even though [s]he does not

explicitly reference such evidence in h[er] decision.”); Simanski v. Sec’y of Health & Human

Servs., 115 Fed. Cl. 407, 436 (2014) (“[A] Special Master is ‘not required to discuss every piece

of evidence or testimony in her decision.’” (citation omitted)), aff’d, 601 F. App’x 982 (Fed. Cir.

2015).

VII. Analysis

Because Petitioner does not allege an injury listed on the Vaccine Injury Table, Petitioner’s

claim is classified as “off-Table.” As noted above, to prevail on an “off-Table” claim, Petitioner

must prove by preponderant evidence that N.A.C. suffered an injury and that this injury was caused

by the vaccinations at issue. See Capizzano, 440 F.3d at 1320.

A. PANS Generally

At hearing, both Dr. Chang and Dr. Gilbert went into extensive detail regarding the history

and development of the PANS criteria, as well as the specific diagnostic criteria themselves.

Dr. Chang first described the development of the diagnostic criteria for PANDAS, a

syndrome he considers a subset of PANS. He testified that PANDAS arose from a recognition

that a subsection of individuals developed a sudden onset of neuropsychiatric symptoms following

infection with Group A Streptococcus (“GAS”). Though GAS infection is a known trigger for a

21

number of disorders,11 these individuals experienced a definitive, acute onset of neuropsychiatric

symptoms following an identified GAS infection. 12

As both experts indicated, however, the PANDAS criteria failed to encompass individuals

who presented with a similar onset of symptoms, yet with no known or identified GAS infection.

Ultimately, the criteria for PANS were formulated to incorporate those patients without

identifiable GAS infections. For these individuals, literature hypothesizes that while the etiology

is currently unknown, various infectious and environmental factors may be causative. Still, the

acuity of onset was preserved as a mandatory criterion, as was the requirement that other

neurologic disorders cannot better explain the symptoms. The following diagnostic criteria were

compiled for PANS:

I. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted

food intake

II. Concurrent presence of additional neuropsychiatric symptoms, with similarly

severe and acute onset, from at least two of the following seven categories:

1. Anxiety

2. Emotional lability and/or depression

3. Irritability, aggression and/or severely oppositional behaviors

4. Behavioral (developmental) regression

5. Deterioration in school performance

6. Sensory or motor abnormalities

7. Somatic signs and symptoms, including sleep disturbances, enuresis or

urinary frequency

III. Symptoms are not better explained by a known neurologic or medical disorder,

such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder or

others.

11

Presenting factors such as chorea or manifestations of rheumatic fever were considered exclusionary

factors in order to separate PANDAS patients from those with Sydenham’s chorea, for example. Swedo et

al., From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS

(Pediatric Acute-onset Neuropsychiatric Syndrome), PEDIATRICS & THERAPEUTICS (2012) (hereinafter

“Swedo”) (filed as Ex. 26).

12

The following five diagnostic criteria must be met to establish a PANDAS diagnosis:

1. Presence of OCD or a tic disorder

2. Prepubertal symptom onset

3. Acute symptom onset and episodic (relapsing-remitting) course

4. Temporal association between Group A streptococcal infection and symptom

onset/exacerbations

5. Associated with neurological abnormalities, (particularly motoric hyperactivity and choreiform

movements)

See Swedo.

22

Note: The diagnostic work-up of patients suspected of PANS must be

comprehensive enough the rule out these and other relevant disorders. The

nature of the co-occurring symptoms will dictate the necessary assessments,

which may include MRI scan, lumbar puncture, electroencephalogram or other

diagnostic tests.

Swedo at 3. See also Chang et al., Clinical Evaluation of Youth with Pediatric Acute-Onset

Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus

Conference, JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY, Vol. 25, No. 1, pp. 3-

13 (2015) (filed as Ex. 17).

Both experts confirmed that the etiology and triggering mechanism for PANS are yet

unknown. Tr. at 120-21; 218-20. Unlike PANDAS, no specific infectious or environmental factor

has been identified. Both experts also confirmed that given the neurologic symptoms involved, it

is likely that PANS also involves basal ganglia dysfunction. Dr. Chang asserted that “the

predominant – the basic idea is that – is a triggering event, which is either known or unknown, and

because of the triggering event there is an inflammatory reaction that for some reason targets the

basal ganglia.” Id. at 116.

Dr. Chang added that PANS developed in individuals with a predisposition, genetic or

otherwise, to this type of neuropsychiatric disorder. Though no genetic component has been

isolated, Dr. Chang hypothesized that a genetic marker may cause some children to be more

susceptible to PANS following triggering events.

Regarding the episodic nature of PANS, further studies hypothesize that chronic static or

progressive course may be indicative of different illnesses, as they indicate the involvement of

autoimmune, rather than autoinflammatory, processes. Frankovich et al., Multidisciplinary Clinic

Dedicated to Treating Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome: Presenting

Characteristics of the First 47 Consecutive Patients, JOURNAL OF CHILD AND ADOLESCENT

PSYCHOPHARMACOLOGY, Vol. 25, No. 1, pp. 38-47 (2015) (filed as Ex. 21).

1. PANS versus Tourette syndrome (“TS”)

Studies further acknowledge that there may not be a clear distinction between the

mechanisms leading to gradual onset of these symptoms, as seen in SC or TS, and the mechanisms

resulting in a sudden onset of these symptoms, as observed in PANS or PANDAS patients. As

studies regarding PANDAS are more prevalent, the similarities between PANDAS and other

neurologic disorders have been repeatedly discussed. The classification of PANDAS as a separate

disorder is still widely debated. Researchers and clinicians have considered whether PANDAS is

a variant of acute rheumatic fever, and “controversy does exist among some neurologists regarding

the validity of PANDAS as a subset of OCD/tics versus its being a forme fruste of RF (SC).” Cox

et al., Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics

and Obsessive-Compulsive Disorder, JOURNAL OF CHILD AND ADOLESCENT

PSYCHOPHARMACOLOGY, Vol. 25, No. 1, pp. 76-85 (2015) (filed as Ex. 19).

23

Dr. Chang asserted that N.A.C. did not have TS because the mechanism and presentation

of TS is different than that of PANS, and that N.A.C. did not exhibit the presentation usually

observed in TS. Tr. at 141. He stated that TS presented gradually, first with an onset of motor

tics, followed by vocal tics. Id. Comorbidities such as OCD and ADHD arise gradually following

tic presentation. Id. Dr. Chang continued that the mechanism for TS may differ from that of

PANS. Id. TS may have an underlying genetic component, as discussed by Dr. Gilbert in his

expert report, that makes its development unavoidable. Id. at 142. Rather, TS, unlike PANS, does

not require a secondary trigger in order for symptoms to present. Id. at 143. Dr. Gilbert testified

that there is no biological way to distinguish PANS from OCD or anorexia nervosa plus other

symptoms. Tr. at 219.

2. Pre-Existing Tics

According to both experts, there are several comorbidities that can coincide with a PANS

diagnosis. Dr. Chang testified that it was not uncommon for other neuropsychiatric disorders such

as mood disorders, ADHD, or autism to develop in PANS patients. He further added that a prior

history of tics would not preclude a diagnosis of PANS, provided that the onset of OCD and two

other secondary symptoms was acute.13 The Swedo article further clarified that the onset of OCD

need not be novel. Mild, pre-existing obsessions do not preclude a PANS consideration, either;

such symptoms can precede the sudden onset of severe OCD associated with PANS. Swedo at 3.

In fact, Dr. Chang indicated that if N.A.C. had pre-existing tics, that would have made him more

susceptible to developing PANS. Chang Supplemental Rep. at 1.

Respondent presented testimony from Dr. Gilbert that N.A.C. had vocal and motor tics that

pre-dated his October 2012 vaccinations. See Tr. at 331-43, 352-60. Ex. F.

Q. Dr. Gilbert, what do you observe in this video?

A. So N.A.C. at this point, five months prior to the vaccination, has tics. So there’s

a number of tics that we see in this video. They’re both motor and phonic or vocal

tics. One of the tics is a blink. Now all children blink, but in N.A.C.’s case, he

draws in extra facial muscles and combines this with a head tipping. So these are

classic early tics that we see in patients that either have provisional tic disorder or

Tourette syndrome or some other condition that’s associated with tics. … Those are

like the tics I see in clinic every week.

…

So the blink that N.A.C. does when he blinks and tips his head at the same time,

where he tips his head down to the left, so that's not just a blink. That's a blinking

tic. That's a classic blinking tic where the brain sends out a patterned message

involving a stereotyped group of muscles of the face and neck. That's a tic.

13

Dr. Chang testified that while tics were often observed in PANS patients, tics were not included as a

primary criterion for diagnosis in order to avoid controversy with neurologists treating Tourette syndrome.

Tr. at 114.

24

Tr. at 338, 340, 356. See Ex. F.

Petitioner testified that N.A.C. did not have any tics prior to the September 26, 2012

vaccinations. She described that her husband was teaching the children how to whistle between

their fingers. Tr. at 381. She stated that N.A.C. never made this noise again after this day. Id. at

382.

Dr. Chang also testified about this issue.

If I never heard that testimony, I would say, boy, that definitely looks and sounds

like a tic, someone's making that noise and someone's blinking their eyes, it very

well could be. Having heard the explanation and also heard the end part of the

video. I'm satisfied that I don't see that necessarily as a tic at all. I mean, it could

just be a boy exerting himself making the squealing noise, and when you do that,

you tend to close your eyes. If, you know, you're going to make a big, loud noise,

it's not abnormal to close your eyes. I didn't notice any -- you know, Dr. Gilbert is

definitely more of a tic expert than I am, but I didn't notice anything unusual

compared to normal childhood development, if that were the context.

Tr. at 388-89.

Dr. Gilbert’s expertise in this area is superior to that of Dr. Chang. I have considered all

of the testimony on this point, and while Dr. Gilbert’s testimony provides preponderant evidence

that N.A.C. experienced tics prior to his September 26, 2012 vaccinations, this issue is not

dispositive. Because tics are not a primary criterion for a PANS diagnosis, the existence of tics

prior to the allegedly-causal vaccinations does not foreclose a PANS diagnosis.

3. Autism Spectrum Disorder

Respondent presented some evidence that N.A.C. has autism.

a. Medical Records

On August 27, 2013, N.A.C. saw Dr. Loma-Miller at Children’s Hospital’s neurology

office. Ex. 2 at 4. Dr. Loma-Miller noted that Petitioner expressed interest in having N.A.C.

evaluated for autism. Id. Dr. Loma-Miller’s assessment noted N.A.C.’s history of Tourette

syndrome and Dr. Loma-Miller “agree[d] with [N.A.C.’s] mom that he may be in the spectrum of

autism, but however, it is not clear cut….” Id. Dr. Loma-Miller referred N.A.C. to Developmental

Pediatrics for an autism evaluation.

On August 11, 2014, N.A.C. was seen at the Children’s Hospital pediatric neurology office

by Dr. Matthew S. Warren. Ex. 2 at 2. The record notes his routine visits with the office’s

neurologist, Dr. Loma-Miller, as well as N.A.C.’s history of vocal and motor tics and diagnosis of

Tourette syndrome. Id. The record indicates a concern that N.A.C. fits into the autism spectrum.

Id.

b. School Records

25

Petitioner and N.A.C.’s teacher provided responses on the GARS-3 indicating, in the

opinion of the assessor that “it is very likely that [N.A.C.] demonstrates behaviors consistent with

an Autism Spectrum Disorder.” Ex. 40 at 55. At the end of her report, Ms. Reel indicated that

N.A.C. “may be autistic.” Id. at 55.

c. Dr. Gilbert’s Testimony and Supplemental Expert Report

In his supplemental expert report Dr. Gilbert stated that N.A.C. misuses the pronoun “you,”

which is a characteristic in children with Autism Spectrum Disorder. Gilbert Supplemental Rep

at 1. Dr. Gilbert further stated that the video seems to indicate that “N.A.C. had early signs of

ASD that were missed.” Id. In addition to the pronoun misuse, N.A.C. “becomes quickly agitated

and frustrated, his gait appears somewhat uncoordinated and hypotonic.” Id. at 1-2. N.A.C. had

a history of screaming spells during infancy, and coupled with his agitation in the video, Dr. Gilbert

stated that it is possible N.A.C. has sensory hypersensitivity, which is “often seen in children with

ASD.” Id. at 2.

This supplemental expert report is in line with Dr. Gilbert’s testimony at hearing, where he

indicated that N.A.C.’s abnormal speech and other behavior was consistent with autism spectrum

disorder. See Tr. at 240. See also id. at 238 where Dr. Gilbert testified that “tics happen a lot in

kids with autism.”

d. The Significance of Autism with Respect to a PANS Diagnosis

Ultimately, while it may be more likely than not that N.A.C. has autism, it is not necessary

for me to reach that determination. Respondent’s expert stated that children with ASD are more

likely to develop tics and OCD. Dr. Gilbert testified:

And what has been shown in the past year is that a number of genes are in common

between autism and Tourette syndrome, so that they may not really be so distinct as

we have thought they were clinically. That said, as I have mentioned, we see a lot of

kids with autism that have tics, and a lot of kids that have tics that show some of the

symptoms of autism. So I think those genetic findings kind of confirm a common

clinical observation.

Tr. at 362-63; see also Gilbert Supplemental Rep. at 1 where Dr. Gilbert states that “children with

ASD commonly have tics”.

While an autism diagnosis could explain the likelihood that a child will later develop tics

and/or OCD, it does not, in and of itself, rule out a PANS diagnosis.

B. N.A.C. Meets the Diagnostic Criteria for PANS

During the hearing, both experts testified at length regarding the diagnostic criteria for

PANS. Both Dr. Chang and Dr. Gilbert agreed that PANS was the acute onset of severe OCD or

food restriction, accompanied in time by two of the seven secondary criteria. The experts added

26

that a PANS diagnosis can only arise when another neuropsychiatric disorder cannot better explain

the individual’s symptoms. Dr. Chang and Dr. Gilbert agreed that N.A.C. experienced a sudden

onset of neuropsychiatric symptoms that could not easily be defined by current presentation

descriptions of known psychiatric disorders. Dr. Gilbert did note, however, that while not

common, tics and/or TS can manifest in a similar acute manner.

Dr. Chang testified that N.A.C. presented with sudden onset of symptoms on October 9,

2019. When reviewing N.A.C.’s PANS presentation, he confirmed that in his opinion, N.A.C. met

each of the criteria and subcategories required for a PANS diagnosis. First, Dr. Chang confirmed

that N.A.C.’s symptom presentation met the definition of acute onset. Dr. Chang identified

N.A.C.’s repetitive behaviors as examples of OCD. Dr. Chang added that N.A.C. also exhibited

patterns of food restriction, though less assuredly since weight loss was not noted in the records.

N.A.C.’s OCD patterns of behavior, however, satisfied the first PANS criterion. Dr. Chang then

testified that N.A.C. exhibited symptoms in each of the seven subcategories of the secondary

PANS criteria. Dr. Gilbert agreed that N.A.C.’s presentation satisfied the requirement of

concurrent presence of additional neuropsychiatric symptoms, although he testified that N.A.C.

met four, as opposed to seven of the secondary criteria. Tr. at 317. Finally, when discussing

whether N.A.C. met the third PANS criterion, Dr. Chang explained that he did not believe any

other illness better described N.A.C.’s condition.

Dr. Gilbert stated that in his view “the evidence does not support that N.A.C. has a primary

tic disorder.” Gilbert Supplemental Rep. at 2. He also wrote in his supplemental expert report, “I

do not believe that N.A.C. has PANS.” Id. However, this statement is contrary to a portion of Dr.

Gilbert’s testimony at hearing.

Q. So based off of everything you just said, do you think that N.A.C. in this case

has PANS?

A. Yes. He has an acute neuropsychiatric syndrome. What I don’t think is that we

have any reason to think that his syndrome is immune-mediated or was caused by

a vaccine.

Tr. at 221. While this testimony took place before Dr. Gilbert saw the videos of N.A.C. exhibiting

what he described as pre-existing tics, his initial statement that N.A.C. has PANS was not

explained or clarified.

Based on the available record and the testimony of both witnesses, I find Petitioner has

provided preponderant evidence that N.A.C. had a sudden onset of neuropsychiatric symptoms

and that such symptoms generally meet the current diagnostic criteria for PANS. First, and in

accordance with Dr. Chang’s testimony, I find that N.A.C.’s symptoms sufficiently satisfy the

three diagnostic criteria for PANS. N.A.C. presented to the emergency room on October 9, 2012

with an acute onset of neuropsychiatric symptoms. Specifically, Petitioner reported to the provider

that N.A.C. had recently developed repetitive behavior, accompanied by motor tics, emotional

lability, and anxiety. At the hearing, Petitioner testified that these behaviors began approximately

30 hours after vaccination. Though there is evidence that N.A.C. already had tics prior to his

September 26, 2012 vaccinations, Petitioner successfully established that the remainder of the

27

symptoms reported at that appointment developed acutely. Notably, the record indicates that

N.A.C.’s symptoms on that date included OCD-type behavior and at least two of the secondary

symptoms, emotional lability and anxiety. See Ex. 5 at 1-5. Finally, since PANS involves the

acute onset of this specific grouping of symptoms, I find, in accordance with Dr. Chang’s

testimony, that the PANS diagnostic criteria best describe N.A.C.’s presentation.

C. Petitioner has not Carried her Burden of Proof

1. Althen Prong 1: There is not Preponderant Evidence that Vaccines Can Cause PANS

As stated repeatedly in the literature, the etiology and mechanism for PANS is unknown.

Studies suggest that, as is the case for PANDAS, similar infections may serve as possible PANS

triggers. Frankovich at 44. In PANDAS, the mechanism for causation has been identified and is

comparable to that of SC. Cross-reaction with group A beta-hemolytic streptococcus infection

leads to production of autoantibodies against lysoganglioside and increased activation of

calmodulin-dependent protein kinase II (CaMKII). Targeted receptors on the neuronal cells of the

basal ganglia may lead to altered dopamine production and basal ganglia dysfunction resulting in

abnormal movement. In fact, autoimmunity is a possible mechanism in several disorders with

similar presentations, as antineuronal antibodies have been implicated in tic and OCD development

associated with strep infections, and significantly higher ANA levels are observed in SC, OCD,

and Tourette syndrome patients. See Cox at 1; Cunningham and Cox, Autoimmunity against

dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea

and beyond, ACTA PHYSIOL 2016, 216, pp. 90–100 (filed as Ex. 20); Kirvan et al., Antibody-

mediated neuronal cell signaling in behavior and movement disorders, JOURNAL OF

NEUROIMMUNOLOGY 179 (2006), pp. 173–179 (filed as Ex. 24). Furthermore, such a mechanism

for causation explains the development of specific symptoms rather than generalized evidence of

basal ganglia dysfunction.

Studies exploring the triggering event and mechanism for PANS are much less common,

however. Though inflammation continues to be a hypothesis for PANS causation, the mechanism

for inflammation is yet unknown. Frankovich et al., Five Youth with Pediatric Acute-Onset

Neuropsychiatric Syndrome of Differing Etiologies, JOURNAL OF CHILD AND ADOLESCENT

PSYCHOPHARMACOLOGY, Vol. 25, No. 1, pp. 31-37 (2015) (filed as Ex. 22). For example, several

studies have indicated that PANS may also develop following a mycoplasma infection, suggesting

that similar cross-reaction mechanisms may be involved with other infectious agents apart from

strep infection. Kim et al., Obsessive-Compulsive Disorder Related to Mycoplasma-Associated

Autoimmune Encephalopathy with Basal Ganglia Involvement, JOURNAL OF CHILD AND

ADOLESCENT PSYCHOPHARMACOLOGY, Vol. 26, No. 4, pp. 400-02 (2016) (filed as Ex. 23).

At hearing, Dr. Chang proffered a theory of causation by which PANS may develop

following vaccination. Dr. Chang posited that the influx of cytokines following vaccination led to

a severe inflammatory response by which the blood brain barrier was penetrated and the basal

ganglia was targeted. Dr. Chang testified:

I can’t be sure at all about the exact mechanism behind it. … I would say that the

immune stimulation somehow led to an inflammatory reaction that crossed the

28

blood-brain barrier and affected probably the basal ganglia, among other areas, of

the child’s brain and led to this acute inflammatory neuropsychiatric condition.

Tr. at 196-97.

Dr. Chang’s theory that PANS occurs following vaccinations involves several steps. First,

vaccinations result in the release of cytokines. Second, cytokines increase the permeability of and

then cross the blood brain barrier. Third, in genetically-susceptible individuals, cytokines cause

targeted inflammation of the basal ganglia. Fourth, this targeted inflammation causes PANS.

a. Does Vaccination Promote the Production of Cytokines?

It is established in the Vaccine Program that vaccination does promote the production of

cytokines, although I note that Petitioner did not file literature on this point. Dr. Chang eludes to

cytokine production in his testimony when he says, “the trigger [vaccination] triggers an immune

reaction that then leads to the whole inflammatory cascade, including cytokine – inflammatory

cytokine production…” Tr. at 121. While some cytokine production is a normal vaccine reaction,

there is no indication in the record regarding the level of production necessary to lead to an

inflammatory cascade.

I note that special masters have found general cytokine-based theories of causation are not

persuasive. Zumwalt on behalf of L.Z. v. Sec’y of Health & Human Servs., No. 16-994V, 2019

WL 1953739, at *18 (Fed. Cl. Spec. Mstr. Mar. 21, 2019) (noting that “[t]he fact that vaccines are

known to stimulate cytokine production . . . does not amount to a reliable causation theory that

such stimulation is necessarily disease-causing”); Inamdar v. Sec’y of Health & Human Servs.,

No. 15-1173V, 2019 WL 1160341, at *17 (Fed. Cl. Spec. Mstr. Feb. 8, 2019) (noting that the

proposition that vaccines can cause diseases by “induc[ing] the production of proinflammatory

cytokines . . . has several deficiencies”); McCabe v. Sec’y of Health & Human Servs., No. 13-

570V, 2018 WL 3029175, at *47-55 (Fed. Cl. Spec. Mstr. May 17, 2018); McGuire v. Sec’y of

Health & Human Servs., No. 10-609V, 2015 WL 6150598 at *12-18 (Fed. Cl. Spec. Mstr. Sep.

18, 2015) (noting that the petitioner had failed to introduce “persuasive evidence to rebut the

IOM’s conclusion that no evidence supports a conclusion that cytokines cause a disease”).

As Chief Special Master Corcoran noted in Dean v. Sec’y of Health & Human Servs., “The

most immediately apparent weakness in this case's causation theory is the heavy lifting it assigns

to the post-vaccination cytokine production process as the cause of almost all of the pathologic

effects of the vaccines at issue.” Dean v. Sec’y of Health & Human Servs., No. 13-808V, 2017

WL 2926605, at *16 (Fed. Cl. Spec. Mstr. June 9, 2017). The same is true in Petitioner’s case.

There has been no testimony helpful to Petitioner’s theory regarding the level of cytokine

production after vaccination. In fact, when asked whether he knew “the level of cytokine creation

that happens after vaccination,” Dr. Chang responded, “No, I’m not familiar with the exact

level…” Tr. at 160. Accordingly, while I believe it has been established that vaccination induces

cytokine production, Petitioner has not presented evidence through her expert or through literature

as to the level of that production, or what level is required to be pathologic.

b. Do Cytokines Increase the Permeability of the Blood-Brain Barrier?

29

While Petitioner did address the question as to whether vaccination can lead to permeability

of the blood-brain barrier, the analysis was cursory.

Q. Is the proinflammatory cytokine tumor necrosis factor alpha expressed after

vaccination?

A. Yes, it is.

Q. Can the same proinflammatory cytokines cause the blood-brain barrier to

become more permeable?

A. They can, yes.

Tr. at 123-24. There was no further discussion on this point, and no literature was filed in support

of the proposition that cytokines result in increased permeability of the blood-brain barrier.14

In order for cytokine expression to so severely alter the function of the basal ganglia, pro-

inflammatory cytokines present at the site of vaccination must then enter the bloodstream and cross

the blood-brain barrier at a particularly weak juncture. As the cells supporting the blood-brain

barrier form “very tight junctions,” Dr. Gilbert testified that these junctions would first need to be

loosened before cytokines can cross and “produce inflammation” in basal ganglia structures. Tr.

at 228. Dr. Chang stated that he was not able to provide an explanation regarding how this process

occurs. (Stating “somehow they [the antibodies] would get past the blood-brain barrier…” and “I

don’t think the answers [how cytokines cross the blood-brain barrier] are that clear.”) Id. at 120,

160. Dr. Gilbert, however, added that he found it unlikely such processes could occur in the span

of 24 hours. Id. at 228.

The ability of cytokines to cross the blood-brain barrier has been discussed in numerous

cases in this Program. Special Master Moran in McGuire considered the ability for TNF-α, in

particular, to cross the blood-brain barrier. McGuire v. Sec’y of Health & Human Servs., No. 10-

609V, 2015 WL 6150598 (Fed. Cl. Spec. Mstr. Sept. 18, 2015). In a similar fashion to Dr. Chang,

Petitioner’s expert in McGuire failed to provide an explanation as to how TNF crosses the blood-

brain barrier or the method by which it may create permeability of the blood-brain barrier. Due to

the lack of a reliable theory for how cytokines may cross the blood-brain barrier following HPV

vaccination, Special Master Moran discounted that aspect of Petitioner’s theory. Id. at *14. In the

present case, I find that Petitioner similarly has failed to provide a sound and reliable explanation

by which vaccination-induced cytokine expression can lead to cytokines traversing the blood-brain

barrier.

14

In Dean, 2017 WL 2926605, Chief Special Master Corcoran discussed a study upon which Petitioners

relied to show how cytokines could increase the permeability of the blood-brain barrier. He ultimately

found that even with literature filed addressing the issue, “it [was] not enough by itself to establish

preponderant evidence that vaccination would more likely than not allow permeation of the blood-brain

barrier simply due to cytokine upregulation expected to be caused by the vaccine.” Dean, 2017 WL

2926605, at *17. No such literature was filed in this case.

30

c. Does an Upregulation in Cytokines Cause PANS?

Petitioner failed to present preponderant evidence that rapid cytokine cascade and

generalized inflammatory response to vaccinations is a likely mechanism by which targeted basal

ganglia dysfunction can result. While a “link between inflammation and psychiatric disorders”

has been noted (See Chang et al., Special Issue on Pediatric Acute-Onset Neuropsychiatric

Syndrome, JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY, Vol. 25, No. 1, pp. 1-

2 (2015) (filed as Ex. 18)), there is not preponderant evidence that generalized inflammation can

result in the targeted dysfunction observed in disorders of the basal ganglia. Specifically, no theory

was presented as to how or why generalized cytokine expression would target only certain basal

ganglia structures. Dr. Chang generally stated that the basal ganglia may have been accessible due

to its proximity to vascular structures of the brain adding that “we don’t know exactly why it would

attack the basal ganglia.” Tr. at 120.

In fact, Dr. Gilbert described this part of Dr. Chang’s theory as “unlikely.” Tr. at 366. Dr.

Gilbert stated:

So in the rare cases that we see in centers like ours where there is an encephalitis

that is triggered by something and causes inflammation and psychiatric symptoms,

those symptoms are not restricted to the symptoms on the PANS list. There are

always additional symptoms like seizures, like loss of motor skills to a much more

extreme degree, like movement disorders besides tics. He didn’t have any of those.

So, therefore, I think it’s unlikely.

Id.

In attempting to link cytokine production with PANS, Petitioner filed a study measuring

cytokine expression in youth with tic disorders which found elevated levels of TNF-α during

symptom exacerbation compared to levels during remission. The study was conducted on a total

of 21 individuals, and the results for TNF were the only statistically significant value. 15 Indeed,

the authors of the study concluded that “despite [the] findings, some disagreement still exists…

[S]ome groups… have noted no correlations between TNF and tic disorder.” Parker Athill at 5.

Dr. Gilbert discussed this study during the hearing, and noted that:

[T]he problem when you do a big study and you do a lot of comparisons is you

have some findings that are statistically different by chance, particularly if you have

a small sample like you have in this paper where you don’t have that many kids in

either group. So we have one P value out of seven that’s barely significant in two

small groups of papers, and that is sort of the level of evidence that we have about

cytokines being part of this process.

Tr. at 226-27.

15

P value for TNF was 0.05, the threshold value for significance measurements. Dr. Gilbert testified that

“out of all two, three, four, five, six, seven cytokines there, there’s only one that reached that threshold.

How much below that threshold is it? It’s right at the threshold. It’s at the 5 percent threshold.” Tr. at 226.

31

Regardless of the findings, the results of this study may not be extrapolated so far as to

suggest that cytokine expression is involved in the inciting processes of PANS. The study found

that TNF was elevated during tic exacerbation. It is not clear from the study whether TNF caused

tic exacerbation or whether it was a by-product. This study also does not suggest that vaccinations

incite rapid cytokine cascades that result in targeted inflammation of the basal ganglia.

There is scant evidence to suggest that vaccinations may serve as triggering events for

PANS or that cytokine expression is even a significant factor in movement disorders or similar

neurologic disorders. A survey of PANS patients provided self-reported data of PANS flare-up

following flu vaccination. Calaprice at 1. The article aimed to survey purported PANS patients

to determine what may have caused their disease. One main flaw with the paper (the authors did

not include an epidemiologist or an immunologist), is that the authors trust the participants who

filled out the survey did in fact have PANS. Tr. at 253. Dr. Gilbert noted that some of the

participants did not have the acute component of PANS, meaning their symptoms were reported

as chronic. Id. at 254. He summarizes the issues with this study by stating, “There was no attempt

made to verify independently the cause (patient-reported antecedent events) or the effect (meeting

the criteria for PANS), the temporal interval, the “dose,” or the presence or chronicity of other

behavioral diagnoses.”16

Additionally, Petitioner filed the Leslie article, which found that the onset of some

neuropsychiatric disorders may be temporally related to prior vaccinations. Leslie at 1. Dr. Gilbert

testified as to the “major flaws” associated with this study. See Tr. at 242. The authors of the

study (an economist, an attorney/philanthropist, and two psychiatrists, with the notable lack of

participation from an immunologist and an epidemiologist) looked at the associations between

vaccines and medical events. As a control, they chose two events that one would assume could

not be related to vaccines (broken bones and open wounds). Id. at 245. They also selected

conditions related to PANS and PANDAS such as anorexia nervosa, tics, and OCD. Dr. Gilbert

testified that the results indicated that you were 7% more likely to have suffered a broken bone if

you had received a vaccination in the past 12 months. Id. at 246. Further, the results from the

study also indicate that you are 11% less likely to suffer from depression if you had received a

vaccine in the past 12 months. Id. at 247. According to Dr. Gilbert, these findings “make me

think, hmmm, maybe there’s a problem with the way this study was designed.” Id. at 246. In

summary, Dr. Gilbert testified convincingly that the results of this study were not reliable and

constituted “statistical noise.” Id. at 247.

Petitioner also discussed an article that Dr. Gilbert wrote with four other authors (See

Martino et al., Immunopathogenic Mechanisms in Tourette Syndrome: A Critical Review, MOV

DISORD. 2009, pp. 1267–79, (filed as Ex. 44)). In that article, the authors hypothesize that

“symptoms observed in TS patients, such as tics, OC symptoms, and depressive/anxiety

symptoms, might also be directly or indirectly precipitated by cytokines.” Id. at 9. The conclusion

of the one paragraph devoted to a discussion of cytokines in this ten-page article states, “However,

16

Gilbert et al., A Pediatric Neurology Perspective on Pediatric Autoimmune Neuropsychiatric Disorder

Associated with Streptococcal Infection and Pediatric Acute-Onset Neuropsychiatric Syndrome, THE

JOURNAL OF PEDIATRICS, May 21, 2018 (filed as Ex. C, Tab 4).

32

currently clear evidence of cytokine-induced neural dysfunction in TS is lacking and should be

addressed in future studies.” Id. This article is consistent with Dr. Gilbert’s testimony at hearing

that Dr. Chang’s proposed causative mechanism is no more than a hypothesis. 17 Tr. at 219.

While the exact role of cytokines in this process is investigated, literature has yet to support

cytokine expression as a sound and reliable theory of causation in the development of PANS. As

Dr. Gilbert testified at hearing, “there’s no evidence of cytokine expression involvement in PANS

that’s credible.” Tr. at 375-76. Petitioner is not required to produce medical literature to establish

vaccine causation. When literature is submitted, the special master can consider that literature as

part of the Althen prong 1 analysis. Andreu, 569 F.3d at 1379. Along the same lines, there is not

any consensus regarding the role of inflammation in causing tics or OCD.18 It is, therefore, not

clear what, if any, factors can serve as triggering events for PANS and how such triggering events

cause PANS. Proof that the proffered medical theory is plausible or possible does not satisfy a

petitioner’s burden. See Boatmon, 941 F.3d at 1359-60.

I do not find it probable that PANS can be caused by a cytokine cascade and, as such, find

that Petitioner failed to meet her burden in presenting preponderant evidence linking N.A.C.’s

vaccinations to PANS under Althen prong 1.

d. Molecular Mimicry

Although only addressed in passing, Petitioner’s expert did discuss the concept of

molecular mimicry as a potential causation mechanism for PANS. During the initial part of his

direct examination, Dr. Chang discussed two hypothetical mechanisms, that he described as

immunologic and inflammatory. In the immunologic mechanism (molecular mimicry), the

antigens “look a little bit enough like the host brain tissue that the host would make antibodies

against that, thinking that that might be a defense mechanism.” Tr. at 119. During his testimony,

Dr. Chang clarified that his causative theory in this case was the inflammatory theory. Dr. Chang

testified as follows:

Q. So you wrote in your report that PANS is thought to be inflammatory and/or

immunologic. And in this case in particular, it sounds like you’re saying you think

this is more of the inflammatory –

17

Several times during the hearing, Dr. Gilbert referenced “high quality scientific literature” and “class I

evidence” and getting to “99 percent” regarding a theory. Tr. at 219, 221, 227. I recognize that this level

of evidence is not required in the Vaccine Program, and that instead, Petitioner is required to present a

sound and reliable theory that establishes each Althen prong by preponderant evidence. I have applied that

standard in this case.

18

See Donald L. Gilbert, MD, MS, Inflammation in Tic Disorders and Obsessive-Compulsive Disorder:

Are PANS and PANDAS a Path Forward?, JOURNAL OF CHILD NEUROLOGY, 2019 (filed as Ex. C, Tab 3)

stating, “At this time, among highly experienced and respected clinicians and researchers spanning relevant

disciplines, there is substantial controversy regarding a role for inflammation in producing tics and

obsessive-compulsive disorder.” Dr. Gilbert’s testimony at hearing was similar: “to date we don't have

evidence that PANS is an inflammatory disorder. That's an ongoing area of investigation. Some PANS

cases may turn out to be inflammatory over the next 20 years, some may not. It may not be inflammatory

at all.” Tr. at 376.

33

A. Inflammatory, exactly. Right.

Q. So why do you say that in this specific case?

A. I would say that more because of the acuity of the symptoms. The cytokine

reaction is so quick. The inflammatory reactions are so quick. … But I would say

because of that, it makes more sense to me that this would be something that would

be more cytokine/inflammatory cascade-related than something that would be more

antibody cross-reacting, which often can take a little bit longer. I understand – my

understanding is limited in that area, but I understand some other disorders can take

longer to manifest in which there is molecular mimicry or antibody [sic] that

actually cross react.

Q. So when you talk about the production of antineuronal antibodies … is that for

the immune-mediated response?

A. That’s more for the immune – what we think about is the, right antibody

mediator response.

Tr. at 191-92.19 Based on Dr. Chang’s own testimony, I do not find molecular mimicry to be a

viable causation theory in this case. The onset of symptoms so quickly after vaccination is not

consistent with the adaptive immune response inherent in the theory of molecular mimicry. 20

2. Althen Prong 2: There is not Preponderant Evidence that N.A.C.’s Vaccinations Did

Cause PANS

The second Althen prong provides that petitioners must demonstrate by a preponderance

of the evidence that there is “a logical sequence of cause and effect” between the vaccination and

the illness. Althen, 418 F.3d at 1278. I note at the outset that my findings with respect to the first

Althen prong make it impossible for me to conclude that Petitioner successfully established that

N.A.C.’s vaccines “did cause” his PANS. However, even assuming I had determined that

Petitioner successfully established a sound and reliable medical theory, she still has not

19

Dr. Chang testified about his support for an inflammatory theory of causation several times during the

hearing. See also Tr. at 159-60, 203.

20

See Mosley v. Sec’y of Health & Human Servs., No. 08–724V, 2015 WL 2354316 (Fed. Cl. Spec. Mstr.

Apr. 27, 2015) (finding onset of TM one day after tetanus vaccination was too soon to support the immune

activation required for vaccine causation); Crosby v. Sec’y of Health & Human Servs., No. 08–799V, 2012

WL 13036266 (Fed. Cl. Spec. Mstr. June 20, 2012) (finding a 24-hour window between vaccination and

symptom onset was not medically appropriate in the context of a molecular mimicry theory); Flores v.

Sec’y of Health & Human Servs., No. 10–489V, 2013 WL 5587390 (Fed. Cl. Spec. Mstr. Sept. 12, 2013)

(finding the cause of a stroke one day after vaccination could not have been immune-mediated

inflammation), aff’d, 115 Fed. Cl. 157 (2014).

34

preponderantly demonstrated a logical sequence of cause and effect between N.A.C.’s

vaccinations and his illness.

a. Treating Physicians

In weighing evidence, special masters are expected to consider the views of treating

doctors. Cappizano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1326 (Fed. Cir. 2006).

The views of treating doctors about the appropriate diagnosis are often persuasive because the

doctors have direct experience with the patient whom they are diagnosing. See McCulloch v. Sec’y

of Health & Human Servs., No. 09-293V, 2015 WL 3640610, at *20 (Fed. Cl. Spec. Mstr. May

22, 2015).

In this case, no treating physician has diagnosed N.A.C. with PANS. Setting the diagnosis

aside and looking to the underlying symptoms, no treating physician has attributed any of N.A.C.’s

tics or OCD to his vaccinations. In fact, on October 15, 2012, Dr. Loma-Miller (a neurologist)

assessed N.A.C. and specifically stated “I explained to the mother that I do not think that these

abnormal movements are related to the vaccines. There was no specific data in the medical

literature to support such concerns.” Ex. 2 at 11. No other treating physician commented on

N.A.C.’s PANS (or any symptoms associated with PANS) as developing from the vaccines he

received. 21

b. There is no Medical Record Evidence that N.A.C. Experienced Immune

Activation

Dr. Chang’s prong 1 theory of causation is that cytokines produced after vaccination

crossed N.A.C.’s blood-brain barrier, targeted the basal ganglia, and resulted in PANS. However,

Dr. Chang admitted that there was no evidence that any of these steps occurred in N.A.C.’s case.

Dr. Chang testified, “That’s correct. There’s no way of knowing [the level of cytokines created in

N.A.C.’s case post-vaccination] for sure unless he had his blood drawn for those factors at that

time.” Tr. at 160. When asked “Is there any evidence of permeability of the blood-brain barrier

having that characteristic in N.A.C.’s case?” Dr. Chang responded, “Not that I’m aware of.” Id.

at 161. Finally, when asked “How would we know if there was inflammation in N.A.C.’s basal

ganglia?” Dr. Chang responded that brain imaging would have needed to have been done very

quickly. He acknowledged that it was not done in this case. Id. at 162.

As Dr. Gilbert noted in his expert report, “in N.C.’s case, there are no medical diagnostic

tests that support that his immune system was activated in any unusual, disease-causing way.

There was no immune testing done at all.” Gilbert Rep. at 13. While these test results may not be

21

Petitioner testified at hearing that the ER doctor told her “there’s a possibility” N.A.C.’s vaccinations

caused his onset of symptoms. Tr. at 26. She further testified that her family doctor also indicated N.A.C.’s

vaccinations could have caused his tics and OCD: “And I asked Dr. John, I said, Dr. John, could vaccines

cause this? And he said, yes, there’s a good possibility.” Tr. at 31. I decline to credit this testimony over

the contemporaneous medical records, which do not reference such comments. See Ex. 5 at 1-18; Ex. 8 at

3-4.

35

necessary for Petitioner to meet her burden under Althen prong 2, the lack of such evidence does

not advance Petitioner’s case.

Further, there is no indication that N.A.C. showed any reaction to the vaccinations he

received. The medical records do not suggest that he developed a post-vaccination fever or

malaise. In other words, there is no indication in N.A.C. of a release of cytokines above that which

would normally be expected to occur. The only support that Petitioner provides in asserting that

there is a logical sequence of cause and effect between the vaccinations and the injury is the injury

itself coupled with its temporal proximity to vaccination. This showing is insufficient. For the

reasons discussed above, there is not preponderant evidence of a logical sequence of cause and

effect between the vaccinations that N.A.C. received and his development of PANS. Petitioner

has therefore failed to sustain her burden under Althen prong 2.

3. Althen Prong 3: Petitioner has not Demonstrated that N.A.C. Developed PANS in a

Medically-Appropriate Onset Interval after Vaccination

The timing prong contains two parts. First, a petitioner must establish the “timeframe for

which it is medically acceptable to infer causation” and second, he must demonstrate that the onset

of the disease occurred in this period. Shapiro v. Secʼy of Health & Human Servs., 101 Fed. Cl.

532, 542-43 (2011), recons. denied after remand on other grounds, 105 Fed. Cl. 353 (2012), aff’d

without op., 503 F. App’x 952 (Fed. Cir. 2013). I find that Petitioner has not established the

timeframe for which it is medically acceptable to infer causation, and because of this has not

established that N.A.C. developed PANS in such a medically-accepted time period.

a. N.A.C. Developed PANS the Day after his Vaccinations

N.A.C. received his vaccinations on September 26, 2012. Petitioner informed Dr. Loma-

Miller that N.A.C. “started having episodes of abnormal movements consisting of neck flexion,

shoulder shrugging and throat clearing episodes” on September 27, 2012. Ex. 2 at 10. Consistent

with this entry in the medical records, Petitioner testified at hearing that N.A.C. experienced a

reaction the next day after his vaccinations, approximately 30 hours later. Tr. at 15.

b. Petitioner has not Established the Timeframe for which it is Medically

Acceptable to Infer Causation

While the record establishes that N.A.C. developed his first symptoms of PANS

approximately one day after his vaccinations, neither expert spent much time discussing the

medically-appropriate interval between vaccination and onset of PANS. Dr. Chang provided

limited testimony on this issue.

Q. So what about the triggering event. Is there anything in your research or in the

literature that talks about the triggering event and then onset –

A. That it has to be within a certain amount of time of the actual – not per se.

That’s something that we’ve talked about. For example, we use strep as the best

example of that. We always say, well, how soon after a strep infection do you need

36

to have this happen? And unfortunately, there’s been no consensus about that

because it seems like there’s a variety of presentations that can happen the day after

you get, you know, a sore throat. It can happen the week after you get the sore

throat and a fever.

I would say that usually anything more than a few weeks after it would be very

unlikely to be that case. So in my personal opinion, I would say usually it’s one to

two weeks. However, that’s, again, not born out by any research or even by

consensus because people have different opinions on that.

Tr. at 188. It is unclear why Dr. Chang discussed one to two weeks when onset in this case took

place approximately one day after vaccination. It is possible Dr. Chang was referring to onset of

symptoms in a case that developed during molecular mimicry.

Dr. Chang did provide additional testimony regarding prong 3 when questioned by

Petitioner’s counsel on redirect examination.

Q. How rapid is cytokine expression following vaccination?

A. Oh. Again, I’m not a vaccination expert. But my understanding is that

following any kind of this type of provocation with antigen, whether live or dead,

you get very rapid cytokine response. …

Q. Hours? Days?

A. Yeah. I would say within hours.

Q. Does that – so given the rapidity of onset, if you assume that vaccination was

the triggering event and symptoms manifested within a day or so post-vaccination,

does the cytokine expression theory explain the rapid acute onset then?

A. Well, it indicates that, yes, you would have the rapid inflammatory cascade.

And so, yes, it does in my mind explain that. One possibility of why it’s so rapid.

Tr. at 203. While this testimony does suggest that Dr. Chang believes 24 hours is an appropriate

temporal onset interval based on the causation theory he presented, this testimony merely states

his belief. A special master is not required to accept an expert’s ipse dixit. Snyder, 88 Fed. Cl. at

743. Dr. Chang does not explain how a rapid cytokine response can cause onset of PANS in one

day. Although not required, he also does not cite to any literature in support of this proposition.

In fact, it is difficult to square this testimony with Dr. Chang’s earlier statement that there was “no

consensus” about an appropriate onset interval. Id. at 188. Thus, Petitioner has not established

that Althen prong 3 has been met in this case based on Dr. Chang’s say-so. She instead needed to

establish that this opinion constituted a sufficiently reliable medical or scientific explanation. The

evidence presented was insufficient in this regard.

37

Further, Dr. Gilbert testified he believed onset in approximately one day was “unlikely.”

Tr. at 366. He specifically testified that “the proposed mechanism of a vaccine causing a change

in the brain that quickly that’s restricted to tics and OCD symptoms, seems to me extremely

unlikely based on my experience with other things that have a biological marker like NMDA

receptor encephalitis.” Id.

Petitioner does not meet her burden by simply showing a proximate temporal association

between the vaccination and the injury. Grant, 956 F.2d at 1148 (quoting Hasler v. United States,

718 F.2d 202, 205 (6th Cir. 1983), cert. denied, 469 U.S. 817 (1984) (stating “inoculation is not

the cause of every event that occurs within the ten day period [following it].... Without more, this

proximate temporal relationship will not support a finding of causation”)). While the record in

this case establishes that N.A.C. developed PANS between 24-30 hours after vaccination, this fact

alone does not provide preponderant evidence that such a short temporal interval is medically

appropriate. Petitioner has not met her burden to provide preponderant evidence with respect to

Althen prong 3.

VIII. Conclusion

Petitioner’s desire to understand the abrupt onset of her son’s condition is understandable.

Equally understandable is her belief that N.A.C.’s vaccinations caused him to develop PANS, due

to their temporal proximity to the onset of his illness. However, upon careful evaluation of all the

evidence submitted in this matter, including the medical records, the testimony, as well as the

experts’ opinions and medical literature, I conclude that Petitioner has not shown by preponderant

evidence that she is entitled to compensation under the Vaccine Act. Her petition is therefore

DISMISSED. The clerk shall enter judgment accordingly. 22

IT IS SO ORDERED.

s/ Katherine E. Oler

Katherine E. Oler

Special Master

22

Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by each filing (either jointly

or separately) a notice renouncing their right to seek review.

38